Medical Toxicology

© Ministry of Health , General Directorate of Poison Control Centers , 2016
King Fahd National Library Cataloging-in-Publication Data
Ministry of Health
Medical Toxicology Guide. /Ministry of Health .-
Riyadh , 2016
1- Poisoning 2- Poisoning - Diagnosis

I-Title
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EDITOR IN CHIEF
Ph. Raed Abdulaziz Al Khayyal
BSc Pharm, MBA (UK)
Director General,
Directorate of Poison Control and Forensic Chemistry Centers
EDITOR
Dr. Fawaz Ali Al-Mousa
BSc, MSc, PhD (UK)
Toxicology Consaltant,
Assistant Director General & Director of Technical Affairs,
Directorate of Poison Control and Forensic Chemistry Centers
Medical Toxicology Guide

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AUTHORS
Dr. Ali Gado Dr. Hany Gouda

MD, MSc, PhD. MD, MSc, PhD.
Consultant Medical Toxicologist, Consultant Medical Toxicologist,
General Directorate of Poison Control Centers General Directorate of Poison Control Centers
and Forensic Chemistry and Forensic Chemistry
Dr. Islam Gamaleddin Dr. Ahmed Refat

MD, MSc, PhD (CAN), CISAM. MD, MSc, PhD.
Consultant Medical Toxicologist, Consultant Medical Toxicologist,
General Directorate of Poison Control Centers General Directorate of Poison Control Centers
and Forensic Chemistry and Forensic Chemistry
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Expert advisers
Dr. Mohamed M. Hosam El-Din Dr. Amir El Seddawy

MD, MSc, PhD MD, MSc, PhD
Consultant Medical Toxicologist, Madina PCC Consultant Medical Toxicologist, Qassim PCC
Dr. Mohamed Siam Dr. Mohamed Khaled

MD, MSc, PhD MD, MSc, PhD
Consultant Medical Toxicologist, Madina PCC
Consultant Medical Toxicologist, Asir PCC
Dr. Hanan Fathy Dr. Essam Hafez

MD, MSc, PhD MD, MSc, PhD.
Consultant Medical Toxicologist, Dammam PCC
Consultant Medical Toxicologist, Qassim PCC

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Preface 1
As a part of our commitment towards improving the quality of care and our mission to advance the
practice of Medical Toxicology in the kingdom, we are proud to introduce this valuable document. In
this practice guide, we hand-picked some of the most common poisonings encountered by health care
providers in the kingdom.
We designed this document to be a quick and easy pocket tool that can guide physicians,
pharmacists and nurses on how to effectively manage and stabilize acute poisoning cases along with
the aid of a medical toxicologist. This guide incorporates the most updated information from several
reliable medical toxicology resources. Moreover, we have enriched this guide with several valuable
charts, forms and antidote tables to aid the frontline health care providers to deal with commonly
encountered poisoning cases in a seamless, step wise approach.
We are dedicated to continually improve and update this guide and incorporate more topics on
regular basis in order to better meet the needs of the health care providers as well as the public. This
guide comes in perfect alignment with our strategic initiatives that are aimed to push the medical
toxicology service forward all across the kingdom. We would like to thank all of those who worked
hard in order for this valuable document to see the light and are looking forward to achieve more goals
and initiatives in the near future.
Ph. Raed Abdulaziz Al Khayyal

Director General
Directorate of Poison Control & Forensic Chemistry Centers,
Ministry of Health, K.S.A.
Medical Toxicology Guide I

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PREFACE 2
Medical Toxicology is a medical subspecialty focusing on the diagnosis, management and

prevention of poisoning and other adverse health effects due to medications, occupational,
environmental toxins, and biological agents. It is necessary to establish evidence based medical source
for management of acute intoxicated cases in Saudi Arabia. General Directorate of Poison Control
Centers delighted to present 1st edition of Medical Toxicology Guide, which distills the major
principles and concepts of medical toxicology practice. It is hoped that the guide will be useful to staff
members in medical toxicology practice, as well as targeted personnel from other disciplines, who want
to have a strong foundation in medical toxicological concepts and principles.
Care has been taken to confirm the accuracy of the information presented and to describe generally
accepted practices. However, application of this information in a particular situation remains the
professional responsibility of the practitioner. I invite the readers to send us their suggestions of ways
to improve this guide at [email protected] . Finally, I would like to acknowledge all individuals who
were involved in this project.
Dr. Fawaz Ali Al Mousa

Toxicology Consultant,
Assistant Director General & Director of Technical Affairs,
Directorate of Poison Control Centers & Forensic Chemistry,
Ministry of Health, K.S.A.
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TOPIC PAGE
PREFACE I
TABLE OF CONTENT III
LIST OF CHARTS VI
LIST OF FORMS VI
LIST OF ABREVIATIONS VII
GENERAL TOXICOLOGY
General approach to acutely poisoned patients 1

Dr. ALI GADO MD, MSc, PhD.
Toxidromes 10
Dr. ISLAM GAMALEDDIN MD, MSc, PhD (CAN), CISAM.
Investigations 13
Decontamination 14
Enhancement of elimination 19
Dr. HANY GOUDA MD, MSc, PhD.
Admission criteria for a poisoned patient 22
SYSTEMIC TOXICOLOGY
ANALGESICS AND ANTIINFLAMMATORY DRUGS

Acetaminophen 25
Salicylates 35
Non-Steroidal Anti-inflammatory Drugs 43
FOODS & DIETARY AGENTS

Vitamins 48
Dr. AHMED REFAT MD, MSc, PhD.
Iron 53
Food Poisoning 59
Botulism 65
PHARMACEUTICALS
Antidiabetic Drugs 70
Anticholinergics 77
Medical Toxicology Guide III

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CARDI0PULMONARY MEDICATIONS
Beta-blockers 81
Calcium Channel Blockers 87
Cardiac Glycosides 93
Theophylline 101
PSYCHOTROPIC MEDICATIONS
Lithium 109
Tricyclic Antidepressants 113
Antipsychotic Drugs 119
Benzodiazepines 125
SUBSTANCE OF ABUSE
Amphetamines and Cathinones 130
Cocaine 135
Opiates 138
Cannabis 146
Ethanol 152
HOUSEHOLD PRODUCTS
Caustics 158
Hydrocarbons 164
Methanol 170
Paraphenylenediamine 176
PESTICIDES
Aluminum and Zinc Phosphide 179
Organophosphates and Carbamates 183
Pyrethrins and Pyrethroids 189
Warfarin and Related Rodenticides 194
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GASEOUS POISONS
Carbon Monoxide 199
NATURAL TOXINS AND ENVONOMENATION

Snake Bite 205
Scorpion Sting 216
NON-TOXIC INGESTIONS 221

ROLE OF TOXICOLOGY LABORATORY 224

SUBSTANCES OF ABUSE TESTING: (SPECIMEN COLLECTION) 228

ASYMPTOMATIC PATIENT PRESENTATION
Dr. AHMED REFAT MD, MSc, PhD. 235
ANTIDOTES 244
list of antidotes 261 -262
Medical Toxicology Guide V

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LIST OF CHARTS
CHART I: GENERAL APPROACH TO POISONED PATIENTS P. 2

CHART II: ACETAMINOPHEN POISONING P. 33
CHART III: TRICYCLIC ANTIDEPRESSANTS POISONING P. 117
CHART IV: SNAKE BITE P. 214
CHART V: SCORPION STING P. 219
LIST OF FORMS
SNAKE BITE OBSERVATION FORM P. 212
MEDICAL TOXICOLOGY HISTORY INTAKE FORM P. 240
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LIST OF ABBREVIATIONS
ABG Arterial Blood Gases

AC Activated Charcoal
ACLS Advanced Cardiac Life Support
ALT Alanine Transaminase
AST Aspartate Transaminase
AXR Abdominal X- Ray
BUN Blood Urea Nitorgen
CBC Complete Blood Count
CCB Calcium Channel Blocker
CNS Central Nervous System
CO Carbon Monoxide
CVP Central Venous Pressure
CVS Cardiovascular system
CPK Creatine Phosphokinase
CXR Chest X- Ray
ECTR Extracorporeal Therapy
EKG Electrocardiogram
GCMS Gas Chromatography Mass Spectrometry
GCS Glasgow Coma Score
INR International Normalized Ratio
LFT Liver Function Tests
MDAC Multiple Dose Activated Charocal
NAC N-acetyl Cysteine
NaHCO3 Sodium Bicarbonate
NAPQI N-acetyl-p-benzoquinoneimine
NSAID Non-steroidal anti-inflammatory drug
OPIDN Organophosphate agent-induced delayed neuropathy
PCLS Pediatric Cardiac Life Support
PTT Partial Thromboplastin Time
PT Prothrombin Time
RFT Renal Function Tests
TCA Tricyclic Antidepressant
Medical Toxicology Guide VII

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GENERAL TOXICOLOGY
WHAT IS TOXICOLOGY?
Toxicology is "the science of poisons."
More descriptive definition: "The study of the adverse effects of chemicals or
physical agents on living organisms".
MAJOR PATHOPHYSIOLOGIC TOXIC MECHANISMS:

Toxic substances have 9 common major pathophysiologic mechanisms:
1. Substances that produce local tissue damage (corrosives).
2. Toxins that produce damage to the lungs through aspiration
(hydrocarbons) or systematically (paraquat).
3. Substances that may stimulate or depress the CNS and produce coma
(opioids, sedative-hypnotics) or convulsions (cocaine, amphetamines).
4. Compounds that modulate the autonomic nervous system producing
cholinergic effects (organophosphorus and carbamates insecticides)
or anticholinergic action.
5. Substances that may affect the heart, producing myocardial
dysfunction (tricyclic antidepressants), dysrhythmias (quinidine),
hypertension (cocaine, amphetamine), and hypotension (β blockers
and calcium channel blockers).
6. Substances that damage the liver (paracetamol) or kidneys (metals).
7. Substances that interfere with the transport or tissue utilization of
oxygen (cyanide, hydrogen sulphide and carbon monoxide) resulting
in hypoxia.
8. Substances that disturb the acid-base balance such as methanol
toxicity which produces metabolic acidosis.
9. Hematological toxicity as seen in warfarin and super-warfarin toxicity.
GENERAL APPROACH TO ACUTELY POISONED PATIENTS

Objectives:
To acquire a systematic approach to the resuscitation, work-up, diagnosis
and treatment of acutely poisoned patients.
Medical Toxicology Guide 1

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GENERAL APPROACH TO
POISONED PATIENTS
Check gag and cough reflexes.

AIRWAY WITH CERVICAL If impaired, perform
Position the patient.
SPINE SUPPORT Clear the airway.
endotracheal intubation
Check by pulse oximetry Assess and treat:

Assist with bag and mask Ventilatory failure
BREATHING Hypoxia
Administer O2
Bronchospasm
Obtain ABG
Assess and treat:

Measure pulse and BP Bradycardia and A-V block
ECG monitoring QRS interval prolongation
CIRCULATION Tachycardia
Insert 1-2 IV lines
Hypo and hypertension
Obtain routine
Ventricular arrhythmias
Assess and treat:

Recognize and treat hypoglycemia
Coma
ALTERED MENTAL STATUS Monitor Temperature
Seizures
Urinary catheterization
Hypothermia
Hyperthermia
History Look for:

CLINICAL DIAGNOSIS Physical examination Toxidromes
Laboratory investigation Lab Investigations (Routine)
Toxicology screen
Skin and ocular decontamination

DECONTAMINATION Activated charcoal for oral
ingestions
ANTIDOTES Administer Antidotes if available
Multiple Dose Activated Charcoal

ENHANCEMENT OF Alkaline Diuresis
ELIMINATION Hemodialysis
Hemoperfusion
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GENERAL PRINCIPLES FOR MANAGEMENT OF ACUTE POISONING:

- Treat the patient, not the poison.
- Supportive care is the mainstay of management.
- Patients presenting with acute poisoning must be accurately, and
thoroughly assessed, and provided with prompt therapy.
- It is essential to determine if the poisoning:
- Is life-threatening and is causing deterioration in vital functions.
- Poses a potential hazard.
- Is possibly harmless.
- In case of a life-threatening poisoning, emergency treatment begins with
the initial rapid assessment and resuscitation.
- While assessing the severity of the poisoning, information regarding the
toxic agent (e.g., name, amount, route, duration of exposure, time since
exposure and prior treatment received) are necessary.
- It should be borne in mind that often the histories are incorrect concerning
the substance, quantity, and even actual exposure. However, early
identification of the toxic substance can save time and decrease the risk of
toxicity and complications, particularly where a specific antidote could be
life-saving or can prevent organ damage. Obtaining the original left over
from the suspected toxic agent or its container is more reliable for rapid
and positive identification of the poison.
- Call the regional Poison Control Centre for information (800-4428-800 or
937).
- An early collection of biological samples is warranted to establish baseline
values for monitoring toxic agents e.g., blood, urine, and other body fluid
samples.
- Risk factors such as age, current medications, history of medical/
psychiatric illnesses, and allergy to drugs, drug abuse, and pregnancy
should also be considered.
- Patients could present to the ER without symptoms for the following
possible reasons:
1- Exposure to a non-toxic substance (See list of non-toxic substances
P. 221).
2- Ingestion of insufficient amounts of a poison to result in poisoning.
3- Delayed absorption of the toxic substance (common with
belladonna alkaloids, antihistamines, phenothiazines, atropine,

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tricyclic anti-depressants and ingestion of toxins while stomach is

full (except for fat-soluble poisons).
4- Ingestion of sustained release preparations in which the
absorption is delayed and prolonged.
5- Delayed symptoms if only the metabolite of the substance
ingested is toxic and not the substance itself (e.g. methanol that is
metabolized to formic acid, etc.).
- Carefully record the events and procedures in cases where suicide is
suspected.
- Always fill up the history intake and reporting form for poisoned cases.
EMERGENCY EVALUATION AND LIFE-SAVING TREATMENT

- Primary assessment and resuscitation – the ABCDEs.
- Secondary assessment – history, detailed clinical examination and
laboratory evaluation (establishing diagnosis).
I- PRIMARYASSESSMENT AND RESUSCITATION – THE ABCDES
- Immediate Stabilization: In infants and children ABC (Airway, Breathing,
and Circulation); in adults CAB (Circulation, Airway, and Breathing)
A= AIRWAY with cervical spine control:
Assessment:
- The most prevalent factor contributing to mortality from drug overdose
is loss of airway protective reflexes with subsequent airway obstruction
by a flaccid tongue, aspiration of gastric contents, or respiratory
depression.
- All poisoning patients should be managed as if they have a potentially
compromised airway.
- Patients who are awake and talking are likely to have intact airway
reflexes, but should be monitored closely, as a deterioration of their
condition, can result in rapid loss of airway control.
- In lethargic or obtunded patients, the gag or cough reflexes may be
indirect indicators of the patient`s ability to protect the airway. If there
is any doubt regarding the patient`s ability to protect his airway, it is
best to perform endotracheal intubation.
Treatment:
- Optimize the airway position and clear the airway.
- Perform endotracheal intubation if indicated.
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B= BREATHING:
- Assess breathing (respiratory rate, depth, rhythm and sounds). Normal
respiratory rate in adults varies from 12-18 breaths / minute. Any
respiratory rate >20 or <10/min is abnormal in adults (infants normal
respiratory rate is) 25-30/min.
- Ensure adequate ventilation and oxygenation. Quickly obtain bedside
pulse oximetry and arterial blood gases.
- If the patient is not breathing or breathing inadequately (O 2 saturation <
90% and pCO2 > 50 mm Hg), begin ventilation with a bag-valve-mask
(BVM) and give 100% O2.
- If the patient is breathing but O2 saturation is between 90 - 95 %,
supplement with high flow O2.
- Breathing difficulties are the major cause of morbidity and mortality in
poisoned patients.
- Assess and treat ventilatory failure, hypoxia and bronchospasm.
C= CIRCULATION
- Insert IVs ⇒ Draw blood ⇒ Begin IV infusion ⇒ Monitor, pulse, and
blood pressure ⇒ CPR if no pulse and ACLS for arrhythmias and shock ⇒
Continuous EKG monitoring.
- Assess and treat Bradycardia and A-V block, QRS interval prolongation,
Tachycardia, Hypotension, Hypertension and possible cardiac
arrhythmias.
D= DISABILITY (NERVOUS SYSTEM)
- Determine the level of consciousness using the AVPU method:
- A = Alert, V = Responds to verbal stimuli, P = Responds to painful stimuli
and U = Unresponsive.
- Continuously assess the level of consciousness.
- Assess pupil size, reactivity and extra ocular movements.
- Check for reflexes and other neurological signs (dystonia, rigidity, and
dyskinesia) and rhabdomyolysis.
- Treat seizures promptly with Diazepam (0.1 - 0.2 mg/kg IV slow
injection), can repeat q 1-2 hrs as needed. You can use Lorazepam 0.05-
0.1mg/kg IV slow injection or Midazolam 0.05-0.1mg/kg IV or IM in
place of Diazepam, depending upon the availability. Phenobarbitone (15
mg/kg IV) slowly can be used if convulsions remain uncontrolled with
Diazepam.

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- Coma or stupor is the most common serious complications in acute

poisoning.
- Consider excluding other causes of coma (trauma, meningitis,
encephalitis, and CVA)
1- Maintain the airway, assist ventilation and administer oxygen.
2- Unless specifically contraindicated within the first 5 minutes of
managing a patient with an altered mental status due to an
unknown cause, four therapeutic agents should be considered:
(a) Hypertonic dextrose 0.5–1.0 gm/kg of D50W for an adult, or a
more dilute dextrose solution (D10W or D25W) for a child.
The dextrose is administered to diagnose and treat or
exclude hypoglycemia.
(b) Thiamine 100 mg IV for an adult (usually unnecessary for a
child) to prevent or treat Wernicke`s encephalopathy.
(c) Titrated naloxone beginning at 0.04 mg IV for an adult or child
with suspected opioid-induced respiratory compromise.
(d) High- flow oxygen (8–10 L/min) to treat hypoxia.
- Monitor core temperature (rectal) and maintain normothermia.
Associated hypothermia should be assessed and treated by rewarming
(blankets, warm IV fluids, and warm mist inhalation) slowly to prevent
rewarming arrhythmias. Do not treat associated bradycardia. Do not
give excessive fluids.
- Patients with life-threatening hyperthermia (temperature > 40°C or
>104°F), should be treated immediately according to the following step-
wise approach:
1. Maintain the airway, assist ventilation and administer oxygen.
2. Give glucose containing IV fluids, control seizures, agitation.
3. Start external cooling with tepid (lukewarm) water sponging and
fanning, the aim is to bring the temperature to 38.6°C.
4. Exclude other causes of hyperthermia (drug withdrawal, heat stroke,
thyrotoxicosis, meningitis, encephalitis, or other systemic infections).
5. For malignant hyperthermia, administer Dantrolene (1-10 mg/kg IV).
6. In case of anticholinergic poisoning, antidote treatment may reduce
hyperthermia.
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E = EXPOSURE WITH ENVIRONMENTAL CONTROL

- The poisoned patient should be completely undressed and examined
thoroughly, particularly for signs of trauma, burns, puncture marks,
rash, petechiae, etc. removal of clothing is also warranted for necessary
skin decontamination.
- Assess and treat anaphylaxis.
- Assess and treat rhabdomyolysis by:
1- Obtaining serum creatinine and creatine phosphokinase (CPK)
levels.
2- Administering IV fluids; maintain urine flow to 3-5 ml/kg/hr.
3- Mannitol 0.5 gm/kg IV can be considered in patients with oliguria.
4- Alkalinize urine by adding 100 mEq of sodium bicarbonate to each
liter of D5W.
- Maintain airway and ventilation in cases presenting with dystonia,
dyskinesia, and rigidity.
- For dystonia, administer Diphenhydramine 0.5-1mg/kg IM.
- For dyskinesia, administer Diazepam, if uncontrolled, search for the
cause (spider bite/malignant hyperthermia or Neuroleptic syndrome),
and treat accordingly.
II- SECONDARY ASSESSMENT – DIAGNOSIS OF POISONING

- After the primary assessment and resuscitation, the patient should
undergo a secondary assessment. as follows:
1- A careful history.
2- A detailed clinical examination.
3- Clinical laboratory tests.
History:
- Often: Incomplete, unreliable or unobtainable.
- Sources: Patient, friends, family, empty pill containers.
- Inquire about all the drugs taken, including prescribed as well as,
over the counter medications, herbs, and vitamins.
- Ask family members or friends, about any prescription or over the
counter medication known to be used by the patient or others in
the house.
- Obtain any available drugs for later testing.
- Ask about the dose, time, and route of administration.

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- Inquire about liver, renal, cardiac and pulmonary disease,

concurrent medications, previous overdoses, substance abuse and
smoking.
- History should be directed towards identifying the following:
1- Type of poison (chemical, drug, insect bite/sting, plant).
2- Amount / quantity.
3- Route of exposure.
4- Time since exposure.
5- Reason for exposure.
6- Time of onset of symptoms in relation to exposure.
7- Treatment received prior to arrival to hospital.
Physical examination:
- A physical examination should be performed rapidly, but
thoroughly. Key elements of the directed examination include an
evaluation of the mental status, pupil size and reactivity, skin
moisture, bowel sounds, and bladder size (urinary retention).
Characteristic breath or skin odors may help identify the etiology of
coma.
- The detailed clinical examination is essential to diagnose poisoning
and should include the following:
1) Reassessment of vital functions. Carefully examine chest for
respiratory and cardiovascular functions.
2) Assess neurological status. The level of consciousness is
usually assessed in the secondary assessment by using the
Glasgow Coma Score (GCS). A GCS of 8 or less strongly
indicates that the patient will not be capable of adequately
protecting his airway and may require endotracheal
intubation. Patients who are drowsy or stuporous will often
not require intubation provided they are nursed on their side
and continually assessed, e.g., in alcohol or benzodiazepine
over dose.
3) Assess psychosis, agitation and changes to the cognitive
function.
4) Assess for any other neurological changes (e.g., reflexes,
motor dysfunction, extra ocular movements, etc).
5) Examine carefully pupil-size, reaction, nystagmus, and fundus.
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6) Examine skin for temperature, dry/moist, colour (pale,

cyanosed), bleeding, rash, piloerection, bullae, burn injury,
sting / bite marks, and needle tracks.
7) Examine gastrointestinal system starting from the mouth (oral
mucosa burn, breath odor) abdominal tenderness, bowel
sounds, abdominal distension, and check the stools.
8) Examine genitourinary system for distension of bladder, and
check for urine output and color of urine.
9) Record the body weight of the patient.

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TOXIDROMES
- They are characteristic clinical signs and symptoms suggesting a specific
drug class.
- They need high index of suspicion, history and good physical
examination.
- Common Toxidromes include: Sympathomimetic – cholinergic –
anticholinergic – opiate - sedative hypnotic - withdrawal (alcohol,
benzodiazepines and opiates).
Sympathomimetic Toxidrome
Mental status Pupils Vital signs Other manifestations Examples of toxic agents
Hyperalert, Mydriasis Hyperthermia, Diaphoresis, tremors, Cocaine, amphetamines,
agitation, tachycardia, hyper-reflexia, cathinones, ephedrine,
hallucinations, hypertension, seizures pseudoephedrine,
paranoia wide pulse caffeine,
pressure, phenylpropanolamine,
tachypnea, theophylline,
hyperpnea
Anticholinergic Toxidrome
Hypervigilance, Mydriasis Hyperthermia, Dry flushed skin, dry Antihistamines, tricyclic
agitation, tachycardia, mucous membranes, antidepressants
hallucinations, hypertension, decreased bowel cyclobenzaprine,
delirium with tachypnea sounds, urine orphenadrine,
mumbling retention, myoclonus, antiparkinson agents,
speech, coma choreoathetosis, antispasmodics
picking behavior, phenothiazines,
seizures(rare) atropine, scopolamine,
belladonna alkaloids (eg,
Jimson Weed)
Cholinergic Toxidrome
Confusion, coma Miosis Bradycardia, Salivation, urinary and Organophosphate and
hypertension or fecal incontinence, carbamate insecticides,
hypotension, diarrhea, emesis, nerve agents, nicotine,
tachypnea or diaphoresis, pilocarpine,
bradypnea lacrimation, GI physostigmine,
cramps, edrophonium,
bronchoconstriction, bethanechol, urecholine
muscle fasciculations,
seizures, and
weakness
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Cholinergic Toxidrome
Examples of toxic
Mental status Pupils Vital signs Other manifestations
agents
Confusion, Miosis Bradycardia, Salivation, urinary and Organophosphate
coma hypertension or fecal incontinence, and carbamate
hypotension, diarrhea, emesis, insecticides, nerve
tachypnea or diaphoresis, agents, nicotine,
bradypnea lacrimation, GI pilocarpine,
cramps, physostigmine,
bronchoconstriction, edrophonium,
muscle fasciculations, bethanechol,
seizures and weakness urecholine
Opioid Toxidrome
Mental status Pupils Vital signs Other manifestations Examples of toxic
agents
CNS Miosis Hypothermia, Hyporeflexia, Opioids (eg, heroin,
depression, bradycardia, pulmonary edema, morphine,
coma hypotension, needle marks methadone,
apnea & oxycodone,
bradypnea hydromorphone,
diphenoxylate
Sedative-hypnotic Toxidrome
agents
CNS Miosis Hypothermia Hyporeflexia Benzodiazepines,
depression, (usually) bradycardia, barbiturates,
confusion, hypotension, carisoprodol,
stupor, coma apnea & meprobamate,
bradypnea glutethimide,
alcohols, zolpidem
Withdrawal Toxidrome
agents
Alter mental Mydriasis Hyperthermia, tremors, Withdrawal (EtOH,
status tachycardia, hyperreflexia, BDZ, opiates)
hypertension & seizures, nausea,
hyperventilation vomiting
Serotonin Toxidrome
Examples of toxic
agents
Confusion, Mydriasis Hyperthermia, Tremors, myoclonus, MAOIs alone or with:
agitation, tachycardia, hyperreflexia, clonus, SSRIs, meperidine,
coma hypertension & diaphoresis, flushing, dextromethorphan,
tachypnea trismus, rigidity, TCAs & L-tryptophan
diarrhea

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Hallucinogens Toxidrome
Examples of toxic
agents
Hallucinations, Mydriasis Hyperthermia, Nystagmus Phencyclidine, LSD,
perceptual (usually) tachycardia, mescaline,
distortions, hypertension psilocybin, designer
depersonalization, & tachypnea amphetamines (e.g.,
synesthesia, MDMA ["Ecstasy"])
agitation
Comparison between anticholinergic and sympathomimetic

Toxidromes
Anticholinergic Sympathomimetic
Skin Dry Diaphoresis
Bowel sound Inhibited Hyperactive
Urine retention Present Absent
Pupil Dilated fixed Dilated reactive
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INVESTIGATIONS
Routine:
- Random blood glucose (RBS), electrolytes (Na, K, Cl, Ca, Ph), renal
function tests (RFT) (BUN, Creatinine), liver function tests (LFT) (ALT
AST, Bilirubin, ALP), ABGs, and CBC.
- General laboratory tests are more useful than toxicology screens.
Specific:
- Are indicated in following cases:
1) Intentional ingestions
2) Unknown substance.
3) The substance can potentially produce moderate to severe toxicity.
- Blood tests in which the specific drug levels are of clinical
significance, commonly requested and should be readily available:
Acetaminophen, Salicylates, Digoxin, Carbamazepine,
Phenobarbitone, Phenytoin, Valproate, Theophylline, Iron, and
Lithium.
- Qualitative Urine Assays in which the substance is commonly
screened for (positive or negative): Amphetamines, Barbiturates,
Cocaine, Opiates, Propoxyphene, Phencyclidine, Tricyclic
antidepressants, Sedative-Hypnotics, and Cannabis.
- Toxicology screen is used for confirmatory purposes and does not
modify the management of the patient.
Additional Tests:
- Electrocardiogram (EKG) for TCA or other cardiotoxic drugs,
arrhythmias and ischemia.
Radiological Tests:
- Chest X-ray (CXR) for aspiration pneumonia, non-cardiogenic
pulmonary edema (NCPE).
- Abdominal X-ray (AXR) is useful in screening for ingestions of radio-
opaque materials.
- Radiodense substances that may be visible on AXR.
- Chloral hydrate, heavy metals, Iron, Phenothiazines, enteric coated
preparations, sustained release preparations and drug packets.

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DECONTAMINATION
Surface Decontamination:
Skin:
Indications: In poisoning with corrosives, hydrocarbons and toxins rapidly
absorbed through the skin e.g. organophosphates.
Method:
 Be careful not to expose yourself or other care providers to
potentially contaminated substances and wear protective gear.
 Remove contaminated clothing and flush exposed areas with
copious running water or saline.
Eyes:
Indications: In corrosives and hydrocarbons and chemical irritants.
Method: Act quickly to prevent serious damage to the cornea.
1. Flush exposed eye with copious tap water or saline.
2. If available, instill local anesthetic drops first to facilitate eye
irrigation.
3. Remove the victim's contact lenses.
4. Position the victim in the supine position under a tap or use
intravenous tubing to direct the stream of water.
5. Do not instill any neutralizing solution.
6. After completing irrigation, check the conjunctival and corneal
surface. Patients with serious injures should be referred to the
ophthalmologist immediately.
Inhalation Decontamination:
Indications: Injury to the respiratory system is often caused by irritant
gases and fumes.
Method:
 Be careful not to expose yourself or other care providers to
potentially contaminated substances without adequate respiratory
protection.
 Remove the victims from the area of exposure and give
supplemental O2 and assess ventilation if necessary. Observe
closely for evidence of upper respiratory tract oedema.
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 Observe for early signs and symptoms) of late onset non-

cardiogenic pulmonary oedema (e.g., tachypnea, dyspnea, and
hypoxia).
Gastrointestinal Decontamination:
Indications:
- The decision to perform GI decontamination is based upon:
1. The specific poisons ingested.
2. Time from ingestion to presentation at the ER.
3. Presenting symptoms.
4. Anticipated severity of poisoning.
- GI decontamination is most likely to be of benefit if patients present
with the following:
1. Recent ingestion of toxins (usually within one to two hours).
2. Ingestion of a poison and an amount suspected to cause
toxicity.
3. No clinical signs (e.g., somnolence) that render decontamina-
tion dangerous.
- GI decontamination should not be carried out if the agent and
amount ingested are nontoxic, if the agent is considered fully
absorbed due to delayed presentation, or if the toxin is not
responsive to decontamination.
METHODS OF GIT DECONTAMINATION:

1. Single dose of activated charcoal (AC):
Activated charcoal is a fine, black, odorless powder. It is made from
combustion of organic material & treated to increase surface area.
A) Action: Reduces the systemic absorption of many drugs by
adsorption of drugs to the surface of charcoal. It also acts to
enhance elimination by disrupting substantial enterohepatic
recirculation.
B) Dose: 1-2 gm/kg in adults and 0.5–1 gm/kg in children.
C) Complications: Adsorb any other oral antidotes administered.
Gastrointestinal side effects include fullness, abdominal pain,

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nausea, vomiting, constipation, GI obstruction, diarrhea and

aspiration.
D) Contraindications:
1. Coma or convulsions
2. Absence of bowel sounds
3. Perforation or Intestinal obstruction – Need for endoscopy
(Caustics)
4. Late presentation - Toxins poorly adsorbed by AC.
E) Agents for which activated charcoal is not effective (does not
adsorb the poison):
1. Heavy metals: Arsenic, Lead, Mercury, Iron, Zinc and
Cadmium.
2. Inorganic ions: Lithium, Sodium, Calcium, Potassium,
Magnesium, Fluoride, and Iodide.
3. Corrosives: Acids and Alkalis.
4. Hydrocarbons: Alkanes, Alkenes, Alkyl halides, and Aromatic
hydrocarbons.
5. Alcohols: Acetone, Ethanol, Ethylene glycol, Isopropanol and
Methanol.
6. Essential oils.
2- Multiple-Dose Activated Charcoal (MDAC):

A) Indications:
- Very large ingestions of toxic substance.
- Drugs remaining in the GIT as sustained release and enteric
coated preparations.
- Drugs forming concretions e.g. salicylates and phenobarbital.
- Drugs slowing GIT motility e.g. anticholinergic and
carbamazepine.
- Interruption of enterohepatic recirculation as in digoxin
toxicity.
- Facilitation of transluminal diffusion from the body into the
bowel lumen (“Gut dialysis”) as in theophylline.
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B) Dose:
- When the decision has been performed to use multiple-dose
activated charcoal, a repeat dose may be given every 2 to 6
hours. A uniform dose has not been established. Suggested
regimens involve:
- 0.5 g/kg every 2-4 hours.
- 20 g every 2 hours, 40 g every 4 hours or 60 g every 6
hours.
- The duration of treatment has not been established. A
typical approach is to continue it for 24 to 48 hours.
- Continuous nasogastric instillation of activated charcoal,
0.25-0.5 g/kg/h, has been recommended to decrease the
incidence of emesis.
- When the first dose of activated charcoal is associated with
cathartic, subsequent doses of activated charcoal should not
be administrated with a cathartic because of the high risk
incidence of fluid and electrolyte disturbances. Note that
some active charcoal preparations already contain a
cathartic.
3- Gastric Lavage:
- To date, the evidence to support a beneficial role for gastric lavage
in reducing the severity, recovery time or improving outcome for
poisoned patients is weak, even if started within 60 minutes.
According to the American Academy of Clinical Toxicology (AACT)
and the European Association of Poison Control Centers and Clinical
Toxicologists (EAPCCT), most of the studies that were performed to
study the efficacy of gastric lavage did NOT provide evidence to
support its use and the studies that reported benefit from gastric
lavage had significant flaws that rendered them weak. We currently
do NOT recommend the routine use of gastric lavage if at all, as
there are no clear guidelines to indicate the conditions where it is
appropriate to use it (2). In the rare event that an attending
physician is considering to perform gastric lavage for a particular
patient, we advise that he/she would consult a medical toxicologist
prior to performing the procedure.

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4- Whole Bowel Irrigation (WBI):

- Consists of using the surgical bowel-cleansing solution polyethylene
glycol in a balanced, isotonic electrolyte salt solution (movicol, etc.).
A) Action: Whole-bowel irrigation is a method of flushing the
gastrointestinal tract in an attempt to reduce further
absorption of drugs.
B) Procedure:
- The solution is administered as 0.5L/hr in children < 5 years &
1-2 L/hr for adults.
- It is administered by nasogastric tube or orally.
- The end-point is recovery, and return of the drug to
therapeutic levels.
C) Indications:
- Substances poorly adsorbed by AC (iron, lead). Sustained-
release or Enteric coated tablets.
- In cases of body packers (cocaine, heroin).
D) Contraindications:
- Extensive hematemesis, paralytic ileus, bowel obstruction
and, perforation or peritonitis.
E) Complications:
- Nausea & vomiting, aspiration and, decreasing the
effectiveness of activated charcoal.
5- Surgery & Endoscopy:

Surgery and endoscopy are occasionally indicated for
decontamination of poisoned patients if the other methods
failed. Generally, this method is used for body packers
(cocaine, heroin) and bezoars formation in drugs like,
salicylate, iron, and barium.
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ENHANCEMENT OF ELIMINATION
Indications for enhanced elimination:
1. Patients who fail to respond adequately to full supportive care.
2. Patients in whom the normal route of elimination of the drug is
impaired.
3. Patients in whom the amount of drug absorbed is high or its
concentration is high enough in the serum to indicate that serious
morbidity or mortality are eminent.
4. Patients with concurrent disease or in an age group (very young or
old) associated with increased risk of morbidity or mortality from
the overdose.
5. Patients with concomitant electrolyte imbalances that could be
addressed by hemodialysis as lactic acidosis associated with
metformin toxicity.
- Certain methods are applied to enhance excretion of the poison from the
blood after being absorbed. They include the following:
I. Multiple doses Activated Charcoal (MDAC) previously discussed.
II. Manipulation of Urine pH:
Mechanism:
It is the change of the urine pH in order to present the drug for the kidney
in its ionized form. Drugs can be weak acids or bases. If they are rendered
ionized, they are not reabsorbed easily by the renal tubules, so they are
readily excreted.
Alkalization of urine:
Drugs likely to respond to urinary alkalinization are usually characterized
by:
1. Being predominantly eliminated unchanged by the kidney.
2. Distributed primarily in the extracellular fluid compartment.
3. Minimally protein-bound and weak acids such as, salicylates and
phenobarbitone, which have greater ionization and better excretion at
urine pH of 7.5 - 8.
1) Indications:
Salicylates, phenobarbital, chlorpropamide, formate, diflunisal,
fluoride, methotrexate, the herbicide chlorphenoxyacetic acid and
poisons producing hemolysis and rhabdomyolysis.

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2) Methodology:
Add 150 mEq (3 ampoules of 8.4%) of NaHCO3 to 1 liter of D5W to
provide an isotonic solution and 20-40 mEq of potassium chloride/ liter
are added as needed to maintain normokalemia. Administer 10-20
mL/kg initially as a bolus then infuse at 2-3 mL/kg/hr. It should be
infused at a rate sufficient to induce a urine output of 2-3 mL/kg/hr.
Urine pH should be frequently checked every 1-2 hrs.
3) Precautions:
- Keep urinary pH at 7.5-8.
- Keep urine output at 3-5 ml/Kg/hr closely observing input / output
chart.
- Normal renal functions should be ascertained before the start of
diuresis.
- Blood pH and electrolytes should be monitored, especially serum K as
the infusion of NaHCO3 may lead to hypokalemia.
- Auscultate the lung bases for the possibility of pulmonary oedema.
4) Complications:
- Acid-base and electrolyte imbalance.
- Fluid overload with pulmonary and cerebral edema.
III. Dialysis (Extracorporeal Elimination)
 The principle of dialysis is to allow blood to circulate in contact with a
semi-permeable membrane to remove substances from the blood via a
concentration gradient. Dialysis is beneficial when renal functions
become impaired.
 Dialyzable drugs should have the following characteristics:
A) Have a small volume of distribution (<1L/kg).
B) Have low protein binding.
C) Have small molecular weight < 500 Daltons.
D) High water solubility.
E) Low endogenous clearance (< 4 ml/min/kg).
 Examples of dialyzable drugs: Alcohols, Phenobarbital, Lithium,
Salicylates, and Theophylline.
A. Hemodialysis
In addition to removal of toxins, it can correct acid-base and electrolyte
disturbances, and extracellular fluid volume overload.
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Complications: Hypotension, muscle cramps, elimination of therap-

eutically administered drugs, bleeding tendency (due to heparin),
deep venous thrombosis (DVT), air embolism, electrolyte imbalance,
infection, and hepatitis.
Contraindications: Non-dialyzable toxic agents, patients with coagulo-
pathy, patients with uncorrected hypotension.
B. Peritoneal dialysis
Peritoneal dialysis is a relatively simple method to enhance xenobiotic
elimination. It is too slow to be clinically useful. Peritoneal dialysis is
therefore, never the method of choice unless hemodialysis and
hemoperfusion are unavailable.
Complications: Intra-abdominal bleeding, perforation of abdominal
organs, peritonitis, dehydration or over-hydration.
Contraindications: Pregnancy, abdominal hernia or respiratory distress.
C- Hemoperfusion:
This method allows blood derived from the radial artery to pass through
a cartridge coated with activated charcoal to adsorb poisons existing in
the plasma. It can be done for toxins with high protein binding, or for
those having big molecular weight, and also in lipid-soluble drug. The
poison must be adsorbed to charcoal.
Complications: Trapping of white blood cells and platelets causing a
reduction in the platelet count, reduction in (serum calcium,
glucose), hypotension, adsorption of therapeutically administered
drugs.

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ADMISSION CRITERIA FOR A POISONED PATIENT
ADMISSION OF ASYMPTOMATIC PATIENTS:

Any individual presenting with ingestion of a toxic substance must be
admitted under observation for 4 hrs after which he/she can be discharged
if still asymptomatic except in the following conditions:
1. Ingestion of a poison with a delayed onset of action.
2. Intake of sustained release or enteric-coated preparations.
3. Toxic level of the poison in the blood analysis.
4. Intake of a substance that is known to be highly toxic.
ADMISSION OF SYMPTOMATIC PATIENTS:
Patients that are symptomatic but are stable e.g., normal vital signs, normal
acid base balance, electrolytes, normal consciousness level, and the level of
the drug/poison is not highly elevated, can be admitted to the inpatient
unit.
INTENSIVE CARE UNIT (ICU) ADMISSION:
Patients presenting with acute poisoning are often admitted to the ICU,
mainly for close observation and monitoring. Intensive care units allow
healthcare providers the best opportunity to minimize the risk of morbidity
and mortality. Patients should be admitted to the ICU based upon the
following:
1) Severity of illness:
- The Acute Physiology and Chronic Health Evaluation (APACHE II/III), the
Mortality Probability Model (MPM II), and the Pediatric Risk of Mortality
(PRISM II/III) are widely utilized and generally accepted severity-of-illness
models that utilize physiologic parameters and other factors in order to
estimate risks and predict outcomes in critically ill patients.
- The Glasgow Coma Score (GCS) is a commonly used bedside tool to
quickly assess the severity of physiologic derangement and altered
neurologic status.
2) Drug-induced end-organ toxicity:
- The presence of certain signs, symptoms, or abnormal diagnostic tests
requires ICU observation or intervention. Examples of clinical conditions
that require ICU care:
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A. Vital signs: Profound alteration in any vital sign, including

temperature.
B. Central nervous system (CNS): Delirium, coma, convulsion and status
epilepticus.
C. Respiratory: Dyspnea, persistent hypoventilation, acute lung injury,
and hypoxia.
D. Cardiac: Dysrhythmias, hypotension, hypertension, and tissue
ischemia.
E. Hepatic: Liver failure.
F. Renal/metabolic: Severe metabolic acidosis and electrolyte
disturbances.
3) Extremes of age:
- Such as infants and elderly patients who have chronic medical
problems.
4) Physiologic monitoring and specialized treatment:
- The ICU setting offers highly skilled staff. It also provides a nurse-to-
patient ratio that allows for frequent or continuous monitoring of
basic physiologic parameters and invasive monitoring.
- Most critically ill poisoned patients that have acute reversible
conditions requiring supportive care measures (e.g., ventilator
support, vasopressor support and close monitoring).
- Most often, supportive care measures improve the outcome of
critically ill, poisoned patients more than antidotes and specialized
treatments.
CRITERIA FOR DISCHARGING POISONED PATIENTS
- Poisoned patients that were admitted as a result of positive clinical
manifestations can be discharged after a period of observation not
less than 24 hrs after normalizing all abnormal clinical signs,
symptoms and laboratory analysis.
- Patients in which delayed complications are expected, follow up
appointments are warranted for early detection and possible
intervention to control these complications.

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REFERENCES:
1. Toxicology, American Academy of Clinical, Centres, European Association of Poisons and
Toxicologists, Clinical, 2005: ‘Position Papers: Gastrointestinal Decontamination, Clinical
Toxicology, 42:2, 237 URL: http://dx.doi.org/10.1081/Clot.
2. Benson BE, Hoppu K, Troutman WG, Bedry R, Erdman A, Höjer J, Mégarbane B,
Thanacoody R, Caravati EM; 2013: American Academy of Clinical Toxicology; European
Association of Poisons Centres and Clinical Toxicologists. Position paper update: gastric
lavage for gastrointestinal decontamination. Clin Toxicol (Phila). Mar;51(3):140-6.
3. Flomenbaum NE, Goldfrank LR, Hoffman RS, Howland M A, 2011: Initial Evaluation of the
Patient: Vital Signs and Toxic Syndromes In: Goldfrank’s Toxicologic Emergencies, 9th
edition, Nelson LS, Lewin NA, Howland MA, Hoffman RS, Goldfrank LR, Flomenbaum NE
(Eds), McGraw-Hill, New York 2011. p. 36-44.
4. Olson, K. R., & California Poison Control System, 2006: Poisoning & drug overdose.New
York: Lange Medical Books/McGraw-Hill.
5. Chyka PA, Seger D, Krenzelok EP, Vale JA; 2005: American Academy of Clinical
Toxicology; European Association of Poisons Centres and Clinical Toxicologists.
6. Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005;43(2):61-87
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SYSTEMIC TOXICITY
ANALGESICS & ANTIINFLAMMATORY DRUGS
ACETAMINOPHEN POISONING
(PARACETAMOL POISONING)
INTRODUCTION:
- Acetaminophen [APAP] poisoning is one the most prevalent causes of
medication-related poisoning and death worldwide. Serious poisoning
from acetaminophen can result following a single acute ingestion or
through the repeated ingestion of supratherapeutic doses.
- Toxic dose: (150-200 mg/kg or a total dose of 6-7 gm in adults), check
increased frequency of dosing, check time of ingestion and time delay.
- Epidemiology:
Common: Intentional overdose is common
Mild: Toxicity is typically mild if the patient is treated early
Unusual: Death is unusual, developing in patients who present after 24
hours or in whom treatment is mistakenly withheld.
Rare: "Chronic" acetaminophen toxicity may result from repetitive,
supra-therapeutic dosing; such poisonings are usually unintentional
and occur in adults with acute, persistent pain syndromes or in
persistently febrile infants. Adults who ingest greater than 4 g/day
for more than 1 day, and infants less than 2 years of age who are
given more than 150 mg/kg/day for more than 1 day may be at
increased risk.
MECHANISM OF TOXICITY:
- Approximately 90% of acetaminophen normally undergoes hepatic
conjugation with glucuronide and sulfate to form inactive
metabolites, which are eliminated in the urine
- A small fraction of unchanged acetaminophen (< 5%) and other minor
metabolites reach the urine but are not thought to be clinically
relevant.
- The remaining fraction, usually ranging from 5-15%, is oxidized by the
cytochrome-P 450 system (CYP2E1) resulting in the formation N-
acetyl-p-benzoquinoneimine (NAPQI).

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- Glutathione quickly combines with NAPQI. The resulting complex is then

converted to nontoxic cysteine or mercaptate conjugates, which are
eliminated via the kidneys.
- In overdose, the usual metabolic pathways are over burdened, and
acetaminophen is metabolized by CYP2E1 to the reactive metabolite
(NAPQI). Glutathione is able to detoxify NAPQI via conjugation, but
when hepatic glutathione stores become depleted, the metabolite
alternatively binds to macromolecules in the hepatocyte resulting in
cell death and hepatic necrosis.
CLINICAL MANIFESTATIONS:
- Stage I (up to 24 hrs. after overdose): Patients are asymptomatic or have
nonspecific clinical findings (e.g., nausea, vomiting, and malaise).
Liver functions are normal at this stage.
- Stage II (24-72 hrs. after overdose): Right upper quadrant pain, elevation
in liver enzymes, prothrombin time (PT) and international
normalized ratio (INR) and in severe cases, evidence of
nephrotoxicity (elevated BUN, creatinine, oliguria) and/or
pancreatitis (elevated serum amylase and lipase).
- Stage III (72-96 hrs.): Evidence of liver failure (jaundice, coagulopathy,
encephalopathy) and in severe cases acute renal failure, metabolic
acidosis and multi-organ failure. Death most commonly occurs in
this stage.
- Stage IV (4-14 days) recovery phase: Hepatic regeneration, which
generally takes several days to a few weeks, becomes complete in
survivors.
DIFFERENTIAL DIAGNOSIS:
- Toxicologic: Carbon tetrachloride, hepatotoxic mushrooms, halothane,
idiosyncratic drug reactions, pennyroyal oil, and iron.
- Non-Toxicologic: Viral hepatitis A, B, and C, Epstein-Barr virus,
cytomegalovirus, varicella), inborn errors of metabolism,
hepatobiliary disease, and reye syndrome.
INVESTIGATIONS:
- Routine:
1) Monitor serum glucose.
2) Serum electrolytes, ALT, AST, PT, bilirubin, albumin, BUN, creatinine.
3) ABG.
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4) EKG.
5) Salicylate level.
6) Pregnancy test in all women of childbearing age.
- The first AST serves as a screen to detect preexistent hepatic
disease.
- Measuring the ALT and INR every 12 hrs for any patient who
develops ALT elevation.
- Elevated ALT and AST and prolonged PT, bilirubin, glucose, and
alkaline phosphatase, indicate the degree of liver failure.
- Specific:
- Paracetamol serum level at 4 hrs post-ingestion (see nomogram).
- Apply the level on the nomogram in all cases except in chronic
ingestion, use of sustained release tablets, alcoholic or
hepatotoxic medications (liver toxicity line would be much
lower).
ADMISSION CRITERIA:
- Patients who require treatment with N-acetylcysteine are generally
admitted to the hospital, although selected patients (presenting early
with no evidence of liver injury) may be treated with acetyl cysteine
and managed in an emergency department observation unit. Patients
with acute liver failure should be admitted to the ICU and may require
transfer to a facility with liver transplantation service.
TREATMENT:
- Stabilization:
- Airway, breathing, and circulation (ABC) should be evaluated and
stabilized as necessary if the patient came in stage II or III.
- Decontamination:
- Preferably within 1hr of ingestion, give activated charcoal up to 4
hrs post ingestion except in slow release preparations you can
give charcoal after 4 hrs (Administer NAC by IV route if
indicated).
- Antidote:
NAC (N-Acetyl cysteine) start early when indicated.
- Indications for NAC therapy include:
1. Serum acetaminophen concentration drawn at 4 hrs or more
following acute ingestion of an immediate-release

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preparation is above the "treatment" line of the treatment

nomogram for acetaminophen poisoning.
2. A suspected single ingestion of greater than 150 mg/kg (7.5 g
total dose regardless of weight) in a patient for whom the
serum acetaminophen concentration will not be available
until more than eight hrs from the time of the ingestion.
3. Patients with an unknown time of ingestion and a serum
acetaminophen concentration of >10 µg/mL (66 µmol/L).
4. Patients with a history of APAP ingestion and evidence of any
liver injury.
5. Patients with delayed presentation (>24 hrs after intake and
a history of excessive acetaminophen ingestion) with
laboratory evidence of liver injury (ranging from mildly
elevated aminotransferases to fulminant hepatic failure).
- The updated treatment nomogram:
1. All patients with serum acetaminophen level on or > 100 µg/
mL at 4 hrs and 15 µg/mL at 15 hrs after ingestion should
receive N-acetyl cysteine (Parvolex) based on the new
treatment nomogram, wether the risk factors for
hepatotoxicity are present or not.
2. If the timing of paracetamol ingestion is unknown, including
when ingestion has occurred over an extended period of one
hour or more ‘staggered overdose’, N-acetylcysteine should
always be administered without delay (the nomogram should
not be used).
3. Administer the initial dose of N-acetyl cysteine as an infusion
over 60 minutes to minimize the risk of common dose-
related adverse reactions.
4. Hypersensitivity is not a contraindication to treatment with
N-acetyl cysteine.
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New treatment nomogram for acute acetaminophen overdose
- Dose and route of administration:

- IV administration of NAC is favored for patients who present
acutely following ingestion and have any of the following:
1. Vomiting.
2. Pregnancy.
3. Contraindications to oral administration (i.e., pancreatitis,
bowel ileus or obstruction, bowel injury).
4. Patients who refuse oral administration.
5. Patients with evidence of hepatic failure.
- IV NAC 20 hrs course: Loading dose 150 mg/kg in 200ml of D5W
(for adults) over 1hr followed by 50 mg/kg in 500ml of D5W (for
adults) over 4 hrs followed by 100 mg/kg in 1000 ml of D5W (for
adults) over 16 hrs. Beware of anaphylactic reaction
(bronchospasm, hypotension, wheals, and laryngeal edema). Give
adrenaline 0.5 ml SC and IV steroids.
- IV NAC 48 hrs course: Loading dose 140 mg/kg followed by 70
mg/kg over 4 hrs for 12 doses or 72 hrs course = 17 doses

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(superior to the 20hr course when started 16-24 hrs post

ingestion).
- Oral NAC: Loading dose 140 mg/kg followed by 70 mg/kg/4 hrs for
17 doses.
- N- Acetyl Cysteine: Preliminary evidence indicates that the
antidote, N-acetylcysteine (NAC), crosses the placenta and should
be administered to a pregnant woman with the same indications
as patients who are not pregnant. An infant born to a mother with
acetaminophen toxicity should receive a 48-hour course of
intravenous NAC.
- Extracorporeal treatment (ECTR) (hemodialysis):
- Effectively removes acetaminophen from the blood.
- Indications:
- ECTR is recommended in the following:
1. If the APAP is > 1000 µg/mL (6620 μmol/L) and NAC was NOT
administered.
2. In cases presenting with altered mental status, metabolic
acidosis, with an elevated lactate, and an APAP is > 700
µg/mL (4630 μmol/L) and NAC is NOT administered.
3. In cases with an altered mental status, metabolic acidosis, an
elevated lactate, and an APAP is more than 900 µg/mL (5960
μmol/L) even if NAC is administered.
- Choice of ECTR:
- Intermittent hemodialysis is the preferred ECTR in patients
with APAP poisoning.
- Cessation of ECTR:
- ECTR is recommended until sustained clinical improvement is
apparent.
NB: NAC therapy should be continued during ECTR at an increased rate.
- Supportive treatment:
1. Antiemetics (metoclopramide or ondansterone).
2. Monitor and treat hypoglycemia of liver failure. Vitamin K may
improve coagulopathy.
- Indications for Liver Transplantation:
King's College Hospital criteria for liver transplantation in
paracetamol-induced acute liver failure: If arterial pH <7.3 or
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arterial lactate >3.0 mmol/L after adequate fluid

resuscitation.
OR if all three of the following occur in 24-hour period:
1- Creatinine >300 μmol/L.
2- PT >100 seconds (INR >6.5).
3- Grade III/IV encephalopathy.
NB: Some sources recommend measuring serum acetaminophen,
international normalized ratio (INR), serum bicarbonate, and
serum creatinine after completion of treatment and resuming
treatment if any value is abnormal.
- Chronic acetaminophen toxicity (Repeated Ingestions):
In children < 6 years of age:
- 200 mg/kg or more over a period of 8-24 hours,
- 150 mg/kg or more per day for 2days.
- 100 mg/kg or more per day for 3 days or more.
Patients > 6 years of age:
- 10 gm or 200 mg/kg (whichever is less) over 24-hour period.
- 6 gm or 150 mg/kg (whichever is less) per day for 2 days or
longer.
- Important Tips
- Nonspecific symptoms: nausea, vomiting, abdominal pain
(Could be mixed wirh viral syndrome)
- Diagnosis is dependent on the history. Laboratory analysis
(Liver enzymes) may be helpful.
- Serum concentration does not correlate with toxicity.
Indications for NAC in Chronic Toxicity:
- Elevated AST or ALT (should be monitored for 36 hours after
the last ingested dose)
- Paracetamol level > 10 μg/mL
- Symptomatic patients with normal ALT and AST
- Discharging Criteria:
- From the emergency department: "Patients may be
discharged if":
- The time of ingestion is certain.
- The serum acetaminophen level is below the possible
toxicity level.

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- A psychiatric evaluation has been performed.

- From the hospital: "Patients may be discharged after a full
course of NAC, if":
- Liver and renal function tests are normal or improving.
- After a psychiatric evaluation, if needed.
- Patient Educations
- Dangers of over counter medications:
- The health-care professional should educate patients on
the potential dangers of over-the-counter medications.
- Simultaneous usage of acetaminophen preparations:
- Patients should be cautioned that simultaneous use of
more than one acetaminophen product may lead to
inadvertent overdose.
- Substitution of acetaminophen preparations:
- Substitution of inappropriate formulation (e.g., use of an
adult acetaminophen suppository in a child instead of a
pediatric one) may result in toxicity.
COMMON PITFALLS:
- Evaluation:
- Failure to determine the accurate time of ingestion.
- Failure to consider the possible effects of anticholinergic
medications or use of sustained released medication on the
accuracy of the 4-hour acetaminophen concentration.
- Treatment:
- Failure to decontaminate patients who are less than 2 hours
post ingestion.
- Ending treatment for patients who have elevated
transaminases or detectable serum acetaminophen
concentrations.
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COMMON PITFALLS:
Evaluation:
- Failure to determine the accurate time of ingestion.
- Failure to consider the possible effects of anticholinergic
medications or use of sustained released medication on the
accuracy of the 4-hour acetaminophen concentration.
Treatment:
- Failure to decontaminate patients who are less than 2 hours post
ingestion.
- Ending treatment for patients who have elevated transaminases or
detectable serum acetaminophen concentrations.

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REFERENCES
1. Brok J, Buckley N, Gluud C, 2006: Interventions for paracetamol (acetaminophen) overdose.
Cochrane Database Syst Rev; CD003328.
2. Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH, 1988: Efficacy of oral N-acetylcysteine in
the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976
to 1985). N Engl J Med; 319:1557.
3. Rumack BH, Bateman DN, 2012: Acetaminophen and acetylcysteine dose and duration:
past, present and future. Clin Toxicol (Phila); 50(2):91-8.
4. Woodhead JL, Howell BA, Yang Y, et al , 2012: An analysis of N-acetylcysteine treatment for
acetaminophen overdose using a systems model of drug-induced liver injury. J Pharmacol
Exp Ther; 342:529
5. Bateman DN, Dear JW, Thanacoody HK, et al, 2014: Reduction of adverse effects from
intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled
trial. Lancet; 383:697
6. Betten DP, Cantrell FL, Thomas SC, et al, 2007: A prospective evaluation of shortened
course oral N-acetylcysteine for the treatment of acute acetaminophen poisoning. Ann
Emerg Med; 50:272
7. Bond GR, Requa RK, Krenzelok EP, et al, 1993: Influence of time until emesis on the efficacy
of decontamination using acetaminophen as a marker in a pediatric population. Ann Emerg
Med; 22:1403.
8. Wu ML, Tsai WJ, Deng JF, Yang CC, 1999: Hemodialysis as adjunctive therapy for severe
acetaminophen poisoning: a case report. Zhonghua Yi Xue Za Zhi (Taipei); 62:907.
9. Dart RC, Erdman AR, Olson KR, et al, 2006: American Association of Poison Control Centers
(2006). Acetaminophen poisoning: an evidence-based consensus guideline for out-of-
hospital management. Clin Toxicol (Phila).; 44(1):1-18.
10. Buckley N, Eddleston M , 2005: Paracetamol (acetaminophen) poisoning. Clinical evidence
(14): 1738–44.
11. Park BK, Dear JW, Antoine DJ., 2015: Paracetamol (acetaminophen) poisoning. BMJ Clin
Evid. 2015 Oct 19;. pii: 2101.
12. Wallace CI, Dargan PI, Jones AL, 2002: Paracetamol overdose: an evidence based flowchart
to guide management. Emerg Med J; 19:202.
13. Gosselin S, Juurlink DN, Kielstein JT, Ghannoum M, Lavergne V, Nolin TD, et al.,
2014:Extracorporeal treatment for acetaminophen poisoning: Recomm-endations from the
EXTRIP workgroup. Clinical toxicology; 52(8):856-67
14. MHRA Paracetamol Expert Group 2012, http//www.mhra.gov.uk/groups/pl-p/documents
/drugsaftetymessage/con 184709.pdf
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SALICYLATES
INTRODUCTION:
- Salicylates are widely used agents found in hundreds of over-the-
counter (OTC) medications and in several prescription drugs,
making poisoning with salicylates an important cause of morbidity
and mortality.
- Salicylates are used as analgesic agents for the treatment of mild
to moderate pain and as an anti-inflammatory agent. Salicylate
toxicity is a complex problem that may occur after acute or chronic
ingestion of salicylates.
TOXIC DOSE:
- The maximum adult dose should not exceed 3900 mg/24 hrs) for
more than 10 days. Mild to moderate toxicity (150-300 mg/kg),
severe (301-500 mg/kg) and fatal >500 mg/kg.
EPIDEMIOLOGY:
- Salicylates poisoning is common.
- Salicylates toxic manifestations following exposure are typically
mild to moderate degree.
- Death develops in cases who are inadequately treated or in whom
the clinical diagnosis is missed (usually the elderly with an
underlying medical pathological condition and chronic salicylate
toxicity).
CAUSES
- Salicylates poisoning is usually caused by a suicidal attempt.
- Chronic salicylates ingestion from therapeutic error is also
common.
- Child neglect should be considered if the patient is less than 1 year
of age; intentional attempt in patients over 6 years of age.
RISK FACTORS:
- Children between 4 and 12 years of age who ingest aspirin during a
hyperthermic condition may be at risk for Reye's syndrome.
- Elderly patients with underlying pathological conditions have a 25-
30% mortality rate from chronic salicylate intoxications.
DRUG AND DISEASE INTERACTION:
- Acetazolamide accelerate salicylate poisoning by enhancing CNS
penetration.

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- Salicylates inhibit cyclooxygenase enzyme, which results in a decrease
in prostaglandin formation, and platelet dysfunction.
- Salicylates stimulate the respiratory center, leading to hyperventilation
and respiratory alkalosis.
- They are weak acids and impair renal function, which leads to
accumulation of inorganic acids.
- Salicylates also interfere with the Krebs cycle (limiting ATP production)
and uncouple oxidative phosphorylation, resulting in lactic
acidosis and the generation of heat.
- Finally, the induction of fatty acid metabolism yields ketone bodies.
The outcome of these metabolic processes is a wide anion gap
metabolic acidosis.
- Salicylate poisoning produces discordance between plasma and
cerebrospinal fluid (CSF) glucose concentrations. Despite
normal plasma glucose, CSF glucose may be low.
- Phase 1: Characterized by hyperventilation resulting from direct
respiratory center stimulation, leading to respiratory alkalosis
and compensatory alkaluria. Potassium, sodium and
bicarbonate are excreted in the urine. This phase may last as
long as 12 hrs.
- Phase 2: Characterized by paradoxic aciduria in the presence of
continued respiratory alkalosis occurs when a sufficient
amount of potassium has been lost from the kidneys. This
phase may begin within 6 hrs and may last 12-24 hrs.
- Phase 3: Characterized by dehydration, hypokalemia, and progressive
metabolic acidosis. This phase may begin 4-6 hrs after
ingestion in a young infant or 24 hrs or more after ingestion in
an adolescent or adult.
•Nausea, vomiting, diaphoresis, tinnitus, vertigo, hyperventilation,
tachycardia, and hyperactivity are the earliest signs and symptoms of
salicylate toxicity.
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- Mild to moderate toxicity: GI disturbances, tinnitus, tachypnea, and

respiratory alkalosis.
- Severe toxicity: Metabolic acidosis, hyperpnea, diaphoresis, fever,
altered mental status, seizures, coma, rhabdomyolysis,
cerebral edema, pulmonary oedema up to death.
- Chronic overdoses present more slowly and may be less pronounced,
especially in the elderly, and may consist mainly of neurologic
manifestations such as confusion, delirium, agitation, and
seizures. Coagulopathy, hepatic injury, and dysrhythmias are
rare complications of severe overdose.
- Delayed toxicity: The onset of clinical toxicity and peak serum levels
may be delayed in patients with ingestion of sustained release
or enteric coated salicylate, or if pylorospasm or
pharmacobezoar develop. Patients should be monitored until
serial serum salicylate levels are declining and clinical
symptoms have improved.
- Differential diagnoses include conditions that cause anion gap
metabolic acidosis (e.g. iron, methanol, isopropanol, sepsis,
and alcoholic ketoacidosis). Salicylate toxicity should also be
considered in elderly patients with an altered mental status.
INVESTIGATIONS:
- Routine:
- Monitor serum glucose.
- Serum electrolytes, ALT, AST, PT, bilirubin, albumin, BUN, creatinine.
- ABGs for patients with moderate to severe toxicity, and all patients
undergoing urinary alkalinization.
- EKG.
- CBC, INR and PTT in patients with clinical evidence of moderate to
severe toxicity.
- Acetaminophen level.
- Pregnancy test in all women of childbearing age.
- 12-lead EKG.
- Imaging studies: Chest X-ray, abdominal ultrasonography, endoscopy
and obtain a CT brain for altered mental status.

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- Specific:
- Serial salicylate levels every 1-2 hrs until levels have peaked and are
declining. Interpret the salicylate level in account of blood pH. A
decreasing serum salicylate concentration can reflect either an
increased tissue distribution with increased toxicity or an increased
clearance with decreased toxicity. A decreasing serum salicylate
level accompanied by a decreasing or low blood pH should be
presumed to reflect serious or worsening situation, not an
improvement. Blood salicylate concentration 15-25 mg/dl is
considered within therapeutic range. Concentrations >25 mg/dl are
associated with signs and symptoms of toxicity.
Admission criteria:
- Admit patients with major signs and symptoms (e.g., neurologic,
cardiopulmonary, and metabolic) to an intensive care unit under the
care of a medical toxicologist.
- Admit patients with minor signs and symptoms (e.g., tinnitus,
nausea) to an observational unit or medical ward.
- Admit the following patients, regardless of salicylate levels:
1. Infants and elderly individuals.
2. Individuals with chronic salicylism.
3. Ingestion of sustained-release products.
TREATMENT:
Stabilization:
- ABCs: Airway, breathing, and circulation should be evaluated and
stabilized as necessary.
- Patients who are comatose or presenting with altered mental
status may need mechanical respiratory support and
endotracheal intubation. If the patient requires intubation,
monitor end-tidal CO2 and arterial blood gases frequently and
maintain the preintubation minute ventilation to prevent
severe acidosis.
- Dehydration, concomitant electrolyte abnormalities, and
hypoglycemia must be immediately corrected.
Decontamination:
- Activated charcoal (AC) adsorbs salicylates effectively and should be
given (1 gm/kg up to 50 gm PO) within 1-2 hrs of ingestion to
patients who can protect their airway and are not actively vomiting
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and all intubated patients via orogastric tube. Patients who present
after 2 hrs may benefit from AC because of delayed absorption due
to enteric-coated tablets, pylorospasm, or bezoar formation.
- Multiple doses of AC if no contraindication: 25 gm by mouth q 2 hrs
for 3 doses or 50 gm/PO q 4 hrs for 2 doses after the initial dose is
given.
- Whole bowel irrigation (WBI) is not routinely used for salicylate
toxicity but can be considered for massive ingestions of sustained
preparation or enteric-coated drugs in an alert and cooperative
patient.
Symptomatic:
- Monitor with CVP especially in patients with cardiac disease, non
cardiogenic pulmonary oedema, and renal compromise.
- Correct dehydration with 0.9% saline 10 to 20 mL/kg/hr over 1-2 hrs
until a good urine flow is obtained (at least 3 to 6 mL/kg/hr).
- Correct acidosis by administering 1-2 mEq/kg NaHCO3 by IV bolus
and begin urinary alkalinization.
Specific:
Alkalinization by sodium bicarbonate
Indications:
1. Serum salicylate >30 mg/dL and rising.
2. CNS symptoms and signs and tachypnea regardless of salicylate
level.
Aim: To treat and prevent acidemia and to promote salicylate
elimination by the kidneys.
Goal: to keep urine PH 7.5 - 8. Arterial PH should not rise above
7.55.
Contraindications: Renal failure, heart failure, and NCPE.
Method: Place 150 mEq (3 ampoules of 8.4%) of NaHCO3 in 1 liter
of D5W to provide an isotonic solution and 20-40 mEq of
potassium chloride/ liter are added as needed to maintain
normokalemia. Administer 10 to 20 mL/kg initially as a bolus,
and then infuse at 2-3 mL/kg/hour. The rate of infusion should
be sufficient to induce a urine output of 2-3 mL/kg/hr. Urine pH
should be checked frequently every 1-2 hrs.

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N.B. Monitor closely fluid overload, hypokalemia, hypocalcaemia and

hypernatremia.
N.B. Hypokalemia and dehydration limit the effectiveness of urine
alkalization.
Hemodialysis
Indications:
1. Patients with high serum salicylate levels (greater than 90 to 100
mg/dL after acute overdose, or 50 - 60 mg/dL with chronic
intoxication).
2. Significant CNS abnormalities such as altered mental status, cerebral
edema, or seizures.
3. Acute lung injury or respiratory failure.
4. Impaired glomerular filtration rate not responding to volume
repletion.
5. Deteriorating clinical condition.
6. Significant hyperthermia (an indicator of mitochondrial toxicity from
salicylates)
7. Co-ingestion of a substance that may exacerbate salicylate toxicity.
8. Refractory/profound acidemia.
9. Refractory/profound electrolyte disturbance.
10. Inability to administer sodium bicarbonate as in cases of renal
insufficiency/failure or pulmonary edema.
11. Rising serum salicylate concentrations inspite of sodium bicarbonate
administration
- Follow Up
- Patient Monitoring:
- Continuous respiratory and cardiac monitoring should be done in
symptomatic cases.
- Patients should be revaluated frequently for abnormal mental status
development and should have serial detection of serum
electrolyte and salicylate levels.
- Patients with rising salicylate levels, disturbed consciousness level,
seizure, acute respiratory distress syndrome, or respiratory
acidosis should be close monitored in an intensive care unit.
- Expected Course and Prognosis:
- Acute salicylates intoxication typically starts within hours of salicylates
ingestion and resolves within 24-48 hours depending on severity
of salicylates toxicity; a complete recovery is usually expected.
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- Chronic salicylates intoxication may start within days to weeks of

salicylate ingestion and recovers over 48-72 hours once
treatment is started.
- Permanent complications of hypoxia or cerebral edema may present.
- Discharge Criteria/Instructions
- From the emergency department.
Asymptomatic or minimally symptomatic cases may be
discharged after gastrointestinal decontamination procedure,
close observation for 4-6 hours, and a psychiatric assessment,
provided that serial salicylate levels decreased significantly and
acid-base status condition is normal.
- From the hospital.
Asymptomatic cases may be discharged after signs of poisoning
resolve, serum electrolytes and renal function return to normal
baseline, serial serum salicylate levels decreased to 30 mg/dl,
and a psychiatric assessment is completed, if required.
COMMON PITFALLS:
- The nomogram is not useful; it can both overestimate and
underestimate the severity of toxicity.
- Single determinations of salicylate levels are not sufficient because
absorption may be delayed and erratic.
- Do not discharge patients unless it is clear that serial salicylate
concentrations are declining.
- Sedation or intubation of the patient could lead to compromises in the
patient's own respiratory drive, and has been associated with
abrupt decompensation likely due to worsening metabolic
acidosis and increasing the salicylate concentration in the CNS. If
the patient requires intubation, it is imperative that respiratory
alkalosis be maintained.
- Hypokalemia will interfere with urinary alkalinization.
- In young children, the initial respiratory alkalosis is transient. They
often have a predominant metabolic acidosis (and in severe
cases also respiratory alkalosis) on presentation.

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REFERENCES:
1. Chyka PA, Erdman AR, Christianson G, Wax PM, Booze LL, Manoguerra AS,
Caravati EM, Nelson LS, Olson KR, Cobaugh DJ, Scharman EJ, Woolf AD, Troutman WG,
2007: “Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital
management”. Clinical Toxicology (Philadelphia, Pa.) 45 (2): 95–131
2. Marx M, John, 2006: Rosen’s emergency medicine: concepts and clinical practice.
Mosby/Elsevier. p. 2342 ISBN 978-0-323-02845-5
3. Vale JA, Kulig K, 2004: Position paper: gastric lavage”. Journal of Toxicology. Clinical
Toxicology 42 (7): 933–43.
4. Chyka PA, Erdman AR, Christianson G, et al., 2007: “Salicylate poisoning: an evidence-
based consensus guideline for out-of-hospital management”. Clinical Toxicology
(Philadelphia, Pa.) 45 (2):95–131.
5. R. Baselt, 2011: Disposition of Toxic Drugs and Chemicals in Man, 9th edition, Biomedical
Publications, Seal Beach, CA, pp. 20-23.
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NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

INTRODUCTION:
- Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most
common classes of medications prescribed. Despite the high
rates of acute ingestion, few patients experience poor outcomes,
and most require no medical intervention or supportive care
alone.
TOXIC DOSE:
- In general ingestions of less than 100 mg/kg of most NSAIDs (except
mefenamic acid and phenylbutazone) are unlikely to cause any
significant toxicity. Massive overdoses that produce severe
clinical toxicity are seen with ingestions greater than
approximately 400 mg/kg.
EPIDEMIOLOGY:
- Non-steroidal anti-inflammatory drugs poisoning is common.
- Toxic manifestations following exposure are typically mild, with death
occurring in rare conditions secondary to gastrointestinal
bleeding effect.
CAUSES:
- Pattern of poisoning is usually accidental in pediatrics, intentional in
adults.
- Child neglect or abuse should be considered if the patient is less than 1
year of age.
DRUG AND DISEASE INTERACTIONS:
- Alcoholics and cases with peptic ulcer are predisposed to
gastrointestinal bleeding.
- Advanced age or preexisting renal impairment predispose to renal
intoxications.
- Use with anticoagulants elevates the risk of bleeding tendency.
- Many of the adverse effects, and probably all or most of the acute
toxicities of the NSAIDs, are associated primarily with the
inhibition of cyclooxygenase 1 (COX-1). However, the high anion
gap metabolic acidosis that rarely occurs with NSAIDs overdose
results from the formation of weakly acidic NSAID metabolites,
hypotension, and relative hypoxia. There is no sufficient
evidence to point that inhibition of COX-1 itself is responsible for
the production of the metabolic acidosis.

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- The most common signs and symptoms are generally nonspecific and
include nausea, vomiting, drowsiness, blurred vision, and
dizziness.
- Less than 0.5% of these patients experience severe harm (e.g.,
hypothermia, convulsions, metabolic acidosis, coma and acute
renal failure). Mefenamic acid ingestion commonly presents with
convulsions.
- CVS: Hypotension and cardiovascular collapse have been reported
following massive ibuprofen overdose.
- CNS: ataxia, nystagmus, headaches, and disorientation, convulsions
and coma.
- Hematological: Aplastic anemia, bleeding gums, diffuse petechial rash
and agranulocytosis after ingestion of phenylbutazone.
- Allergic reactions: Urticaria, asthma and anaphylaxis.
- Acid base abnormalities: An increased anion gap metabolic acidosis
may be seen after large ingestions of NSAIDs, particularly
ibuprofen, naproxen, and phenylbutazone.
- EKG and electrolytes: Cardiac dysrhythmias and electrolyte
abnormalities.
- Evidence of impaired renal function (increased serum creatinine,
hyperkalemia, decreased urine volume, or weight gain).
INVESTIGATIONS:
- Routine:
- Blood glucose, to rule out hypoglycemia as the cause of any
alteration in mental status.
- Acetaminophen and salicylate levels, to rule out these common
co-ingestions
- EKG, to rule out conduction system poisoning by coingestants
that affect the QRS or the QTc intervals.
- Pregnancy test in all women of childbearing age
- In symptomatic patients and those with large ingestions:
1. Tests of renal function (BUN, creatinine), Serum electrolytes
and arterial blood gases (ABGs) should be obtained.
2. In bleeding patients, hemoglobin and platelet counts should
be measured.
- Specific:
- NSAID serum concentrations are generally not helpful.
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TREATMENT:
- Stabilization:
ABCs: Airway, breathing, and circulation should be evaluated
and stabilized as necessary.
- Decontamination:
Activated charcoal (AC) in patients who present within 2 hrs of
an acute ingestion, unless specific contraindications exist e.g.,
bowel obstruction, perforation, aspiration risk, etc.
1. Correction of metabolic acidosis by NaHCO3.
2. Seizures are treated in standard fashion with benzodiazepines.
3. Hypothermia generally responds to active external warming
(e.g., heating blanket).
4. Hemodialysis in patients with acute renal failure.
- Observation 4-6 hrs for patients with minor ingestions who are
asymptomatic.
- A 24-hour observation is recommended in cases of mefenamic acid and
phenylbutazone. Patients who present with signs of severe toxicity (e.g.,
pH <7.3, acute renal dysfunction, altered mental status), suicidal patients,
and with other medical or psychosocial concerns should be admitted.
- FOLLOW UP:
- Patient monitoring
- Respiratory function tests, CNS depressed condition, and acid-
base status should be monitored in symptomatic cases.
- Expected course and prognosis
- Peak effects usually develop within hours.
- Most patients recover within 24 hours with supportive care.
- Possible complications are gastrointestinal bleeding and renal
impairment.
- Discharge Criteria and instruction
- From the emergency department. Asymptomatic cases without
documented metabolic acidosis may be discharged after
decontamination procedure, observation for four hours, and
psychiatric assessment, as indicate.
- From hospital. Patients may be discharged when mental condition
has returned to normal status, renal function has stabilized, and
gastrointestinal bleeding has completely resolved.

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PITFALLS:
- Diagnosis
- Because cases usually misidentify analgesics, the physician needs
to rule out acetaminophen and salicylate as co-ingestants
possibilities.
- Follow-Up
- Because delayed renal and hepatic toxic manifestations may
develop after overdose ingestion of phenylbutazone, patients
should be close followed for several days.
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REFERENCES:
1. Nelson, Lewis S., 2011: Nonsteroidal Antiinflammatory Drugs In: Goldfrank’s Toxicologic
Emergencies, 9th edition, Nelson LS, Lewin NA, Howland MA, Hoffman RS, Goldfrank LR,
Flomenbaum NE (Eds), McGraw-Hill, New York. p. 575-585
2. Smolinske SC, Hall AH, Vandenberg SA, et al, 1990: Toxic effects of nonsteroidal anti-
inflammatory drugs in overdose. An overview of recent evidence on clinical effects and
dose-response relationships. Drug Saf; 5:252
3. Volans G, Monaghan J, Colbridge M, 2003: Ibuprofen overdose. Int J Clin Pract Suppl;54
4. Levine M, Khurana A, Ruha AM, 2010: Polyuria, acidosis, and coma following massive
ibuprofen ingestion. J Med Toxicol; 6:315.
5. Holubek W, Stolbach A, Nurok S, et al, 2007: A report of two deaths from massive
ibuprofen ingestion. J Med Toxicol; 3:52.
6. Gambaro G, Perazella MA, 2003: Adverse renal effects of anti-inflammatory agents:
evaluation of selective and nonselective cyclooxygenase inhibitors. J Intern Med;
253:643.
7. McElwee NE, Veltri JC, Bradford DC, Rollins DE, 1990: A prospective, population-based
study of acute ibuprofen overdose: complications are rare and routine serum levels not
warranted. Ann Emerg Med; 19:657
8. Nelson L, Shih R, Hoffman R, 1995: Aplastic anemia induced by an adulterated herbal
medication. J Toxicol Clin Toxicol; 33:467.
9. Kingswell RS, 1981: Mefenamic acid overdose. Lancet; 2:307.
10. Hall AH, Smolinske SC, Stover B, et al, 1992: Ibuprofen overdose in adults. J Toxicol Clin
Toxicol; 30:23.

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FOODS AND DIETARY AGENTS
VITAMINS
INTRODUCTION:
Description:
- Acute toxicity is uncommonly after ingestion of vitamin products
that do not contain iron. Vitamins A and D may produce toxicity, but
usually only after chronic use. Serious poisoning has been reported
in individuals attempting to mask urine drug screens by ingesting
large quantities of niacin to adulterate urine sample.
Forms and uses:
- Although there are hundreds of formulations, the primary vitamins
involved here are vitamin A, C, D, E, folic acid, thiamine (B1),
riboflavin (B2), cyanocoblamin (B12), biotin, niacin, pantothenic acid,
and pyridoxine (B6).
Toxic dose:
- A single ingestion must be very large to cause toxicity.
- A chronic ingestion of large amount may develop poisoning.
- Vitamin A.
- Acute ingestion of more than 12,000 IU/kg is considered toxic.
- Chronic ingestion of more than 25,000 IU/d for 2-3 weeks may
develop toxicity.
- Vitamin C.
- Acute intravenous doses of more than 1.5 g and chronic
ingestion of more than 4 g/day have develop nephropathy.
- Vitamin D.
- Acute ingestion is highly unlikely to develop toxicity.
- In pediatrics, chronic ingestion of more than 5000 IU/d for
several weeks may develop in toxicity (adults >25,000 IU/d).
- Niacin.
- Acute ingestion of more than 100 mg may produce a dermal
flushing reaction. Immediate-release products are more likely to
develop flushing than are the timed-release preparations.
- Ingestion of 2.5 g develops nausea, vomiting, dizziness,
hypoglycemia followed by hyperglycemia, and coagulopathy.
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- Pyridoxine.
- Chronic ingestion of 2-5 g/d for several months has developed in
neuropathy.
Pathophysiology:
- Vitamin A.
- The mechanism by which excessive amounts of vitamin A
develop increased intracranial tension is unknown.
- Vitamin C.
- Chronic excessive use and large IV doses can develop increased
levels of the metabolite oxalic acid. Urinary acidification
stimulates calcium oxalate crystal formation, which can lead to
nephropathy or acute renal impairment.
- Vitamin D.
- Chronic ingestion of excessive amounts of vitamin D accelerates
calcium absorption and produces hypercalcemia.
- Niacin.
- The most common side effects of niacin are cutaneous flushing
and pruritus mediated by prostaglandin release.
- Pyridoxine.
- Chronic overdose may alter neuronal conduction velocity,
resulting in paresthesias and muscular incoordination.
Epidemiology:
- Toxicity is common in Saudi Arabia and toxic effects are very rare.
Causes:
- In children, acute toxicity is usually an unintentional over dose
CLINICAL MANIFESTAIONS
- Most acute overdoses of multivitamins are associated with nausea,
vomiting, and diarrhea.
- Vitamin A.
- Chronic vitamin A poisoning is characterized by dry, peeling
skin; alopecia; and signs of increased intracranial tension
(headache, disturbed consciousness level, and blurred vision
[pseudotumor cerebri]). Bulging fontanelles have been
described in infants. Hepatic impairment may develop jaundice
and ascites.

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Vitamin C. -
- Calcium oxalate crystals may develop acute renal impairment or
chronic nephropathy.
- Vitamin D.
- Chronic excessive use of vitamin D is accompanied with
hypercalcemia, producing weakness, disturbed mental
condition, GI upset, renal tubular impairment, and occult
cardiac dysrhythmias.
- Vitamin E.
- Chronic excessive use of vitamin E can develop nausea,
headaches, and weakness.
- Vitamin K.
- Vitamin K can develop hemolysis in newborns (especially if they
are G6PD deficient).
- Niacin
- Acute ingestion of niacin, but not niacinamide (nicotinamide),
may develop unpleasant, dramatic cutaneous flushing and
pruritus that may persist for a few hours.
- Intentional ingestion of large amounts in an attempt to produce
a negative urine drug screen “adulteration” has caused nausea,
vomiting, abdominal pain, palpitations, dizziness, and
hypoglycemia, followed by persistent hyperglycemia, anion gap
metabolic acidosis, hypotension, and coagulopathy.
- Chronic excessive use (particularly of the sustained-release
form) has been associated with hepatitis.
- Pyridoxine.
- Chronic excessive pyridoxine use may produce peripheral
neuropathy.
- Vitamins.
- Large doses of B vitamins may deepen the yellow color of urine,
and riboflavin may develop yellow perspiration.
INVESTIGATIONS
General Tests:
- Useful laboratory tests in such cases involve CBC, electrolytes, glucose,
BUN, calcium, creatinine, liver aminotransferases, and urinalysis.
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Specific Tests:
- Vitamin A.
- Serum vitamin A (retinol) or carotenoid assays may help in the
diagnosis of hypervitaminosis A.
- Vitamin D.
- Levels of 25-hydroxy vitamin D are helpful in assessing excessive
intake and are increasingly available through clinical laboratories
TREATMENT
A. Emergency and supportive measures.
- Fluid loss. Treat fluid losses caused by gastroenteritis with
replacement therapy of IV crystalloid solutions.
- Increases intracranial tension. Treat vitamin A-induced elevated
intracranial tension if they develop.
- Hypercalcaemia. Treat vitamin D-induced hypercalcemia if they
develop.
- Pruritus. Non-steroidal anti-inflammatory agents may prevent or
alleviate prostaglandin-mediated niacin flushing or pruritus.
B. Specific drugs and antidotes.
- There is no specific antidote for hypervitaminosis toxic conditions.
C. Decontamination procedures.
- Usually, gut decontamination is unnecessary unless a toxic dose of
vitamin A or D has been reported or the product contains a toxic
amount of iron.
D. Enhanced elimination procedures.
- All form of elimination enhancement such as, forced diuresis,
dialysis, and hemoperfusion are of no clinical benefit.
FOLLOW UP
Expected course and prognosis
- Most cases can be expected to make a full recovery with cessation
of vitamin supplement and with supportive care.
Discharge criteria/instructions.
- Asymptomatic cases may be discharged after from emergency
department or hospital following evaluation of coingestants and
psychiatric evaluations, if required.

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Patient education.
- The case should be instructed to discontinue taking the vitamin
formulation involved.
PITFALLS
- Vitamin and “alternative” medications are not considered a
medicine by the patient. The history should be actively specify this
information.
REFERENCES:
1. Mastroiacovo P, Mazzone T, Addis A, Elephant E, Carlier P, et al. (1999) High vitamin A intake
in early pregnancy and major malformations: a multicenter prospective controlled study.
Teratology 59: 7-11
2. Toxic Exposure Surveillance System (2004). "Annual Report" . American Association of Poison
Control Centers.
3. Ronstein, A. C.; Spyker, D. A.; Cantilena, L. R.; Green, J. L.; Rumack, B. H.; Dart, R. C. (2011).
"2010 Annual Report of the American Association of Poison Control Centers' National Poison
Data System (NPDS)
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IRON
INTRODUCTION:
- Iron is found in several different forms and in different medicinal
formulations. Iron poisoning is particularly common among children.
It is valuable to identify the amount of elemental iron not the iron
salt.
- The most common iron formulations used are ferrous sulfate, ferrous
gluconate and ferrous fumarate which contain 20%, 12% and 33%
elemental iron respectively.
- To children, iron tablets may resemble candy. Multivitamins used by
mothers during pregnancy are the main source of lethal ingestions
among children. Children's chewable multivitamins usually have small
amounts of iron therefore toxicity rarely occurs.
- Sustained release formulations or enteric-coated iron preparations may
be absorbed at a slower rate. This is an important consideration when
interpreting serum iron concentrations.
Toxic dose:
- 20 to 60 mg/kg is mildly to moderately toxic and > 60 mg/kg can cause
severe symptoms and mortality.
EPIDEMIOLOGY
- Iron poisoning is common.
- Toxic manifestations following exposure are typically mild to moderate
degree.
- Death develops as a result of large amount of iron ingestions with
delayed patient presentation.
CAUSES
- Acute iron overdose is usually suicidal in adults and accidental in children.
- The possibility of child neglect should be considered in patients under 1
year of age; suicide attempt in patients over 6 years of age.
- Iron produces a direct corrosive effect on mucosal tissue and may result
in hemorrhagic necrosis and perforation. Hypovolemia can occur as a
result of fluid loss from the gastrointestinal tract.
- Iron absorbed in excess of protein binding capacity causes cellular
dysfunction, resulting in lactic acidosis and necrosis. Iron can induce
oxidative stress and free-radical production.

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CLINICAL MANFESTATIONS:
Clinical course
- Gastrointestinal (GI) phase: (0.5 to 2 hrs) includes vomiting, abdominal
pain hematemesis, diarrhea (can be bloody or dark coloured),
lethargy, shock, acidosis, and coagulopathy. Iron can cause necrosis to
the GI tract as a result of it`s corrosive effect on the GI mucosa. Loss
of large amounts of fluids or blood could lead to shock. Severe
gastrointestinal hemorrhagic necrosis could result from acute iron
toxicity.
- Latent phase: (6-24 hrs) includes apparent recovery. Continue to observe
patient closely.
- Shock and metabolic acidosis phase: (6-72 hrs) includes severe shock,
metabolic acidosis, cyanosis, and fever. Increased total peripheral
resistance, decreased plasma volume, hemoconcentration, decrease
in total blood volume, hypotension and CNS depression have been
reported.
- Hepatotoxicity/hepatic necrosis phase: (2-4 days) includes possible
hepatotoxicity. Thought to be a direct action of iron on the
mitochondria. Acute lung injury may also occur at this stage.
- Bowel obstruction phase: (days to weeks) includes GI scarring and
strictures. GI obstruction as a result of gastric or pyloric scarring may
occur as a late complication of iron`s corrosive effect. This can also be
seen in sustained release preparations.
INVESTIGATIONS:
- Recommeneded for ingestions of more than 40 mg/kg of elemental iron.
Routine:
- Serum electrolytes, BUN, glucose, ALT, AST and bilirubin.
- ABG in moderately and severely poisoned patients (anion gap metabolic
acidosis).
- CBC, PT and PTT.
- Urine analysis: With the use of deferoxamine, it binds free iron creating
ferrioxamine which is excreted in the urine. Urine containing
ferrioxamine may be brick orange or "vin rosé"in colour.
Specific:
- Measurement of serum iron concentration (SIC) is useful for confirming
the diagnosis of iron ingestion. The best estimate of the severity of
the overdose can be determined by performing a SIC measurement
within 4-6 hrs of the ingestion. For slow-release iron, a SIC should be
obtained at 8 hrs. It cannot always be correlated with the severity or
the clinical phase of iron intoxication.
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Radiographic evaluation:
- Plain abdominal X-ray for patients who may have ingested more than 40
mg/kg of elemental iron or who have significant symptoms should be
performed. The presence of radiopaque pills in the stomach confirms
the ingestion of iron. However, many liquid iron preparations and
chewable vitamins with low concentrations of iron are not visible, it
does not necessarily mean that the ingestion was insignificant.
DIFFERENTIAL DIAGNOSIS
- The differential diagnosis of iron poisoning is broad given the range of
clinical findings (high anion gap metabolic acidosis, hepatotoxic
poisons, GIT irritants).
TREATMENT
Stabilization:
- Assess airway, breathing, and circulation; stabilize as necessary
Decontamination:
- The decontamination modality of choice is whole bowel irrigation (WBI)
using a naso-gastric colonic lavage solution 30mL/kg/hr until rectal
effluent is clear (contraindicated if there are signs of bowel
obstruction or hemorrhage).
- Charcoal is of NO benefit.
- WBI is indicated:
- If X-ray reveals tablets, or capsules ingested
- In symptomatic patients
Antidote:
Desferrioxamine
- It is an iron-chelating agent that when binds to iron forms a non harmful
water soluble desferroxamine-iron complex, that is easily excreted by
the kidney.
Administer desferrioxamine if:
- Serum iron levels > 90 µmol/L
- Serum iron level 60 - 90 µmol/L and tablets are visible on X-ray or patient
is presenting with nausea, vomiting, diarrhea, abdominal pain,
haematemesis and fever.
- Patients presenting with serious or worsening symptoms of altered
conscious state, hypotension, tachycardia, tachypnoea and metabolic
acidosis pH< 7.1.
Dose:
- Desferrioxamine 15 mg/kg/hr IV. Reduce the rate after 4-6 hrs so that the
total intravenous dose does not exceed 80 mg/kg/24 hrs.

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- If oliguria or anuria develops, peritoneal dialysis or haemodialysis are

warranted to remove ferrioxamine (The compound formed after
chelation of iron).
- Determination of the endpoint for chelation therapy is difficult.
Significant poisoning usually requires 12 - 16 hrs. However, it is
recommended to continue desferrioxamine until:
- Patient is asymptomatic.
- Anion-gap metabolic acidosis is resolved.
- Iron level is < 54 µmol/L.
- As desferoxamine has been associated with pulmonary toxicity with the
prolonged use more than 24 hrs, consult with the medical toxicologist
when indicated.
Pregnancy:
- Use of desferoxamine for iron poisoning with pregnancy improves
maternal condition therapy improves condition for the fetus.
Supportive care:
- Volume resuscitation to maintain euvolemia. Hypovolemic shock is the
major cause of mortality during the first phase of iron intoxication.
Patients who present with severe gastrointestinal symptoms require
urgent intensive management to maintain effective circulating blood
volume.
FOLLOW UP:
PATIENT MONITORING
- Iron level, CBC, serum electrolytes, and hemodynamic close monitoring
should be repeated frequently over the first few hours in patients
with acute iron toxic effects to assess response to therapeutic
maneuver.
- If abdominal radiographs appear tablets, repeat radiographic films are
indicated to assess the efficiency of decontamination.
EXPECTED COURSE AND PROGNOSIS
- Most patients develop gastrointestinal manifestations, are treated with
deferoxamine therapy, and resolve over 12-48 hours.
- In severe cases, manifestations develop rapidly and may lead to a course
persisting several days and complicated by multiple complicating
effects of shock.
- In iron poisoning patients without shock or coma, mortality is < 1%.
- Shock or coma predicts mortality of 50% with supportive treatment, 10%
with supportive treatment and deferoxamine therapy.
- Scarring from local corrosive iron effects may lead in gastrointestinal
obstruction 4 to 6 weeks after severe iron toxicity.
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DISCHARGE CRITERIA/INSTRUCTIONS
Patients may be discharged after observing for at least 6 hours post

ingestion, if they have all of the following:
-Absence of vomiting
-Amount of ingestion is < 20 mg/kg of elemental iron
-Serum iron level < 300 mcg/dL at 4-6 hours post ingestion.
Suicidal patients should be evaluated by a psychiatrist
COMMON PITFALLS
- Failure to provide adequate amounts of intravenous fluids.
- Delaying the administration of desferrioxamine till the serum iron level is
obtained in patients that are already symptomatic.
- Making treatment decisions based on the total iron binding capacity.
- Failure to recognize patients in the latent phase
- Excessive reliance on the SIC in management decisions
- Inaccurate calculation of the dose of elemental iron ingested
- Inadequate desferrioxamine dose
- Giving prochlorperazine drug and desferrioxamine together
- Failure to appreciate that desferrioxamine may falsely lower serum iron
concentration

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REFERENCES:
1. Perrone J, 2011: Iron In: Goldfrank’s Toxicologic Emergencies, 9th edition, Nelson LS, Lewin
NA, Howland MA, Hoffman RS, Goldfrank LR, Flomenbaum NE (Eds), McGraw-Hill, New York.
p. 530-545
2. Liebelt, EL and Kronfol, R , 2014 : Acute iron poisoning. UPTODATE 2014:
http://www.uptodate.com/contents/ Acute iron poisoning, Dec 2014
3. Olson, K. R., & California Poison Control System. (2006). Poisoning & drug overdose. New York:
Lange Medical Books/McGraw-Hill
4. Bronstein AC, Spyker DA, Cantilena LR Jr, et al, 2011: 2010 Annual Report of the American
Association of Poison Control Centers’ National Poison Data System (NPDS): 28 th Annual
Report. Clin Toxicol (Phila) 2011; 49:910.
5. Morris CC, 2000: Pediatric iron poisonings in the United States. South Med J; 93:352.
6. Osterhoudt, KC, Burns Ewald, M, Shannon, M, et al. 2006: Toxicologic emergencies. In:
Textbook of Pediatric Emergency Medicine, 5th, Fleisher, GR, Ludwig, S, Henretig, FM (Eds),
Lippincott Williams and Wilkins, Philadelphia. p.979.
7. Juurlink DN, Tenenbein M, Koren G, Redelmeier DA, 2003: Iron poisoning in young children:
association with the birth of a sibling. CMAJ; 168:1539.
8. Anderson BD, Turchen SG, Manoguerra AS, Clark RF, 2000: Retrospective analysis of
ingestions of iron containing products in the united states: are there differences between
chewable vitamins and adult preparations? J Emerg Med; 19:255.
9. Watson WA, Litovitz TL, Rodgers GC Jr, et al, 2005: 2004 Annual report of the American
Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med
2005; 23:589.
10. Tenenbein M., 2005: Unit-dose packaging of iron supplements and reduction of iron poisoning
in young children. Arch Pediatr Adolesc Med; 159:557.
11. Madiwale T, Liebelt E, 2006: Iron: not a benign therapeutic drug. Curr Opin Pediatr; 18:174.
12. Fernández S, Castro P, Nogué S, Nicolás JM, 2014 : Acute iron intoxication: change in urine
color during chelation therapy with deferoxamine. Intensive Care Med. Jan;40(1):104.
13. Vichinsky E, Torres M, Minniti CP, Barrette S, Habr D, Zhang Y, Files B; 2013 : study
CICL670A2201 investigators. Efficacy and safety of deferasirox compared with deferoxamine
in sickle cell disease: two-year results including pharma cokinetics and concomitant
hydroxyurea. Am J Hematol. Dec;88 (12):1068-73.
14. Sankar J, Shukla A, Khurana R, Dubey N, 2013: Near fatal iron intoxication managed
conservatively. BMJ Case Rep. 2013 Jan 31; 2013. pii: bcr2012007670. Doi 10.1136/bcr-2012-
007670.
15. Spiller HA, Wahlen HS, Stephens TL, et al. 2002: Multi-center retrospective evaluation of
carbonyl iron ingestions. Vet Hum Toxicol; 44:28.
16. Klein-Schwartz W, 2000: Toxicity of polysaccharide--iron complex exposures reported to
poison control centers. Ann Pharmacother; 34:165.
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FOOD POISONING
INTRODUCTION:
- Food poisoning occurs as a result of ingesting food or water that
contains bacteria, viruses, parasites or the toxins created by these
germs. Most food poisonings are caused by common bacteria such as,
staphylococcus or E coli.
- Food poisoning can affect one person or a group of people who share
the same food. It is more commonly encountered after eating at
picnics, school cafeterias, large social events and at restaurants.
- A food poisoning outbreak is defined by the following 2 criteria:
- Similar illness, often gastrointestinal, in a minimum of 2 people.
- Evidence of food as the source.
EPIDEMIOLOGY
- The true incidence of food poisoning is unknown because several cases
are mild and unreported or misdiagnosed.
- Multiple cases presenting at the same time in roughly the same place
typically result from a common exposure source.
CAUSES
- Food poisoning develops from ingestion of contaminated vegetables,
fruit, salads, fried rice, pastries, corn flour, milk, cheese, and salads, or
contaminated water.
DRUG AND DISEASE INTERACTIONS
- Toxic manifestations, especially dehydration, are more marked in
pediatric and the elderly, although death from shock and fluid
depletion is rare even in these populations.
- The pathogenesis of diarrhea in food poisoning could be classified into
either non-inflammatory or inflammatory types.
- Non-inflammatory diarrhea is caused by the action of enterotoxins on
the secretory mechanisms of the mucosa of the small intestine,
without invasion. This results in large volumes of watery stools in the
absence of blood, pus, or severe abdominal pain. Occasionally,
profound dehydration may result. Examples include Vibrio cholerae,
Enterotoxic Escherichia Coli, Staphylococcus, Giardia Lamblia,
Cryptosporidium, Rotavirus, Norovirus, and Adenovirus.
- Inflammatory diarrhea is caused by the invasion and destruction of the
mucosa by a cytotoxin. The colon or the distal small bowel are
commonly involved. The diarrhea is often bloody mucoid with
abundant leukocytes. Patients are commonly febrile and may exhibit
a toxic appearance. Dehydration is less likely to be seen with the
inflammatory than with noninflammatory diarrhea. Examples include

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Campylobacter Jejuni, Vibrio Parahaemolyticus, Enterohemorrhagic

and Enteroinvasive E Coli, Yersinia Enterocolitis, Entamoeba
Histolytica, Salmonella and Shigella species.
- The clinical presentation of food poisoning may vary in degree and
combination of symptoms. These symptoms may present as follows:
- Abdominal pain: Most severe in inflammatory diarrhea; the
- Presence of painful abdominal muscle cramps suggests
underlying electrolyte loss.
- Vomiting: A major presenting symptom of Staph Aureus, B
Cereus, or Norovirus.
- Diarrhea: Does not usually last more than 2 weeks.
- Headache.
- Fever: The presence of fever suggests that it is an invasive disease or that
the infection originated outside the GI tract.
- Stool changes: Bloody or mucousy if invasion of intestinal or colonic
mucosa; profuse rice-watery if cholera or a similar process.
- Reactive arthritis: Seen with Salmonella, Shigella, Campylobacter, and
Yersinia infections.
- Bloating: May be caused by giardiasis.
- Dehydration: Signs of dehydration (thirst, dizziness, light-headedness).
- More serious cases of food poisoning can result in life-threatening
neurologic, hepatic, and renal syndromes leading to permanent
disability or death.
ADMISSION CRITERIA
- Patients with hypotension.
- Severe electrolyte abnormalities.
- Respiratory distress or any other complication.
COMPLICATIONS:
- Dehydration is the most common complication.
- Less common complications:
o Arthritis. o Hemolytic uremic syndrome
o Bleeding. (E Coli).
o Damage to the nervous o Swelling or irritation in the
system. pericardium.
o Kidney problems. o Guillain-Barré syndrome
(Campylobacter infection)
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INCUBATION
LIKELY MICROBES LIKELY FOOD SOURCES
PERIOD
Prepared Food, E.G., Salads,
S. aureus 1 to 6 hr.
Dairy And Meat
Vomiting
B. cereus 1 to 6 hr. Rice, Meat.

Shellfish, Prepared Foods,
Norwalk-like viruses 24 to 48 hr.
Salads, Sandwiches And Fruits.
C. perfringens 8 to 16 hr. Meat And Poultry.
Fecally Contaminated Food Or
Watery Diarrhea
Enterotoxigenic E. coli 1 to 3 days

MAJOR PRESENTING SYMPTOM
Water.
Fecally Contaminated Food Or
Enteric viruses 10 to 72 hr.
Water.
Vegetables, Fruit,
C. parvum 2 to 28 days
Unpasteurized Milk And Water.
C. cayetanensis 1 to 11 days Imported Berries And Basil
Poultry, Unpasteurized Milk,
Campylobacter spp 2 to 5 days
Water.
Inflammatory Diarrhea
Eggs, Poultry, Meat,

Non-typhoidal
1 to 3 days Unpasteurized Milk Or Juice
salmonella
And Fresh Produce.
Ground Beef, Unpasteurized
Shiga toxin-producing
1 to 8 days Milk And Juice, Raw Vegetables
E. coli
And Water.
Fecal Contamination Of Food
Shigella spp 1 to 3 days
And Water
V. parahemolyticus 2 to 48 hr. Raw Shellfish
INVESTIGATIONS:
Routine:
- CBC with differential count.
- Serum glucose and Serum electrolyte assessment.
- BUN and creatinine levels.
- ALT, AST and Bilirubin.
- Obtain flat, upright abdominal radiographs if the patient
experiences bloating, severe pain or obstructive symptoms or if
the clinical picture suggests perforation and to document or rule
out differential diagnosis.
Specific:
- Stool Gram staining for WBCs: To aid in the differentiation
between invasive and noninvasive organisms.

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-
Microscopic examination of the stool: To help in the detection of
any ova and parasites.
- Bacterial culture for enteric pathogens: Recommended when a
stool sample shows positive results for WBCs or blood or if
patients exhibit fever or symptoms persisting for longer than 3-4
days
- Blood culture in notably febrile patients.
- Clostridium difficile assay: To help exclude antibiotic-associated
diarrhea in patients receiving antibiotics or in those with a history
of recent antibiotic use.
- Ask for food samples and vomitus for analysis.
Others:
- You may check for levels of pseudo cholinesterase, carboxy
hemoglobin (COHb), MetHb, iron, and lead. Whenever needed to
document or rule out differential diagnosis.
TREATMENT:
Stabilization:
Immediately rehydrate with:
- Oral rehydration mixtures to replace fluids and minerals lost
through vomiting and diarrhea.
- If the patient has diarrhea and is unable to drink, you may need to
administer intravenous fluids. Start IV infusion by 0.9% NaCl or
ringers lactate, guided by the degree of dehydration, pH, urine
output, and previous diseases (hypertension and CHF).
- Cases presenting with shock may be treated under central venous
pressure (CVP) guide.
Supportive treatment:
- Antiemetic (metoclopramides), Antispasmodics, Antipyretics
(paracetamol).
- Plenty of fluid and rest.
- Antibiotics may be started whenever possible as cephalosporin (for
children) or quinolones (for adults) may be given for patients with
fever, leucocytosis, and pus cells in stool (enteroinvasive FP). Do
not give antibiotics for the toxigenic type of food poisoning.
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PATIENT DISHCARGE:
- Discharge the patient when condition is stabilized, and no other
differential diagnosis is still considered, blood pressure normalized,
renal function and dehydration corrected, patient can depend on
his oral hydration (no vomiting).
COMMON PITFALLS:
- Consider closer observation periods for the elderly, very young,
chronically ill, immunosuppressed, or those who might be
predisposed to dehydration.
- Inform patients that reheating food will not destroy the toxin.
- Contact your local public health department so that they may
monitor for other possible outbreaks, especially if multiple patients
are involved.

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REFERENCES:
1. Schiller LR, Sellin JH, 2010: Diarrhea. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger
& Fordtran’s Gastrointestinal and Liver Disease. 9th ed. Philadelphia, PA: Saunders
Elsevier;:chap 15.
2. Sodha SV, Griffin PM, Hughes JM, 2009: Foodborne disease. In: Mandell GL, Bennett JE,
Dolin R, eds. Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, PA: Elsevier
Churchill Livingstone; chap 99.
3. Craig SA, 2013: Gastroenteritis. In Marx JA, Hockberger RS, Walls RM, et al, eds. Rosen’s
Emergency Medicine: Concepts and Clinical Practice. 8th ed. Philadelphia, PA: Mosby
Elsevier; chap 94.
4. Goldfrank, L. R., & Flomenbaum, N. (2010). Goldfrank’s toxicologic emergencies. New York:
McGraw-Hill.
5. American Medical Association, 2004: Diagnosis and management of food borne illness, a
primer for physicians and other health care professionals, 2004: http://www.cdc.gov/
mmwr /preview /mmwrhtml /rr5304a1.htm. April 16, 2004 / 53(RR04);1-33.
6. Masoumi Asl H, Gouya MM, Soltan-Dallal MM, Aghili N, 2015: Surveillance for foodborne
disease outbreaks in Iran, 2006-2011. Med J Islam Repub Iran. 2015 Nov 3;29:285.
eCollection. PubMed PMID: 26913248; PubMed Central PMCID: PMC4764277.
7. Xerry J, Gallimore CI, Iturriza-Gomara M, Gray JJ, 2009: Tracking the transmission routes of
genogroup II noroviruses in suspected food-borne or environmental outbreaks of
gastroenteritis through sequence analysis of the P2 domain. J Med Virol. Jul;81(7):1298-
304.
8. Logan NA, 2012: Bacillus and relatives in foodborne illness. J Appl Microbiol.
Mar;112(3):417-29.
9. Lee JH, Shin H, Son B, Ryu S, 2012: Complete genome sequence of Bacillus cereus
bacteriophage BCP78. J Virol. Jan; 86(1):637-8.
10. Doheny K, 2013: Most common foods for foodborne illness: CDC report. Medscape Medical
News. January 30, 2013. Available at http://www.medscape.com/viewarticle/778455.
Accessed February 6, 2013.
11. Painter JA, Hoekstra RM, Ayers, et al. 2013 : Attribution of foodborne illnesses,
hospitalizations, and deaths to food commodities by using outbreak data, United States,
1998- 2008. Emerg Infect Dis. March;19:3.
12. Sherman PM, Wine E. Emerging intestinal infections. Gastroenterology & Hepatology
Annual Review. 2006;1:50-54.
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BOTULISM
INTRODUCTION:
- Botulism is a potentially life-threatening neuroparalytic syndrome resulting
from the effect of a neurotoxin released by the Clostridium botulinum
bacteria.
- C. botulinum is a heterogeneous group of gram-positive, rod-shaped,
spore-forming anaerobic bacteria.
- Several forms of botulism exist, including foodborne botulism, infant
botulism, wound botulism, adult enteric infectious botulism, inhalational
botulism (from bioterrorism events), and iatrogenic botulism (from
cosmetic use of botulinum toxin).
- The spores of C. botulinum are heat resistant, and can survive heating at
100ºC at for five hours or more. On the other hand, spores can be
destroyed by heating at 120ºC for five minutes.
- The C. Botulinum spores will germinate and grow into toxin-producing
bacilli under the following conditions:
1) Restricted oxygen exposure (either an anaerobic or semi-anaerobic
environment)
2) Low acidity (pH > 4.6) water
3) A temperature of 25 to 37ºC for ideal growth; however, some strains
may grow in temperatures as low as 4ºC.
- The toxin itself is tasteless and odorless. If ingested, the toxin is primarily
absorbed by the stomach and small intestine, although the large intestine
is capable of absorbing the toxin as well. The toxin is resistant to
degradation by gastric acidity and human alimentary enzymes.
TOXIC DOSE:
- Botulinum toxin is perhaps the most potent poison known to man. A dose
as low as 0.05 µg of toxin can be fatal.
EPIDEMIOLOGY:
- It is important to perform a thorough history to identify possible exposures
in patients presenting with a syndrome suggestive of botulism. This
includes a history of home canning, exposure to other possible food
sources (including honey in infants <12 months of age), injection drug use,
and cosmetic use of botulinum toxin.

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- After entering the cell's cytoplasm, the toxin causes an irreversible
modulation in stimulation-induced acetylcholine release in the same
presynaptic nerve terminal.
Symptoms of botulism in adults
Time to symptom onset varies by route of exposure
Foodborne botulism
- Gastrointestinal symptoms often precede symptom onset
- Neurologic symptoms arise 12-36 hours after toxin ingestion (range 6 hours
to 10 days)
Wound botulism
- Gastrointestinal symptoms absent
- Neurologic symptoms likely arise within 2 weeks of exposure (but incubation
period not well defined)
Inhalational botulism
- Gastrointestinal symptoms absent
- Neurologic symptoms arise about 6 hours after exposure
Common symptoms
- Cranial nerve palsies are typically the first symptoms
- Blurry or double vision may indicate extraocular muscle paralysis
- Ptosis is a common early finding
- Facial weakness, difficulty speaking and difficulty swallowing may also occur
- Involvement of the autonomic nervous system may lead to dry mouth and
throat (which can be mistaken for pharyngitis)
- Postural hypotension
- Nausea and vomiting
- Symmetric muscle weakness then progresses downward from the muscles of
the head and neck to the feet
- Loss of head control may be notable early in course
- Weakness of the pharyngeal muscles may lead to airway collapse
- Weakness of chest wall muscles and diaphragm may also lead to respiratory
distress or arrest
- Rate of descending paralysis varies from hours to days (likely dose related)
- Sensation and mental status are usually unaffected
Symptoms of botulism in infants
- In addition to neck and muscle weakness (floppy baby syndrome)
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- Poor feeding
- Diminished suckling or ability to cry
- Constipation
- Respiratory distress
DIAGNOSIS:
A thorough history and physical examination are essential.
- A high degree of suspicion is needed for diagnosis as confirmatory testing
takes > 1 day and immediate antitoxin treatment is needed
- Consider the diagnosis of botulism in patients presenting with a matching
clinical syndrome
- Cranial nerve palsies, particularly when symmetric descending flaccid
paralysis without sensory affection
- Potential epidemiological risk factor preceding gastrointestinal illness
- IV drug use, particularly heroin
- Age < 1 year, particularly if accompanied by honey ingestion
- Serum assays for botulinum toxin are often negative in cases of infant
botulism. The diagnosis is confirmed by the isolation of C. botulinum spores
from the stool and via the identification of botulinum toxin in stool samples.
However, these tests take time.
- Thus, a presumptive diagnosis should be made based upon the clinical
presentation and electrophysiologic findings (electromyogram [EMG]), while
the confirmatory stool studies are pending.
- Myasthenia gravis
- Lambert-Eaton myasthenic syndrome (LEMS)
- Tick paralysis
- Guillain-Barré syndrome, poliomyelitis, stroke, and heavy metal
intoxication.
- Tetrodotoxin and shellfish poisoning and antimicrobial-associated
paralysis.
TREATMENT:
Any patient presenting with clinical signs, symptoms, or history suspicious for
botulism should be hospitalized immediately and closely observed for signs of
respiratory failure.
Monitoring:
- Pulse oximetry, spirometry, arterial blood gas measurement, and clinical
evaluation of ventilation, perfusion, and upper airway integrity.

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- Respiratory failure the most common cause of mortality in these patients.

- Prompt intubation with mechanical ventilation will dramatically decrease
the risk of mortality in patients with insufficient or worsening upper airway
competency and those with a reduced vital capacity.
- Infants and severe cases may require prolonged mechanical ventilation.
Antitoxin:
- Equine serum heptavalent botulism antitoxin is used to treat children older
than one year of age and adults; human-derived botulism immune globulin
has been successfully used for infants less than one year of age.
- The antitoxin should be given to the patient as soon as possible and should
not be delayed while awaiting results of diagnostic studies.
- For adults, one vial 10 ml should be administered intravenously (IV) diluted
in 0.9% Saline and administered by slow IV infusion. A second vial may
be administered within 2-4 hrs if symptoms worsen. For children aged
1-17 years, 20-100 percent of the adult dose should be given. For
infants < 1 year of age, 10 percent of the adult dose should be given.
There does not appear to be any benefit from additional doses.
- Antibiotics are not recommended for infant presenting with botulism or
for adults with suspected gastrointestinal botulism as this could lead to
lysis of intraluminal C. botulinum which could increase the amount of toxin
available for absorption.
Other treatments:
- In cases of foodborne botulism, laxatives, enemas, or other cathartics may
be given, provided no significant ileus is present.
- Patients presenting with wound botulism should have a thorough wound
debridement, even if the wound appears unimpressive. These patients
should receive tetanus boosters.
Prevention:
- The most significant aspect of botulism prevention is the proper handling
of food and preparation. Good home canning techniques (e.g., following
pressure canners' /cookers' instructions regarding minimum cooking time,
pressure, and temperature) will destroy spores.
- Food from damaged cans should not be consumed. Botulism toxin is heat
labile; therefore, boiling home-canned foods for at least 10 minutes before
consumption will render the food safe.
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- The prevention of infant botulism is limited to the avoidance of honey in

infants less than 12 months.
- The most important measure for the prevention of wound botulism is
prompt medical evaluation and treatment of infected wounds.
Recommendations:
- When botulism is suspected, the clinician should contact the Regional
Health Authority immediately for assistance and to obtain a supply of
antitoxin.
- If the clinical suspicion for botulism is high and symptoms are progressing,
antitoxin should be administered as soon as possible and should not be
delayed while awaiting results of diagnostic studies.
REFERENCES
1. Kerner J. Neue Beobachtungen uber die in Wurtemburg so haufig vorfallen Vergiftung durch den
Genuss gerauchter Wurst. Tubingen, 1820. In: Food Infections and Food Intoxications, Damon SR
(Ed), Williams and Wilkins, Baltimore 1928. p.67.
2. Abrutyn E. Botulism. In: Principles of Internal Medicine, 14th ed, Fauci AS, Isselbacher KJ,
Braunwald E (Eds), McGraw-Hill, New York 1998. p.904.
3. Yiannakopoulou E. Serious and long-term adverse events associated with the therapeutic and
cosmetic use of botulinum toxin. Pharmacology 2015; 95:65.
4. Arnon SS, Schechter R, Inglesby TV, et al. Botulinum toxin as a biological weapon: medical and
public health management. JAMA 2001; 285:1059.
5. Chertow DS, Tan ET, Maslanka SE, et al. Botulism in 4 adults following cosmetic injections with
an unlicensed, highly concentrated botulinum preparation. JAMA 2006; 296:2476.
6. Dowell VR Jr. Botulism and tetanus: selected epidemiologic and microbiologic aspects. Rev
Infect Dis 1984; 6 Suppl 1:S202.
7. Bleck TP. Clostridium botulinum (botulism). In: Principles and Practice of Infectious Diseases, 6th
ed, Mandel, GL, Bennett JE, Dolin R (Eds), Churchill Livingstone, Philadelphia 2005. p.2822.
8. Barash JR, Arnon SS. A novel strain of Clostridium botulinum that produces type B and type H
botulinum toxins. J Infect Dis 2014; 209:183.
9. Dover N, Barash JR, Hill KK, et al. Molecular characterization of a novel botulinum neurotoxin
type H gene. J Infect Dis 2014; 209:192.
10. Aureli P, Fenicia L, Pasolini B, et al. Two cases of type E infant botulism caused by
neurotoxigenic Clostridium butyricum in Italy. J Infect Dis 1986; 154:207.
Jin R, Rummel A, Binz T, Brunger AT. Botulinum neurotoxin B recognizes its protein receptor with
high affinity and specificity. Nature 2006; 444:1092.

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PHARMACEUTICALS
ANTIDIABETIC DRUGS
(HYPOGLYCEMICS AGENTS)
INTRODUCTION:
- Sulfonylurea agents are commonly used in the treatment of type II
diabetes mellitus. They can achieve euglycemia when used correctly.
However, hypoglycemia may result if renal clearance is impaired or the
patient does not eat as required. Sulfonylureas could often cause
hypoglycemia with overdose or when ingested by nondiabetic patients.
- Biguanides which include phenformin and metformin are
antihyperglycemic agents that are less likely to cause hypoglycemia.
They are used as both monotherapy and in combination with other oral
hypoglycemics. They can accentuate hypoglycemia induced by other
types of antidiabetics. The most serious toxic manifestation from acute
or chronic biguanide toxicity is lactic acidosis. Phenformin has
been withdrawn from the market due to the high rate of lactic
acidosis assocaited with the use of the drug. Currently, metformin is the
principal biguanide in clinical use.
TOXIC DOSE:
- One pill may cause hypoglycemia in a non-diabetic child or adult.
PATHOPHYSIOLOGY:
- Sulfonylurea agents cause hypoglycemia by:
↑Stimulating pancreatic insulin release
↓Suppressing glucagon release.
EPIDEMIOLOGY:
- Oral hypoglycemic poisoning is common.
- Hypoglycemic toxic effects are typically mild following accidental
exposure, but may be severe after large, intentional ingestion.
- Death from oral hypoglycemic medication is rare, occurring in untreated
cases with severe hypoglycemia.
- Infants and children have smaller glycogen stores than adults and are
prone to more developing hypoglycemic manifestations.
RISK FACTORS:
- Conditions that decrease sulfonylurea excretion (hepatic and renal
impairment)
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- Conditions deplete glycogen stores (starvation, alcohol abuse, hepatic

disease) predispose to hypoglycemic manifestations.
DRUG AND DISEASE INTERACTION:
- Hypoglycemia may be accelerted by cimetidine, ethanol, insulin,
salicylates, phenylbutazone, sulfonamides, beta-blockers, enalapril,
chloramphenicol, gemfibrozil, ranitidine, clofibrate, and warfarin.
- A disulfiram-like response manifestation may occur upon intake of
alcohol.
- Sulfonylureas reduce blood glucose levels mainly through stimulating

endogenous pancreatic insulin secretion and secondarily through
enhancing the sensitivity of peripheral insulin receptors and reducing
glycogenolysis.
- Biguanides reduce hepatic glucose production, absorption of glucose
from the intestine, while promoting peripheral glucose uptake and
utilization. It does not stimulate insulin release. Therefore, it is not likely
to produce acute hypoglycemia. Severe lactic acidosis is a rare but very
serious side effect of metformin overdose.
- Metformin Associated Lactic Acidosis (MALA):
- Metformin promotes the conversion of glucose to lactate in the
splanchnic bed of the small intestine. Metformin also inhibits
mitochondrial respiratory chain complex, leading to decreased
hepatic gluconeogenesis from lactate, pyruvate, and alanine.
- Clinically significant accumulation of lactate usually occurs with
the presence of other comorbid medical conditions, such as,
renal insufficiency, liver disease, alcohol abuse and heart failure.
- Acarbose is an α -glucosidase inhibitor reduces postprandial
blood glucose concentrations through delaying the digestion
of ingested carbohydrates,
- Troglitazone reduces hepatic glucose output and improves the
response to insulin at the cellular level.

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- Vital Signs: Hypothermia, tachypnea, hypertension, tachycardia
- Pupils: May be normal or fixed and dilated
- Cardiovascular Dysrhythmias: Atrial fibrillation, ventricular
ectopy
- Skin: Decreased turgor, Diaphoresis, Pallor
- Neurologic: Tremor, agitation, dépressions, coma, siezures,
neurologic déficits
- The onset of hypoglycemia may be delayed depending on the
type of drug used and the route of administration.
Manifestations of hypoglycemia include agitation, confusion,
coma, seizures, tachycardia, and diaphoresis.
- The serum levels of potassium and magnesium may be
decreaseed.
- Note that manifesations of hypoglycemia may be masked in
patients receiving β -adrenergic blocking agents.
- Metformin or phenformin induced lactic acidosis may present
with nonspecific symptoms such as malaise, vomiting, myalgias,
and respiratory distress.
- Thiazolidinediones and α glucosidase
- Overdose with thiazolidinediones and α glucosidase inhibitors
does not usually result in acute toxicity, yet hepatic dysfunction
may occur with chronic use.
- Overdose involving sulfonylureas or insulin should be considered
in any patient with hypoglycemia. Other causes of hypoglycemia
that should be suspected include alcohol ingestion (especially in
children) and fulminant hepatic failure.
- Diabetic patients presenting with an elevated anion gap
metabolic acidosis may have MALA or diabetic ketoacidosis. The
condition can be dissected based on the history (concurrent
illness, recent oral intake, and intentional ingestion) and the
presence or absence of hyperglycemia, ketosis and
hyperlactatemia.
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INVESTIGATIONS:
Routine:
- Liver function tests, BUN, creatinine and urine output to assess
kidney perfusion.
- Random blood glucose.
- Serum electrolytes.
- Arterial blood gases or oximetry.
- EKG monitoring
- Pregnancy test for all women of childbearing age.
- If metformin is suspected, serum lactate level and arterial blood
gases should be assessed.
Specific:
- The mainstay of laboratory investigations is frequent monitoring
of serum blood glucose levels. Concentrations of many agents
can be determined in laboratories, but have little utility in acute
clinical management.
TREATMENT
Stabilization:
- Assess airway, breathing, and circulation; stabilize as necessary.
Treat coma and seizures if they occur.
Decontamination:
- Oral activated charcoal is the mainstay of decontamination in
case of ingestion of large or unknown amounts of oral
hypoglycemic agents unless there are specific contraindications
such as, bowel obstruction or GI perforation.
- The clinician must assess aspiration risk, including mental status
and ability to protect the airway, in all patients before any
attempts to administer AC.
Specific therapy:
- Administer glucose as soon as possible after drawing a baseline
blood sample for later blood glucose determination. For adults,
administer 50% dextrose (D50W), 1-2 mL/kg; for children,
administer dextrose 25% (D25W), 2-4 mL/kg.
- Monitor serum glucose levels closely for several hours after the
last infusion of dextrose. Administer repeated glucose boluses

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and 5–10% dextrose (D5W–D10W) as needed to stabilize the

serum glucose levels at or above 100 mg/dL.
Octreotide:
- Patients with a sulfonylurea overdose and symptomatic
hypoglycemia should be treated with both intravenous dextrose
and octreotide. Octreotide inhibits insulin release from
pancreatic β -islet cells through acting as a somatostatin
analogue. In adults, the dose of octreotide is 50-150 μg IM, or SC,
injection q 6 hrs. In children the dose is 1 - 1.5 μg/kg (up to 150
μg) q 6 hrs. Octreotide may also be given as an IV bolus over
several minutes or by continuous IV infusion.
- Octreotide should be administered for 24 hrs. After octreotide is
discontinued, the patient is monitored for hypoglycemia for
another 24 hrs to ensure there is no remaining drug or active
metabolite. If hypoglycemia recurs during this period, we suggest
restarting octreotide therapy for another 24 hrs. In addition, two
serum glucose measurements should be obtained 30 minutes
apart during the first hour, and every 4-6 hrs thereafter provided
euglycemia is maintained
- Patients with a single episode of hypoglycemia during
therapeutic sulfonylurea use (not overdose) are treated by
intravenous dextrose to correct symptomatic hypoglycemia, no
need for octreotide and follow-up blood glucose level.
- Use sodium bicarbonate only for patients with severe
metformin-associated metabolic acidosis (arterial pH below
7.10), with the target of maintaining the pH above 7.15, until the
acute toxicity resolves. Excessive admininstration of sodium
bicarbonate may increase intracellular acidosis.
Hemodialysis for metformin:
- Hemodialysis has shown success in treating patients with
metformin-associated lactic acidosis due to chronic use or acute
overdose. Hemodialysis may be used in patients who are
critically ill, who have a severe metabolic acidosis (pH < 7.1), who
fail to improve with supportive care, or in whom renal
insufficiency is present.
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- Hemodialysis should be conducted with the use of bicarbonate

buffer, as the main benefit of hemodialysis is in correcting the
metabolic acidosis rather than in removing metformin.
N.B.
- A person who ingests sulfonlyureas should be admitted if:
- Hypoglycemia develops.
- It is a deliberate overdose.
- The patient is a child, even in the absence of hypoglycemia.
- The onset of lactic acidosis may take several hours. So patients
presenting with an acute ingestion should be kept under
observation for at least 6-8 hrs. Patients who have no clinical
manifestations and have stable blood glucose and a normal acid-
base status may be discharged after 6-8 hrs of stablity.
COMMON PITFALLS:
- Unawareness with the fact that severe hypoglycemia can lead to
focal neurological deficits and focal seizures.
- Failure to observe patients with sulfonylurea or meglitinide
overdose for at least 8 hrs.
- Administering prophylactic dextrose to patients with sulfonylurea
or meglitinide overdose who are asymptomatic or euglycemic.
- Failure to appreciate that excessive glucose administration
stimulates insulin secretion and can result in hypoglycemia
especially in sulfonylurea or meglitinide poisoning.

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REFERENCES:
1. Davidson JA, Liebl A, Christiansen JS, Fulcher G, Ligthelm RJ, Brown P, Gylvin T, Kawamori R,
2009 : Risk for nocturnal hypoglycemia with biphasic insulin aspart 30 compared with
biphasic human insulin 30 in adults with type 2 diabetes mellitus: a meta-analysis. Clin
Ther. Aug;31(8):1641-51.
2. Levine M, Ruha AM, Lovecchio F, et al, 2011: Hypoglycemia after accidental pediatric
sulfonylurea ingestions. Pediatr Emerg Care; 27:846.
3. Spiller HA, Sawyer TS, 2006: Toxicology of oral antidiabetic medications. Am J Health Syst
Pharm; 63:929.
4. Harrigan RA, Nathan MS, Beattie P, 2001: Oral agents for the treatment of type 2 diabetes
mellitus: pharmacology, toxicity, and treatment. Ann Emerg Med; 38:68.
5. Tornio A, Niemi M, Neuvonen PJ, Backman JT, 2012: Drug interactions with oral antidiabetic
agents: pharmacokinetic mechanisms and clinical implications. Trends Pharmacol Sci;
33:312.
6. Holstein A, Beil W, Kovacs P. , 2012: CYP2C metabolism of oral antidiabetic drugs—impact
on pharmacokinetics, drug interactions and pharmacogenetic aspects. Expert Opin Drug
Metab Toxicol; 8:(12):1549-63.
7. Shobha JC, Muppidi MR., 2010: Interaction between voriconazole and glimepiride. J
Postgrad Med; 56:44-5.
8. Boglou P, Steiropoulos P, Papanas N, Bouros D., 2012: Hypoglycaemia due to interaction of
glimepiride with isoniazid in a patient with type 2 diabetes mellitus. BMJ Case Rep. 2013
Apr 16;2013. pii: bcr2012008528. doi: 10.1136/bcr-008528
9. Menzies DJ, Dorsainvil PA, Cunha BA, Johnson DH. Severe and persistent hypoglycemia due
to gatifloxacin interaction with oral hypoglycemic agents. Am J Med 2002;113:232.
10. Spiller HA. Management of sulfonylurea ingestions. Pediatr Emerg Care 1999; 15:227.
11. Holstein A, Hammer C, Hahn M, et al., 2010: Severe sulfonylurea-induced hypoglycemia: a
problem of uncritical prescription and deficiencies of diabetes care in geriatric patients.
Expert Opin Drug Saf; 9:675.
12. Ginde AA, Pallin DJ, Camargo CA Jr, 2008: Hospitalization and discharge education of
emergency department patients with hypoglycemia. Diabetes Educ. Jul-Aug;34(4): 683-91
13. Garber AJ, Clauson P, Pedersen CB, Kølendorf K, 2007: Lower risk of hypo glycemia with
insulin detemir than with neutral protamine hagedorn insulin in older persons with type 2
diabetes: a pooled analysis of phase III trials. J Am Geriatr Soc. Nov;55(11):1735-40.
14. Mathioudakis N, Everett E, Golden SH, 2016: Prevention and management of insulin-
associated hypoglycemia in hospitalized patients. Endocr Pract. Apr 4. [Epub ahead of print]
PubMed PMID: 27042740.
15. Bosse GM., 2011: Antidiabetic and hypoglycemic agents. In: Goldfrank’s Toxicologic
Emergencies, 9th ed, Goldfrank LR, Nelson LS, Lewin NA, et al (Eds), McGraw-Hill, New York.
p.714.
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ANTICHOLINERGICS
INTRODUCTION
- Anticholinergic drugs toxicity is commonly encountered, and familiarity
with the management of this syndrome is essential. Discussion of
specific agents that can cause an anticholinergic toxidrome and the
general approach to the poisoned patient are found separately (See
General Toxicology section P. 10)
SUBSTANCES POSSESSING ANTICHOLINERGIC PROPERTIES
CLASS EXAMPLES
Antihistamines Chlorpheniramine, Cyproheptadine,
Doxylamine, Hydroxyzine,
Diphenhydramine, Meclizine,
Promethazine.
Neuroleptics Chlorpromazine, Clozapine, Mesoridazine,
Olanzapine, Quetiapine, Thioridazine.
Tricyclic antidepressants Amitriptyline, Amoxapine, Clomipramine,
Desipramine, Doxepin, Imipramine,
Nortriptyline.
Antiparkinsonian drugs Trihexyphenidyl, Benztropine.
Ophthalmic drugs Atropine, Cyclopentolate.
Antispasmodics Clidinium, Dicyclomine, Hyoscyamine,
Oxybutynin, Propantheline.
Plants Jimson Weed (Datura stramonium), Deady
Nightshade (Atropa belladonna), Henbane
(Hyoscyamus niger).
CLINICAL FEATURES:
Anticholinergic toxicity is almost always a clinical diagnosis
Manifestations of anticholinergic toxicity include:
- Flushing due to cutaneous vasodilation ("red as a beet").
- Anhydrosis ("dry as a bone").
- Hyperthermia due to loss of sweating ("hot as a hare").
- Blurry vision due to nonreactive mydriasis and paralysis of
accommodation ("blind as a bat").
- Agitated delirium ("mad as a hatter").
- Urinary retention ("full as a flask").

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- Decreased bowel sounds (can cause paralytic ileus so be aware

not to administer activated charcoal if suspected).
- Tachycardia.
- Dehydration.
INVESTIGATIONS:
Routine:
- Bed side RBS to exclude hypoglycemia.
- ABGs and Electrolytes (Na, K, Ca, Mg).
- BUN, Creatinine, ALT, AST, Creatine Kinase.
- Serum Paracetamol and Salicylates.
- EKG.
- Pregnancy test for females in childbearing period.
Specific:
- Confirm intake through blood screening for tricyclic
antidepressants, neuroleptics and antihistamines.
TREATMENT:
Stabilization:
- Secure the airway, breathing, and circulation and proper safe
restraining in patients with severe agitation and/or
hallucinations.
Decontamination:
- Administer activated charcoal (1 gm/kg, maximum 50 gm) to
patients with intact mental status or a secure airway and likely
recent ingestion of an anticholinergic agent.
Antidote:
- Patients who manifest both peripheral and moderate central
(moderate to severe agitation/delirium) anticholinergic toxicity,
without contraindications to physostigmine should be treated
with this medication; 0.5-2 mg (0.02 mg/kg IV, up to a maximum
of 0.5 mg/dose in pediatric patients). Physostigmine should be
given by slow IV push, over five minutes (after consulting with
the regional poison control center).
- Treat agitation and seizures with benzodiazepines (e.g.,
Lorazepam 1-2 mg IV push; may repeat as needed)
- Some differentiating features between classes of drugs causing
anticholinergic manifestations:
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- Because so many classes of drugs and toxins have anticholinergic

effects, clinicians must differentiate pure anticholinergic
poisoning from poisonings in which anticholinergic toxicity
represents only one aspect.
1) Tricyclic antidepressants can produce anticholinergic
effects.
a) Occur soon after overdose.
b) Quinidine-like effects (resulting in a prolonged QRS
interval) and α -blockade (resulting in hypotension)
are usually more prominent.
2) Phenothiazines have modest anticholinergic effects, but
their sedating and α -blocking properties (hypotension)
tend to predominate.
3) Although sympathomimetic drug overdose and serotonin
syndrome may present with manifestations similar to
anticholinergics such as, agitation, tachy-cardia, and
hyperthermia. Yet, sympathomimetic overdose and
serotonin syndrome generally cause diaphoresis, in
contradistinction to anticholinergic overdose.
4) In agitated, hyperthermic patients with altered mental
status, salicylate overdose should also be considered.
COMMON PITFALL
- The administration of phenothiazines or butyrophenones (e.g.,
haloperidol) is contraindicated in managing agitation induced by
anticholinergic substances.

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REFERENCES:
1. Bronstein AC, Spyker DA, Cantilena LR Jr, et al. , 2009: 2008 Annual Report of the
American Association of Poison Control Centers’ National Poison Data System (NPDS):
26th Annual Report. Clin Toxicol (Phila) 2009; 47:911.
2. Litovitz TL, Klein-Schwartz W, Dyer KS, et al. 1998: annual report of the American
Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg
Med; 16:443.
3. Watson WA, Litovitz TL, Rodgers GC Jr, et al. 2004 Annual report of the American
Med 2005; 23:589.
4. Litovitz TL, Klein-Schwartz W, Rodgers GC Jr, et al. 2001 Annual report of the American
Med 2002; 20:391.
5. Perharič L, Juvan KA, Stanovnik L. , 2013 : Acute effects of a low-dose
atropine/scopolamine mixture as a food contaminant in human volunteers. J Appl
Toxicol. Sep;33(9):980-90.
6. Derinoz O, Er A. , 2012 :Inability to walk, disequilibrium, incoherent speech,
disorientation following the instillation of 1% cyclopentolate eyedrops: case report.
Pediatr Emerg Care; 28:59.
7. Derinoz O, Emeksiz HC., 2012: Use of physostigmine for cyclopentolate overdose in an
infant. Pediatrics; 130:e703.
8. Gharavifard M, Razavi M, Ghandehari Motlagh M, Ziyaeifard M., 2014: Central
Anticholinergic Syndrome due to Hypoxia-Induced Bradycardia in a Child with Difficult
Intubation Undergoing Complete Dental Restoration: A Case Report. J Dent (Tehran).
Sep;11(5):610-2
9. McCarron MM, Challoner KR, Thompson GA. ., 1991: Diphenoxylate-atropine (Lomotil)
overdose in children: an update (report of eight cases and review of the literature)
Pediatrics; 87:694
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CARDIOPULMONARY MEDICATIONS
BETA-BLOCKERS
(β -BLOCKERS)
INTRODUCTION:
- Beta blockers are widely available and are mainly used for the treatment
of heart failure, hypertension, arrhythmias, angina pectoris, migraine,
and glaucoma. Many patients presenting with beta-blocker overdose will
concurrently suffer from underlying cardiovascular diseases or will be
taking other cardiac medications, both of which may aggravate beta-
blocker overdose.
EPIDEMIOLOGY
- Beta blocker toxicity is uncommon.
- Toxic manifestations following exposure are typically mild to moderate,
with death developing in cases including co-ingestants or large amount.
CAUSES
- Toxic exposure is usually intentional type.
- Child neglect or abuse should be considered if the patient is less than one
year of age, suicide attempt if the patient is over six years of age.
RISK FACTORS
- Cases with hypersensitive reactive airways condition may develop
bronchospasm even at therapeutic doses.
- Elderly patients and those with underlying cardiovascular pathological
condition may be intolerant of hypotension.
- Seizures and hypoglycemia are more common presentation in pediatrics,
particularly with propranolol exposure.
- Co-ingestion of calcium channel blocker or digitalis medication may
worsen bradycardia, dysrhythmias, & hypotension toxic effects.
- Co-ingestion of other antihypertensives drugs may worsen hypotension
toxic degree.
- The manifestations of beta blockers toxicity depend on the specific agent
and dose involved. In addition to blocking beta-adrenergic receptors,
three properties affect toxicity which include the following:

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- Membrane stabilizing activity (MSA): (e.g., propranolol, acebutolol)

inhibition of fast sodium channels of myocytes, which can result in a
widened QRS interval.
- Lipophilicity: Beta blockers with high lipid solubility (e.g., propranolol)
rapidly cross the blood-brain barrier into the CNS, predisposing to
neurologic sequelae such as seizures and delirium.
- Intrinsic sympathomimetic activity (ISA): Several agents act as partial
agonists at the beta receptor binding site. This results in less
bradycardia and hypotension when administered in therapeutic and
supratherapeutic doses.
Cardiac:
- Bradycardia and hypotension are the most commonly observed effects
and in significant overdoses can result in severe myocardial depression
and shock.
- Ventricular dysrhythmias are seen more frequently following
propranolol and acebutolol.
- Other manifestations:
- Effects of severe toxicity include mental status change, seizures,
hypoglycemia, and bronchospasm.
- Early recognition and prompt treatment of hypoglycemia is critical.
EKG findings
- Slowing of conduction velocity across the AV node, resulting in PR
prolongation, slow automaticity within the SA node, resulting in
bradycardia.
- QRS prolongation is more commonly seen in poisoning with beta
blockers with membrane stabilizing activity.
- In severe poisoning, the electrocardiogram (EKG) can show any
bradydysrhythmia, and can progress to asystole.
INVESTIGATIONS:
Routine:
- Liver function tests, BUN, creatinine and urine output to assess kidney
perfusion.
- Blood glucose may be low. The presence of hypoglycemia in a non-
diabetic patient may help to distinguish β blockers poisoning from
poisoning by CCBs.
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- EKG monitoring and serum electrolytes.

Specific:
- Serum concentrations of most β-blockers can be measured, they
cannot be obtained in time to be clinically useful.
- Blood glucose, serum electrolytes including calcium. If calcium is
administered repeatedly, levels of calcium should be measured every
4-6 hrs if calcium is to be administered frequently.
- If a decision is made to administer insulin/glucose treatment regimen,
glucose and K levels must be measured every 30 to 60 minutes.
- Other classes of antihypertensive or antidysrhythmic drugs (e.g. CCBs,
β-blockers, digoxin, and clonidine).
- CCB toxicity is more frequentlty associated with hyperglycemia, while
β-blockers toxicity is associated with hypoglycemia.
- Nausea and vomiting are more commonly observed with digoxin
toxicity than β-blocker toxicity. Digoxin toxicity could result in a
scooped ST segment depression on the EKG.
- Cholinergic agents toxicity present with bradycardia but also includes
other characteristic features (DUMBBLES)
TREATMENT
Stabilization:
- Assess airway, breathing, and circulation and stabilize as necessary.
- Control hypotension and bradycardia: Administer boluses of isotonic IV
fluids: Give atropine 1 mg IV (up to 3 doses)
Decontamination:
- Single-dose activated charcoal; whole bowel irrigation should be
considered if the patient ingested extended-release preparation.
Specific therapy: for severe poisoning (e.g., profound hypotension)
- Glucagon: Administer 5 mg IV bolus (if the initial IV fluids and atropine
were ineffective). Glucagon may be repeated if the initial bolus was
ineffective.
- Calcium chloride (via central venous access): 10-20 mL of 10 % solution
or calcium gluconate IV 30-60 mL of 10 % solution
- Vasopressors (e.g., epinephrine) can be used for hypotension

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- High-dose insulin and glucose: Administer a bolus of 1 unit/kg IV of

regular, short-acting insulin, followed by continuous infusion of 0.5
unit/kg/hour IV. The infusion rate can be increased until hypotension is
corrected or dose becomes 2 units/kg/hour.
- Intravenous lipid emulsion (20 % solution): Give 1.5 mL/kg over 2
minutes, followed by 1.5 mL/kg infusion over 60 minutes.
Other potential treatments include:
- Sodium bicarbonate (e.g., prolonged QRS complex), magnesium
(ventricular dysrhythmia),
- Consult the cardiologist to consider intraaortic balloon pump and/or
temporary transvenous pacing.
- Hemodialysis has a minimal role in the treatment of β-blocker
overdose and is effective only with hydrophilic, minimally protein-
bound β-blockers. Hemodiyalysis could be effective with drugs like
nadolol, sotalol, acebutolol, and atenolol but not with metoprolol,
propranolol, and timolol.
FOLLOW UP:
- PATIENT MONITORING
- Continuous close cardiac and hemodynamic monitoring.
- Serum glucose in diabetics and pediatrics.
- Pulmonary condition in patients with reactive hypersensitive airways
status.
- EXPECTED COURSE AND PROGNOSIS
- Most cases do well with gastrointestinal decontamination procedure
and supportive care maneuver. Factors producing greatest risk for
complications include:
- Advanced age
- Underlying pathological conditions (especially cardiovascular)
- Co-ingestion of other cardiac depressant drugs (calcium channel
blockers, digitalis, clonidine, etc.)
- Massive amount of ingestion of sustained release preparation.
- DISCHARGE CRITERIA/INSTRUCTIONS
- From the emergency department. Patients who have ingested an
immediate-release formulation and are asymptomatic other than mild
bradycardia may be discharged after gastric decontamination
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procedure, a six-hour observation period, and psychiatric assessment,

if required.
- From the hospital. Patients may be discharged following
gastrointestinal decontamination procedure, recovery of cardiac
manifestations, and psychiatric assessment, if required.
- PATIENT EDUCATION
- Patients should be instructed carefully on usage and dosage of
ophthalmic formulations.
- Patients should be warned to avoid simultaneous use of beta-blockers
and other drugs with similar actions (calcium channel blocker, digitalis)
when possible.
COMMON PITFALLS
- Failure to determine whether the drug ingested was an immediate or
extended release formulation, potentially leading to inappropriate
treatment and disposition decision. Failure to check Finger stick glucose
as β-blockers can cause hypoglycemia.
- Lack of appreciation that β-blockers with membrane stabilizing activity
can cause delayed repolarization, cardiac conductive disorders (widened
QRS) and ventricular tachyarrhythmias.
- Failure to anticipate seizures with lipophilic β-blockers such as
propranolol.
- Failure to appreciate that sotalol has potassium channel blocking effects
and can cause a prolonged QT interval and torsade de pointes.
- Failures to appreciate that severe poisoning are likely to require invasive
monitoring, multiple pharmacological treatment, and mechanical
hemodynamic support.

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REFERENCES:
1. Brubacher J, 2011: Adrenergic Antagonists In: Goldfrank’s Toxicologic Emergencies, 9th ed,
Goldfrank LR, Nelson LS, Lewin NA, et al (Eds), McGraw-Hill, New York. p.926.
2. Ellen Lemkin E, 2014: Beta blocker poisoning UPTODATE 2014: http://www.uptodate.com/
contents/ Beta blocker poisoning. june ,2014
3. Samuels TL, Uncles DR, Willers JW, et al, 2011: Logging the potential for intravenous lipid
emulsion in propranolol and other lipophilic drug overdoses. Anaesthesia 2011; 66:221.
4. Lee J. 2004: Glucagon use in symptomatic beta blocker overdose. Emerg Med J; 21:755.
5. Holger JS, Engebretsen KM, Fritzlar SJ, et al., 2007: Insulin versus vasopressin and
epinephrine to treat beta-blocker toxicity. Clin Toxicol (Phila) ; 45:396.
6. Page C, Hacket LP, Isbister GK. ., 2009: The use of high-dose insulin-glucose euglycemia in
beta-blocker overdose: a case report. J Med Toxicol; 5:139.
7. Stellpflug SJ, Harris CR, Engebretsen KM, et al. ., 2010: Intentional overdose with cardiac
arrest treated with intravenous fat emulsion and high-dose insulin. Clin Toxicol (Phila) ;
48:227.
8. Doepker B, Healy W, Cortez E, Adkins EJ. ., 2014: High-dose insulin and intravenous lipid
emulsion therapy for cardiogenic shock induced by intentional calcium-channel blocker and
Beta-blocker overdose: a case series. J Emerg Med; 46:486.
9. Love JN, Howell JM, Klein-Schwartz W, Litovitz T., 2006: Lack of toxicity from pediatric
beta-blocker exposures. Hum Exp Toxicol; 25:341.
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CALCIUM CHANNEL BLOCKERS

INTRODUCTION:
- Calcium channel blockers (CCBs) are used widely in the management of
angina pectoris, hypertension, cardiac arrhythmias, and other disorders.
They are available in both rapid-release and extended-release
preparations. The latter are more widely used clinically. Patients can
develop severe signs of toxicity if they ingest more than 5 to 10 times the
usual dose. Overdoses of CCBs could frequently result in life-threatening
conditions.
TOXIC DOSE
- Ingestion of a gram or more of verapamil, nifedipine, or diltiazem can
develop serious poisoning and possible death in an adult.
- The other preparations in this class appear less toxic, but few data are
available on overdose exposure.
EPIDEMIOLOGY
- Calcium channel blocker toxicity is uncommon
- Toxic manifestations following exposure are typically mild to moderate.
- Death occurs in cases involving co-ingestants or a massive overdose
exposure.
CAUSES
- Toxic ingestion is usually intentional type.
RISK FACTORS
- Elderly patients and those with underlying cardiovascular pathological
may be intolerant of even mild hypotensive toxic effect.
- Hepatic impairment decreases CCB hepatic elimination.
- Co-ingestion of beta-blockers, digitalis, or class I antidysrhythmic
medications may worsen bradycardia, dysrhythmias, and hypotension.
- Co-ingestion of other antihypertensives medications may worsen
hypotension.
- CCBs attenuate the influx of calcium through cellular calcium channels.
They mainly act on vascular smooth muscles and the heart. Additionally,
they produce coronary and peripheral vasodilation, reduce cardiac
contractility, slow (AV) nodal conduction, and suppress sinus node
activity.

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CCBs are divided into two major categories:

- Dihydropyridines, preferentially affect the vasculature such as
nifedipine and amlodipine. They are potent vasodilators that have little
negative effect upon cardiac contractility or conduction at therapeutic
dosages.
- Non-dihydropyridines, such as verapamil and diltiazem are more
selective towards the myocardium and they are weak vasodilators that
negatively modulate cardiac conduction and contractility.
- Dihydropyridine intoxication results in arterial vasodilation and reflex
tachycardia, whereas diltiazem and verapamil toxicity cause peripheral
vasodilation reduced cardiac inotropy, and bradycardia. However, as
the dose is increased, this selectivity can be lost, and dihydropyridine
CCBs may affect the myocardium and conduction systems like
verapamil and diltiazem.
Cardiac manifestations:
- Hypotension and bradycardia are often seen only in verapamil or
diltiazem poisoning. However, bradycardia may also be seen with
severe dihydropyridine poisoning.
- Jugular venous distension and other signs of heart failure may be
noted in some cases.
Non-cardiac manifestations:
- Nausea and vomiting, abnormal mental status (stupor and confusion),
and metabolic acidosis (probably resulting from hypotension).
- Reduced insulin release leads to hyperglycemia.
- Noncardiogenic pulmonary edema (NCPE) from increased
transcapillary hydrostatic pressure.
INVESTIGATIONS:
Routine:
- Liver function tests, BUN, and creatinine, as well as urine output to
assess renal perfusion.
- Blood glucose measurement may reveal hyperglycemia, which is
caused by inhibition of calcium-mediated insulin release; however, this
elevation is rarely clinically significant, except for diagnostic purposes.
The presence of hyperglycemia in a non-diabetic patient may help to
distinguish CCB from β-blocker poisoning.
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- Serum electrolytes including calcium should be assessed.

- Arterial blood gases or oximetry, and EKG monitoring
Specific:
- Serum drug levels are not widely available. Detection of diltiazem and
verapamil is possible using comprehensive urine toxicology screening.
TREATMENT
Stabilization:
- Assess airway, breathing, and circulation and stabilize as necessary
- Monitor the vital signs and EKG for at least 6 hrs after an alleged
ingestion.
Decontamination:
- Single-dose activated charcoal. Consider whole bowel irrigation if an
extended-release preparation has been ingested.
Treatment of hypotension and bradycardia:
- Intravenous crystalloid (hypotension): Isotonic saline 500-1000 mL
boluses.
- Atropine (bradycardia): 1 mg IV (0.02 mg/kg in children); may repeat
for 3 total doses.
- For patients with severe CCB poisoning (e.g., profound hypotension
refractory to crystalloid boluses and atropine), give multiple
simultaneous interventions, including all of the following: Calcium
salts, glucagon, high-dose insulin and dextrose, vasopressors & lipid
emulsion therapy.
Specific therapy:
Intravenous calcium (hypotension and/or bradycardia)
- Bolus therapy:
- Calcium chloride – 10-20 mL of 10 % solution (via central venous
access if possible)
- Calcium gluconate – 30-60 mL of 10 % solution.
- Continuous infusion of 0.5 mEq calcium/kg/hour.
- Monitor serum calcium and EKG for evidence of hypercalcemia.
Glucagon (bradycardia)
- Bolus therapy:
- Glucagon 1-5 mg IV push, may repeat up to 15 mg total.

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- Continuous infusion:
- Determine the bolus amount needed to obtain response;
administer this "response dose" every hour as a continuous
infusion.
Vasopressor support (hypotension)
- Norepinephrine: begin 2 μg/minute IV, titrate rapidly to systolic
blood pressure 100 mmHg
Hyperinsulinemia with euglycemia (HIE) therapy (hypotension)
- Relative hypoglycemia and hypokalemia must be corrected prior
to initiating high-dose insulin therapy.
Bolus therapy:
- Regular insulin 1 unit/kg IV
- Dextrose 25-50 gm IV; repeat for hypoglycemia; give potassium
for hypokalemia.
Maintenance infusions:
- Regular insulin: Start infusion at 0.5 unit/kg/hour IV; titrate
upwards until hypotension is corrected or maximum dose of 2
units/kg/hr is reached.
- Dextrose 0.5 gram/kg per hour; titrate to euglycemia.
Lipid emulsion
- Lipid emulsion to patients with hypotension refractory to other
therapies. Administer 1.5 mL/kg of 20% lipid emulsion over 2-3
minutes as an IV bolus, followed by an infusion of 0.25 mL/kg/min.
If possible, discontinue after 30-60 minutes.
- If the above measures fail, consult the cardiologist to consider the
following:
- Transvenous cardiac pacing
- Intraaortic balloon pump
- Cardiopulmonary bypass
- Extracorporeal membrane oxygenation
PATIENT MONITORING
- Continuous respiratory, cardiac, and hemodynamic close monitoring
should be instructed.
- Serum glucose should be frequent monitored in diabetics and pediatrics.
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- Most patients do well with gastrointestinal decontamination and
supportive care.
- Course may be prolonged and complicated in cases with massive
ingestion, advanced age, underlying cardiovascular pathological
condition, or co-ingestion of other cardiac depressant drugs.
- Sequelae of prolonged toxic hypotensive effect may develop in severe
toxic cases.
- From the emergency department. Asymptomatic cases may be
discharged following gastric decontamination maneuver, six hours of
close observation, and psychiatric assessment, if needed. Ingestion of a
sustained-release preparation usually warrants 24-hours close
observation.
- From the hospital. Patients may be discharged following gastrointestinal
decontamination procedure, recovery of cardiac toxic effects, and
psychiatric assessment, if required.
COMMON PITFALLS
- Failure to consider CCB poisoning in patients with hypotension,
bradycardia or AV block, particularly when hyperglycemia is present.
- Failure to appreciate that ingestion of single pill may be lethal in a
toddler.
- Failure to consider whole bowel irrigation or multiple doses activated
charcoal for patients with overdoses of extended-release preparations.
- Failure to initiate HIE therapy in a timely manner.

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REFERENCES:
1. DeRoos F , 2011: Calcium Channel Blockers In: Goldfrank’s Toxicologic Emergencies, 9th ed,
Goldfrank LR, Nelson LS, Lewin NA, et al (Eds), McGraw-Hill, New York. p.912-920.
2. Barrueto F, 2016 Calcium Channel Blockers poisoning UPTODATE:
http://www.uptodate.com/ contents/calcium-channel-blocker-poisoning.
3. Anand V, Nair S. An unusual toxicity with beta blocker and calcium channel blocker. Indian J
Crit Care Med. 2015 Aug;19(8):496-8.
4. Ashraf M, Chaudhary K, Nelson J, Thompson W: Massive overdose of sustained-release
verapamil: A case report and review of literature. Am J Med Sci 1995;310:258-263.
5. Bailey B: Glucagon in Î²-blocker and calcium channel blocker overdoses: A systematic
review. J Toxicol Clin Toxicol 2003;41:595-602.
6. Belson MG, Gorman SE, Sullivan K, Geller RJ: Calcium channel blocker ingestions in children.
Am J Emerg Med 2000;18:581-586.
7. Boyer EW, Duic PA, Evans A: Hyperinsulinemia/euglycemia therapy for calcium channel
blocker poisoning. Pediatr Emerg Care 2002;18:36-37.
8. Durward A, Guerguerian AM, Lefebvre M, Shemien SD: Massive diltiazem overdose treated
with extracorporeal membrane oxygenation. Pediatr Crit Care Med 2003;4:372-376.
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CARDIAC GLYCOSIDES
INTRODUCTION:
Cardiac glycosides affect the heart and they are recognized by presence of a
common steroid nucleus at the heart of these drugs. The most common
product is digoxin. Other preparations include digitoxin, ouabain, lanatoside
C, deslanoside, and gitaline. Both digoxin and digitoxin have a narrow
therapeutic index and toxicity is common.
TOXIC DOSE
Ingestion of greater than 10 mg digoxin by an adult or more than 4 mg
by a child has been fatal.
EPIDEMIOLOGY
- Digoxin toxicity is uncommon.
- Toxic manifestations following exposure are typically mild degree.
- Death develops in cases with unrecognized digoxin toxicity.
CAUSES
- Poisoning usually results from suicidal attempt.
RISK FACTORS
- Underlying cardiac pathological condition may predispose to
dysrhythmia.
- The elderly require smaller amount of digitalis and are more likely to have
an underlying disease that predisposes to toxicity.
- Concurrent use of other drugs (beta-blocker, calcium channel blocker)
can cause severe bradycardia or more conduction delay.
- Quinidine, quinine, verapamil, diltiazem, amiodarone, erythromycin, and
tetracycline may rise digoxin levels.
- Nifedipine, spironolactone, triamterene, and amiloride decrease renal
clearance of digoxin.
- Warfarin can increase free digoxin level in the blood
- Renal impairment depresses digitalis elimination.
- Hepatic failure depresses digitoxin elimination.
- Hypokalemia, hypercalcemia, hypomagnesemia, induce sympathetic
system activity, and hypothyroidism may augment digitalis toxicity.
- Inhibition of the Na-K ATPase-dependent myocardial sarcolemmal pump.
The increase in intracellular sodium prevents the sodium-calcium

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transporter from pushing calcium outside the myocyte, which increases

intracellular calcium and augments inotropy
- The increase in intracellular calcium may lead to premature contractions
and stimulate arrhythmias. Cardiac glycosides shorten repolarization of
the atria and ventricles, reducing the refractory period of the
myocardium, thereby increasing automaticity and the risk for
arrhythmias.
- The increase in vagal tone results in decreased conduction through the
sinoatrial and atrioventricular nodes.
- Peripheral vasodilation and reduced afterload.
Non-cardiac manifestations:
Acute Toxicity:
- Following an asymptomatic period of several minutes to several
hours, the first set of symptoms are usually anorexia, nausea,
vomiting, or abdominal pain.
- CNS: Lethargy, confusion, and weakness that are not caused by
hemodynamic changes.
Chronic Toxicity:
- Chronic toxicity is often difficult to identify due to its slow
development.
- Symptoms may include those with acute poisonings; however, they
are often less obvious.
- Gastrointestinal symptoms, as well as delirium, confusion,
disorientation, drowsiness, headache.
- Visual changes may include experiencing yellow halos around light,
scotomas, blindness, hallucinations and seizures may rarely occur.
Cardiac manifestations:
- Digoxin toxicity can produce bradycardia, heart block, different
types of cardiac arrhythmias that may evolve and change rapidly.
Thus, performing continuous cardiac monitoring and obtaining
serial electrocardiograms (EKG) is important in the setting of
toxicity.
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Acute Toxicity:
- The initial increased vagal tone at the sinoatrial (SA) and
atrioventricular (AV) nodes results in a bradydysrhythmia that is
responsive to atropine.
Chronic Toxicity:
- Ventricular tachydysrhythmias are more common in patients with
chronic or late acute poisoning than they are in early acute
poisoning.
Toxicologic:
- Poisoning with β-blockers, calcium channel blockers, and α-agonists
(e.g., clonidine) can present with bradycardia and hypotension
being prominent features. (Clonidine poisoning leads to greater
CNS depression, respiratory depression, and miosis).
Non-toxicologic:
- Hypothermia, hypothyroidism, myocardial infarction, and
hyperkalemia from other causes.
INVESTIGATIONS:
Routine:
- Liver function tests, BUN, creatinine and urine output to assess
kidney perfusion.
- Blood glucose to rule out hypoglycemia.
- Serum electrolytes.
- EKG monitoring.
Specific:
Serum digoxin concentration
- It does not necessarily correlate with toxicity, but may be used in
some cases to determine the dosing of antidotal therapy with Fab
fragments.
- Following the administration of Fab fragments, serum
immunoassays of digoxin are unreliable as they measure both
bound and unbound drug. Fab treatment frequently causes an
elevation in the measured digoxin concentration despite a free
digoxin level approaching zero. The measurement of "free" digoxin

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concentrations may be helpful in determining when a patient can

restart digoxin, if desired.
N.B. Elevated digoxin levels have been identified in pregnant women,
newborns, and patients with acromegaly, subarachnoid hemorrhage, liver
disease, and renal failure due to endogenous digoxin-like substances.
Electrolyte abnormalities
Serum potassium concentration
- Inhibition of Na-K-ATPase in both heart and skeletal muscles, leads
to an increase in extracellular potassium. Therefore, hyperkalemia
is an important indicator of acute digitalis toxicity. It is a better
predictor of lethality than either the initial EKG changes or the
serum digoxin concentration. (K > 5.5 mEq/L is a poor prognostic
sign). Note that simply correcting the hyperkalemia does not
increase patient survival; it is a marker of, and not the cause of, the
morbidity and mortality
- In chronic toxicity, hypokalemia is of greater concern. Several
electrolyte abnormalities, including hypokalemia, hypomagnesemia
and hypercalcemia, increase patient susceptibility to the toxic
effects of digoxin.
TREATMENT:
Stabilization:
- Assess airway, breathing, and circulation; stabilize as necessary
- Continuous cardiac and pulse oximetry monitors
- EKG monitoring.
- The treatment for any clinically significant arrhythmia from digitalis
toxicity, such as those producing hypotension with digoxin -specific
antibody (Fab) fragments.
- With the availability of digoxin - specific antibody (Fab) fragments
antibodies, all other therapies are considered equivocal.
Decontamination:
- Activated charcoal should be given within 1-2 hrs of digoxin
ingestion to patients who can protect their airway and are not
actively vomiting. Repeated doses of activated charcoal
administration (1 gm/kg/2–4 hrs for up to 4 doses) may assist in
reducing serum concentration.
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Antidote:
- Antidotal therapy with antibody (Fab) fragments
- Early recognition of digitalis toxicity and prompt administration of
Fab fragments is essential for the successful treatment of severe
poisoning.
- Fab fragments are highly effective and safe and have transformed
the management of cardiac glycoside poisoning.
- Recommendations for administration of digitalis antibody
fragments:
- Life-threatening or hemodynamically unstable arrhythmia (e.g.,
ventricular tachycardia,+++ VF, asystole, complete heart block,
Mobitz II heart block, symptomatic bradycardia)
- Hyperkalemia (serum potassium >5-5.5 mEq/L [>5-5.5 mmol/L])
- Evidence of end-organ dysfunction from hypoperfusion (e.g., renal
failure, altered mental status)
- Serum digoxin level is > 10 ng/mL (13 nmol/L) in acute ingestions,
or > 4 ng/mL (5.1 nmol/L) in chronic ingestions
- Intake of more than 10 mg or a child more than 4 mg acutely.
- Calculating the dose of fab fragments:
Acute digoxin toxicity:
- If the digoxin level or amount ingested is known, administer
empiric doses of 10 vials of Fab fragments which should be
repeated if clinical response is inadequate. Children can be
adequately treated with 5 vials and the dose can increase
based on clinical response.
- Amount of digoxin ingested is known but concentration is
unknown
- No. of vials = Amount ingested (mg) × 0.8 ÷ 0.5
- Steady state digoxin concentration is known
- No. of vials = Serum Digoxin (ng/mL) × Pt Wt (kg) ÷ 100
Chronic digoxin toxicity:
- Patients with acute symptoms and without known serum
digoxin concentration:
- Administer empiric doses of 6 vials (240 mg) of Fab
fragments for adults and older/larger pediatric patients.
If steady state digoxin concentration is known:

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- No. of vials = Serum Digoxin (ng/mL) × Pt Wt (kg) ÷ 100

Chronic toxicity without severe signs:
- Chronic toxicity without manifestation of acutely life-
threatening arrhythmias (e.g., AV nodal blockade present
on EKG but patient maintains normal blood pressure and
stable mental status), half the recommended dose can be
given initially as administration of a full dose can result in
acute decompensated heart failure or atrial fibrillation
with rapid ventricular response.
Supportive:
- A serum K level > 5 mEq/L warrants consideration of Fab treatment.
If Fab fragments are not immediately available, severe
hyperkalemia should be managed using IV glucose, insulin, and
sodium bicarbonate.
- If Fab fragments are not immediately available, symptomatic
bradycardia or bradyarrhythmia can be managed with atropine.
(0.5 mg IV in adults; 0.02 mg/kg IV in children, minimum dose 0.1
mg) and hypotension with IV boluses of isotonic crystalloid. Life-
threatening ventricular arrhythmias are treated according to the
algorithms of advanced cardiac life support.
PATIENT MONITORING
- Continuous close cardiac and hemodynamic monitoring should be
instituted and serum potassium level followed closely.
- Recovery is usually complete, but often complicated by patient's
underlying pathological condition.
- Sequelae of hypotensive or hypoxic effects may occur.
- Improvement within 30 minutes of digoxin Fab treatment is predicted if
complications of shock, hypoxia, or a coingestant have not developed.
DISCHARGE CRITERIA AND INSTRUCTIONS
- From the emergency department. Asymptomatic cases with nontoxic
digoxin level, normal EKG, and normal electrolytes levels may be
discharged following gastrointestinal decontamination procedures, six
hours of close observation, and psychiatric assessment, if required.
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- From the hospital. Patients may be discharged following gastrointestinal

decontamination procedure, recovery of cardiac toxic manifestations,
and psychiatric assessment, if required.
COMMON PITFALLS
- Failure to appreciate that signs of toxicity may be delayed up to 8 hrs
after acute ingestion.
- Digoxin has a slow redistribution phase, so high serum concentrations
are expected for several hours following doses. A single high digoxin
concentration in an otherwise asymptomatic patient is not an indication
for treatment.
- Failure to appreciate that digoxin assays may not yield a measurable
digoxin level with ingestion of cardiac glycosides from plants.
- Failure to appreciate that difference between acute and chronic cardiac
glycosides poisoning.

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REFERENCES:
1. Michael Levine M, Ayrn O'Connor A,N, 2016: digitalis-cardiac-glycoside-poisoning
UPTODATE: http://www.uptodate.com/ contents/ digitalis poisoning.
2. Chhabra N, Valento M, Bryant SM, Aks SE, 2015: Digoxin-Specific Antibody Fragment
Dosing: A Case Series. Am J Ther. May 5. [Epub ahead of print] PubMed PMID: 26057142.
3. Tatlısu MA, Çekirdekçi Eİ, Akyüz Ş, Nurkalem Z. 2015: A case of Mobitz type II
atrioventricular block due to Nerium oleander poisoning successfully managed with digoxin-
specific Fab antibody fragments. Turk Kardiyol Dern Ars. Oct;43(7):648-50.
4. Mowry JB, Burdmann EA, Anseeuw K, Ayoub P, Ghannoum M, Hoffman RS, Lavergne V,
Nolin TD, Gosselin S;, 2016 : EXTRIP Workgroup. Extracorporeal treatment for digoxin
poisoning: systematic review and recommendations from the EXTRIP Workgroup. Clin
Toxicol (Phila). Feb;54(2):103-14.
5. Nordt SP, Clark RF, Machado C, Cantrell FL. ,2016: Assessment of Digoxin-Specific Fab
Fragment Dosages in Digoxin Poisoning. Am J Ther. Jan-Feb;23(1):e63-7.
6. Chan BS, Buckley NA.,2014: Digoxin-specific antibody fragments in the treatment of digoxin
toxicity. Clin Toxicol (Phila). 2014 Sep-Oct;52(8):824-36.
7. Jang DH, Spyres MB, Fox L,2014: Manini AF. Toxin-induced cardiovascular failure. Emerg
Med Clin North Am. 2014 Feb;32(1):79-102.
8. Pautas E, Lopez C, Gouronnec A, Gravelaine S, Peyron I, Lapostolle F., 2012: [Focus on
digitalis intoxication in the elderly. Report of a case treated with digoxin-specific Fab
antibody fragments]. Geriatr Psychol Neuropsychiatr Vieil. Dec;10(4):355-63.
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THEOPHYLLINE
INTRODUCTION:
- Theophylline has been widely used as a bronchodilator for the
treatment asthma and COPD and is commonly used to treat neonatal
apnea in preterm infants.
- The incidence of poisoning has significantly declined in recent years due
to the decrease in prescribing theophylline for asthmatic patients.
Theophylline poisoning is uncommon, but serious toxicity and deaths
are reported every year.
TOXIC DOSE:
- The manifestations of acute toxicity (e.g., vomiting) may occur with low
dose as 7.5 mg/kg. Theophylline has a narrow therapeutic index.
EPIDEMIOLOGY:
- Theophylline toxicity is uncommon
after acute overdose and moderate to severe after chronic overdose
- Death is more likely after chronic theophylline overdose and in
pediatrics or the elderly patients.
CAUSES:
- Excessive therapeutic dosing is the most common pattern of toxicity;
serum theophylline levels should be monitored closely when rising
maintenance theophylline dose.
- Decreased metabolism leading to elevated serum theophylline levels
may result from drug interactions, alcoholic liver impairment, and
congestive heart failure.
- Chronic theophylline overdose is usually accidental exposure, iatrogenic
errors, or the result of medication interactions.
- Acute theophylline overdose is usually a non-accidental incident in
adults and accidental in pediatrics.
- Child abuse should be considered if the patient is less than one year of
age; suicide attempt if the patient is more than six years of age
RISK FACTORS:
- Cases over 60 or under three years of age are at highest risk for severe
complications (dysrhythmia, seizure) after chronic overdose.
- Hepatic dysfunction may predispose a patient to theophylline toxicity.

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- Many medications decrease the rate of theophylline metabolism and
may cause intoxication: allopurinol, cimetidine, ciprofloxacin,
clarithromycin, disulfiram, pentoxifylline, pipenidic acid, propafenone,
propranolol, tacrine, thiabendazole, enoxacin, erythromycin, ethanol,
estrogen, idrocilamide, interferon A, methotrexate, mexiletine,
norfloxacin, ofloxacin, pefloxacin, ticlopidine, troleandomycin, and
verapamil.
- Pharmacology: It inhibits phosphodiesterase, which in an increase in
cyclic adenine monophosphate and catecholamine release, and is also
an antagonist at the adenosine receptor site.
- Toxicology: Increase catecholamine levels (epinephrine and
norepinephrine) cause tachycardia, hypotension, anxiety, and
hyperglycemia. Adenosine receptor antagonism may cause seizures.
- Mild to moderate toxicity:
Nausea, vomiting, abdominal pain, sinus tachycardia, sustained
complex atrial or ventricular ectopy, tremor, agitation, hypokalemia,
hyperglycemia, hypophosphatemia, and hypercalcemia can develop.
- Severe toxicity:
Seizures, rhabdomyolysis, hypotension, and ventricular dysrhythmias
can occur.
- Chronic overdose:
GIT symptoms may be absent. Severe effects, such as seizures and
significant dysrhythmias, are more common with chronic overdoses
than with acute overdoses. The onset of symptoms may occur
abruptly.
- Evaluation and clinical assessment:
- CNS: Agitation, hyperventilation, headache and convulsions.
- CVS: Pulse (rate, rhythm) for tachycardia and arrhythmias and
blood pressure.
- GIT: Nausea & vomiting (may be bloody), abdominal pain, thirst,
diarrhea.
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- Theophylline toxicity should be considered in any patient presenting
with seizures, agitation, tachyarrhythmias, hypotension, or persistent
vomiting, particularly if there is hypokalemia and hyperglycemia.
However, patients with chronic intoxication may present with few overt
symptoms. Other toxic agents to consider in patients with these
symptoms include: β 2 adrenergic agonists, cocaine, amphetamine, iron
and salicylates.
INVESTIGATIONS:
Routine:
- Monitor serum glucose, serum electrolytes, and ABGs.
- Monitor CPK levels and renal function in patients with seizures. Institute
continuous cardiac monitoring and obtain an EKG.
- Paracetamol and salicylate levels.
Specific:
- Serum theophylline concentrations.
- Serial theophylline levels are required at 2 hrs then every 2 hrs until
peak levels are reached or start to decline.
- If a slow release preparation has been ingested, continue measuring
levels at 4 hrs intervals after decline or plateau to ensure detection
of a secondary peak.
- Therapeutic serum levels: The therapeutic steady-state serum
concentration for theophylline ranges from 10-20 µg/mL (56-111
µmol/L).
- Morbidity correlates with serum theophylline concentration in
patients with acute toxicity but not in patients with chronic toxicity.
ADMISSION CRITERIA:
- Admit all patients with:
- Acute ingestion of > 10 mg/kg.
- Chronic intoxication.
- Ingestion of slow release preparations.
- Any ingestion while on a maintenance dose of theophylline.
- Ingestion of an unknown quantity.
- All symptomatic patients.

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Because of the potential for severe toxicity, most patients should be

considered for admission to an intensive care setting.
TREATMENT:
Stabilization:
- ABCs: airway, breathing, and circulation (ABC) should be evaluated and
stabilized.
- Control vomiting by metoclopramide intravenously (initial dose 0.1
mg/kg up to 20 mg) may be used in addition to ondansetron (initial
dose: 0.15 mg/kg up to 12 mg intravenously) + H2 blocker or proton
pump inhibitors.
Decontamination:
- Activated charcoal 1gm/kg initially unless altered conscious state
(protect airway first) then 0.5gm/kg/ 4 hourly.
- Whole bowel irrigation (WBI) is not routinely used but can be
considered for massive ingestions of sustained preparation or enteric-
coated drugs in an alert and cooperative patient.
- Hypotension: Initial treatment for hypotension consists of a rapid
infusion of isotonic saline (initial dose: 20 mL/kg, up to 1 L) and
treatment of any cardiac arrhythmias. If hypotension does not respond
to fluid administration and/or treatment of cardiac arrhythmias, a
pure α-adrenergic agonist (such as phenylephrine) or a predominant
α-adrenergic agonist (such as norepinephrine) should be used.
- Cardiac arrhythmias should be treated according to ACLS or PACLS.
Esmolol is safe for use in theophylline-poisoned patients with asthma
and has also been used effectively to terminate supraventricular
tachycardia. In children, the dose is 100-500 µg/kg, IV, given over 1min.
In adults, rapid IV infusion of 500 µg/kg over 1min is followed by a
continuous infusion of 50 μg/kg infusion for at least 4 min.
- If the patient has a depressed level of consciousness, arrhythmias or
intractable vomiting, the patient may be in a need for intubation.
- For Agitation and seizures administer benzodiazepines (e.g., lorazepam
0.1 mg/kg, repeat in 1-2 minutes if seizures continue) or
phenobarbitone (20 mg/kg, maximum initial dose: 1 gm). Phenytoin
should be avoided in all patients with theophylline toxicity.
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- Potassium supplementation (e.g., 40 mEq of KCL/L in intravenous fluids

run at 1-1.5 times maintenance) for hypokalemic theophylline
poisoned patients with potassium <3 mEq/L or with ventricular
arrhythmias.
- Metabolic acidosis after theophylline poisoning rarely requires specific
intervention (e.g., administration of sodium bicarbonate), unless
severe (e.g., pH < 7.0).
Elimination Enhancement:
Haemodialysis:
Indications for hemodialysis:
In acute overdose:
- Patients with seizures or significant cardiac arrhythmias (e.g.,
ventricular tachycardia).
- Peak theophylline level: ≥ 80 µg/mL (448 µmol/L).
- Peak theophylline level: ≥ 60 µg/mL (336 µmol/L) with any of the
following comorbidities:
- Inability to tolerate multiple-dose activated charcoal (e.g.,
intractable vomiting, gastrointestinal ileus or obstruction).
- Impaired theophylline metabolism (e.g., liver disease, heart
failure).
- High risk for seizures or history of epilepsy (see 'Seizures'
above).
- Increased susceptibility to toxicity including age > 65 years
or < 6 months, ischemic heart disease, and/or severe
chronic lung disease.
In chronic overdose:
- Any patient who has already experienced a significant
arrhythmias or seizures.
- If the plasma theophylline concentration approaches 40-60
μg/mL.
- Infants < 6 months old or adults > 65 years of age.
- Theophylline levels of 30-40 μg/mL (168-224 μmol/L).
N.B. For asymptomatic patients: Administer activated charcoal 1gm/kg

and observe for 4 hrs. If no symptoms appear, the patient did not ingest

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slow release preparation and serum theophylline levels are < 20 μg/mL,
the patient can be discharged.
FOLLOW UP:
PATIENT MONITORING
- Serial serum theophylline level should be monitored every 2-4 hours
until it decreases and patient clinically improves.
- An EKG should be recorded and continuous close cardiac monitoring
instructed.
- Serum electrolytes levels should be close monitored daily, more often
during acute intoxication as ordered.

- Acute intoxication
- Patients generally do well with adequate gastrointestinal
decontamination procedures and multiple-dose activated
charcoal administration.
- Effects usually peak in the first 12-hours and then subside.
- Toxicity onset may be delayed or prolonged after oral intake of
sustained-release preparation.
- Chronic intoxication
- There is a high risk of complications and death than with acute
theophylline intoxication, especially for patients over 60 or under
three years of age and those with significant underlying
pathological conditions.
- Aggressive treatment with early hemodialysis may improve the
outcome in these cases.
- Possible sequelae involve neurologic impairment from
intractable seizures, dysrhythmia, or toxic hypotension.
- Intestinal obstruction, paralytic ileus, and severe constipation
from multiple-dose activated charcoal may be life threatening.
- Severe myocardial ischemia may develop from increased oxygen
demand.
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From the Emergency Department
- Patients may be discharged when:
- Serum levels decrease below 25 µg/mL.
- Manifestations of intoxications are recovered.
- Psychiatric assessment, if required, has been done.
- All drugs should be reviewed before patient discharge to avoid
recurrent drug interactions.
From the Hospital
- Patients may be discharged when:
- Serum levels decrease below 25 µg/mL.
- Manifestations of intoxications are recovered.
- Patient is passing activated charcoal stool.
- Psychiatric assessment, if required, has been done.
- All drugs should be reviewed before patient discharge to avoid
recurrent drug interactions.
PATIENT EDUCATION:
- Patients should be educated about risk of drug interactions and the
dangers of increasing theophylline dosage without monitoring serum
theophylline levels.
COMMON PITFALLS:
- Selective β-adrenergic agonists (such as dobutamine) and mixed α - β
adrenergic agonists (such as epinephrine) should not be used.
- The control of nausea and vomiting with an antiemetic and the early
administration of activated charcoal is very important in order to prevent
further absorption and enhance elimination of theophylline.
- Patients who have ingested sustained-release formulations may not
develop peak serum concentrations for 24 hours.
- Patients with chronic toxicity may develop severe clinical effects abruptly.

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REFERENCES:
1. Perry H, 2016: Theophylline-poisoning poisoning UPTODATE: http://www.uptodate.com/
contents/ Theophylline poisoning.
2. Hocaoglu N, Yıldıztepe E, Bayram B, Aydın B, Tunçok Y, Kalkan S. , 2014: Demographic and
Clinical Characteristics of Theophylline Exposures between 1993 and 2011. Balkan Med J.
Dec;31(4):322-7.
3. Chan TY, Gomersall CD, Cheng CA, Woo J. , 2009: Overdose of methyldopa, indapamide and
theophylline resulting in prolonged hypotension, marked diuresis and hypokalaemia in an
elderly patient. Pharmacoepidemiol Drug Saf. Oct;18(10):977-9.
4. Bishnoi M, Chopra K, Kulkarni SK, 2007: Theophylline, adenosine receptor antagonist
prevents behavioral, biochemical and neurochemical changes associated with an animal
model of tardive dyskinesia. Pharmacol Rep. Mar-Apr;59(2):181-91.
5. Makino S, Adachi M, Ohta K, Kihara N, Nakajima S, Nishima S, Fukuda T, Miyamoto T; ,
2006: Safety of Sustained-Release Theophylline and Injectable Methylxanthines
Committee; Asthma Prevention and Management Guidelines Committee. A prospective
survey on safety of sustained-release theophylline in treatment of asthma and COPD.
Allergol Int. 2006 Dec;55(4):395-402.
6. Huber W, Eckel F, Hennig M, et al., 2006: Prophylaxis of contrast material-induced
nephropathy in patients in intensive care: acetylcysteine, theophylline, or both? A
randomized study. Radiology; 239:793.
7. Hurley KF. , 2007: Does the administration of intravenous aminophylline improve survival in
adults with bradyasystolic cardiac arrest? CJEM; 9:26.
8. Sessler CN.,1990: Theophylline toxicity: clinical features of 116 consecutive cases. Am J Med
1990; 88:567.
9. Bronstein AC, Spyker DA, Cantilena LR Jr, et al. , 2009: 2008 Annual Report of the American
Association of Poison Control Centers' National Poison Data System (NPDS): 26th Annual
Report. Clin Toxicol (Phila); 47:911.
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PSYCHOTROPIC MEDICATIONS
LITHIUM
INTRODUCTION:
- Lithium carbonate was approved in the United States for the treatment of
acute mania and bipolar disorder. Lithium has a relatively narrow
therapeutic index. A significant proportion of patients on chronic lithium
therapy experience at least one episode of toxicity during treatment.
Lithium is found to accumulate intracellularly in the brain and the
kidneys. Elderly patients are at higher risk for lithium toxicity due to both
a lower glomerular filtration rate and a reduced volume of distribution.
- Lithium is a naturally occurring metal that possesses chemical similarity to
+ +
Na and K . The specific mechanism by which it stabilizes mood is not
known. It is thought to modulate the CNS by altering nerve conduction,
cortisol and monoamine metabolism, and increasing serotonin.
+ +
- At the renal tubules, lithium was found to compete with Na and K .
Conditions that increase renal sodium reabsorption (dehydration)
decrease lithium elimination.
- Chronic toxicity typically occurs as a result of medication interactions,
renal impairment and in dehydrated patients due to decreased renal
clearance.
Acute Toxicity:
- Early GI symptoms (nausea, vomiting, and diarrhea).
- Neurologic manifestations are a late finding. They include sluggishness,
ataxia, confusion or agitation, and neuromuscular excitability, that can
present as irregular coarse tremors, fasciculations, or myoclonic jerks.
Severe lithium intoxication can lead to seizures, status epilepticus, and
encephalopathy.
- EKG abnormalities: T-wave flattening or inversion, prolongation of the
QTc, sinoatrial nodal dysfunction, and bradycardia may occur and
malignant dysrhythmias.
Chronic Toxicity:
- Predominantly neurologic findings: Mental status is often altered and
can progress from confusion to stupor, coma, and seizures. Tremor,

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fasciculations, hyperreflexia, choreoathetotic movements, clonus,

dysarthria, nystagmus, and ataxia may occur.
- Renal: Nephrogenic diabetes insipidus and a chronic tubulointerstitial
nephropathy,
- Cardiac: Dangerous arrhythmias or other important clinical effects are
rare. Flattened T waves, prolonged QTc intervals, and bradycardia.
- Endocrine disorders: Hypothyroidism and hyperparathyroidism and
diabetes insipidus.
- Hematological: Leukocytosis and an increase in neutrophils and aplastic
anemia.
Acute-on-Chronic Toxicity:
- Patients are at risk for signs and symptoms of both acute and chronic
toxicity.
ADMISSION CRITERIA:
- Patients with symptoms of lithium toxicity are admitted to a monitored
setting for observation, regardless of the serum lithium concentration.
- Patients with severe symptoms (e.g., altered mental status, seizures)
are admitted to an intensive care setting.
- Discharge is appropriate once patients are asymptomatic with
stabilization of serum lithium concentration below 1.5 mEq/L (1.5
mmol/L), spaced for 24 hrs and no rebound manifestations
(disorientation, agitation or any neurological signs)
- Extrapyramidal effects from other medications.
- Neuroleptic malignant syndrome and serotonin syndrome from other
agents.
- Sepsis, CNS infections, or intracranial catastrophes (massive
hemorrhage or stroke).
INVESTIGATIONS:
Routine:
- Monitor serum glucose, serum electrolytes (particularly sodium),
urinalysis, serum BUN creatinine, ALT, AST, and WBC.
- ABG: lithium intoxication may cause a low anion gap.
- Screen for any co-ingestants (e.g., paracetamol and Salicylate levels).
- EKG (QT, T, ST wave's changes) and urine analysis and urine output.
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- CT scan of the brain may be warranted if the etiology of altered

mentation is not identified.
- Chest x-ray may be indicated to monitor pulmonary edema and in
patients with worsening symptoms or known large ingestions.
Specific:
- Therapeutic serum lithium is 0.5-1.3 mmol/l. Serum lithium
concentrations often do not correlate with clinical signs of toxicity in
patients with acute ingestions. However, it correlates more closely with
clinical signs in patients with chronic toxicity.
- Thyroid function tests.
TREATMENT:
Stabilization:
Decontamination:
- Whole bowel irrigation with polyethylene glycol should be considered
with a large ingestion or ingestion of a sustained-release product.
- Do not give activated charcoal as it is not effective.
Specific:
- Rehydrate the patient. Beware of existing renal insufficiency or
congestive heart failure. Best IV fluids are normal saline. Do not
attempt to eliminate lithium using diuretics.
Hemodialysis is indicated for:
- Acute over dose patients with level > 4 mEq/L.
- Chronic over dose patients with level > 2.5 mEq/L.
- Severe neurological signs such as stupor with level > 2.5 mEq/L.
- Patients with mild signs of toxicity and renal impairment.
- Patients who cannot tolerate rehydration (as CHF or arrhythmia).
- Recheck lithium level immediately post-dialysis and importantly 6-12
hrs post-dialysis.
- Request another hemodialysis session if lithium rises once again, or
previous indications still exist.

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REFERENCES:
1. Greller HA, 2011: Lithium In: Goldfrank’s Toxicologic Emergencies, 9th ed, Goldfrank LR,
Nelson LS, Lewin NA, et al (Eds), McGraw-Hill, New York. p.1054-1064.
2. Perrone J, Chatterjee, 2016: Lithium poisoning UPTODATE: http://www.uptodate.com/
contents/ Lithium poisoning.
3. Lavonas EJ, Buchanan J.., 2015: Hemodialysis for lithium poisoning. Cochrane Database Syst
Rev. Sep 16;9:CD007951.
4. Schaffer A, Isometsä ET, et al., 2015: Epidemiology, neurobiology and pharmacological
interventions related to suicide deaths and suicide attempts in bipolar disorder: Part I of a
report of the International Society for Bipolar Disorders Task Force on Suicide in Bipolar
Disorder. Aust N Z J Psychiatry. Sep;49(9):785-802.
5. Soriano-Barceló J, Alonso MT, et al., 2015: A case with reversible neurotoxicity after 2 years
of dementia secondary to maintenance lithium treatment. J Psychiatr Pract. Mar;21(2):154-
9.
6. Goel S, Nasa P, et al., 2015: Lithium overdose: early hemodialysis is the key! Saudi J Kidney
Dis Transpl. Jan;26(1):122-4
7. Goyal R, Ali Y. Severe neurotoxicity associated with low-level serum lithium and risperidone
after 25 years of uncomplicated lithium therapy. J Clin Psychopharmacol. 2014
Oct;34(5):e4-5.
8. Roberts DM, Gosselin S. ., 2014: Variability in the management of lithium poisoning. Semin
Dial. Jul-Aug;27(4):390-4.
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TRICYCLIC ANTIDEPRESSANTS
INTRODUCTION:
- Tricyclic antidepressants (TCAs) are still used for depression and other
indications. Consequently, TCA poisoning, which can be life-threatening
and remains a significant clinical issue. It is common for a patient to
present to the emergency department with minimal clinical abnormalities
and to then develop life-threatening cardiovascular and CNS toxicity
within 2 hours. TCAs have a low toxicity threshold, so a small increase
over the therapeutic range may result in toxicity.
- Inhibition of presynaptic neurotransmitter reuptake (norepinephrine and
serotonin) is the primary mechanism for the therapeutic effects of
tricyclic antidepressants (TCAs). Following acute overdose, the following
molecular changes often lead to important clinical consequences:
- Blockade of cardiac fast sodium channels.
- Antagonism of central and α-1 adrenergic receptors.
- Antagonism of histamine (H1) receptors.
- Antagonism of CNS gamma-aminobutyric acid (GABA) A receptors.
Cardiac:
- Sinus tachycardia is common in TCA overdose, likely due to
anticholinergic effects and hemodynamic decompensation causing a
reflex tachycardia. Hypotension is common following significant TCA
poisoning, and mortality from TCA overdose is due largely to
refractory hypotension.
- Cardiac conduction abnormalities may contribute to hypotension.
- Ventricular tachycardia and ventricular fibrillation (VT and VF) are
more common in severe poisonings (e.g., severe acidosis,
hypotension), particularly those involving extreme QRS prolongation.
CNS manifestations:
- Mental status changes, such as a decreased level of consciousness
(due to antihistaminic effects) or, less frequently, delirium (due to
anticholinergic effects), are common following TCA overdose.
- TCA poisoning can cause seizures, likely due to the antagonistic
effects of TCAs on the GABA-A receptor

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Anticholinergic manifestations:
- TCAs have anticholinergic effects and signs such as hyperthermia,
flushing, dilated pupils that respond poorly to light, delirium,
intestinal ileus, and urinary retention.
INVESTIGATIONS:
Routine:
- Monitor serum glucose, serum electrolytes (particularly sodium),
urinalysis, serum BUN creatinine, ALT, AST.
- Acetaminophen and salicylate levels.
- Urinalysis should be repeated in patients at risk for rhabdomyolysis.
- Serial ABG are performed in severe toxicity to monitor the acid-base
status.
Specific:
- Continuous cardiac monitoring for arrhythmias until the patient
becomes free of any symptoms or signs of cardiac toxicity for at least
4hrs.
- EKG changes in severe TCAs poisoning include:
- Prolongation of the QRS >100 msec.
- Abnormal morphology of the QRS (e.g., deep, slurred S wave in
leads I and AVL)
- Abnormal size and ratio of the R and S waves in lead AVR: R wave
in AVR > 3 mm; R to S ratio in AVR > 0.7
- Measurement of TCA concentrations:
- Qualitative (urine) and quantitative (serum) TCA testing have
limited therapeutic and prognostic utility in the acute setting.
- Other agents with anticholinergic effects may produce a similar
clinical appearance.
TREATMENT:
Stabilization:
- Assess airway, breathing, and circulation and stabilize as
necessary.
- Because patients with TCA poisoning can deteriorate very rapidly,
early intubation is advised for patients with CNS depression
and/or hemodynamic instability.
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- Monitor the vital signs and EKG for at least 6 hrs after alleged
ingestion.
Decontamination:
- Administer activated charcoal if the patient presents within 2 hrs
of ingestion unless gastrointestinal complications (ileus,
obstruction) are suspected. Dose is 1 gm/kg (maximum dose 50
gm). The patient’s ability to protect the airway or the need for
intubation should be considered before using activated charcoal.
Treatment of hypotension or arrhythmia:
Sodium bicarbonate for cardiac toxicity (WIDE QRS COMPLEX)
- Sodium bicarbonate is the standard initial therapy for hypotension
or arrhythmia due to TCA toxicity. It is indicated in patients with
widening of the QRS interval > 100 msec or a ventricular
arrhythmia.
- The initial dose of hypertonic sodium bicarbonate is 1-2 mEq/kg,
given as a rapid IV push through a large bore IV catheter. In adults,
one common approach is to give 2-3 vials or prefilled syringes (50
mL each) of 8.4 % sodium bicarbonate. If there is no response
observed after the administration of the initial dose, it may be
repeated after 5 minutes. It is advisable to run a continuous 12-
lead EKG during the infusion to monitor for the presence (or
absence) of narrowing of the QRS complex, a decrease in the R
wave amplitude in lead AVR, or resolution of any arrhythmia.
- If the QRS narrows after bolus therapy, begin a continuous IV
infusion of 150 mEq of sodium bicarbonate in 1 L of D5W and
infuse at 250 mL/hour in adults.
- Frequent arterial blood pH measurements should be obtained
during treatment with sodium bicarbonate; a reasonable goal pH
is 7.50-7.55. Volume overload, hypokalemia, hypernatremia, and
metabolic alkalosis may result from prolonged bicarbonate
infusions, and clinical and laboratory parameters must be
followed closely to avoid these complications.
- Measure the arterial pH hourly until it reachs the normal range
and stable. After that, measurements may be obtained every 4-6
hrs. The serum potassium concentration should be measured
concurrently with the arterial pH.

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- Hypotension: Treat with intravenous boluses of isotonic

crystalloid. If patient remains hypotensive despite aggressive
volume resuscitation you can treat with a vasopressor. α-
adrenergic agonists (e.g., neosynephrine, norepinephrine) are
preferred.
- Infusion of lipid emulsion should be considered in patients with
refractory hypotension or dysrhythmias.
Seizures: Treat with benzodiazepines (e.g., diazepam 5 mg IV or
lorazepam 2 mg IV) Do NOT treat with phenytoin
- Despite prominent anticholinergic toxicity in some patients with
TCA poisoning, physostigmine is contraindicated as it is associated
with cardiac arrest in the setting of TCA toxicity.
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REFERENCES:
1. Gheshlaghi F, Mehrizi MK, Yaraghi A, Sabzghabaee AM, Soltaninejad F, Eizadi-Mood N,
2013:. ST-T segment changes in patients with tricyclic antidepressant poisoning. J Res
Pharm Pract. Jul;2(3):110-3.
2. Eren Cevik S, Tasyurek T, Guneysel O., 2014: Intralipid emulsion treatment as an antidote in
lipophilic drug intoxications. Am J Emerg Med. Sep;32(9):1103-8.
3. Cao D, Heard K, Foran M, Koyfman A,. 2015: Intravenous lipid emulsion in the emergency
department: a systematic review of recent literature. J Emerg Med. Mar;48(3):387-97
4. Basol N, Erbas O.,2016: The effects of diltiazem and metoprolol in QTc prolongation due to
amitriptyline intoxication. Hum Exp Toxicol. Jan;35(1):29-34.
5. Aguilera P, Garrido M, Lessard E, Swanson J, Mallon WK, Saldias F, Basaure C, Lara B,
Swadron SP., 2016: Medication Overdoses at a Public Emergency Department in Santiago,
Chile. West J Emerg Med. Jan;17(1):75-80
6. Van den Berg MJ, Bosch FH. , 2014 : Case Report: Hemodynamic Instability Following Severe
Metoprolol and Imipramine Intoxication Successfully Treated With Intravenous Fat
Emulsion. Am J Ther. Sep 18.
7. Sanaei-Zadeh H., 2012: Response to "Tricyclic antidepressants intoxication in Tehran, Iran:
epidemiology and associated factors". Hum Exp Toxicol. May;31(5):528.
8. Franssen EJ, Kunst PW, Bet PM, et al. . , 2003 : Toxicokinetics of nortriptyline and
amitriptyline: two case reports. Ther Drug Monit; 25:248.
9. Lynch R.. , 2002: Tricyclic antidepressant overdose. Emerg Med J; 19:596.
10. Kerr GW, McGuffie AC, Wilkie S.. , 2001 : Tricyclic antidepressant overdose: a review. Emerg
Med J; 18:236.
11. Glauser J.,2000: Tricyclic antidepressant poisoning. Cleve Clin J Med; 67:704.
12. Liebelt EL.,2011: Chapter 73: Cyclic antidepressants. In: Goldfrank's Toxicologic
Emergencies, 9th, Nelson LS, et al. (Ed), McGraw-Hill, New York 2011.
13. Citak A, Soysal DD, Uçsel R, et al. , 2006: Seizures associated with poisoning in children:
tricyclic antidepressant intoxication. Pediatr Int; 48:582.
14. Brahmi N, Thabet H, Kouraichi N, et al.,2007: [Brugada syndrome and other cardiovascular
abnormalities related to tricyclic antidepressants ans related drugs intoxication]. Arch Mal
Coeur Vaiss; 100:28.
15. Bebarta VS, Waksman JC. ,2007: Amitriptyline-induced Brugada pattern fails to respond to
sodium bicarbonate. Clin Toxicol (Phila); 45:186.
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ANTIPSYCHOTIC DRUGS
(INCLUDING PHENOTHIAZINES)
INTRODUCTION:
Description:
- Phenothiazines, butyrophenones, and other related medications are used
widely to treat psychosis and agitated depression. In addition, some of
these medicatics (eg, prochlorperazine, promethazine, and droperidol)
are prescribed as antiemetic drugs.
- Suicidal overdoses are common, but because of the high toxic therapeutic
ratio, acute overdose rarely develops in death.
- A large number of newer therapeutic agents that often are referred to as
“atypical antipsychotics” have been developed. Atypical antipsychotics
differ from other neuroleptic agents in their binding to dopamine
receptors and their acts on dopamine-mediated behaviors.
- Overdose experience with these agents is limited.
Forms and uses:
- They are used as antiemetic agents, pain medications, antipsychotic
agents, and anxiolytic agents; they are also prescribed in the treatment of
allergic reactions and hiccups.
Toxic dose:
- Extrapyramidal reactions, anticholinergic side effects, and orthostatic
hypotension are often seen with therapeutic antipsychotic doses.
- Tolerance to the sedating effects of the antipsychotics is reported, and
patients on chronic therapy may tolerate much larger doses than do
other cases.
- The toxic dose after acute ingestion is highly variable.
- Serious CNS depression and hypotension may occur after ingestion of
200–1000 mg of chlorpromazine in children or of 3–5 g in adults.
- Poisoning varies widely by phenothiazines toxic exposure, but ingestion
of several grams has been associated with death.
Pathophysiology:
- A variety of pharmacologic mechanisms are responsible for toxicity,
involving mainly the cardiovascular and central nervous systems.
- Cardiovascular system toxic action.
- Anticholinergic effects may develop tachycardia.

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- Alpha-adrenergic blockade may develop hypotension, especially

orthostatic hypotension. With very large overdoses of some
antipsychotic agents, quinidine-like membrane-depressant effects
on the heart may develop.
- Many of antipsychotic agents can produce QT prolongation.
- Central nervous system toxic action.
- Neurological depression. Centrally mediated sedation and
anticholinergic effects lead to CNS depression.
- Constricted pupil. Alpha-adrenergic blockade develops small pupils
despite anticholinergic effects on other systems.
- Dystonic reactions. Extrapyramidal dystonic reactions are relatively
common with therapeutic doses and probably are caused by
central dopamine receptor blockade.
- Seizures. The seizure threshold may be lowered by unknown
mechanisms.
- Poikilothermia. Temperature regulatory control is disturbed.
- Toxicokinetics.
- Antipsychotic medication have large volumes of distribution (Vd =
10-30 L/kg), and most have long elimination half-lives (eg,
chlorpromazine half-life = 18-30 hours). Elimination is mainly by
hepatic metabolism.
Epidemiology:
- Antipsychotic toxicity is common.
- Toxic manifestations following exposure are typically mild to
moderate toxic degree.
- Death from antipsychotic overdose is rare, occurring in cases with
delayed antipsychotic medication treatment or co-ingestions.
Causes:
- Antipsychotic toxicity is usually attributable to a suicidal attempt.
- Child toxicity is reported as accidental form of toxicity.
Risk factors:
- Pediatrics are more susceptible to the extrapyramidal side
manifestations of prochlorperazine.
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- In geriatric cases hepatic impairment may result in antipsychotic

medication accumulation from therapeutic doses.
- Antipsychotic toxicity is mainly manifested in the cardiovascular system and
CNS. Anticholinergic intoxication may occur as a result of ingestion of
benztropine (Cogentin) or other co-administered drugs.
- Mild antipsychotic intoxication develops sedation, small pupils, and
postural hypotension. Anticholinergic effects include dry mouth, loss of
sweating, tachycardia, and urinary retention. Controversy, clozapine
causes hypersalivation through an unknown aetiology.
- Severe antipsychotic intoxication may cause coma, seizures, and
respiratory arrest. The EKG usually shows prolongation of QT-interval
and occasionally prolongation of QRS complex. Hypothermia or
hyperthermia may occur. Clozapine can develop a prolonged
confusional state and rarely cardiac toxicity.
- Extrapyramidal dystonic manifestations of therapeutic antipsychotic
doses include torticollis, jaw muscle spasm, oculogyric crisis, rigidity,
bradykinesia, and pill-rolling tremor.
- Neuroleptic malignant syndrome. Patients on chronic antipsychotic
therapy may develop the neuroleptic malignant syndrome, which is
characterized by rigidity, hyperthermia, sweating, lactic acidosis, and
rhabdomyolysis.
- Agranulocytosis. Clozapine therapy has been associated with
agranulocytosis.
- Chemical sensitivity reaction. Promethazine can produce severe tissue
damage after perivascular extravasation, intraneural, or perineural
injection. IV administration is not recommended unless the line is
freely flowing and the promethazine drug is given very slowly.
INVESTIGATIONS
General Tests:
- EKG and cardiac monitoring:
EKG effects are similar to type 1 antidysrhythmics effects such as
quinidine like action (QRS or QT prolongation, ventricular dysrhythmia) .

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Sinus tachycardia is common and indicates sufficient

antipsychotic drug absorption to produce anticholinergic effects.
- Other useful laboratory and general tests:
electrolytes, glucose, BUN, creatinine, creatine kinase (CK), arterial
blood gases or oximetry, abdominal radiography (radiopaque pills), and
chest radiography.
Specific Tests:
- Quantitative antipsychotic blood levels are not routinely available and
do not help in diagnosis or treatment.
- Qualitative antipsychotic screening may easily detect phenothiazines
in urine or gastric juice, but butyrophenones such as haloperidol
medication are usually not included in basic toxicologic screens
TREATMENT
Emergency and supportive measures
- Keep an open airway and assist ventilation if required.
- Administer supplemental 100% oxygen.
- Treat coma, seizures, hypotension, and hyperthermia if they develop.
- Close monitor vital signs and EKG for at least 6 hours and admit the
cases for at least 24 hours if there are signs of significant toxicity.
- Pediatrics with antipsychotic toxicity should be evaluated for possible
intentional abuse.
Specific drugs and antidotes.
- There is no specific antidote.
- Dystonic reactions.
- Give diphenhydramine, 0.5-1 mg/kg IM or IV, or benztropine.
- QRS-interval prolongation.
- Treat quinidine-like cardio toxic effects with Na bicarbonate, 1-2
mEq/kg IV.
- Hypotension.
- Hypotension from these drugs probably involves vasodilation
induced by alpha1 receptor blockade. Treat with IV fluids and, if
needed, a vasoconstrictor such as norepinephrine or
phenylephrine.
- Theoretically, medications with beta-2 activity (eg, epinephrine,
isoproterenol) may worsen hypotension.
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- QT prolongation.
- QT prolongation and torsade may respond to magnesium infusion
or overdrive pacing.
Decontamination.
- Give activated charcoal orally if conditions are appropriate.
- Gastric lavage is not necessary after small to moderate ingestions if
activated charcoal can be adminstrated promptly.
Enhanced elimination.
- Owing to extensive tissue distribution “large volume of distribution”,
these drugs are not effectively removed by dialysis or hemoperfusion.
- Repeat-dose activated charcoal has not been evaluated completely.
FOLLOW UP
Patient monitoring
- Close continuous respiratory and cardiac monitoring and serial EKGs
should be instructed.
- Fluid and electrolytes levels, liver and renal function tests, and clinical
indicators of toxicity should be followed.
- Most cases who overdose on phenothiazines recover within 24-48
hours.
- Death may develop in severe cases involving dysrhythmia, seizures,
hypotension, or hyperthermia
Discharge criteria/instructions
- From the emergency department. Cases may be discharged if they did
not develop seizure or QRS widening, hypotension, or dysrhythmia
(other than mild transient sinus tachycardia) during 6 hours of close
observation, and after they have received GIT decontamination and, if
indicated, a psychiatric evaluation.
- From the hospital. Cases may be discharged from the hospital after all
clinical manifestations have resolved (hypotension, QRS widening, CNS
depression, and dysrhythmia) and after the EKG record has been return
normal for 24 hours duration.

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PITFALLS
Diagnosis
- Extended-release products may require admission and extended close
observation.
Treatment
- Incomplete decontamination may result in prolonged manifestations or
delayed deterioration course.
Follow-up
- Inadequate observation time may result in missing late antipsychotic
complications of extrapyramidal manifestation or neuroleptic
malignant syndrome.
REFERENCES:
1. Pawlak J, Dmitrzak-Weglarz M, Skibinska M, Szczepankiewicz A, Leszczynska-Rodziewicz
A, et al. (2013) Suicide attempts and psychological risk factors in patients with bipolar
and unipolar affective disorder. Gen Hosp Psychiatry 35: 309-313.
2. Field RI (2010) Antipsychotic medications are spelling legal trouble for drugmakers. P T
35: 621-622.
3. Olson, Kent (2011). Poisoning and Drug Overdose, Sixth Edition (Poisoning & Drug
Overdose) (Kindle Locations 4751-4754). McGraw-Hill Education.

4. Healy D (2005) Psychiatric drugs explained. (4thedition). Britain: Elsevier Limitedpp: 8.
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BENZODIAZEPINES
INTRODUCTION:
Description:
- The drug class of benzodiazepines includes many compounds that vary
widely in potency, duration of action, presence or absence of active
metabolites, and clinical usage.
- Three non-benzodiazepines compounds; eszopiclone, zaleplon, and
zolpidem, have similar clinical effects and are included here.
- In general, death from benzodiazepine overdose is rare unless the
medications are combined with other CNS-depressant preparations, such
as ethanol, opioids, and barbiturates.
- Newer potent, short-acting benzodiazepines agents have been
considered the sole cause of death in recent reported forensic cases.
Forms and uses:
- The benzodiazepines formulations are used as sedatives, anxiolytics, and
muscle relaxants, and include alprazolam (Xanax), brotizolam,
chlordiazepoxide (Librium), chlorazepate (Tranxene), clobazam,
clonazepam (Clonopin), diazepam (Valium), estazolam (Prosom),
flurazepam (Dalmane), halazepam, lorazepam (Ativan), lormetazepam,
medazepam, midazolam (Versed), nitrazepam, oxazepam (Serax),
prazepam, temazepam (Restoril), triazolam (Halcion).
Toxic dose:
- Generally, the toxic therapeutic ratio for benzodiazepines is very high. For
example, oral overdoses of diazepam have been reported in excess of 15-
20 times the therapeutic dose without serious depressive action of
consciousness level.
- However, respiratory arrest has been reported after ingestion of 5 mg of
triazolam and after rapid IV injection of diazepam, midazolam, and many
other benzodiazepines.
- Also, ingestion of another medication with CNS-depressant properties
(eg, ethanol, barbiturates, and opioids) probably will produce additive
toxic CNS inhibitory effects.

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Pathophysiology:
- Benzodiazepines augment the action of the inhibitory neurotransmitter
gamma-aminobutyric acid (GABA). They also inhibit other neuronal
systems by poorly detected mechanisms.
- Hyperpolarization due to transmembrane chloride ion flux through a
GABA-mediated channel produces decreased neuronal excitability “High
threshold Status”. Benzodiazepines toxic effects are typically mild to
moderate.
- The result is generalized depression of spinal reflexes and the reticular
activating system. This can lead to coma and respiratory arrest.
- Benzodiazepines respiratory arrest.
- It is more likely with newer short-acting benzodiazepines
agents such as triazolam, alprazolam, and midazolam.
- It has also been reported with “Non-benzodiazepine agent”
zolpidem.
- Benzodiazepines cardiopulmonary arrest.
- It has occurred after rapid injection of diazepam, possibly
because of CNS-depressant effects or because of the toxic
effects of the diluent propylene glycol.
- Pharmacokinetics properties. Most of these benzodiazepines
medications are highly protein-bound (80-100%).
Epidemiology:
- Benzodiazepines intentional ingestion is common
- Death develops rarely, usually involving coingestant of neurological
depressant agent such as ethanol, which augment respiratory depression
- Young children are at increased risk of accidental poisoning.
- The elderly cases are at risk, usually due to depressed renal and hepatic
metabolic and excretory function.
Causes:
- Toxic ingestion is usually reported both intentional and unintentional
cases.
Drug interactions:
- Toxic manifestations may be enhanced with co-ingestion of CNS
depressants such as, ethanol, barbiturates, or other CNS depressants.
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- Onset benzodiazepines of CNS depression may be observed within 30-120
minutes of ingestion, depending on the type of compound.
- Lethargy, slurred speech, ataxia, “silent” coma, and respiratory arrest
may develop.
- Generally, patients with benzodiazepine-induced coma have hyporeflexia
and midposition or small pupils. Hypothermia may present.
- Serious complications are more likely when newer short-acting
benzodiazepines agents are involved or when other depressant drugs
have been coingested.
INVESTIGATIONS
General Tests:
- Other useful laboratory tests include glucose, arterial blood gases, and
pulse oximetry.
Specific Tests:
- Benzodiazepines detection test:
- Serum benzodiazepines drug levels are often available from
commercial toxicology laboratories but are rarely of value in
emergency management.
- Urine and blood qualitative screening may direct rapid confirmation
of exposure.
- Immunoassays are sensitive to the benzodiazepines that metabolize
to oxazepam (eg, diazepam, chlordiazepoxide, and temazepam), but
may not detect newer benzodiazepines or those in low
concentrations “pseudonegative results”.
TREATMENT
Emergency and supportive procedures:
- Protect the airway and assist ventilation if required.
- Treat coma, hypotension, and hypothermia if they develop “as general
toxicology section”.
- Hypotension usually responds effectively to supine position and IV
fluids.
Antidotes.
Flumazenil
- Flumazenil is a specific benzodiazepine receptor antagonist that can
rapidly reverse benzodiazepine coma.

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- However, because benzodiazepine toxicity by itself is rarely fatal, the

role of flumazenil in routine treatment has not been established.
- It is administered IV with a starting dose of 0.1-0.2 mg, repeated as
needed up to a maximum of 3 mg.
- It has some important potential drawbacks:
- It may develop seizures in patients who have co-ingested
medications with proconvulsant activity effect.
- It may develop acute withdrawal, including seizures and autonomic
instability, in cases who are benzodiazepines addicted.
- Resedation is common when the drug wears off after 1-2 hours
“short ½ life”, and repeated flumazenil dosing or a continuous
infusion is often required.
Decontamination.
- Consider activated charcoal if the ingestion occurred within the
previous 30 minutes and other conditions are appropriate.
activated charcoal can be given promptly.
- There is no benefit role for diuresis, dialysis, or hemoperfusion.
- Repeat-dose charcoal has not been completed studied.
FOLLOW UP
Patient monitoring
-Cases should have close continuous respiratory & hemodynamic monitoring.

- Cases usually regain consciousness within 24 hours.
- Most cases recover completely unless hypoxia develops
- From the emergency department. Asymptomatic cases may be
discharged after decontamination procedures, a 6-hour close
observation period, and psychiatric assessment, if required.
- From the hospital. Cases may be discharged when vital signs and
mental condition become stable & after psychiatric assessment, if
indicated.
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PITFALLS
Diagnosis
- Manifestations of benzodiazepine toxicity may closely resemble
other medical conditions (both other ingestions and non-toxicologic
conditions “hypoxia, hypoglycemia, intracranial injury, meningitis,
encephalitis, or postictal state), resulting in misdiagnosis.
Treatment
- Benzodiazepine Agents with long half-lives may require extended
observation and care.
REFERENCES:
1. Rush CR, Baker RW, Wright K. Acute behavioral effects and abuse potential of trazodone,
zolpidem and triazolam in humans. Psychopharmacology (Berl). 1999;144( 3): 220– 233.
Sanger DJ. The pharmacology and mechanisms of action of new generation, non-
benzodiazepine hypnotic agents. CNS Drugs. 2004;18( suppl 1): 9– 15 (discussion 41, 43–
45).
2. Ruiz, Pedro; Strain, Eric C. (2014). The Substance Abuse Handbook (Ruiz, Handbook for
Substance Abuse) (p. 101).
3. Olson, Kent (2011). Poisoning and Drug Overdose, Sixth Edition . McGraw-Hill Education.
4. Carter LP, Richards BD, Mintzer MZ, et al. (2006). Relative abuse liability of GHB in
humans: a comparison of psychomotor, subjective, and cognitive effects of
supratherapeutic doses of triazolam, pentobarbital, and GHB.
Neuropsychopharmacology.;31( 11): 2537– 2551.

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SUBSTANCES OF ABUSE
AMPHETAMINES AND CATHINONES

INTRODUCTION:
- Methamphetamine is a sympathomimetic amine that first appeared as a
nasal decongestant in the form of benzedrine inhaler. Furthermore, it is
also used for the treatment of attention deficit hyperactivity disorder,
obesity and as an off-label treatment for narcolepsy. Currently, there is a
worldwide epidemic use of recreational methamphetamine and other
amphetamine-derived stimulants such as methylenedioxymeth-
amphetamine (MDMA) also known as ECSTASY. This is more commonly
noticed among youth as it is 10 times more potent than amphetamine.
- Synthetic cathinones (bath salts) are analogues of a naturally occurring
substance found in the leaves of Catha edulis (Khat), but characteristics
similar to other amphetamines would be expected based upon their
structural similarities.
TOXIC DOSE:
- The toxic dosage is variable; therefore, serial observation of the patient is
used to evaluate the degree of severity.
- Repeated amphetamine users develop tolerance; therefore, higher doses
are needed to develop toxicity.
PATHOPHYSIOLOGY:
- Amphetamines are indirectly acting sympathomimetic substances that
stimulate norepinephrine release & have direct agonist actions on alpha-
and beta-adrenergic receptors.
EPIDEMIOLOGY:
- Amphetamine poisoning is common, with wide regional variations in the
incidence of abuse pattern.
degree.
- Death develops in cases abusing amphetamines at escalating doses.
CAUSES:
- Poisoning often develops from recreational abuse.
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- Methamphetamine produces its stimulant effects indirectly through
being incorporated into cytoplasmic vesicles where it displaces
epinephrine, norepinephrine, dopamine, and serotonin into the cytosol.
As cytosolic concentrations rise, neurotransmitters diffuse out of the
neuron and into the synapse where they activate postsynaptic receptors.
Meth-amphetamine also inactivates neurotransmitter reuptake
transporter systems. These two processes result in adrenergic receptor
activation. The lone modulatory response to such stimulation is
degradation by catechol-O-methyl transferase (COMT), a slow, saturable
degradation pathway.
- On the other hand, the full mechanism of action of cathinones is not fully
understood but some cathinone analogues such as methylone and
pyrovalerone are hypothesized to inhibit reuptake of norepinephrine and
dopamine with serotonin like effects.
CLINICAL FEATURES:
- CNS: Amphetamine and/or cathinones generally cause feelings of
euphoria, empathy, excitement, and wellbeing as well as CNS
hyperstimulation and agitation.
- Cardiac: Hypertension, tachycardia, hyperthermia, mydriasis and dia-
phoresis, combativeness, hallucinations, paranoia, confusion, myoclonus,
and in rare cases seizures.
- Musculoskeletal: Persistent myoclonus and tremors.
- Skin: Injection of amphetamines has been associated with extensive cellu-
litis, abscess formation, and necrotizing fasciitis leading to amputation.
- Renal: Acute renal injury with evidence of acute tubular necrosis has been
reported after abuse of synthetic cathinones.
- Miscellaneous: Less commonly, seizures, stroke, myocardial infarction
and hypertensive crisis may be the leading presentation of amphetamine
and/or cathinone toxicity.
- Electrolytes: Hypokalemia, hyponatremia, hypermagnesemia, and
elevated anion gap acidosis are common findings following amphetamine
intoxication.

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DISTINGUISHING AMPHETAMINE TOXICITY FROM CATHINONE TOXICITY

- The most distinguishing feature of overdose with a synthetic cathinone
compared to amphetamine is the prolonged duration of effect observed
with cathinones. Many reports of “bath salt” cases describe agitated
delirium and psychotic features lasting for days to even weeks. These
compounds should be considered a possible cause in any case with such
prolonged symptoms.
- Toxicologic: Anticholinergics, hallucinogens, withdrawal from benzo-
diazepines and cocaine overdose.
- Non toxicologic: Thyrotoxicosis, pheochromocytoma, heat stroke and
paranoid schizophrenia.
INVESTIGATIONS:
Routine:
- Bed Side RBS to exclude hypoglycemia.
- ABGs and Electrolytes.
- Serum Paracetamol, Salicylates.
- EKG.
- Pregnancy test for females in child bearing period.
Specific:
- Urine screening for amphetamines and cathinones as well as, other
drugs of abuse (Benzodiazepines, Barbiturates, Cannabis and Alcohol)
to identify polydrug use.
- Amphetamine can be qualitatively tested in urine using immunoassay
technique. Positive results indicate recent amphetamine intake (2-3
days).
- CT brain to exclude cerebral hemorrhage.
TREATMENT:
Stabilization:
- The mainstay of management is to secure airway, breathing, and
circulation and control sympathetic overstimulation and agitation.
- Standard rapid sequence medications are to be used. Manage severe
hypertension initially with benzodiazepines (e.g., Lorazepam, 1-2 mg
IV, may repeat as necessary. In the case of absence of IV access,
midazolam 3-5 mg IM, may repeat as needed).
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- If hypertension is refractory, administer nitroprusside infusion 0.25-10

μg/kg/min IV infusion or phentolamine 5-15 mg IV bolus every 5-15
min.
- Chest pain: Administer oxygen, aspirin and nitroglycerin if chest pain
does not respond to benzodiazepines. DO NOT administer β-blocking
agents.
Decontamination:
- Administer one dose of activated charcoal (1 gm/kg, maximum dose
50 gm) for ingestions occurring within less than 1 hour if airway is
protected.
Symptomatic:
- Agitation and/or seizures: Administer benzodiazepines (e.g.,
Lorazepam 1-2 mg IV or midazolam 3-5 mg IM). These medications may
be repeated as needed.
- Hyperthermia: Active external cooling and benzodiazepines.
- Hyponatremia: If hyponatremia is mild or moderate (above 115
mEq/dL), restrict fluids.
- If Hyponatremia causes persistent seizures: Administer
benzodiazepines (e.g. lorazepam 1-2 mg IV or midazolam 3-5 mg IM).
May be repeated as needed. Additionally, if serum sodium = or < 115
mEq/dL, administer hypertonic saline (3% or 513 mEq/L) 100 mL as IV
bolus. If seizures persist, administer one or two additional doses of 100
mL over 10 minutes each.
- The treatment of children with amphetamine intoxication is similar to
that of adults, but special consideration should be directed towards
aggressive cooling measures and close monitoring of vital signs and
urine output. Hydration should be sufficient to maintain urine output.
COMMON PITFALLS:
- In case of agitation, DO NOT give butyrophenones (e.g., haloperidol)
and DO NOT give Phenytoin
- In patients presenting with hyperthermia DO NOT give antipyretics.

- In case of hyponatremia presenting with seizures; monitor serum
sodium closely; DO NOT give phenytoin.

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REFERENCES:
1. Chiang WK. Amphetamines., 2011: In: Goldfrank’s Toxicologic Emergencies, 9th, Goldfrank
LR. (Ed), McGraw-Hill, New York. p.1078.
2. Winstock AR, Mitcheson LR, Deluca P, et al. ., 2011: Mephedrone, new kid for the chop?
Addiction; 106:154.
3. Warrick BJ, Hill M, Hekman K, et al. ., 2013:A 9-state analysis of designer stimulant, "bath
salt," hospital visits reported to poison control centers. Ann Emerg Med; 62:244.
4. Lynton RC, Albertson TE. ., 2004:Amphetamines and designer drugs. In: Medical Toxicology,
3rd, Dart RC. (Ed), Lippincott Williams & Wilkins, Philadelphia. p.1071.
5. Meng H, Cao J, Kang J, et al. ., 2012: Mephedrone, a new designer drug of abuse, produces
acute hemodynamic effects in the rat. Toxicol Lett; 208:62.
6. Nicholson PJ, Quinn MJ, Dodd JD. Headshop heartache: ., 2010: acute mephedrone 'meow'
myocarditis. Heart 2010; 96:2051.
7. Adebamiro A, Perazella MA. ., 2012: Recurrent acute kidney injury following bath salts
intoxication. Am J Kidney Dis; 59:273.
8. Dorairaj JJ, Healy C, McMenamin M, Eadie PA. ., 2012: The untold truth about "bath salt"
highs: A case series demonstrating local tissue injury. J Plast Reconstr Aesthet Surg; 65:e37.
9. ElSohly MA, Jones AB. ., 1995: Drug testing in the workplace: could a positive test for one of
the mandated drugs be for reasons other than illicit use of the drug? J Anal Toxicol; 19:450.
10. Gibbons S. ., 2012:'Legal highs'--novel and emerging psychoactive drugs: a chemical
overview for the toxicologist. Clin Toxicol (Phila); 50:15.
11. Tekulve K, Alexander A, Tormoehlen L. ., 2007 : Seizures associated with synthetic cathinone
exposures in the pediatric population. Pediatr Neurol; 51:67.
12. De Silva DA, Wong MC, Lee MP, et al. ., 2011: Amphetamine-associated ischemic stroke:
clinical presentation and proposed pathogenesis. J Stroke Cerebrovasc Dis; 16:185.
13. Centers for Disease Control and Prevention (CDC). . 2011: Emergency department visits
after use of a drug sold as "bath salts"--Michigan, November 13, -March 31,. MMWR Morb
Mortal Wkly Rep 2011; 60:624.
14. Levine M, Levitan R, Skolnik A. ., 2013: Compartment syndrome after "bath salts" use: a
case series. Ann Emerg Med . Apr;61(4):480-3.
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COCAINE OVERDOSE
INTRODUCTION:
- Cocaine is a natural stimulant (sympathomimetic) that increases energy
and produces euphoria. Cocaine is extracted from the leaves of the
coca plant (Erythroxylum coca), which is indigenous to the Andean
highlands of South America. Cocaine produces toxicity in virtually every
organ system, principally via hemodynamic effects.
Cocaine produces its stimulant effects through 3 main pathways:
- Blockade of the reuptake of biogenic amines especially norad-
renaline at the adrenergic receptors through blockade of reuptake.
- Elevation of the levels of the excitatory amino acids glutamate and
aspartate in the brain, particularly in the nucleus accumbens.
- Blocking slows or blocks nerve conduction and act as a local
+
anaesthetic by altering the recovery of the neuronal Na channels.
CLINICAL FEATURES:
Cocaine overdose may present with clinical features very similar to
amphetamine overdose, and the main presentation could be, stroke,
angina or myocardial infarction.
- Cardiac: Chest pain, hypertension, tachycardia and shortness of
breath.
- Lungs: Decreased Breath sounds after smoking crack can lead to
pneumothorax.
- Neurological: Agitation, headache, focal neurological symptoms, and
extremity symptoms are particularly worrisome.
- Hyperthermia may occur.
- Pupils: Mydriasis.
- Extremities: reduced pulse volume could suggest vascular pathology
e.g., Aortic Dissection.
- GIT: Ischemic colitis, mesenteric vascular occlusion.
- Kidney: Renal infarction, renal failure as a result of rhabdomyolysis.
- Toxicological: Anticholinergics, hallucinogens, amphetamine, cathinone
and withdrawal from benzodiazepines.
- Non toxicological: Thyrotoxicosis, pheochromocytoma, heat stroke, and
paranoid schizophrenia.

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INVESTIGATIONS:
Routine:
- Bed Side RBS to exclude hypoglycemia
- ABGs, BUN, Creatinine, ALT, AST, Creatine Kinase.
- EKG and Pregnancy test for females in child bearing period.
Specific:
- Urine toxicology screen for cocaine metabolite (Benzoylecgonine) as
cocaine is rapidly eliminated. Benzoylecgonine can still be detected in
urine for up to 3 days using immunoassay and Gas Chromatography
Mass Spectometry (GCMS). Screen for other drugs of abuse for
confirmation of intake.
- Driven by clinical symptoms (e.g. Cardiac enzymes for suspected MI
and CT for suspected aortic dissection.
- CT brain to exclude cerebral hemorrhage
TREATMENT:
Stabilization:
- Airway: Succinylcholine is relatively contraindicated in rapid sequence
intubation; consider rocuroniu (1 mg/kg IV) or other non-depolarizing
agents as an alternative.
Symptomatic:
- Psychomotor agitation: Administer benzodiazepines (e.g., diazepam 5-
10 mg IV q 3-5 minutes until agitation controlled)
- Severe symptomatic hypertension:
- Administer diazepam (5 mg IV) or lorazepam (1 mg IV); may repeat q
5 minutes until sedated.
- Aspirin 325 mg PO (Contraindicated if aortic dissection is suspected)
- Nitroglycerin 0.4 mg SL.
- Phentolamine 1-5 mg IV, repeats as necessary and hold if systolic
blood pressure < 140 mmHg.
- In case of QRS widening, administer 1-2 meq/kg of NaHCO3.
COMMON PITFALLS
- The administration of β-Blockers is contraindicated in controlling cocaine-
induced hypertension.
- Administration of phenothiazines and butyrophenones is contraindicated
as they decrease seizure threshold
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REFERENCES:
15. Stolberg VB. .,2002: The use of coca: prehistory, history, and ethnography. J Ethn Subst Abuse 2011;
10:126.
16. Zimmerman JL.,2002:. Cocaine intoxication. Crit Care Clin 2012; 28:517.
17. Nadeem S, Nasir N, Israel RH. .,2002: Löffler's syndrome secondary to crack cocaine. Chest 1994;
105:1599.
18. Afonso L, Mohamad T, Badheka A. ., 2010: Drugs of Abuse and Cardiotoxicity. In: Comprehensive
Toxicology, 2nd, McQueen CA, Bond JR, Lamb K, at al. (Eds), Elsevier,. Vol 1-14, p.339.
19. Ramachandaran S, Khan AU, Dadaparvar S, Sherman MS. ., 2004: Inhalation of crack cocaine can mimic
pulmonary embolism. Clin Nucl Med 2004; 29:756.
20. Kleerup EC, Koyal SN, Marques-Magallanes JA, et al. ., 2002: Chronic and acute effects of "crack" cocaine
on diffusing capacity, membrane diffusion, and pulmonary capillary blood volume in the lung. Chest;
122:629.
21. Delaney K, Hoffman RS. , 1991: Pulmonary infarction associated with crack cocaine use in a previously
healthy 23-year-old woman. Am J Med; 91:92.
22. Harrell PT, Trenz RC, Scherer M, et al.,2002:. Cigarette smoking, illicit drug use, and routes of
administration among heroin and cocaine users. Addict Behav; 37:678.
23. Forrester JM, Steele AW, Waldron JA, Parsons PE. , 2012: Crack lung: an acute pulmonary syndrome with a
spectrum of clinical and histopathologic findings. Am Rev Respir Dis; 142:462.
24. McCormick M, Nelson T. .,2007: Cocaine-induced fatal acute eosinophilic pneumonia: a case report. WMJ;
106:92.
25. Devlin RJ, Henry JA. , 2008: Clinical review: Major consequences of illicit drug consumption. Crit Care;
12:202.
26. Maybauer MO, Rehberg S, Traber DL, et al. .,2002: [Pathophysiology of acute lung injury in severe burn
and smoke inhalation injury]. Anaesthesist; 58:805.
27. Oh PI, Balter MS. ., 1992: Cocaine induced eosinophilic lung disease. Thorax; 47:478.
28. Strong DH, Westcott JY, Biller JA, et al. .,: Eosinophilic "empyema" associated with crack cocaine use.
Thorax; 58:823.
29. Maeder M, Ullmer E. ., 2003: Pneumomediastinum and bilateral pneumothorax as a complication of
cocaine smoking. Respiration; 70:407.
30. Janes SM, Ind PW, Jackson J. ., 2004: Images in Thorax. Crack inhalation induced pneumomediastinum.
Thorax; 59:360.
31. Patel RC, Dutta D, Schonfeld SA. ., 1987: Free-base cocaine use associated with bronchiolitis obliterans
organizing pneumonia. Ann Intern Med; 107:186.
32. O'Donnell AE, Mappin FG, S O'Donnell AE, Mappin FG, Sebo TJ, Tazelaar H. ., 1991: Interstitial pneumonitis
associated with "crack" cocaine abuse. Chest; 100:1155.
33. Klinger JR, Bensadoun E, Corrao WM. .,2002: Pulmonary complications from alveolar accumulation of
carbonaceous material in a cocaine smoker. Chest; 101:1171.
34. Murray RJ, Albin RJ, Mergner W, Criner GJ. , 1988: Diffuse alveolar hemorrhage temporally related to
cocaine smoking. Chest; 93:427.
35. Janjua TM, Bohan AE, Wesselius LJ. .,2001: Increased lower respiratory tract iron concentrations in
alkaloidal ("crack") cocaine users. Chest; 119:422.
36. van der Klooster JM, Grootendorst AF. .,2002: Severe bullous emphysema associated with cocaine smoking.
Thorax 2001; 56:982.
37. Baldwin GC, Choi R, Roth MD, et al.,2002: Evidence of chronic damage to the pulmonary microcirculation in
habitual users of alkaloidal ("crack") cocaine. Chest; 121:1231

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OPIATES
INTRODUCTION:
- Opiates are part of a larger class of drugs, the opioids. Opioid abuse is a
worldwide problem and mortality from opioid overdose is common and
increasing.
EPIDEMIOLOGY:
- Opiates intoxication is common
- Toxic manifestations following narcotic exposure are typically moderate,
with death occurring from central respiratory depression.
CAUSES:
- Manner of use is typically intentional in adults, accidental in pediatrics.
RISK FACTORS:
- Persistent severe intolerable pain (e.g., severe toothache or headache)
may predispose to overuse.
- Narcotics potentiate CNS depressive effect of sedative-hypnotic
medications and other respiratory depressants drugs.
- Meperidine and monoamine oxidase inhibitors formulation may develop
serotonin syndrome.
- Methadone serum levels are declined by chronic use of carbamazepine,
phenytoin, and rifampin, developing withdrawal.
- Opiates produce their effects through activation of mu opioid receptor
subtype. Theses receptors are G-protein coupled receptors and are
responsible for mediating reward, withdrawal and analgesia. Mu
receptors are located centrally and peripherally. Activation of the central
mu receptors is responsible for mediating responses such as euphoria,
respiratory depression, analgesia and miosis. Activation of peripheral mu
receptors produces constipation and cough suppression.
- Changes in mental status ranging from mild euphoria or lethargy to coma.
- Miotic (Pinpoint) pupils.
- Decreased bowel sounds.
- Decreased to normal heart rate and blood pressure.
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- Hypoventilation (The best predictor of opioid poisoning).

- Important: Patients presenting with normal pupils does not exclude
Opioid Intoxication. Drugs like Meperidine and Propoxyphene may
present with normal pupils. Other co-ingestants such as
sympathomimetics or anticholinergics may present with normal pupils.
TOXICITIES OF SPECIFIC AGENTS:
- In addition to the general features described above, some agents have
specific toxicities. A brief description of the notable, yet infrequent,
effects and characteristics of several opioids commonly encountered in
the overdose patient follow:
- Buprenorphine – Partial opioid agonist, may induce withdrawal in
opioid-dependent patients.
- Dextromethorphan – Serotonin syndrome, at high doses exhibits
some µ effects of opioids (miosis, respiratory and CNS depression),
but is not a pure opioid agonist.
- Fentanyl – Very short acting.
- Hydrocodone – Often combined with acetaminophen.
- Meperidine – Seizure, serotonin syndrome (in combination with other
agents).
- Methadone – Very long-acting; QTc prolongation, Torsades de Pointes.
- Oxycodone – Often combined with acetaminophen; possible QTc
interval prolongation.
- Propoxyphene – QRS prolongation and seizures
- Tramadol – Seizures.
INVESTIGATIONS:
Routine:
- Bed Side RBS to exclude hypoglycemia.
- ABGs, Electrolytes.
- EKG.
- Pregnancy test for females in child bearing period.
Specific:
- Urine screening for opiates as well as other drugs of abuse
(Benzodiazepines, Barbiturates, Cannabis and Alcohol) to identify
polydrug use.

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Toxic agent Defining Features
Antihistamines Anticholinergic toxidrome
Antipsychotics Pupils not constricted, bowel sounds normal
Barbiturates Mild to severe hypotension, serum concentration
β-adrenergic antagonists �Cardiovascular findings (hypotension�, bradycardia)
more prominent than mental status findings
Calcium�Channel blockers Cardiovascular� findings (hypotension, bradycardia, or
tachycardia) more prominent than mental status findin�s
Carbamaze�ine Serum �c oncentration
Carbon monoxide Carboxyhemoglobin level
Clonidine Bradycardia and hypotension
Cyclic antidepressants QRS prolongation, hypotension, tachycardia
Ethanol Pupils and bowel sounds normal, serum concentration
Ethylene glycol Pupils and bowel sounds are normal
Hypoglycemic agents Serum glucose concentration
Isoniazid History of seizures, normal pupils and bowel sounds
Isopropanol Pupils and bowel sounds normal
Lithium Tremor, hyper-reflexia, serum concentration
Methanol Pupils and bowel sounds normal
Organic-phosphorous Cholinergic toxidrome
compounds
Phencyclidine Nystagmus (horizontal, vertical, or rotary)
Sedative-hypnotic agents Pupil size normal to decreased, bowel sounds normal
and less respiratory depression
TREATMENT:
Stabilization:
The main aim of Naloxone administration is the reversal of respiratory
depression and not full regaining of consciousness or precipitating
withdrawal.
- Reversal of respiratory depression with therapeutic opioid use and
after postoperative overdose: If the O2 saturation is <94 % on room
air but the patient is breathing spontaneously, administer 100%
supplemental oxygen followed by IV naloxone 0.04 to 0.4 mg; given
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or IM. Methodology: Dilute 0.4 mg/mL (1 mL) into 9 mL of 0.9%

saline to reach a total volume of 10 mL to achieve a 0.04 mg/mL (40
μg/mL) concentration.
- If the patient is apneic, ventilate using a bag-valve mask attached to
100% supplemental oxygen and administer naloxone in doses of 0.2-
2 mg IV or IM. If no response occurs after a total of 5-10 mg of
naloxone, reconsider the diagnosis and perform tracheal intubation.
- In case of absence of IV access, Naloxone can be administered IM.
Repeat until ventilation becomes adequate. If the desired response is
not observed after a total dose of 0.8 mg, consider other causes of
respiratory depression. Naloxone may be given endotracheal (off-
label route) as 2-2.5 times the initial IV dose.
- Continuous IV infusion: For use with exposures to long-acting opioids
(e.g. methadone) or sustained-release products or if hypoventilation
recurs following the initial naloxone bolus.
- Administer additional bolus doses aiming to restore adequate
ventilation. When ventilation is adequate, a naloxone infusion can
replace frequent rebolusing. Begin the infusion rate at 2/3 of the
total dose of naloxone needed to restore breathing, delivered every
hour. Adjust the infusion rate as needed to assure adequate
ventilation and prevent withdrawal symptoms.
- Opioid-dependent patients that are under treatment for cancer pain:
Administer naloxone IV 0.04-0.08 mg (40-80 μg) slow IV push every
30-60 seconds until improvement of symptoms. If the patient does
not show any response after a total naloxone dose of 1 mg, consider
other causes of respiratory depression.
- If the respiratory rate is ≥ 12 breaths/minute and O2 saturation is >94
% on room air, observe the patient in a monitored setting and
frequently reassess. End-tidal CO2 monitoring using capnography is
an excellent means to monitor ventilation.
- If the patient develops signs of opioid withdrawal, stop the infusion.
If respiratory depression returns, start the infusion at half the
original rate.
- The patient is medically stable for transfer or discharge when the
mental status and ventilation remain normal for more than one hour
after cessation of naloxone.

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FOLLOW UP:
PATIENT MONITORING
- Respiratory and cardiac status must be monitored continuously.
- Possible sequelae involve renal impairment and neurological damage
secondary to prolonged seizure and myocardial or CNS damage from
hypoxic effects.
- The prognosis is detected by the hypoxic damage that developed
before management or the muscle damage from lying on an extremity
for a prolonged duration.
- From the emergency department. For most narcotics, asymptomatic
cases may be discharged following decontamination procedure, a six
hour observation period, and psychiatric assessment, if required.
- From the hospital. Cases may be discharged after mental condition,
EKG, and vital signs records return to normal values, and
decontamination procedures and psychiatric assessment are
completed, if required.
PITFALLS:
DIAGNOSIS
- Pinpoint pupils sign may be obscured by hypoxic effect or components
that develop mydriasis, such as scopolamine.
- Several medical formulations containing narcotics also contain
acetaminophen or aspirin
FOLLOW-UP
- Discharge of the patient immediately after naloxone therapy may allow
the recurrence of respiratory depression status outside of the
emergency department.
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Frequently encountered opioids and their equivalence to 10 mg Morphine

Source Serum Half-
Life
Approximate
Equivalence Important Clinical Features
(Hours)* To 10 Mg
Morphine
Injection
(Mg)
IMPORTANT: The Doses Included Here Are NOT Recommended For The Initiation Of Therapy; They Provide Equivalents
For The Purpose Of Comparing Different Opioids.
Natural
Morphine 1.9 +/– 0.5 10 SC/IM/IV -
30 PO
Codeine 2.9 +/– 0.7 75 SC/IM/IV Metabolized by CYP2D6 to active drug (morphine).
130 to 200 PO Metabolism and effects are subject to pronounced individual
variability. Single oral doses over 65 mg tend to produce
disproportionately greater adverse effects than analgesia.
Semi-synthetic
Hydromorphone 2.4 +/– 0.6 1.5 SC/IM/IV Hepatically metabolized to metabolites that can accumulate
7.5 PO in organ failure and prolong effects. Some metabolites have
been linked to neurotoxicity.
Oxycodone 2.6 (2.1-3.1) 20 to 30 PO Metabolized by CYP3A4 and 2D6. Prolonged effects and
elevated serum concentrations with renal or hepatic
insufficiency. May cause QTc prolongation.
Hydrocodone 4.24 +/– 30 PO
0.99
Diacetylmorphine 5 SC Highly lipophilic causing more rapid CNS effects than
(diamorphine, morphine. Largely metabolized to morphine. Due to
heroin)
abuse potential is not available for clinical use in
many countries.
Synthetic
Meperidine 3.2 +/– 0.8 75 to 100 Excitatory neurotoxicity may occur when
SC/IM normeperidine, a renaly-eliminated metabolite,
300 PO
accumulates.
Methadone 27 +/– 12 10 SC/IM/IV Used in opioid substitution therapy. Can
Highly
variable. See
cause QTc prolongation. May be far more
clinical potent than indicated in this table. Half-Life
features. (up to 150 hours), methadone has the highest
risk among opioids of accumulation and
toxicity during initial titration and after
changes in dose.
Propoxyphene 65 to 130 Usual initial dose for mild analgesia shown; NOT equivalent
(dextropropoxyphe PO• to parenteral morphine 10 mg. Has class IA anti-dysrhythmic
ne) properties, leading to widened QRS, negative inotropy, and
conduction abnormalities. Can cause seizures. Onset of toxic
effects is 15 to 60 minutes in overdose.

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Source Serum Half-

Life
Approximate
Equivalence Important Clinical Features
(Hours)* To 10 Mg
Morphine
Injection
(Mg)
Tramadol 5.5 (4.5-7.5) 50 to 100 Usual initial dose for mild analgesia shown; NOT equivalent
PO• to parenteral morphine 10 mg. Effects NOT completely
reversed by naloxone. Noted to cause seizures. Subject to
interactions including serotonin excess.
Fentanyl 3.7 +/– 0.4 0.05 to 0.1 Short acting when administered IV/IM as a single dose.
SC/IM/IV Highly lipophilic. Parent drug accumulates with repeated or
prolonged administration.
Agonist/antagonist
Pentazocine 2 to 3 30 to 60
SC/IM - 75 to
150 PO
Partial agonist
Buprenorphine 2.33 +/– 0.3 to 0.4 Used in opioid substitution therapy. Significantly
0.24 IM/IV longer duration of effect than 10 mg parenteral
0.4 sublingual
morphine. Metabolized by and subject to
interactions involving CYP3A4.
Gastrointestinally insoluble – not analgesic

Diphenoxylate 2.5 to 5 PO Poor solubility limits potential for parenteral
(anti- injection and abuse. Usually formulated with
diarrheal
atropine (US trade name Lomotil®, 0.025 mg
dose)•
atropine and 2.5 mg diphenoxylate) to further
decrease abuse potential.
Loperamide 2 to 4 PO Very low abuse potential due to lack of effect on
(anti- CNS receptors.
diarrheal
dose)•
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REFERENCES:
1. Substance Abuse and Mental Health Services Administration, Office of Applied Studies. Drug
Abuse Warning Network, 2004: National Estimates of Drug-Related Emergency Department
Visits. DAWN Series D-28, DHHS Publication No. (SMA) 06-4143, Rockville, MD 2006.
2. QuickStats, 2013: Number of Deaths From Poisoning,* Drug Poisoning,† and Drug
Poisoning Involving Opioid Analgesics§ — United States, 1999–2010 ,
ww.cdc.gov/mmwr/preview/ mmwrhtml/ mm6212a7.htm?s_ cid=mm6212a7_e (Accessed
on April 08, 2013).
3. Waldhoer M, Bartlett SE, Whistler JL, 2004: Opioid receptors. Annu Rev Biochem; 73:953.
4. Bonci A, Bernardi G, et al., 2003: The dopamine-containing neuron: maestro or simple
musician in the orchestra of addiction? Trends Pharmacol Sci; 24:172.
5. Aghajanian GK, Wang YY. , 1987: Common alpha 2- and opiate effector mechanisms in the
locus coeruleus: intracellular studies in brain slices. Neuropharmacology; 26:793.
6. Davies G, Kingswood C, Street M. , 1996: Pharmacokinetics of opioids in renal dysfunction.
Clin Pharmacokinet; 31:410.
7. Darke S, Zador D. , 1996: Fatal heroin 'overdose': a review. Addiction; 91:1765.
8. Ghoneim MM, Dhanaraj J, Choi WW. , 1984: Comparison of four opioid analgesics as
supplements to nitrous oxide anesthesia. Anesth Analg; 63:405.
9. Hoffman JR, Schriger DL, Luo JS., 1991: The empiric use of naloxone in patients with altered
mental status: a reappraisal. Ann Emerg Med; 20:246.
10. Fahmy NR, Sunder N, Soter NA. , 1983: Role of histamine in the hemodynamic and plasma
catecholamine responses to morphine. Clin Pharmacol Ther; 33:615.
11. Ashbourne JF, Olson KR, Khayam-Bashi H. , 1989: Value of rapid screening for
acetaminophen in all patients with intentional drug overdose. Ann Emerg Med; 18:1035.
12. Stork CM, Redd JT, Fine K, Hoffman RS. , 1995: Propoxyphene-induced wide QRS complex
dysrhythmia responsive to sodium bicarbonate--a case report. J Toxicol Clin Toxic Toxicol
Clin Toxicol; 33:179.
13. Krantz MJ, Kutinsky IB, et al , 2003: Dose-related effects of methadone on QT prolongation
in a series of patients with torsade de pointes. Pharmacotherapy; 23:802.
14. Berling I, Whyte IM, Isbister GK. , 2013: Oxycodone overdose causes naloxone responsive
coma and QT prolongation. QJM; 106:35.
15. Mills CA, Flacke JW, Flacke WE, et al. , 1990: Narcotic reversal in hypercapnic dogs:
comparison of naloxone and nalbuphine. Can J Anaesth; 37:238.
16. Berlot G, Gullo A, Romano E, Rinaldi A., 1985: Naloxon\e in cardiorespiratory arrest.
Anaesthesia; 40:819.
17. Bertini G, Russo L, Cricelli F, et al., 1992: Role of a prehospital medical system in reducing
heroin-related deaths. Crit Care Med; 20:493.
18. Osterwalder JJ. , 1996: Naloxone--for intoxications with intravenous heroin and heroin
mixtures--harmless or hazardous? A prospective clinical study. J Toxicol Clin Toxicol; 34:409.
19. Dowling J, Isbister GK, Kirkpatrick CM, et al. , 2008: Population pharmacokinetics of
intravenous, intramuscular, and intranasal naloxone in human volunteers. Ther Drug Monit;
30:490.
20. Goldfrank L, Weisman RS, Errick JK, Lo MW. , 1986: A dosing nomogram for continuous
infusion intravenous naloxone. Ann Emerg Med; 15:566.
21. Gill JR, Graham SM., 2002: Ten years of "body packers" in New York City: 50 deaths. J
Forensic Sci; 47:843.
22. Traub SJ, Hoffman RS, Nelson LS. , 2003: Body packing--the internal concealment of illicit
drugs. N Engl J Med; 349:2519.
23. Duberstein JL, Kaufman DM, 1971: A clinical study of an epidemic of heroin intoxication and
heroin-induced pulmonary edema. Am J Med 1971; 51:704.

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CANNABIS
INTRODUCTION:
DESCRIPTION
- Cannabis is the popular name for the dried flowering leaves of
Cannabis sativa, C. indica, and C. ruderalis, the active ingredient of
which is delta-9-tetrahydrocannabinol (THC).
FORMS AND USES
- Other names for illicit cannabis are pot, weed, grass, ganja, hashish,
bhang, charas, dagga, kif, reefer, marilyn, honey oil, fimble, and
gallow grass; Cannabis is sometimes named according to its site of
origin and color (e.g., Panama red or Acapulco gold).
- Sensemilla cannabis indicates to the flowering tops of the female
plant, which contain the highest resin concentration.
- Hashish has a high content of THC and is obtained by extracting
cannabis with a nonpolar solvent solution.
- Cannabis products may be added to food (e.g., cookies or brownies)
(Prohibited in Saudi Arabia) or dissolved for intravenous abuse.
- Pharmaceutical formulation of cannabis involve dronabinol (Marinol)
and nabilone (Cesamet).
- Cannabis cigarettes and synthetic cannabinoids may be utlized
as antiemetics medication usage for chemotherapy-induced
nausea.
- Other suggested medical indications for using THC include pain,
seizures, asthmatic manifestations, glaucoma, and ulcerative
colitis
- Typical adult doosage are dronabinol, 2.5 mg orally twice a day,
and nabilone, 1-2 mg orally twice a day.
TOXIC DOSE
- Acute oral intoxication is very low.
- The calculated human cannabis toxic dose after ingestion exposure is
2
30 mg/kg of cannabis; 15 mg/m of THC has lead to central nervous
system toxic manifestations in cancer patients.
PATHOPHYSIOLOGY
- Cannabis has at least 60 cannabinoid molecular structure, involving
the most active ingredient, THC.
- The concentration of THC in cannabis cigarettes varies from 1% - 8%;
hashish may contain 5% to 10% and hash oil up to 50% concentration.
- After smoking cannabis, approximately 20-50% of the THC is
systemically absorbed, the onset of cannabis effects is 6-12 minutes,
and manifestations may persist up to 3 hours
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- After oral exposure, only 5% - 20% of THC is bioavailable due to first-

pass hepatic metabolism effect. The onset of symptoms is delayed,
30-60 minutes and persists for 4-6 hours
- Comparing cannabis and tobacco smokers, cannabis usage was
associated with a five time increase in carboxyhemoglobin
concentrations and a three time increase in inhaled amount of tar.
- Carcinogenesis. Cannabis is implicated in high risk for mouth, head,
neck, and bronchial cancer.
EPIDEMIOLOGY:
- Cannabis toxicity is common.
- Toxic cannabis effects following all routes of exposure are typically
mild degree.
- Death from cannabis intoxication is rare and is usually resulted from
associated traumatic injuries arising from impaired judgment.
CAUSES:
- Cannabis exposure is nearly always intentional exposure.
- Child neglect or abuse should be considered in pediatric cannabis
intoxication
- Significant toxicity can be seen with accidental pediatric cannabis
exposure by ingestion or inhalation.
DRUG INTERACTIONS
- Cannabis may act synergistically with other central nervous system
depressing substances.
- Cannabis may potentiate cocaine-induced tachycardia and accelerate
a subjective high.
SIGNS AND SYMPTOMS
- Oral or inhalational cannabis abuse leads primarily desirable
neurological effects (a "high").
- Intravenous infusion of dissolved cannabis extract can cause severe
multiorgan toxicity and damage, involving severe gastroenteritis,
fulminant hepatitis, acute renal impairment, anemia, severe
thrombocytopenia, and leukocytosis.
Vital Signs
- Both hypothermia or hyperthermia, tachycardia or bradycardia,
hypotension or hypertension, and bradypnea have been reported.
HEENT
- Conjunctival congestion, dropped intraocular tension, dilated pupil,
horizontal nystagmus, blurred vision, uvula edema, and dryness of the
mouth can develop.

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Pulmonary
- Bradypnea, respiratory irritation, persistent coughing, and
bronchodilation may develop.
Cardiovascular
- Both hypertension or hypotension, tachycardia or bradycardia, and a
chest tightness sensation may develop.
Gastrointestinal
- Increased appetite, decreased gut movement, and constipating effect
may develop.
Renal
- Urine retention may develop.
Musculoskeletal
- Skeletal muscle weakness and abnormal jerking movement may
develop.
Neurologic
- Anti-motivational syndrome may develop in chronic cannabis cases.
- Seizures may develop in cases with a history of previous history of
seizure disorder.
- Mild cannabis toxicity produces euphoria, a degree of somnolence,
heightened awareness, generalized relaxation, alteration in time
perception, and increased appetite also may develop.
- Moderate cannabis toxicity leads to short-term memory impairment,
poor concentration power and poor attention, inability to act multi-
step orders, alternating mood disorders involving laughing episodes
and depression mode episodes, changed thought patterns, and
disorientation status may develop.
- Extreme cannabis toxicity includes decreased power of strength and
coordination capacity, generalized lethargy, ataxia, characteristic
slurred speech, anxiety disorders and impending “fear” of death,
muscle jerking disorder, central respiratory depression, and finally
coma have been detected.
Reproductive
- Decreased sperm production and motility, increased abnormal sperm
count, and decreased ovulation pattern may develop.
Endocrine
- Gynecomastia, as well as depressed levels of testosterone hormone,
luteinizing hormone, growth hormone, and follicle-stimulating
hormone may be detected.
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INESTIGATIONS
General Tests
- Serum electrolytes, BUN, creatinine, and glucose may be indicated to
evaluate other causes of seizures or disturbed conscious level.
- Liver functions tests, coagulation profile studies, and serum creatine
kinase level may be increased in patients with fever or agitation
status.
- EKG, serum paracetamol, and aspirin levels should be detected in an
overdose condition to detect occult ingestion.
- Head CT, lumbar puncture, and toxicology studies should be ordered
as required to detect other causes of seizure and disturbed conscious
level.
- Urine substance of abuse for cannabis may remain positive for several
weeks after acute clinical manifestations have recovered.
Specific Tests
- No specific tests are ordered in minimally symptomatic cannabis
cases.
TREATMENT
- Treatment should focus on airway management and supportive care.
- For paranoia or panic attacks, the patient should be placed in a quiet
room and treated with reassurance in a nonthreatening manner.
- The dose and time of exposure should be determined for all
substances involved.
DIRECTING PATIENT COURSE

Health-care professionals should call a poison control center when:
- Severe cannabis manifestations are reported.
- The acute toxic manifestations are not consistent with acute cannabis
toxic manifestations.
- Co-ingestants, drug interaction, or underlying pathological condition
presents an unusual problem.
Patients should be referred to a health-care professional when:
- Attempted suicide or homicide is possible present.
- Patients or caregivers appear unreliable.
- Severe cannabis effects are reported.
- The poisoning effects are not consistent with cannabis toxicity.

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Admission Considerations
- Inpatient acute cannabis treatment is indicated for patient
persistently abnormal reported vital signs, disturbed consciousness
level, or clinically significant damaged organ intoxications.
DECONTAMINATION
In Hospital
- Gastric lavage is recommended if the patient presents within 1 hour
of a large ingestion or if serious effects are reported.
- A single dose of activated charcoal (1-2 g/kg) should be given if the
patient has ingested a substantial amount of cannabis within the
previous few hours from the time of hospital adminstration.
ANTIDOTES
- There are no specific antidotes for cannabis intoxication.
SUPPORTIVE TREATMENT
- To control agitation, the physician should give a benzodiazepine with
which he has experience.
- For diazepam medication, the adult dosage is 5-10 mg
intravenously; the pediatric dose is 0.2-0.5 mg/kg intravenously,
and doses are repeated at 10-minutes intervals, titrating to
desired effect.
- For lorazepam medication, the adult dosage is 1 to 2 mg
intravenously; the pediatric dosage is 0.05-0.1 mg/kg
intravenously. Doses are repeated at 10-minutes intervals,
titrating to desired effect.
- The patient's respiratory function should be closely monitored for any
cannabis toxic manifestations.
FOLLOW UP
PATIENT MONITORING
- If severe cannabis manifestations or complications occurred,
electrolytes, renal function, and other laboratory tests indicated by
the patient's clinical condition must be monitored.
- Cannabis effects peak rapidly and persist for several hours, followed
by complete resolution unless complications appear.
- Inhalation of cannabis has been associated with chest complication in
the form of pneumothorax and pneumomediastinum
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- From the emergency department or hospital, discharge is indicated
for alert fully consciousness patients with normal reported vital signs,
easy good ambulation, and a reliable noticed caregiver, following
psychiatric assessment, if needed.
PITFALLS
DIAGNOSIS
- It is important to detect other serious or treatable causes of disturbed
consciousness level.
FOLLOW-UP
- Diagnosed cannabis patients should be referred for substance abuse
treatment program.
REFERENCES:
1. Delisi, Lynn E (2008). "The effect of cannabis on the brain: can it cause brain anomalies that
lead to increased risk for schizophrenia?". Current Opinion in Psychiatry 21 (2): 140–50.
2. Jump up^ Denson, TF; Earleywine, M (2006). "Decreased depression in marijuana
users". Addictive behaviors 31 (4): 738.
3. Goldfrank LR. In: Goldfrank NR, Flomenbaum NE, Lewin NA, et al., eds. (2006). Goldfrank’s
Toxicologic Emergencies. 8th ed. New York, NY: McGraw-Hill.
4. Bronstein AC, Spyker DA, Cantilena LR, Green JL, Rumack BH, Dart RC. (2010): Annual Report
of the American Association of Poison Control Centers’ National Poison Data System (NPDS).
Clin Toxicol (Phila). 2011;49( 10): 910– 941.
5. Olson, Kent (2011). Poisoning and Drug Overdose, Sixth Edition (Poisoning & Drug Overdose)
McGraw-Hill Education.

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ETHANOL:
INTRODUCTION:
Description:
- Ethanol is frequently ingested recreationally “Prohibited in Saudi
Arabia”.
Forms and uses:
- Commercial beer, wine, and liquors contain various concentrations of
ethanol. Ethanol also is present in a variety of colognes, perfumes,
aftershaves, and mouthwashes; some rubbing alcohols; many food
flavorings (eg, vanilla, almond, and lemon extracts); pharmaceutical
preparations (eg, elixirs); hand sanitizers; and many other products.
- Ethanol may also serve as a competitive medication in the emergency
management of methanol and ethylene glycol toxicity.
Toxic dose:
- Generally, 0.7 g/kg of pure ethanol (approximately 3-4 drinks) will
develop a blood ethanol level of 100 mg/dL.
- The legal limit for ethanol in Saudi Arabia 30 mg/dL.
- A level of ethanol of 100 mg/dL depresses reaction time and judgment
and may be enough to inhibit gluconeogenesis and produce
hypoglycemia in children and patients with liver impairment, but by
itself it is not enough to develop coma.
- The ethanol level sufficient to develop deep coma or respiratory
depression is widely variable, depending on the individual’s degree of
tolerance to ethanol. Although concentrations above 300 mg/dL
usually cause alcoholic coma in recently onset drinkers, patients with
chronic alcoholism may be awake with alcoholic concentrations of 500-
600 mg/dL or more.
Pathophysiology:
- CNS depressant action:
- Central nervous system (CNS) depression is the primary effect of
acute ethanol toxicity. Ethanol has additive effects with other CNS
depressants medications, such as barbiturates, benzodiazepines,
opioids, antidepressants, and antipsychotics.
- Hypoglycaemic action:
- Hypoglycemia may be caused by impaired gluconeogenesis in
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alcoholic cases with depleted or low glycogen stores (particularly

pediatric and malnutironed cases).
- Predisposing action for multiple pathological conditions:
- Ethanol toxicity and chronic alcoholism also predispose cases to
trauma, exposure-induced hypothermia, GI tract damage and
nervous system, and a number of nutritional disorders and
metabolic disturbances.
- Pharmacokinetics.
- Ethanol is readily completely absorbed from all GIT mucosa (peak,
30-120 minutes) and distributed into the body water (volume of
distribution, 0.5-0.7 L/kg).
- Ethanol elimination is mainly by oxidation in the liver and follows
zero-order kinetics. The average adult case can metabolize about
7-10 g of ethanol per hour, or about 12-25 mg/dL/h. This rate
varies among cases and is influenced by polymorphisms of the
alcohol dehydrogenase enzyme “hyper or hypo metabolizer” and
the activity of the microsomal ethanol-oxidizing enzymes systems.
Epidemiology:
- Accidental ethanol toxicity is common.
Acute intoxication
Mild to moderate toxicity:
With mild to moderate ethanol toxicity, cases exhibit euphoria,
mild incoordination, ataxia, nystagmus, and impaired judgment
and reflexes. Social and moral ethics are loosened, and
aggressive behavior is commonly reported. Hypoglycemia may
develop, especially in pediatrics and persons with depleted
hepatic glycogen stores.
Severe toxicity:
With deep ethanol toxicity, coma, respiratory depression, and
pulmonary aspiration may develop. In these cases, the pupils are
usually constricted, and the temperature, blood pressure, and
pulse rate are often depressed. Rhabdomyolysis may develop
from prolonged immobility.
Chronic intoxication
Chronic ethanol abuse is associated with several complications:

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- Hepatic alcoholic intoxications involves fatty infiltration of the

liver, alcoholic hepatitis, and cirrhosis. Hepatic scarring leads to
portal hypertension, ascites, and bleeding manifestations from
esophageal varices and hemorrhoids; hyponatremia from fluid
retention; and bacterial peritonitis.
- Impaired production of clotting factors, leading to prolonged
prothrombin time. Impaired hepatic metabolism of drugs and
endogenous toxins and even may lead to hepatic encephalopathy.
- Gastrointestinal bleeding may develop from alcohol-induced
gastritis, esophagitis, and duodenitis. Other causes of massive
bleeding in chronic ethanol toxicity involve Mallory-Weiss tears of
the esophagus and ruptured esophageal varices. Acute
pancreatitis is a common cause of abdominal pain and vomiting in
cases of chronic alcoholic toxicity.
- Cardiac disorders involve various cardiac dysrhythmias, such as
atrial fibrillation, that may be associated with potassium and
magnesium depletion and poor caloric intake (“holiday heart”).
Alcoholic cardiomyopathy has been associated with long-term
alcohol use. (Cardiomyopathy was also historically associated with
ingestion of cobalt ingredient used to stabilize beer.)
- Neurologic toxic manifestations involves cerebral atrophy,
cerebellar degeneration, and peripheral stocking-glove sensory
neuropathy.
- Nutritional disorders such as thiamine (vitamin B1) deficiency can
develop Wernicke encephalopathy or Korsakoff psychosis in cases
of chronic alcoholism.
Alcoholic ketoacidosis
- Alcoholic ketoacidosis is a pathological condition that characterized by
anion gap metabolic acidosis and elevated levels of beta-hydroxybutyrate
and, to a lesser extent, acetoacetate. The osmolar gap may also be
elevated, causing this clinical condition to be diagnostic mistaken for
methanol or ethylene glycol poisoning.
Alcohol withdrawal.
- Sudden stoppage after chronic high-level alcohol use often develop
headache, tremulousness, anxiety, palpitations, and insomnia. Brief,
generalized seizures may develop, usually within 6-12 hours of dropped
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ethanol consumption. Sympathetic nervous system overactivity may

progress to delirium tremens, a life-threatening condition characterized
by tachycardia, diaphoresis, hyperthermia, and delirium, which usually
manifests 48-72 hours after cessation of heavy alcohol use. The “DTs”
may develop high morbidity and mortality rates if untreated.
Other problematic situations.
- Alcoholic abusers sometimes intentionally or accidentally ingest ethanol
substitutes, such as isopropyl alcohol, methanol, and ethylene glycol.
- Disulfiram use can cause a severe acute reaction with recurrent ethanol
ingestion.
INVESTIGATIONS
General Tests:
- Suggested laboratory tests in the acutely intoxicated alcoholic case may
include glucose, electrolytes, BUN, creatinine, hepatic enzymes,
prothrombin time (PT/INR), magnesium, arterial blood gases or oximetry,
and chest radiography (if pulmonary aspiration is suspected). Ordered CT
scan of the head if the case has focal neurologic deficits or altered mental
status inconsistent with the level of blood alcohol elevation.
Specific Tests:
- Serum ethanol levels
- Serum ethanol concetration are usually available at most hospital
laboratories.
- Note that serum ethanol levels are approximately 12-18% higher than
corresponding blood ethanol levels.
- Generally, there is only rough relationship between blood ethanol
levels and clinical alcoholic presentation; however, an ethanol level
below 300 mg/dL in a comatose patient should initiate a search for
alternative causes for the disturbed consciousness level condition.
TREATMENT
Emergency and supportive procedures
Acute intoxication.
Mainly supportive treatment.
- Protect the airway to prevent aspiration and intubate and assist
ventilation if required.
- Give glucose and thiamine, and treat coma and seizures if they
develop. “As in general toxicology section”

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- Glucagon is not effective drug for alcohol-induced hypoglycemia.

- Correct alcoholic induced hypothermia with gradual rewarming.
Alcoholic ketoacidosis.
- Treat with volume replacement, thiamine, and supplemental glucose.
“General toxicology and antidote sections”.
- Most cases recover rapidly.
Alcohol withdrawal.
- Manage with benzodiazepines (eg, diazepam, 2-10 mg IV initially and
repeated as indicated) and/or phenobarbital therapy.
Antidotes.
- There is no available specific ethanol receptor antagonist despite
anecdotal documents of powerful arousal effect after administration
of naloxone therapy.
Decontamination procedures.
- Ethanol is rapidly absorbed from GIT, so gastric decontamination is
usually not indicated unless other medication co-ingestion is
suspected. Instruct aspirating gastric contents with a small, flexible
tube if the ethanol ingestion incidence was massive and recent
(within 30-45 minutes).
- Activated charcoal does not effectively adsorb ethanol but may be
administrated if other medication or toxins were co-ingested.
Enhanced elimination procedures.
- Excretion of ethanol normally occurs at a fixed rate of approximately
20-30 mg/dL/h.
- Execratory rates are faster in chronic alcoholism cases and patient
with serum levels more than 300 mg/dL.
- Hemodialysis procedure efficiently removes ethanol, but enhanced
removal is rarely required because supportive care in such cases is
usually sufficient.
- Hemoperfusion and forced diuresis procedures are not effective in
ethanol toxicity.
FOLLOW UP
Patient monitoring
- Pediatric observation for accidental alcoholic toxicity until their blood
alcohol concentration is below 50 mg/dL and there is no evidence of
hypoglycemia is mandatory.
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- Most cases alcoholic intoxicate cases will recover within 4-6 hours.
PITFALLS
- Diagnosis of alcohol toxicity is usually simple, based on the history of
ingestion, the characteristic smell of fresh alcohol or the rotten odor of
acetaldehyde and other metabolic products, and the noticed of
nystagmus, ataxia, and altered mental status. However, other medical
disorders may associate or mimic alcoholic toxicity, such as
hypoglycemia, head trauma, hypothermia, meningitis, Wernicke
encephalopathy, and toxicity with other medications or poisons.
REFERENCES:
1. Gelernter J, Kranzler HR. 2009. Genetics of alcohol dependence. Hum Genet.;126: 91– 99.
2. Grant BF, Stinson FS, Dawson DA, et al. 2004. Co-occurrence of 12-month alcohol and drug
use disorders and personality disorders in the United States: results from the National
Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry.;61: 361– 368.
3. Olson, Kent (2011). Poisoning and Drug Overdose, Sixth Edition. McGraw-Hill Education.
Kindle Edition.
4. Kaner E, Beyer F, Dickinson H, et al. Effectiveness of brief alcohol interventions in primary care
populations. Cochrane Database Syst Rev. 2007;2: CD004148. DOI: 004110.001002/
14651858. CD14654148.
5. Gelernter J, Kranzler HR. 2009. Genetics of alcohol dependence. Hum Genet.;126: 91– 99.

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HOUSEHOLD PRODUCTS
CAUSTICS
INTRODUCTION:
- Caustics and corrosives result in tissue injury by a chemical reaction. The
majority of caustic substances are either acidic or alkaline. The degree of
tissue injury from acidic and alkaline substances is influenced by several
factors such as, the duration of contact with the tissues, the amount and
state (liquid, solid) of the substance involved. Other physical factors
include the pH, concentration and the ability to penetrate the tissues. The
alkaline drain cleaners and the acidic toilet bowl cleaners are responsible
for the most fatalities from corrosive agents.
TOXIC DOSE:
- Variable: The toxic dose varies tremendously by type and concentration of
acid.
EPIDEMIOLOGY:
- Poisoning is common.
- Toxic effects following exposure are typically mild.
- Mortal effects (deaths) occurs after ingestion of a large amount of dilute
solution or a smaller amount of concentrated, highly acidic/alkaline
compounds.
- Occupational effects (exposure) to acid/alkalies mists are associated with
laryngeal cancer.
CAUSES:
- Toxic ingestion is usually accidental in children.
- Adult toxicity is most likely to result from suicidal or occupational
exposure.
- Caustics are typically classified as acids or alkalis. An acid is a proton
donor and causes significant tissue injury when the pH < 3. An alkali is a
proton recipient and causes significant tissue injury when the pH > 11.
- Acids cause coagulative necrosis. Hydrogen ions desiccate epithelial cells,
causing oedema, erythema, tissue sloughing, and necrosis, with the
formation of ulcers and eschars.
- Alkalis cause liquefactive necrosis, a process that involves saponification
of fats and protein dissolution. Cell death occurs as a result of
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emulsification and disruption of cellular membranes. The hydroxide ion in

alkaline agents reacts with tissue collagen and causes it to swell and
shorten. Small vessel thrombosis and heat production occur.
- Signs and symptoms of impending airway irritation or obstruction:
Dyspnea, stridor, hoarseness, dysphonia or aphonia, respiratory distress,
tachypnea, hyperpnea, cough and chest pain.
- Other symptoms and signs of injury: Nausea, vomiting, oropharyngeal
burns (pain or swelling) these are important when identified. However,
significant esophageal damage may occur even in the absence of
oropharyngeal lesions. Other symptoms include, drooling, dysphagia,
abdominal pain, subcutaneous air, hematemesis, melena, tachycardia,
acute peritonitis (abdominal guarding), rebound tenderness, and
diminished bowel sounds.
- Signs of severe injury: Altered mental status, peritoneal signs, perforation,
hypotension, stridor, renal failure, electrolyte disturbance, metabolic
acidosis, hemolysis, and shock.
- Chemical Burns - Thermal burns - Dysphagia
- Gastrointestinal hemorrhage or perforated viscus.
INJURY SEVERITY AND COMPLICATIONS:
Grade Findings Comments
Grade 0 No injury No adverse effects
Grade I Erythema, edema No adverse sequelae
Grade IIa Limited to mucosa No adverse sequelae
Grade IIb Blister, ulceration and May develop strictures
whitish
membrane penetrating the
mucosa
Grade III Extensive necrosis, full High morbidity and
thickness or mortality may result in
frank perforation perforation, mediastinitis,
or peritonitis. Strictures
are seen in the majority.

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INVESTIGATIONS:
Routine:
- Bed Side RBS.
- CBC, BUN, Creatinine, ALT, AST, Creatine Kinase.
- EKG.
- Pregnancy test for females at childbearing period.
Specific:
- Determine type and cross match for blood, and monitor urine output.
- Serum lactate and base deficit are useful prognostic tools.
- MetHb levels, LDH for (phenol), calcium for (oxalates, fluorides) and
urine oxalate.
- Chest X-ray is performed to evaluate for pneumo-mediastinum or free
air under the diaphragm. The absence of these findings DOES NOT rule
out the possibility of necrosis or perforation of the esophagus or
stomach.
- Abdominal x-ray findings to evaluate for pneumoperitoneum, ascites, or
an ingested button battery (metallic foreign body).
- CT scan is useful in the detection of small amounts of extraluminal air
not caught on plain radiographs.
- Several weeks after ingestion, barium contrast X-rays of the upper GI
tract are useful in patients with grade II or III burns to evaluate for
strictures.
TREATMENT:
Stabilization:
- Nothing per oral (NPO) and IV fluids till complete evaluation.
- Do not force the patient to vomit or drink.
- Allow the patient to drink a small amount of water if able to drink for the
purpose of checking for ability to swallow.
Decontamination:
- In ocular burn rinse with 0.9% sodium chloride or running tap water 30-
32 °C for 15 min followed by emergency ophthalmologic consultation.
- In dermal burn: Remove contaminated clothes, brush off particulate
corrosives, and follow with copious irrigation.
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Specific:
Endoscopy:
- It should be performed as soon as possible (best if within 12 hrs and not
more than 24 hrs) in any patient who ingested high volumes of a caustic
substance. The grade of mucosal injury at endoscopy is the strongest
predictive factor for the occurrence of complications and mortality. The
absence of visible oral burns and oedema does NOT reliably exclude the
presence of esophageal or gastric burns.
- In patients in whom endoscopy reveals extensive circumferential burns
(grade IIB or III), a nasogastric tube (NGT) should be placed under direct
visualization during the endoscopic procedure. A NGT should not be
inserted blindly to avoid perforation, or additional injury that can occur
while passing the tube. The NGT can provide a route for nutritional
support during the healing phase and help maintain a lumen during
stricture formation. It can serve as a useful guide for esophageal
dilatation. Consider a useful radiological control 30 days after the
ingestion and an endoscopy 4-6 weeks after the ingestion.
- Consult an otolaryngologist if stridor did not improve for possible
tracheostomy.
- Consult a surgeon and perform abdominal X-ray & amylase if the patient
experienced rebound tenderness, rigidity or severe abdominal pain.
- Analgesia with paracetamol, NSAIDs and morphine are permitted
initially. H2 blockers or proton pump inhibitors IV infusion (0.7-
3.5 mg/kg/day).
- Bronchospasm: Treat with oxygen, inhaled β agonists and consider
systemic corticosteroids. Consider mechanical ventilation if ventilation is
compromised.
- Blood transfusion if Hb is less than 8 gm/dl or rapid hemorrhage
reducing Hb to < 80% of expected value.
- IV fluid followed by total parenteral nutrition (TPN) if stage II or III
corrosion or severe dysphagia or respiratory compromised (inability to
cough). Refer to TPN protocol.
- Antibiotics should be used when indicated.
- Steroids: The use of corticosteroids to prevent stricture formation is
controversial.

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- Oral fluids then liquid diet may be permitted only with caution if
endoscopy was not performed, and the patient does not complain from
dysphagia or respiratory complications. The oral diet should be stopped
if vomiting or bleeding occurred.
- Observe for evidence of bleeding (e.g. hematemesis, melena),
nutritional status and respiratory function.
th th
- Observe for broncho-esophageal fistula that can form on the 7 -10 day
by imaging (cough on drinking).
- Refer to surgery department for treatment and follow-up of any possible
complications from caustic injury.
Admission Criteria:
- Symptomatic patients and those with endoscopically confirmed grade II
or higher burns should be admitted.
- Patients presenting with respiratory distress, grade III burns, or
extensive grade II burns, metabolic acidosis, hemodynamically unstable,
gastrointestinal bleeding, or large ingestions should be admitted to an
intensive care setting.
COMMON PITFALLS:
- Diluting the corrosive by excessive drinking of water or milk as they may
induce vomiting.
- Neutralizing the corrosive.
- Administration of syrup ipecac and performing gastric lavage.
- The use of activated charcoal as it is not effective and potentially
hazardous.
- Insertion of Ryle tube blindly unless endoscopically guided.
- Blind naso or endotracheal intubation.
- The absence of oral burns does NOT reliably exclude the possibility of
significant esophageal burns.
- Patients may have severe tissue necrosis and impending perforation
requiring early surgical intervention without having severe hypotension,
rigid abdomen, or radiographic evidence of intraperitoneal air.
- Patients with any evidence of upper airway involvement require early
airway management before airway edema progresses.
- The extent of eye injury (degree of corneal opacity) may not be apparent
for 48-72 hours after the burn.
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REFERENCES:
1. Gupta, J. M. Croffie, J. F. Fitzgerald, et al. 2001: “Is esophagogastro-duodenoscopy
necessary in all caustic ingestions?” Journal of Pediatric Gastroenterology and Nutrition,
vol. 32, pp. 50–53,.
2. K. Marsha and R. Willie, 2007: “Caustic ingestions and role of endoscopy Editorials,”
Journal of Pediatric Gastroenterology and Nutrition, vol. 32, pp. 8–10,
3. Y. Dogan, T. Erkan, T. Kutlu, et al., 2006: “Caustic gastroesophageal lesions in childhood: an
analysis of 473 cases,” Clinical Pediatrics, vol. 45, no. 5, pp. 435–438,. View at Publisher ·
View at Google Scholar · View at PubMed · View at Scopus
4. R. C. M. Mamede and F. V. de Mello Filho, ., 2002: “Treatment of caustic ingestion: an
analysis of 239 cases,” Diseases of the Esophagus, vol. 15, pp. 210–213,.
5. D. Baskin, N. Urganci, C. Alkim, et al, 2004: “A standardised protocol for the acute
management of corrosive ingestion in children,” Pediatric Surgery International, vol. 20, no.
11-12, pp. 824–828. View at Publisher · View at Google Scholar · View at PubMed · View at
Scopus
6. S. Boukthir, I. Fetni, S. Mazigh Mrad, et al. 2004: “Cortichotherapie à forte dose dans le
traitment des esophagites sévères chez l'enfant,” Archives de Pediatrie, vol. 11, no. 1, pp.
13-17,. View at Publisher · View at Google Scholar · View at Scopus
7. S. Rosseneu, N. Afzal, B. Yerushalmi, et al., 2007: “Topical application of mitomycin-C in
oesophageal strictures,” Journal of Pediatric Gastroenterology and Nutrition, vol. 44, no. 3,
pp. 336-341, 2007.
8. M. L. Kochman, S. A. McClave, H. W. Boyce, et al. 2005: “The refractory and the recurrent
esophageal stricture: a definition,” Gastrointestinal Endoscopy, vol. 62, no. 3, pp. 474-475,
2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
9. Ramasamy K, Gumaste VV, 2003: Corrosive ingestion in adults. J Clin
Gastroenterol;37:119â€“124.
10. Thompson JN: ., 2004: Corrosive esophageal injuries I: A study of nine cases of concurrent
accidental caustic ingestions. Laryngoscope;97: 1060-1066.
11. Lurie Y, Slotky M, Fischer D, Shreter R, Bentur Y. ., 2013: The role of chest and abdominal
computed tomography in assessing the severity of acute corrosive ingestion. Clin Toxicol
(Phila). Nov;51(9):834-7.
12. S. Luzzani, A. Valade, F. Fava, et al., 1992: “Lesions caustiques de l'enfant,” Acta
Endoscopica, vol. 22, pp. 397-404,.
13. T. Lamireau, L. Rebouissoux, D. Denis, et al., ., 2001: “Accidental caustic ingestion in
children is endoscopy always mandatory?” Journal of Pediatric Gastroenterology and
Nutrition, vol. 33, pp. 81–84,.
14. Goldfrank, L. R., & Flomenbaum, N. (2010). Goldfrank's toxicologic emergencies. New York:
McGraw-Hill.

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HYDROCARBONS
INTRODUCTION:
- Hydrocarbons are organic substances that possess carbon and hydrogen
atoms. At room temperature they are usually in liquid form. Kerosene,
gasoline, mineral seal oils, and naphtha are examples of hydrocarbons.
Hydrocarbons are often mixed with agents such as camphor, aniline dyes,
heavy metals, and pesticides. These agents can produce systemic toxicity.
- Types of hydrocarbons: Aliphatic, aromatic, halogenated, metal additives,
pesticide additives and camphor. When history of hydrocarbon exposure is
lacking, characteristic odors can help.
FORMS AND USES:
- Aliphatic hydrocarbons (straight-chain molecules)
- Short-chain forms include methane, ethane, propane, and butane.
- Longer chain molecules are pentane, hexane, heptane, and octane.
- Cyclic hydrocarbons
- Bitumens, creosotes, gasoline, kerosene, mineral seal oil, motor oil,
naphtha, petroleum, shole oils, soots, Stoddard solvent, and other
products are mixtures of various hydrocarbons, which usually do not
include active functional groups such as halogens (chloride, fluoride).
- Organic hydrocarbon solvents are used for extracting, dissolving, or
suspending materials, such as fats, waxes, and resins that are not soluble in
water.
- Solvents are components of paints, adhesives, glues, coatings, and
degreasing/cleaning agents, and are used in the production of dyes,
polymers, plastics, textiles, printing inks, agricultural products, and
pharmaceuticals.
TOXIC DOSE:
- Aspiration of just a few drops can cause aspiration pneumonitis.
- Conversely, ingestion requires large amounts to produce serious toxicity,
unless the hydrocarbon product contains other toxins (halogens,
pesticides).
EPIDEMIOLOGY:
- Hydrocarbon poisoning is common.
- Toxic effects following exposure are typically mild to moderate.
- Death is rare and usually associated with pulmonary aspiration.
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CAUSES:
- Hydrocarbon poisoning is usually accidental.
WORKPLACE STANDARDS:
- Gasoline. ACGIH: TLV TWA is 300 ppm; STEL is 500 ppm.
- Hexane. ACGIH (n-hexane): TLV TWA is 50 ppm. NIOSH (n-hexane): REL
TWA is 50 ppm; IDLH is 1100 ppm. OSHA: PEL TWA is 500 ppm.
- Pneumonitis is common after aspiration of hydrocarbons. The specific
mechanism of pulmonary toxicity is still not clear but is likely to be as a
result of direct toxicity to the lung tissue in addition to destruction of
the surfactant.
- Chlorinated hydrocarbons may increase cardiac sensitization to
catecholamines which in turn produces cardiac dysrhythmias.
- The specific mechanism of CNS depression from hydrocarbon
poisoning is unclear. Halogenated hydrocarbons may also cause
hepatotoxicity, nephrotoxicity, and electrolyte disturbances.
- Vital signs: Fever starts at the time of presentation (38-40°C).
Persistence of fever beyond 48 hrs. Suggests bacterial superinfection.
Pulse oximetry may reveal decreased oxygen saturation.
- Respiratory: Signs of aspiration include coughing, choking, gagging, and
vomiting.
- Signs of respiratory distress tachypnea, dyspnea, cyanosis, wheezing,
diminished resonance on percussion, suppressed or tubular breath
sounds, rales, nasal flaring, and/or grunting respirations.
- Major pulmonary complications include asphyxia, necrotizing
chemical pneumonitis, lipoid pneumonia, and hemorrhagic
pulmonary edema. These complications can rapidly progress to
shock and respiratory arrest. Pneumothorax, subcutaneous
emphysema of the chest wall, and pleural effusion, including
empyema.
- CNS: Somnolence, headache, ataxia, dizziness, blurred vision,
weakness, fatigue, lethargy, stupor, seizures, and coma, depending on
the amount ingested. In addition, hypoxia caused by hydrocarbon
aspiration may cause secondary CNS toxicity, including drowsiness,
tremors, or seizures.

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- Cardiovascular: Cardiac dysrhythmias and myocardial dysfunction.

- Gastrointestinal: Ingestion of aliphatic hydrocarbons causes direct local
irritation, which may be associated with nausea, vomiting, and
hematemesis.
- Hepatic and/or renal tubular necrosis: May be caused by halogenated
hydrocarbons.
- Hematologic: Leukocytosis, which occurs early unrelated to
pneumonitis, hemolysis, hemoglobinuria, and consumptive
coagulopathy.
- Hypoglycemia, CNS infection, pulmonary infection, rheumatologic or
endocrine etiology, poisoning with sedatives e.g. ethanol/
benzodiazepine/barbiturate for example, mental illness.
INVESTIGATIONS:
Routine:
- Bed Side RBS.
- EKG.
Specific:
- Chest X-ray in cases with any respiratory symptoms to be performed
after 12hr from ingestion. (Note: The chest radiograph may be normal
early in the clinical course)
- EKG and continuous cardiac monitoring in patients with moderate to
severe toxicity or chlorinated hydrocarbon exposure.
- Monitor ABG, pulse oximetry, and pulmonary function tests.
- Suspect methemoglobinemia in cyanotic patients who do not show
adequate response to supplemental oxygen, and who may have been
exposed to nitrobenzene or aniline containing hydrocarbons.
- Head CT should be obtained in patients with altered mental status.
- ABG findings: Initial blood gases commonly show mild respiratory
alkalosis with hypoxemia.
- If hypoxemia is not corrected, the patient will later develop metabolic
acidosis.
- Chest radiographic findings: Initial radiographic findings consist of
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multiple, small, patchy densities with ill-defined margins. The lesions

become larger and coalesce as the injury progresses. The lesions
rapidly progress to extensive infiltrates. Emphysema or pneumothorax
may develop.
Admission criteria:
- Symptomatic patients and patients with suicidal intent or massive
ingestion.
- Indications for admission during observation include:
- Patients with normal or mildly abnormal initial chest radiograph
who develop symptoms.
- Patients who develop symptoms related to toxic additives (e.g.,
heavy metals or OPI).
- Patients with mild symptoms and normal chest radiograph who
fail to improve.
- Admit to I.C.U: Patients with CNS manifestations as coma,
dysrhythmias, or respiratory distress.
- Indications for discharge after 6 hrs of observation include:
- Asymptomatic patient with normal chest radiograph.
- Asymptomatic patient with mildly abnormal chest radiography
who does not develop symptoms during the observation period
and who can follow-up in the next day
TREATMENT:
Asymptomatic Patients:
- Perform serial examination with monitoring. These patients should
refrain from oral feeding (NPO) during the initial observation period.
- Discharge if the patient remains asymptomatic for 6 hrs.
- If the patient becomes symptomatic, initial radiographic evaluation
should be performed after 12 hrs.
Symptomatic Patients:
Stabilization:
- ABCs: Airway is always the first priority of treatment in patients with
hydrocarbon poisoning. Administer supplemental oxygen to all
patients, and perform beside pulse oximetry.
Decontamination:
- Cutaneous decontamination in cases of cutaneous exposure:
Decontaminate the skin as soon as possible by removing the involved

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clothing and thoroughly washing the skin with soap and water.
- Don’t use syrup of ipecac, gastric lavage or activated charcoal.
- Supplemental O2 to maintain O2 saturation > 94%.
- Administer β-agonist bronchodilators (e.g, Albuterol) for bronchospasm.
- Administer benzodiazepine (e.g, Lorazepam 0.1 mg/kg) for seizures in
addition to support of airway and breathing.
- Dysrhythmias: Initiate ACLS protocol. Epinephrine and other
sympathomimetics should be used with caution as ventricular
dysrhythmias may be precipitated.
- In severe respiratory distress, consider the use of surfactant (Infasurf®)
3mL/kg intratracheally.
- In patients with respiratory failure: Partial liquid ventilation, high
frequency jet ventilation, extracorporeal membrane oxygenation
(ECMO) and high frequency chest wall oscillation have all been used
with apparent success in cases of severe hydrocarbon pneumonitis.
- Prophylactic use of antibiotics, or corticosteroids should be avoided
with hydrocarbon pneumonitis. Antibiotics used only with signs of
secondary bacterial infection. These signs include:
- Recurrence of fever after the first 48 hrs.
- Increasing infiltrate in chest radiography.
- Leukocytosis after the first 48 hrs.
- Sputum or tracheal aspirate is positive for bacteria.
FOLLOWUP:
Patient Monitoring
- Cardiac and respiratory function should be monitored continuously.
- Expected Course and Prognosis
- Respiratory system toxicity may develop within hours of acute
pulmonary aspiration.
- Recovery from ingestion is usually rapid unless aspiration occurs.
- The prognosis of inhalation or aspiration depends on the degree of
pulmonary injury.
- Systemic poisoning is possible from pulmonary absorption.
- Permanent CNS, pulmonary, or hepatic damage is possible in severe
cases, especially if complicated by hypoxia.
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Discharge criteria and Instruction

- Patients with normal vital signs who are asymptomatic may be
discharged from the emergency department or the hospital following
decontamination and 6-hour observation.
COMMON PITFALLS:
- Failure to aggressively manage the airway can result in death.
- Patients with minimal respiratory symptoms may progress to severe
toxicity over several hours.
- Patients with altered mental status should be ruled out for intracranial
hemorrhage, infection, metabolic disturbance and other toxicological
causes.
REFERENCES:
1. Lewander WJ, Aleguas A. ., 2007: Petroleum distillates and plant hydrocarbons. In: Haddad
and Winchester's Clinical Management of Poisoning and Drug Overdose, 4th, Shannon MW,
Borron SW, Burns MJ. (Eds), Saunders Elsevier, Philadelphia. p.1343.
2. Bronstein AC, Spyker DA, Cantilena LR Jr, et al., 2009: Annual Report of the American
Association of Poison Control Centers' National Poison Data System (NPDS): 27th Annual
Report. Clin Toxicol (Phila); 48:979.
3. Ellenhorn MJ. ., 1997: The hydrocarbon products. In: Ellenhorn's Medical Toxicology:
Diagnosis and Treatment of Human Poisoning, 2nd, Ellenhorn MJ, Schonwald S, Ordog G,
Wasserberger. (Eds), Williams & Wilkins, Baltimore. p.1420.
4. Prasad R, Karmakar S, Sodhi R, Karmakar S. ., 2011: Bilateral hemorrhagic pleural effusion
due to kerosene aspiration. Lung India; 28:130.
5. Wolfsdorf J, Paed D. ., 1976: Kerosene intoxication: an experimental approach to the
etiology of the CNS manifestations in primates. J Pediatr; 88:1037.
6. Food and Drug Administration. Poison control case report summary-calendar year.
Rockville, MD 1984.
7. Tormoehlen LM, Tekulve KJ, Nañagas KA. ., 2013: Hydrocarbon toxicity: A review. Clin
Toxicol (Phila); 52:479.
8. Steele RW, Conklin RH, Mark HM. ., 2014: Corticosteroids and antibiotics for the treatment
of fulminant hydrocarbon aspiration. JAMA; 219:1434.
9. Klein BL, Simon JE. ., 1986: Hydrocarbon poisonings. Pediatr Clin North Am; 33:411.
10. Jolliff HA, Fletcher E, Roberts KJ, et al., 2009: Pediatric hydrocarbon-related injuries in the
United States: 2000-. Pediatrics; 131:1139.
McGraw-Hill.

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METHANOL
INTRODUCTION:
- Methanol poisoning causes fatal intoxications, and even relatively small
ingestions of this alcohol can produce significant toxicity. Rapid
identification of toxicity and early management, are crucial.
- Methanol is frequently found in high concentration in antifreeze and de-
icing solutions, windshield wiper fluid, solvents, cleaners, fuels, and other
industrial products. Most serious poisonings occur following ingestion.
Toxicity is most common after oral intake but has also been reported
after inhalation and dermal exposures.
Toxic dose:
- Oral intake of approximately 1 gm/kg of methanol is considered lethally
toxic. Severe toxicities from methanol have been reported following
ingestions of as little as one teaspoon.
- Methanol is metabolized to formaldehyde and formic acid via alcohol
dehydrogenase and aldehyde dehydrogenase, respectively.
- Formic acid produces a significant anion gap metabolic acidosis and
causes blindness through direct injury to the optic nerve and retina.
Additionally, formic acid causes ischemic or hemorrhagic injury to the
basal ganglia. Metabolic acidosis increases the ability of the toxic
metabolites to penetrate the cells.
Mild to moderate toxicity:
- Ataxia, sedation, and disinhibition.
- Patients may present with abdominal pain, nausea, vomiting, and
headache.
Severe toxicity:
- Severe metabolic acidosis develops 6-12 hrs after intake (if ethanol is
not co-ingested) and may lead to multiorgan dysfunction including
hypotension, tachycardia, dysrhythmias, seizures, coma, pancreatitis,
and acute renal failure.
- Ocular toxicity may develop; manifestations include mydriasis,
hyperemic optic discs, and papilledema. Visual impairment may
develop, which may range from blurry/hazy vision to color vision
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defects to "snowfield" vision to total blindness. Rhabdomyolysis may

occur in severe poisonings.
- Hypomagnesemia, hypokalemia, and hypophosphatemia have also
been reported.
- Permanent sequelae after severe intoxication may include basal
ganglia necrosis with parkinsonian features (i.e., tremor, rigidity,
bradykinesia) and blindness.
Admission Criteria:
- Patients who are acidotic, have visual symptoms, or have serum
methanol concentrations above 25 mg/dL should be admitted.
- Exposure to other alcohols, such as ethanol, ethylene glycol, isopropyl
alcohol, and other glycol ethers.
- Other causes of metabolic acidosis.
INVESTIGATIONS:
Routine:
- Bed Side RBS.
- EKG.
- Calculate the anion gap and osmolar gaps. An elevated osmolal gap (>
10) suggests the presence of toxic alcohols, but a normal osmolal gap
does NOT rule methanol toxicity.
Specific:
- Measurement of serum methanol, ethylene glycol, and ethanol levels.
- Check urine ketones and urine sediment for calcium oxalate.
- Urine ketone (acetone) without acidosis may point to isopropanol
contamination.
- Test for alcohol in gastric aspiration.
- Request fundus examination for any ocular or visual complaint.
- Request brain CT or MRI for probable delayed necrosis of basal
ganglia (putamen and less commonly caudate nucleus) especially for
patients with EKG ischemic signs. An early cerebral oedema may be
noted.

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- Urine ketone (acetone) without acidosis may point to isopropanol

contamination.
- Rising creatinine, hypocalcemia, increased QTc, increased WBC, and
calcium oxalate crystals in urine favor the possibility of ethylene glycol
contamination.
TREATMENT:
- A Rapid decision is critical in the management of the patient poisoned
with methanol. The clinician must often make treatment decisions
without definitive serum drug levels, based only upon history, clinical
suspicion and available laboratory data.
- A diagnosis of methanol poisoning is made if visual complaint is
associated with severe metabolic acidosis (even if partially
compensated) following alcohol ingestion, even if serum methanol
level is not available.
Stabilization:
- ABC: Secure the patient's airway, breathing, and circulation, and
provide appropriate supportive care.
- Endotracheal intubation may be necessary for patients with
significant CNS or respiratory depression. Extreme care must be taken
to increase minute ventilation sufficiently to prevent severe acidemia
in intubated patients.
Decontamination:
- There is no role for activated charcoal (AC), gastric lavage, and syrup
of ipecac in the management of toxic alcohol exposures.
Antidotes:
- Inhibition of the alcohol dehydrogenase enzyme: with either
fomepizole (preferred) or Ethanol (if fomepizole is unavailable)
Indications:
- Plasma methanol concentration greater than 20 mg/dL.
- A documented recent history of ingesting toxic amounts of methanol
and osmolal gap greater than 10 mOsm/L.
- History or strong clinical suspicion of methanol poisoning with at least
2 of the following criteria:
- Arterial pH < 7.3.
- Serum bicarbonate < 20 mEq/L.
- Osmolal gap > 10 mOsm/L.
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Dose:
- Fomepizole: Loading dose: 15 mg/kg over 30 min, followed by 10 mg/kg
q 12 hrs for 4 doses, then if necessary, 15 mg/kg q 12hrs until blood pH
is normal, and serum alcohol concentration < 20 mg/dL.
- Ethyl alcohol if fomepizole is absent
- Ethyl alcohol: Intravenous form loading dose (0.8 gm/kg, 8 mL/kg of
10% ethyl alcohol infused over 1 hour as tolerated). Maintenance
Dose is 110 mg/kg/hr = 11 mL/kg/hr.
- In chronic alcoholism 150 mg/kg/hr = 15 mL/kg/hr.
- During hemodialysis 250 mg/kg/hr = 30 mL/kg/hr.
Ethanol oral form:
- Loading dose 0.8 gm/kg = 4mL/kg of 20% ethanol ingested over 1 hr
added to juice.
- Maintenance dose is 110 mg/kg/hr = 6 mL/kg/hr.
- In chronic alcoholism 150 mg/kg/hr = 8 mL/kg/hr
- During Hemodialysis: 250 mg/kg/hr.
- Administer sodium bicarbonate to correct the systemic acidosis,
which limits the penetration of toxic acids (e.g., formic acid) into end-
organ tissues such as the retina. Dose: Initial dose 1-2 mEq/kg of
sodium bicarbonate via IV bolus for any patient with a pH < 7.3. The
bolus dose is then followed by a maintenance infusion prepared by
mixing 133 mEq of sodium bicarbonate in 1 liter of D5W. This mix is
then infused at a rate of 150-250 mL/hr in adults, or one to two times
the maintenance fluid rate in children. The appropriate rate depends
upon the initial pH, and such parameters as fluid status and serum
sodium concentration. The goal of treatment is maintenance of pH >
7.35.
- Closely observe for respiratory rate, level of consciousness,
hypokalemia and volume overload during NaHCO3 treatment.
- Treating with cofactors: (Folic acid, thiamine, and pyridoxine) to
optimize non-toxic metabolic pathways for the elimination of the
alcohol or its metabolites.
- Administer intravenous folic acid or folinic acid 50 mg every 6 hrs for
the first 24 hrs, and should be continued until the methanol and
formate are eliminated.

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- Thiamine (100 mg IV/day) or pyridoxine (50 mg IV).

- Hemodialysis: is indicated in the setting of known methanol ingestion
if any of the following conditions is present:
- High anion gap metabolic acidosis (>10), regardless of drug
level.
- Evidence of end-organ damage (e.g., visual changes and renal
failure).
- In any patient with a suspected toxic alcohol ingestion and has
severe unexplained anion gap metabolic acidosis and significant
plasma osmolal gap.
- Methyl alcohol concentrations greater than 50 mEq/L, even in
the absence of acidosis or severe symptoms.
- Hemodialysis should be continued until the methanol
concentration is undetectable, and the serum pH returns
to normal.
- Check potassium and methanol levels after each hemodialysis
session and correct hypokalemia.
- Avoid hypoglycemia, hyponatremia, hypokalemia by regular
dextrose and electrolyte infusion.
- Add H2 blocker or proton pump inhibitors.
COMMON PITFALLS:
- Depending on the timing of the presentation, an increased osmolar gap
or an increased anion gap may not always be present. An increased anion
gap will not be present in patients presenting early, and an increased
osmol gap may not be present in patients presenting late.
- When calculating osmolarity, the ethanol level needs to be taken into
account in the calculation.
- A normal osmolal gap does not rule out the possibility of methanol
intoxication.
- Patients who are ethanol intoxicated will have a later presentation of
their acidosis.
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REFERENCES:
1. Barceloux DG, 2002: Bond GR, Krenzelok EP, et al. American Academy of Clinical Toxicology
practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol; 40:415.
2. Sivilotti ML, 2009: Ethanol: tastes great! Fomepizole: less filling! Ann Emerg Med; 53:451.
3. Levine M, Curry SC, Ruha AM, et al. , 2012: Ethylene glycol elimination kinetics and
outcomes in patients managed without hemodialysis. Ann Emerg Med; 59:527.
4. Ghosh A, Boyd R., 2003: Leucovorin (calcium folinate) in "antifreeze" poisoning. Emerg Med
J; 20:466.
5. Hantson P, Vanormelingen P, Lecomte C, et al, 2000:. Fatal methanol poisoning and organ
donation: experience with seven cases in a single center. Transplant Proc; 32:491.
6. Jaff Z, McIntyre WF, Yazdan-Ashoori P, Baranchuk A., 2014: Impact of methanol
intoxication on the human electrocardiogram. Cardiol J.;21(2):170-5. [Medline].
7. Finkelstein Y, Vardi J. , 2002: Progressive parkinsonism in a young experimental physicist
following long-term exposure to methanol. Neurotoxicology. Oct;23(4-5):521-5.
8. Gupta N, Sonambekar AA, Daksh SK, Tomar L., 2013: A rare presentation of methanol
toxicity. Ann Indian Acad Neurol. Apr;16(2):249-51.
9. Sodhi PK, Goyal JL, Mehta DK. , 2001: Methyl alcohol induced optic neuropathy treated witH
intravenous . high dose steroids. Int J Clinic Pract;9:599-602
10. Fraser AD. , 2002: Clinical toxicologic implications of ethylene glycol and glycolic acid
poisoning. Ther Drug Monit; 24:232.
11. Shirey T, Sivilotti M. , 1999: Reaction of lactate electrodes to glycolate. Crit Care Med;
27:2305.
12. Ghosh A, 2003: Boyd R. Leucovorin (calcium folinate) in "antifreeze" poisoning.
Emerg Med J; 20:466.
13. Goldfrank, L. R., & Flomenbaum, N. (2010). Goldfrank's toxicologic emergencies.
New York: McGraw-Hill.

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PARAPHENYLENEDIAMINE
(HAIR DYE)
INTRODUCTION:
- Paraphenylene diamine (PPD) is a dark-coloured hair dye. Sometimes, it
added to henna (Lawasonia alba), as a dye to decorate the palms of the
hands and soles of the feet.
- Toxicity occurs through skin absorption. Yet, systemic toxicity occurs
when it is accidentally or intentionally ingested.
- The lethal dose for humans is estimated to be 10 grams of pure PPD while
2- 3 grams can cause severe toxic effects.
- Paraphenylene diamine is a derivative of paranitroanaline. Upon
oxidation of Paraphenylene diamine, several intermediate compounds
are produced. However, the most toxic compound produced is the
Bondrowski’s base which is a highly allergenic and toxic compound. If
applied topically or ingested, it produces local as well as systemic toxic
effects. It is highly toxic when ingested orally and the outcome depends
mainly on the dose consumed.
- The main clinical manifestations include angioedema leading to dysphasia
and respiratory distress, rhabdomyolysis, intravascular hemolysis, acute
renal failure and hepatic necrosis. PPD poisoning may also result in
myocarditis or fatal arrhythmia.
- The onset of symptoms usually occurs within 1-2 hrs. of ingestion or
contact with the dye.
- Patients with acute poisoning have a characteristic presentation of
painless swelling of the face and neck often requiring urgent
tracheostomy, with bulging eyes, a swollen dry hard protruding tongue
and chocolate brown color of the urine.
- PPD is a poison the affects multiple organs and could result in severe
muscular pain due to rhabdomyolysis. It can also cause acute renal failure
(ARF), flaccid muscle paralysis, severe gastro-intestinal symptoms,
cardiotoxicity and arrhythmias.
- Severe toxicity could be fatal if not treated promptly.
- Cardiac arrest is the main cause of death and it is attributed to
arrhythmia.
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INVESTIGATIONS:
- Routine:
- Bed Side RBS.
- EKG.
- Specific:
- Urine is tested for myoglobin and PPD using chromatographic
techniques for confirmation of intoxication and medico-legal
purposes.
TREATMENT:
- Stabilization:
- Assess airway, breathing, and circulation; stabilize as necessary.
- Decontamination:
- Oral exposure: Prehospital gastrointestinal decontamination is
generally not recommended because of the potential for CNS
depression or persistent seizures and subsequent aspiration.
- Inhalational exposure:
- Monitor for signs of respiratory distress. If the patient exhibits severe
persistent cough or breathing difficulties, administer oxygen and
assist ventilation as required.
- Treat bronchospasm with a β2-adrenergic agonist inhaler.
- Administer systemic corticosteroids in patients with significant
bronchospasm.
- Dermal exposure:
- Remove contaminated clothing and wash exposed area thoroughly
with soap and water.
- Eye exposure:
- Remove contact lenses (if present) and irrigate exposed eyes for 15
minutes with large amounts of normal saline or water. A thorough
ophthalmologic examination is warranted if irritation, lacrimation,
pain, swelling, or photophobia persists after 15 minutes of eye
irrigation.

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- Administer hydrocortisone 4-8 mg/kg/dose initially then 2-4
mg/kg/dose 6 hourly for 48-72 hrs. for the severe hypersensitivity
reaction, the angioedema and as an anti-inflammatory.
- Give Chlorpheniramine maleate 0.25-5 mg/kg/dose in children less
than 5 years and 5-10 mg/kg/dose in children more than 5 years. Dose
can be repeated 4 hourly for up to 24 hrs. if needed.
- Refer the patient to the Otolaryngology department if facial edema is
increasing.
- Acute renal failure was found to be the second life-threatening effect.
Contact nephrology unit for hemodialysis, peritoneal dialysis and/or
haemoperfusion.
- Indications of intubation:
- Moderate or severe respiratory distress.
- ABG abnormalities; PaO2 < 60 on 6 liters O2 or PaCO2 > 50mmHg.
- Deterioration in mental status.
- Absence of breath sounds.
- Cyanosis on 40% FiO2.
- Exhausted patient with decreased respiratory effort.
Asymptomatic cases with normal vital signs need close observation and
monitoring for at least 72 hrs.
REFERENCES:
1. Mendonca S, Barki S, Mishra M, Kumar RS, Gupta D, Gupta P., 2015 : Acute kidney injury:
A rare cause. Saudi J Kidney Dis Transpl. Sep;26(5):980-2.
2. Shigidi M, Mohammed O, Ibrahim M, Taha E. , 2014 : Clinical presentation, treatment
and
3. Outcome of paraphenylene-diamine induced acute kidney injury following hair dye
Poisoning: a cohort study. Pan Afr Med J. Oct 16;19:163.
4. Chaudhary SC, Sawlani KK, Singh K. , 2013 : Paraphenylenediamine poisoning. Niger J Clin
Pract. Apr-Jun;16(2):258-9
5. Elevli M, Civilibal M, Ersoy O, Demirkol D, Gedik AH. , 2014 : Paraphenylene diamine hair
dye poisoning: an uncommon cause of rhabdomyolysis. Indian J Pediatr. Jul;81(7):709-11.
6. Ryoo SM, Sohn CH, Oh BJ, Kim WY, Lim KS. ,2014: A case of severe methemoglobinemia
caused by hair dye poisoning. Hum Exp Toxicol. Jan;33(1):103-5.
7. Prabhakaran AC., 2012: Paraphenylene diamine poisoning. J Nat Sci Biol Med.
Jul;3(2):199-200.
8. Abdelraheem M, Ali el-T, Hussien R, Zijlstra E.,2014: Paraphenylene diamine hair dye
poisoning in an adolescent.Toxicol Ind Health. 2011 Nov;27(10):911-3.
9. Ashraf, W.; Dawling, S.; Farrow, L. J, 1994: "Systemic Paraphenylenediamine (PPD)
Poisoning: A Case Report and Review". Human & Experimental Toxicology 13 (3): 167
10. Chaudhary SC, Sawlani KK, Singh K.,2013: Paraphenylenediamine poisoning. Niger J Clin
Pract. Apr-Jun;16(2):258-9.
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PESTICIDES POISONING
ALUMINUM AND ZINC PHOSPHIDE

INTRODUCTION:
- For many years, aluminum and zinc phosphide have been highly
effective insecticides and rodenticides with the major merits of being
inexpensive and not leaving toxic residue. They are formulated as
compressed discs, tablets or pellets that commonly weigh 3 gms and
contain variable amounts of a single phosphide combined with other
substances such as ammonium carbonate.
- It should be noted that phosphine could be released as a gas from
emesis, faeces, or lavage material. Thus, these materials should be
disposed of in closed containers. However, serious toxicity in health care
providers caring for patients poisoned with metallic phosphides has not
been described. The management of phosphide ingestion is based upon
limited evidence derived from case reports.
- Several mechanisms of toxicity have been proposed, including inhibition
of oxidative phosphorylation, free radical production with the
promotion of lipid peroxidation, and cholinesterase inhibition but none
fully explain the clinical features of poisoning. Mortality often occurs
rapidly within the first day of severe metallic phosphide poisoning
regardless of therapy. Death typically results from cardiac arrhythmias
or refractory shock and cardiac failure.
CLINICAL FEATURES:
GI manifestations:
- Smell of garlic in breath (common).
- Nausea and vomiting.
- Retrosternal and epigastric pain.
- GI bleeding.
- Diarrhea (less common).
Metabolic and Electrolyte disturbances (Cause early mortality):
- Metabolic acidosis, or mixed metabolic acidosis and respiratory
alkalosis are frequent.
- Hypoglycemia has been reported and may be persistent and
severe, but rare.

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CVS manifestations (Cause early mortality)

- Shock and peripheral circulatory failure are particularly
important early signs of toxicity.
- Tachycardia, bradycardia or cardiac arrhythmias (all types of
arrhythmias have been recorded.
Respiratory Manifestations:
- Tachypnea, dyspnea.
- Hemorrhagic pulmonary oedema (could be cardiac or
respiratory in origin) could take up to 48 hours to develop,
crepitations and rhonchi.
Hepatic Manifestations: (Tends to occur late in the course of illness)
- Elevation of ALT and AST.
- Elevation in levels of bilirubin has been recorded in a few
cases.
Renal Manifestations:
- Acute renal failure.
CNS manifestations:
- Anxiety and agitation are common while mentally clear.
INVESTIGATIONS:
Routine:
- Bed Side RBS to exclude hypoglycemia
- ABGs and Electrolytes (Na, K, Ca, Mg.)
- Serum Paracetamol and Salicylates.
- EKG.
- Pregnancy test for females in childbearing period.
TREATMENT:
Early consultation with a poison control center or medical toxicologist is
advised for all patients.
Stabilization:
- Health care providers should take all necessary precautions to
protect themselves from exposure to phosphine gas while
providing care for patients with suspected aluminum or zinc
phosphide ingestion.
- Hypoglycemia, hypokalemia, hypocalcemia and hypomagnese-
mia are common and should be monitored and corrected
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promptly. In some cases, correction of hypokalemia can

reverse cardiac manifestations.
- Provide supplemental oxygen and ventilation as needed and
dictated by the degree of respiratory compromise. Tracheal
intubation may be performed in a standard fashion.
- Provide fluid resuscitation with rapid infusions of isotonic
normal saline to replace obvious fluid losses and to treat
hypovolemic shock.
- Treat hypoglycemia and correct hypokalemia, hypocalcemia
and hypomagnesemia as indicated.
- Treat cardiogenic shock with vasoactive medications as needed
in patients unresponsive to isotonic fluid resuscitation.
- Manage atrial and ventricular arrhythmias according to ACLS
and PCLS guidelines and consult the cardiologist.
Decontamination: (Limited role)
- Gastric Lavage is not advised, as there are reports that it aids
the disintegration of zinc or zluminum phosphide and may
increase the production of phosphine.
- Evidence of the efficacy of activated charcoal in limiting the
toxicity of zinc phosphide is limited.
- Additional Therapies: Additional therapies have been
described, but we strongly encourage consultation with a
regional poison control center or a medical toxicologist,
whenever possible, before giving these treatments.
Adjunct therapies include the following:
- Magnesium infusion – Case series have documented
hypomagnesaemia in some patients poisoned with metallic
phosphides. Hypomagnesaemia should be corrected in all
patients with metallic phosphide poisoning. Nevertheless,
studies of treatment with intravenous magnesium have yielded
mixed results.
- Some trials suggest intravenous magnesium administration can
decrease mortality if hypomagnesaemia is identified and the
regimen chosen raises the magnesium levels. In these trials,
the regimen with the best effect was as follows: 1 gm
magnesium sulfate, IV followed 1hr later by 1 gm given as a

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continuous infusion over 3 hrs and then 1 gm q 6 hours until

recovery or a maximum duration of 5 days.
Insulin and dextrose infusion
- Insulin infusion combined with maintenance of normal blood
glucose using a continuous dextrose infusion was associated
with survival in four of five patients with large ingestions of
aluminum phosphide. Thus, this therapy may be beneficial in
patients who are not responding to supportive care and who
are unlikely to benefit from magnesium infusion.
REFERENCE:
1. Gupta S, Ahlawat SK, 1995: Aluminum phosphide poisoning--a review. J Toxicol Clin Toxicol
1995; 33:19.
2. Banjaj R, Wasir HS. , 1988: Epidemic aluminium phosphide poisoning in northern India.
Lancet; 1:820.
3. Proudfoot AT. , 2009: Aluminium and zinc phosphide poisoning. Clin Toxicol (Phila); 47:89.
4. Rodenberg HD, Chang CC, Watson WA. 1989: Zinc phosphide ingestion: a case report and
review. Vet Hum Toxicol; 31:559.
5. Stephenson JB. , 1995: Zinc phosphide poisoning. Arch Environ Health 1967; 15:83.
6. Singh S, Bhalla A, Verma SK, et al. , 2006: Cytochrome-c oxidase inhibition in 26 aluminum
phosphide poisoned patients. Clin Toxicol (Phila); 44:155.
7. Chugh SN, Ram S, Arora B, et al. , 1991: Incidence & outcome of aluminium phosphide
poisoning in a hospital study. Indian J Med Res; 94:232.
8. Siwach SB, Singh H, Katyal VK, et al. , 1998: Cardiac arrhythmias in aluminium phosphide
poisoning studied by on continuous holter and cardioscopic monitoring. J Assoc Physicians
India; 46:598.
9. Chugh SN, Chugh K, Ram S, Malhotra KC. , 1991: Electrocardiographic abnormalities in
aluminium phosphide poisoning with special reference to its incidence, pathogenesis,
mortality and histopathology. J Indian Med Assoc; 89:32.
10. Hassanian-Moghaddam H, Shahnazi M, Zamani N, Bahrami-Motlagh H. , 2014: Abdominal
imaging in zinc phosphide poisoning. Emerg Radiol; 21:329.
11. Siwach SB, Singh P, Ahlawat S, et al. , 1994: Serum & tissue magnesium content in patients
of aluminium phosphide poisoning and critical evaluation of high dose magnesium sulphate
therapy in reducing mortality. J Assoc Physicians India; 42:107.
12. Chugh SN, Kumar P, Aggarwal HK, et al. , 1994: Efficacy of magnesium sulphate in
aluminium phosphide poisoning--comparison of two different dose schedules. J Assoc
Physicians India; 42:373.
13. Chugh SN, Kamar P, Sharma A, et al. , 1994: Magnesium status and parenteral magnesium
sulphate therapy in acute aluminum phosphide intoxication. Magnes Res; 7:289.
14. Shadnia S, Rahimi M, Pajoumand A, et al. , 2005: Successful treatment of acute aluminium
phosphide poisoning: possible benefit of coconut oil. Hum Exp Toxicol; 24:215.
15. Bogle RG, Theron P, Brooks P, et al. 2006: Aluminium phosphide poisoning. Emerg Med J;
23:e3.
16. Dueñas A, Pérez-Castrillon JL, Cobos MA, Herreros V. , 1999: Treatment of the
cardiovascular manifestations of phosphine poisoning with trimetazidine, a new
antiischemic drug. Am J Emerg Med; 17:219.
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ORGANOPHOSPHATES AND CARBAMATES

INTRODUCTION:
- Organophosphates (OPI) (parathion, fenthion, malathion) and
carbamates (methomyl and aldicarb) are potent cholinesterase inhibitors
that have the ability to cause severe cholinergic toxicity following
cutaneous exposure, inhalation, or ingestion.
- Organophosphates and carbamates exhibit similar clinical manifestations
and toxicity and require similar management following overdose.
- Organophosphates have been used as insecticides, while carbamates are
used in pest control in industrial agriculture to control ectoparasites on
farms and companion animals and for home and garden pest control.
- Several organophosphate nerve agents (e. g, tabun [GA], sarin [GB],
soman [GD]) are used as chemical weapons.
- Organophosphates and Carbamates competitively inhibit pseudo-
cholinesterase and acetylcholinesterase, preventing hydrolysis and
inactivation of acetylcholine. Acetylcholine accumulates at nerve
junctions causing malfunction of the sympathetic, parasympathetic, and
peripheral nervous systems and some of the CNS. Clinical signs of
cholinergic excess can develop.
- There are 4 main pharmacokinetic characteristics that distinguish
carbamates from organo phosphate compounds.
- Carbamates insecticides do not easily cross into the central nervous
system (CNS). Thus CNS effects of carbamates are limited, although
CNS dysfunction may still occur in massive poisonings or may occur as a
result of hypoxia secondary to pulmonary toxicity and paralysis.
- The Carbamate-cholinesterase bond does not “age” as in
organophosphates compound poisoning; thus it is reversible, with
spontaneous hydrolysis occurring typically within several hours.
- Carbamates have rapid onset and short duration of action.
- Generally carbamates are less toxic than organophosphates. Aldicarb is
considered the most toxic carbamates.
Muscarinic:
DUMBBELS (Diarrhea, Urinary incontinence, Miosis, Bradycardia,
Bronchorrhea and bronchospasm, Emesis, Lacrimation, and Salivation).

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Nicotinic:
Tachycardia, hypertension, muscle cramps, muscle fasciculations,
weakness, and respiratory failure.
CNS:
Anxiety, lethargy, confusion, psychosis, convulsions and coma.
Cardiac:
Myocardial ischemia and arrhythmias, including heart block, QTc
prolongation and ventricular dysrhythmias, are occasionally observed
in OPI agent poisoning.
Others:
Metabolic acidosis, pancreatitis, and hyperglycemia can also develop.
Delayed Toxic Syndromes:
Intermediate (neurologic) syndrome:
Some patients poisoned with OPI develop neurological disorder 24-96
hrs after exposure. This neurological disorder consists of characteristic
neurological symptoms that include neck flexion weakness, attenuated
deep tendon reflexes, cranial nerve deficits, proximal muscle
weakness, and respiratory insufficiency. Recovery begins 5-15 days
after onset.
Delayed and long-term neuropathology:
Organophosphates agent-induced delayed neuropathy (OPIDN)
typically occurs 1-3 weeks after ingestion of one of a small number of
specific OPI agents, including chlorpyrifos.
Affected patients present with transient, painful "stocking-glove"
paresthesias followed by an ascending symmetrical motor
polyneuropathy that has a characteristic flaccid weakness of the lower
extremities, which extends to involve the upper extremities. Survivors
of acute organophosphates poisoning may have neurobehavioral
deficits.
Admission Criteria:
- All intentional ingestions should be initially managed as a severe
exposure.
- Determine cholinesterase activity to assess if a significant exposure
occurred.
- Patients who exhibit severe cholinergic manifestations (e.g., muscarinic,
nicotinic or central) should be admitted to an intensive care setting.
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These patients should be continuously monitored, frequently titrated

dosage of antidotes administered, ventilation and inotropes are given as
needed. Consult a medical toxicologist and/or poison center.
- Patients should be monitored closely for 48 hrs after discontinuation of
atropine and oximes for evidence of recurrent toxicity or intermediate
syndromedecreased memory, abstraction, and Parkinsonism which may
be permanent.
- Gastroenteritis and food poisoning.
- Asthma, myasthenic crisis, and cholinergic excess from medications.
INVESTIGATIONS:
Routine:
- Monitor serum glucose, serum electrolytes, ABG.
- BUN, creatinine, Hct, and serum lipase in patients with significant
poisoning.
- EKG (document QT, rate and rhythm).
- Chest X-ray if respiratory complication (failure, PE, aspiration).
Specific:
- Determine plasma (pseudo) and/or red blood cell (True) cholinesterase
activities (plasma is more sensitive, but red cell correlates somewhat
better with clinical signs and symptoms). Depression in excess of 50% of
baseline is generally associated with cholinergic effects.
TREATMENT:
Stabilization:
- ABCs and O2 (oxygen should be provided at first).
- Promptly assess airway and respiratory function. Administer oxygen and
perform sufficient suction of secretions. Endotracheal intubation may be
necessary due to respiratory muscle weakness or bronchorrhea. Avoid
the administration of succinylcholine for rapid sequence intubation as
prolonged paralysis may result.
Decontamination:
- GIT: Do not perform gastric lavage as it could constitute substantial risk
of aspiration in patients with increased secretions and decreased mental
status, and this intervention has never been shown to decrease morbidity
or mortality.

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- Forced emesis is contraindicated because of the risk of aspiration and

seizures.
- Activated charcoal (AC) may be given to patients presenting within one
hour. The standard dose is 1 gm/kg (maximum dose 50 gm).
- Skin and scalp: careful brushing by soap and water. Hair cutting are
essential for successful decontamination (if exposed).
Antidotes:
- Atropine: is used to treat muscarinic effects (e.g. salivation, lacrimation,
defecation, urination, bronchorrhea). Dose: Adults: 1-3 mg IV; children:
0.02 mg/kg IV. Three to five minutes after giving atropine, check the
pulse, blood pressure, pupil size, sweating and chest sounds. If no
response, double the dose and continue doubling the dose q 3-5 minutes
when the response is still absent. Once the parameters have begun to
improve, cease dose doubling. Similar or smaller dose can be used as
required to dry pulmonary secretions. Once secretions are dried,
maintain with an infusion of 10% - 20% of the loading dose every hour.
- Oximes: Oxime therapy should be given to all patients with evidence of
cholinergic toxicity, patients with neuromuscular dysfunction, or patients
with exposures to organophosphates agents known to cause delayed
neurotoxicity.
- Pralidoxime Dose: Adult loading dose 1-2 gm IV (or 30 mg/kg) over 20 min
followed by an infusion of 500-1000 mg/hr (or 8 mg/kg/hr). Children
loading dose 25-50 mg/kg (2 gm maximum) followed by infusion of 10-20
mg/kg/hr.
- Obidoxme (toxogonin): For adults give 1 Amp (250mg) over 15-30 min IV
as a loading dose then 30 mg/hr.
- Oximes should be continued 24 hrs after the patient is free of cholinergic
manifestations.
- N.B. Evidence about the use of oximes to treat OP poisoning is difficult to

interpret. Pralidoxime is not generally recommended in cases of known
exposure to carbaryl (Sevin) due to exacerbation of toxicity in animal
models, although its use/nonuse in such situations is still a matter of
controversy. Until this variability is better confirmed and other
treatments become available, we believe that all organo-phosphorus
poisoned patients should be treated with oxime.
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- Seizures: Organophosphate induced seizures should be treated with a
benzodiazepine (diazepam 5-10 mg IV, lorazepam 2-4 mg IV; repeat as
needed).
- Management of ventricular arrhythmias (torsades de pointes): by Mg
sulphate and atropine, correct hypokalemia and bradycardia. Avoid class
III antiarrhythmics.
COMMON PITFALLS
- Inadequate initial atropinization. Patients with severe toxicity
require rapid administration of large doses. Titrate to the
endpoint or drying pulmonary secretions.
- Monitor respiratory function closely, pulmonary function testing
may provide early clues to the development of respiratory
failure.
- Some component of dermal exposure occurs with most
significant exposures, inadequate decontamination may worsen
toxicity.
- Patients should be monitored closely for 48 hrs after
discontinuation of atropine and pralidoxime for evidence of
recurrent toxicity or intermediate syndrome.

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REFERENCES:
1. Taghavian F, Vaezi G, Abdollahi M, Malekirad AA. ., 2016: Comparative Toxicological Study
between Exposed and Non-Exposed Farmers to Organophosphorus Pesticides. Cell J.
Spring;18(1):89-96.
2. Cha YS, Kim H, Go J, et al. ., 2014: Features of myocardial injury in severe organophosphate
poisoning. Clin Toxicol (Phila); 52:873.
3. Karalliedde L, Baker D, Marrs TC. ., 2006: Organophosphate-induced intermediate
syndrome: aetiology and relationships with myopathy. Toxicol Rev; 25:1.
McGraw-Hill.
5. Konickx LA, Bingham K, Eddleston M. ., 2014: Is oxygen required before atropine
administration in organophosphorus or carbamate pesticide poisoning? - A cohort study.
Clin Toxicol (Phila); 52:531.
6. Eddleston M, Roberts D, Buckley N. ., 2002: Management of severe organophosphorus
pesticide poisoning. Crit Care; 6:259
7. Johnson, MK, Jacobsen, D, Meredith, TJ, et, al. ., 2000: Evaluation of antidotes for
poisoning by organophosphorus pesticides. Emerg Med; 12:22.
8. Eddleston M, Szinicz L, Eyer P, Buckley N. ., 2002: Oximes in acute organophosphorus
pesticide poisoning: a systematic review of clinical trials. QJM; 95:275.
9. Pawar KS, Bhoite RR, Pillay CP, et al. ., 2006: Continuous pralidoxime infusion versus
repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised
controlled trial. Lancet; 368:2136.
10. Tuovinen K. ., 1994: Organophosphate-induced convulsions and prevention of
neuropathological damages. Toxicology2004; 196:31.
11. Stacey R, Morfey D, Payne S. ., 2004: Secondary contamination in organophosphate
poisoning: analysis of an incident. QJM; 97:75.
12. Eddleston M, Roberts D, Buckley N. ., 2002: Management of severe organophosphorus
pesticide poisoning. Crit Care; 6:259.
13. Eddleston M, Juszczak E, Buckley NA, et al. ., 2008 : Multiple-dose activated charcoal in
acute self-poisoning: a randomised controlled trial. Lancet; 371:579.
14. Roberts D, Buckley NA. ., 2005: Alkalinisation for organophosphorus pesticide poisoning.
Cochrane Database Syst Rev; CD004897.
15. Aaron CK. ., 2006: Organophosphates and carbamates. In: Shannon MS, Borron SW, Burns
M, editors. Clinical management of poisoning and drug overdose. 4th edn. Elsevier Science;
New York: 2006.
16. Lotti M. ., 2001: Clinical toxicology of anticholinesterase agents in humans. In: Krieger R,
editor. Handbook of pesticide toxicology. Volume 2. Agents. 2 edn. Academic Press; San
Diego:. pp. 1043–1085.
17. Rotenberg M, Shefi M, Dany S, et al. ., 1995: Differentiation between organophosphate
and carbamate poisoning. Clin Chim Acta; 234:11.
18. United States Environmental Protection Agency. ., 1994: Organophosphate pesticide
information. www.epa.gov/pesticides/op/chlorpyrifos/consumerqs.htm (Accessed on May
03, 2005).
19. Buckley NA, Roberts D, Eddleston M.., 2004: Overcoming apathy in research on
organophosphate poisoning. BMJ; 329:1231.
20. Sevim S, Aktekin M, Dogu O, et al. ., 2003: Late onset polyneuropathy due to
organophosphate (DDVP) intoxication. Can J Neurol Sci; 30:75.
21. Vale A, Lotti M. (2015):Organophosphorus and carbamate insecticide poisoning. Handb
Clin Neurol. 2015;131:149-68.
22. Banerjee et al., 2014: Efficacy of pralidoxime in organophosphorus poisoning: revisiting the
controversy in Indian setting. J Postgrad Med. 2014; 60(1):27-30.
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PYRETHRINS AND PYRETHROIDS

INTRODUCTION:
Description:
- Pyrethrins compounds are naturally presenting insecticides extracted
from the chrysanthemum plant. Pyrethroids are totally synthetically
developed components similar to pyrethrin. Acute human toxicity from
exposure to these insecticides is not common; although, they can
produce dermal and upper respiratory tract irritation and
hypersensitivity anaphylactic reactions. Common pyrethrin-containing
pediculicides component involve A-200, Triple X, and RID.
Forms and uses:
- Naturally occurring components (pyrethrins) involve Pyrethrin I,
Pyrethrin II, Jasmolin I, Jasmolin II, Cinerin I, and Cinerin II.
- Synthetic components (pyrethroids) involve Barthrin, Phenothrin,
Cyfluthrin, Flucythrinate, Fenproponate, Fenproparthrin, Tralomethrin,
and Tralocythrin
- Pyrethrin and pyrethroid insecticides components are specified by their
very rapid "knock down" insect poisoning act.
Toxic dose:
- Allergic pyrethrins/pyrethroids reactions in susceptible exposed case
may occur at any dose.
- Even large ingestions rarely depvelp toxicity.
- Oral toxic dose is estimated as more than 100 - 1,000 mg/kg.
- The lethal acute oral pyrethrins/pyrethroids dose is 10-100 g.
Pathophysiology:
- In insects, pyrethrins and pyrethroids component are rapidly develop
death by paralyzing the nervous system through disturbances of the
membrane ion transport system in nerve axons, and pyrethroids
prolong sodium ion influx and also may block inhibitory
neurotransmitter pathways.
- In mammals, they are generally able to metabolize these pyrethrins
and pyrethroids compounds rapidly and thereby produce them
harmless compounds.

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Epidemiology:
- Pyrethrins/pyrethroids exposure is common, but toxicity is rare.
- Poisoning manifestations following exposure are typically mild degree.
- Pediatrics are considered more sensitive to pyrethrin compound toxic
exposure due to their inability to hydrolyze pyrethrin esters effectively.
- Death may develop after a massive amount of ingestion.
Causes:
- Pyrethrins/pyrethroids toxicity usually develop via inhalation route of
exposure.
- Accidental orally route ingestions also have been reported in Saudi
Arabia.
Risk Factors:
- Jobs at risk for exposure are farmers.
- Cases with allergy are at high risk for pyrethrins/pyrethroids toxicity
- Pyrethrins/pyrethroids poisoning to humans is composed primarily
with hypersensitivity reactions and direct irritant effects.
- Anaphylactic manifestations: Anaphylactic reactions involving
bronchospasm, oropharyngeal edema, and anaphylactic shock may
develop in hypersensitive cases.
- Respiratory manifestations: Inhalation of pyrethrins/pyrethroids
compounds may develop wheezing in persons with asthma.
- Dermal manifestations: Dermal exposure may develop burning,
tingling, numbness, and erythema.
- Ocular manifestations: Accidental ocular exposure during scalp
application of pediculicides component has caused corneal damage,
invoving keratitis and denudation.
- GIT manifestations: With large ingestions (200-500 mL of high
concentrated pyrethrins/pyrethroids solution), the CNS may be
suffered, resulting in seizures, coma, or even respiratory arrest.
INVESTIGATIONS
General Tests:
- Electrolytes levels, random blood glucose, and arterial blood gases or
oximetry are useful and helpful laboratory investigations
Specific Tests:
- Pyrethrins/pyrethroids compounds are metabolized rapidly inside the
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body, and methods for detecting the parent compound are not
routinely available in basic health care service.
TREATMENT
Emergency and supportive procedures:
- Manage bronchospasm and anaphylaxis if they develop “General
toxicology section”
- Observe cases with a history of large pyrethrins/pyrethroids ingestions
for at least 6 hours for any manifestation of neurological depression or
seizures.
Specific medications and antidotes therapy:
- There is no specific antidote for pyrethrins/pyrethroids compounds.
Decontamination procedures:
- Inhalation exposure. Remove cases from exposure site and give
supplemental oxygen 100% if required.
- Dermal exposure. Wash with copious amount of water and soap.
Topical dermal application of vitamin E in vegetable oil was recorded to
relieve paresthesitic sensation effect of pyrethrins/pyrethroids
compounds.
- Ocular exposure. Irrigate with copious amount of water. After
irrigation procedure, perform a fluorescein ophthalmic examination
and refer the case to an ophthalmologist if there is sign of corneal
damage.
- Oral exposure. In the majority of patients, a nontoxic dose has been
ingested and no decontamination procedure is necessary. However,
after a large ingestion of a concentrated pyrethrins/pyrethroids
solution, administer activated charcoal orally if conditions are
appropriate. Gastric lavage is not necessary after small to moderate
ingestions if activated charcoal can be given promptly.
Enhanced elimination techniques:
- Pyrethrins/pyrethroids are metabolized rapidly by the body, and
enhanced elimination procedures would not be expected to enhance
their elimination.
FOLLOW UP
Patient monitoring
- Pulmonary monitoring should be performed in symptomatic cases.
- Close continuous cardiopulmonary monitoring should be applied in

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severe conditions.
- Respiratory manifestation occur shortly pyrethrins/pyrethroids
exposure, peak within an hour, and completely recover over hours to
days with treatment from the onset of toxic exposure.
- Dermal manifestations may take days to weeks for complete recovery.
- Long-term pulmonary or dermal allergic hypersensitivity reactions may
be a consequence.
- Chronic exposure to pyrethrins/pyrethroids component may develop
reactive airway condition.
- Occupational form of asthma from pyrethrin compound has been
recorded in farmers.
- Complications of hypoxia or hypotension may occur in occult, life-
threatening conditions.
- From the emergency department or hospital
- Asymptomatic cases may be discharged following decontamination
procedures, 4-6 hours of close observation
PITFALLS
- Diagnosis:
- The probability of coingestants with pyrethrins/pyrethroids exposure
should be considered, such as hydrocarbons and anti-choline esterase
(OP/ON) insecticides exposures.
- It is critical to closely observe the case for 6 hours for the development
of delayed anaphylactic pulmonary manifestations.
- Treatment:
- It should not be considered that pesticide exposure with respiratory
manifestation is caused by an organophosphate or carbamate only.
- Follow Up:
- It is important to order for a follow-up outpatient clinic visit with an
allergy specialist for all cases with severe allergic manifestations.
- Delayed anaphylactic hypersensitivity to an acute
pyrethrins/pyrethroids exposure may occur, and cases should be
instructed to avoid future recurrent exposures from the same
situations.
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REFERENCES:
1. Boland LA, Angles JM (2010) Felinepermethrin toxicity: retrospective study of 42
cases. J Feline Med Surg12: 61-71
2. Soderlund DM, Clark JM, Sheets LP, Mullin LS, Piccirillo VJ, et al.
(2002) Mechanisms of pyrethroid neurotoxicity: implications for cumulative risk
assessment. Toxicology 171: 3-59

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WARFARIN AND RELATED RODENTICIDES

INTRODUCTION:
Description:
- Dicumarol and other natural anticoagulants compounds are present in
sweet clover. Coumarin derivatives are used both therapeutically and
as rodenticides preparations. Warfarin (Coumadin) is used widely as a
therapeutic anticoagulant drug but is no longer popular as a
rodenticide compound because rodents have become resistant to its
action.
- The most common anticoagulant rodenticides available currently
contain long-acting “superwarfarins” such as brodifacoum,
diphacinone, and valone, which have more powerful and prolonged
anticoagulant actions.
Forms and uses:
- Coumadin is medically used in the prophylaxis and treatment of venous
thrombosis, and pulmonary embolism.
Toxic dose:
- The toxic dose of warfarin and related rodenticides is extremely
variable.
- Warfarin toxic dose: Generally, a single small ingestion of warfarin (eg,
10-20 mg) will not produce serious toxic manifestations (most
rodenticides warfarin preparations contain 0.05% warfarin). On the
opposite side, chronic or repeated ingestion of even small amounts (eg,
2 mg/d) can lead to significant anticoagulant toxic manifestation.
Patients with hepatic impairment, malnutrition, or a bleeding disorders
are at high risk of anticoagulant toxicity. So, a single ingestion does not
result anticoagulation unless a massive amount warfarin is ingested.
- Superwarfarins toxic dose: Superwarfarins compounds are extremely
potent and can have prolonged toxic actions even after a single small
superwarfarins compounds ingestion.
Pathophysiology:
- Warfarin produces vitamin K deficiency by stopping the regeneration
cycle of active vitamin K and thereby the activation of vitamin K
dependent clotting factors II, VII, IX, and X.
- Anticoagulation manifestations is postponed until coagulation factors
are depleted.
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- Due to its relatively short half-life, a single ingestion of warfarin cannot

inhibit synthesis of clotting factors long enough to produce
anticoagulation
Epidemiology:
- Warfarin and related rodenticides toxic exposure is common in Saudi
Arabia.
- Poisonous manifestations following exposure are typically mild to
moderate.
- Death develop in chronic ingestion of warfarin leading to bleeding
disorders.
Causes:
- Toxic warfarin and related rodenticides ingestion is usually accidental,
by a child
Drug interactions:
- Medications potentiate anticoagulant effect of warfarin include:
allopurinol, anabolic steroids, cephalosporin, cimetidine, antidep-
ressants, erythromycin, ethanol, NSAI drugs, sulfonylureas, thyroxin,
and many others drugs.
- Warfarin and related rodenticides may develop bleeding at lower levels
in cases with preexisting coagulation diorders.
- Excessive anticoagulating disorders may produce ecchymoses,
subconjunctival hemorrhage, bleeding gums, or internal bleeding (eg,
hematemesis, melena, hematochezia, menorrhagia, or hematuria). The
most immediately life-threatening sequalae are massive GI bleeding and
intracranial hemorrhage.
- The onset of anticoagulant manifestations from warfarin may be
apparent within 15 hours, but with superwarfarins preparations, peak
manifestations commonly are postponed for up to 2 days after
exposure.
- Persistent anticoagulant effects from warfarin may persist for 5 days,
whereas anticoagulation from superwarfarins compounds may persist
for several weeks, or even months.
INESTIGATIONS
General Tests:
- INR or PT should be detected 12 to 24 hours postingestion to evaluate
coagulation effect; if normal, no further evaluation is needed for cases

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with warfarin ingestion and a normal PT/INR 48 hours after exposure

rules out significant related rodenticides preparations ingestion.
- Partial thromboplastin time, fibrinogen, fibrin degradation products,
complete blood count, platelets, stool test for blood, and blood type and
cross match should be performed in cases with clinically significant
prolongation of INR/PT or reported bleeding.
- Endoscopy may be helpful if clinical evidence of gastrointestinal
bleeding is record.
Specific Tests:
- Serum levels of warfarin are not clinically helpful for medical staff.
TREATMENT
Emergency and supportive procedures.
- If significant bleeding develop, be ready to manage shock with
transfusions of whole blood and fresh frozen plasma (FFP) and perform
immediate neurosurgical consultation if intracranial hemorrhage is
suspected.
- Avoid to precipitate hemorrhage in severely anti-coagulated
intoxicated cases; prevent falls and other trauma.
- Avoid medications that may accelerate bleeding tendency or decrease
metabolic process rate of the anticoagulant.
Antidotes therapy.
Oral Vitamin K1
Indication: Marked prolongation of PT or INR without bleeding.
- Method of administration. Vitamin K1 should be given orally. Adult
dose is 50-100 mg/day initially in single or divided doses. Pediatric dose
is 0.6 mg/kg/day initially in single or divided doses. INR or PT should be
repeated measurement daily, and dose increased as needed to
normalize INR or PT. Dosage may increase more than 200 mg/day in
severe cases
- Caution. Complete reversal may not be desired in cases with medical
indication for therapeutic anticoagulation.
Parental Vitamin K1
- Indication. Severe prolongation of PT or INR and frank bleeding
(The patient should first receive fresh frozen plasma as
described below in symptomatic treatment lines).
- Method of administration. Vitamin K1 should be administered
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intravenously. Vitamin K1 (25-50 mg) should be diluted with D5W or

0.9% saline and infused slowly at a rate not to exceed 1 mg/min. Dose
is not well established in children; initial dose of 0.6 mg/kg or 5-10 mg,
titrated to response, is a reasonable reported starting dose. Dose
should be repeated two to four times daily; clinician should be
prepared to treat any development if anaphylactoid reactions.
Parenteral vitamin K1 in doses as high as 400 mg per day have been
prescribed.
- Adverse effects and precautions. Anaphylactoid reactions and even
death have occurred during intravenous use of vitamin K1. In a patient
who is anticoagulated for prosthetic valve, vitamin K1 should not be
given unless anticoagulation is life-threatening
- No other form of vitamin K should be used (e.g., K2, K3, menadione,
K4, or menadiol).
Decontamination procedures.
- Administer activated charcoal orally if cases are appropriate.
activated charcoal can be given promptly and should be avoided in a
case with prior anticoagulation.
- There is no role for enhanced elimination procedures in cases warfarin
and related rodenticides.
Symptomatic treatment.
Marked coagulopathy and active bleeding disorders
- Fresh-frozen plasma should be given intravenously; the pediatric dose
is 15 - 25 ml/kg, and the adult dose is 2 - 4 units
- On the basis of serial INR and PT measurments, further fresh-frozen
plasma may be indicated.
- Bleeding with anemia. Packed red blood cells should be given as
indicated.
FOLLOW UP
Patient monitoring
- Serial INR or PT close monitoring is performed to guide treatment of
cases with coagulopathy.
- Complications of hypotension from hemorrhage or intracranial

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haemorhage develop rarely.

- If vitamin K treatment is applied before bleeding complications cause
injury, a complete recovery is expected.
- From the emergency department; Asymptomatic cases with acute
single warfarin or related compounds ingestion that is not massive may
be discharged after gastrointestinal decontamination procedures and
psychiatric evaluation, if indicated.
- From the hospital; Cases may be discharged when hemodynamically
stable without active bleeding and when INR or PT is normalizing.
PITFALLS
DIAGNOSIS
- Measuring PT/INR too soon following ingestion may result in a pseudo
sense of security. At least 12-24 hours should elapse before detection
INR or PT.
TREATMENT
- Large doses of vitamin K may be indicated; under treatment is
common.
- Severe warfarin overdose in cases requiring therapeutic
anticoagulation, e.g., patients with prosthetic heart valves, may require
slow partial reversal of anticoagulation; PT should be monitored
several times daily to assist in detecting quantity and times of fresh-
frozen plasma treatment line.
REFERENCES:
1. Gayer G, Desser TS, Hertz M, Osadchy A, Daniel BL, et al. (2011) Spontaneous
suburothelial hemorrhage in coagulopathic patients: CT diagnosis. AJR Am J Roentgenol
197: W887-890.
2. Lim AK, Campbell DA (2013) Haematuria and acute kidney injury in elderly patients
admitted to hospital with supratherapeutic warfarin anticoagulation. Int Urol Nephrol
45: 561-570.
3. Landefeld CS, Beyth RJ (1993) Anticoagulant-related bleeding: clinical epidemiology,
prediction, and prevention. Am J Med 95: 315-328.
4. Olson, Kent (2011-09-04). Poisoning and Drug Overdose, Warfarin Toxicity, Sixth Edition
(Poisoning & Drug Overdose) (Kindle Locations 4751-4754). McGraw-Hill Education.
Kindle Edition.
5. Danaci M, Kesici GE, Kesici H, Polat C, Belet U (2006) Coumadin-induced renal and
retroperitoneal hemorrhage. Ren Fail 28: 129-132.
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CARBON MONOXIDE
INTRODUCTION:
Description:
- Carbon monoxide Gas (CO) is a colorless, odorless, tasteless, and
nonirritating gas “Silent Killer” resulted from the incomplete
combustion of any carbon-containing compound.
Forms and sources:
- Common sources of human CO exposure routes involve accidental
smoke inhalation in fires; automobile exhaust fumes in a closed
space; usage of kerosene, or gas stoves; and, to a lesser extent,
cigarette smoke “both active and passive smoking”. CO toxicity
accounts for frequent emergency department visits every year in the
Saudi Arabia.
Toxic dose:
- Most sources of CO gas can give adequate loads to rapidly develop
life-threatening poisoning.
- Heavy cigarette smoking can give a carboxyhemoglobin level of up to
12% in active cigarette smokers.
- The recommended workplace limit level for CO gas is 25 ppm as an 8-
hours time-weighted average. The CO gas level considered
immediately dangerous to life is 1200 ppm (0.12%). However, the
duration of exposure to CO gas is very critical. Whereas exposure to
1000 ppm (0.1%) eventually will develop in 50% saturation of CO-Hgb,
it may take several hours to reach that level.
- Short exposure to much higher CO levels may give a more rapid
increase in CO-Hgb.
Pathophysiology:
- CO poisoning is a sequelae of tissue hypoxia.
- CO binds to hemoglobin structure with an affinity 250 folds that of
oxygen, leading to reduced oxyhemoglobin saturation degree and
declined blood oxygen-carrying capacity power.
- The oxyhemoglobin dissociation curve is shifted to the left side,
decreasing oxygen delivery at the peripheral tissues.
- CO gas directly inhibits cytochrome oxidase enzyme, more disturbance
cellular function, and it binds to myoglobin, leading to impaired
myocardial contractility power.

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- Fetal hemoglobin is highly sensitive to binding by CO gas, and fetal

carboxy-haemoglobin levels may be higher than maternal carboxy-
hemoglobin concentrations..
Epidemiology:
- Carbon monoxide gas toxicity is one a leading cause of fatal toxicity
world wide.
- Posoning CO effects following exposure are typically related to the
dose of CO gas ( CO concentration × CO duration of exposure).
- CO death is common, and usually develops before the patient reaches
a health-care providing site.
Causes:
- The cause often be accidental.
Risk Factors:
- Working in proximity to an internal combustion device source such as
a furnace or automobile engine rise the risk of carbon monoxide gas
toxicity.
- Infants and children may be at higher risk of CO poisoning because
their CO exposure is raised by high minute respiratory intoxicated air
ventilation volume and high pediatric metabolic rate.
- Elderly cases are more susceptible to CO toxicity and may have a high
incidence of long-term hypoxic CO consequences.
- Carbon monoxide gas poisoning may have teratogenic and
embryotoxic possible effects when the CO exposure has been
sufficient to cause CO maternal poisoning.
- CO exposure during pregnancy may lead to fetal neurological damage,
fetal death, and high incidence of spontaneous abortion.
- Manifestations of CO toxicity are mainly in organs with high oxygen
demands, such as the brain and heart.
- The majority of cases manifest headache, dizziness, nausea, vomiting
and abdominal pain. Cases with ischemic heart disease may represent
with angina or myocardial infarction. With more severe CO exposures,
sluggish thinking, syncopal attacks, marked disturbed consciousness
level up to coma, convulsions, cardiac arrhythmias, hypotension, and
death may develop.
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- Carboxyhemoglobin concentrations do not correlate with the

severity of CO poisoning, however, a CO concentration above 25%
is considered significant, and concentrations more than 50% are
often associated with severe poisoning.
- Recovered patients from severe toxicity may suffer from multiple
neurologic consequences due to a hypoxic-ischemic CO effect, such as
parkinsonism, disturbed personality and memory deficits. Some of
previous mentions sequelae may have a delayed onset of appearance
from several hours to days after CO exposure. Their incidence, may be
as high as 50%.
- CO poisoning during pregnancy may develop in fetal demise.
INESTIGATIONS
General Tests:
- Serum electrolytes, BUN, and creatinine are detected to measure anion
gap metabolic acidosis or renal impairment effect.
- ECG and cardiac enzymes levels in CO symptomatic cases are ordered
to measure possibility of myocardial ischemic CO effect.
- Serial mental status assessments and neuropsychiatric investigations
may be required under certain CO poisoning conditions.
Specific Tests:
- Carboxyhemoglobin level from venous or arterial blood is determined
to prove CO exposure.
- CO concentrations do not correlate well with poisoning severity
degree, except at low CO concentration.
TREATMENT
Emergency and supportive care procedures:
- Keep an open airway and assist ventilation if needed.
If possibility of smoke inhalation has also reported, advice early
intubation for airway protection act.
- Manage coma and seizures if they develop.
- Close continuously monitor the ECG for several hours after CO
exposure.
- Because smoke often contains other toxic gases, put the possibility of
cyanide toxicity, methemoglobinemia occurrence, and irritant gas
damage.

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Specific medications and antidotes management.

100% Oxygen:
- Give oxygen in the highest possible oxygen concentration (100%).
Breathing 100% warm humid oxygen accelerates the release of CO
from hemoglobin to approximately one hour, compared with about
six hours in room air normal respiration.
- Use a small tight-fitting oxygen mask and very high-flow oxygen with
a reservoir (nonrebreather type) or give the oxygen supply by
endotracheal tube.
- Manage until the CO-Hgb level is below 5%.
Decontamination procedure:
- Remove the case immediately from exposure source and administrate
oxygen. Rescuers should wear self-contained breathing apparatus “in
a high potentially CO concentrations incidents”
Hyperbaric oxygen therapy:
- Order hyperbaric oxygen in severe CO poisoning patients.
- Hyperbaric oxygen give 100% oxygen under 2-3 atm of pressure and
can accelerate elimination of CO (half-life decrease to 20 minutes).
- Hyperbaric oxygen will be useful in cases with severe CO poisoning,
especially when there is ready access to a hyperbaric oxygen
chamber.
- Indication of hyperbaric oxygen therapy:
- Coma
- Carboxyhemoglobin level >25%
- Age more than 35 years
- Severe metabolic acidosis conditions
- Abnormal findings in neurologic assessment (cerebral or
cerebellar dysfunction)
- Abnormal findings in cardiovascular assessment (cardiovascular
disturbances)
- Prolonged exposure to CO gas for more than one day.
FOLLOW UP
Patient monitoring
- Close respiratory and cardiac functions monitoring should be applied
continuously in CO symptomatic cases.
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- Most CO cases with mild gas exposure do well with treatment of
100% oxygen by face mask.
- Toxic CO manifestations peak in the first few hours from exposure
and often resolve over a few hours after stoppage of CO exposure.
- Cases with severe CO exposure may incompletely recover.
CO sequelae may range from difficulty in concentration,
personality changes to dramatic persistent vegetative status.
- In some CO cases, initial incomplete recovery is followed by persistent
neurological damage or appearance of delayed neuropsychiatric
disorders.
- From the emergency department. Asymptomatic or minimally CO
symptomatic cases (without history of coma) may be discharged after
100% oxygen management, when they become completely
asymptomatic.
- From the hospital. Cases who face the criteria for hyperbaric oxygen
therapy indicator may be discharged after one or two treatments
lines, if recovered, and following psychiatric assessment, if required.
Follow-up visits should be assigned for further treatment and serial
neurological evaluation.
PITFALLS
DIAGNOSIS
- CO toxicity should be considered in all cases with food poisoning like
symptoms, flulike manifestations, especially if multiple family
members are affected with disturbed consciousness level.
TREATMENT
- It is highly needed to order hyperbaric oxygen therapy for moderately
or severely CO poisoned cases.
- It is essential to detect the source of CO exposure to avoid re-
exposure.
- A blood sample of carboxyhemoglobin level withdrawn a few hours
after end of CO exposure can be misleading sample because CO has
been completely eliminated. Therapy must be based here on clinical
manifestations only.

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FOLLOW-UP
- It is important that the case return if manifestations occur after the recovery from
poisoning for re-evaluation of delayed neurologic CO sequlae.
REFERENCES:
1. Tomaszewski C (2002) Carbon monoxide. In: Goldfrank’s toxicologic emergencies. (7th edn),
McGraw-Hill, New York.
2. Yanir Y, Shupak A, Abramovich A (2002) Cardiogenic shock complicating acute carbon
monoxide poisoning despite neurologic and metabolic recovery. Ann Emerg Med.
3. Olson, Kent (2011). Poisoning and Drug Overdose, Sixth Edition (Poisoning & Drug Overdose).
McGraw-Hill Education.
4. Aslan S, Erol MK, Karcioglu O, Meral M, Cakir Z, et al. (2005) The investigation of ischemic
myocardial damage in patients with carbon monoxide poisoning. Anadolu Kardiyol Derg 5: 189-
193.
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NATURAL TOXINS AND ENVENOMATION
SNAKE BITE
INTRODUCTION:
- All snake species that are medically significant possess one or more pairs
of fangs in the upper jaw. These fangs penetrate the skin of their victims
and tranfer venom through a groove or closed channel into the tissues.
(See the Snake bite chart for the commonest venomous snakes in Saudi
Arabia).
- The potency of the venom and the amount of venom injected vary
considerably. Some snake strikes are "dry" bites in which no venom is
injected.
- Snake venoms are complex mixtures of components that produce local
"digestive" or cytotoxic insult on tissues, in addition to hemotoxic,
neurotoxic, and other systemic effects. The relative predominance of
cytotoxic, hemotoxic, and neurotoxic venom components depends on the
species of the snake and geographic and seasonal variables.
CLINICAL MANIFESTAIONS:
- The first step is to identify whether the snake is poisonous or not. The
easiest way is to diagnose from the bite.
- A venomous snake bite is characterized by
- The bite usually shows 2 holes (refer to canines injecting venom).
- Spreading pain, numbness, and oedema.
- While in non-venomous snake bite:
- Bite site shows multiple teeth impressions
- Absent significant local pain or swelling
I- Vipers (family Viperidae)
- Vipers (family Viperidae) are venomous snakes that include 2
subfamilies, true vipers (Vipernae) and pit vipers (Crotalinae). The
most common types present in Saudi Arabia are the Puff Adder (Bitis
arietans), Palestine Saw-scaled Viper (Echis coloratus‬), Saw-scaled
Vipers (Echis carinatus, and Horned viper (Cerastes cerastes).‬‬
- Viperidae envenomation, mainly hematologic:
- Local manifestations: (Severe)
- Severe progressive pain.

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- Petechiae, serous oozing from the bite site and formation

of blood-filled vesicles.
- Progressively spreading swelling (oedema) and bruising at
the bite site (The circumference of the swollen bitten limb
should be regularly measured and closely observed every
15 minutes). Oedema extends to cover the whole bitten
area.
- Gangrene of the bitten area may occur.
- Systemic manifestations:
- Non-specific systemic effects: Nausea, vomiting, diarrhea,
weakness, light-headedness, diaphoresis, and chills
- Coagulopathy and bleeding.
- Rhabdomyolysis with nephrotoxicity.
- Increased vascular permeability, tachycardia, tachypnea,
and hypotension.
- Neurotoxicity (e.g., oral paresthesia, unusual taste,
fasciculations, altered mental status, seizures). Crotalid
bites usually do not cause neuromuscular weakness with
respiratory depression.
- Russell viper envenomation:
- Russell viper is unique in that it can produce both
hemorrhagic and neurotoxic effects which include:
- Numbness, tingling, cranial nerve dysfunction e.g.
(changes in taste and smell), ptosis and external
ophthalmoplegia, paralysis of facial muscles, aphonia,
and dysphagia.
- Flaccid paralysis of skeletal muscles and respiratory
paralysis.
- Loin pain, hematuria, hemoglobinuria, myoglobinuria,
oliguria/anuria, hyperkalemia and the condition ends
by acute renal failure.
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Grading of Pit Viper Envenomation

Dry Bite Bite mark without severe pain or swelling, normal vital signs,
normal coagulation studies and normal platelet count.
Mild Local pain and swelling, normal vital signs, normal to mildly
abnormal coagulation studies and Platelet count >100,000
Moderate Local pain and moderate swelling, normal vital signs,
abnormal coagulation studies (double PT and PTT) and
platelets <100,000
Severe Shock, altered mental status with or without normal vital
signs, abnormal coagulation studies, Thrombocytopenia
(platelets <20,000)
II. Elapidae (Includes cobras, kraits) mainly neurotoxic

- The most common types present in Saudi Arabia are Arabian Cobra
(Naja Haje Arabicus, and Desert Black Snake (Walterinnesia aegyptia).
- Indistinct fang marks.
- Burning pain (may be absent).
- Mild to moderate oedema (may be absent) and discoloration.
- Serosanguinous discharge (may be absent).
- Paraesthesia around bitten area.
- Muscular incoordination and weakness in the bitten limb.
- Systemic manifestations:
I. Neurotoxicity:
- Pre paralytic stage: Increased salivation and emesis with or without
headache
- Paralytic Stage:
- Dysarthria and dysphagia.
- Visual disturbances (ptosis and external ophthalmoplegia).
- Respiratory distress ends by respiratory failure. Most deaths
occur as a result of respiratory arrest within 36 hrs.
II. Cardiotoxicity:
- Cardio toxins affect the cell membranes directly causing myocardial
depression, cardiogenic shock, and systolic cardiac arrest.

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INVESTIGATIONS:
Routine:
All but trivial pit viper bites require
- Measurement of serum electrolytes, BUN, and creatinine
- ABG and EKG monitoring
Specific:
- A baseline CBC (follow hemoglobin, hematocrit, and platelets), and
coagulation profile (i.e., INR, PT, and fibrinogen). Repeat these
investigations after each course of antivenom and every 4-6 hrs after
initial control has been established.
- Measurement of fibrin degradation products.
- Urine analysis: Color, red cell casts and proteinuria.
- Bite site serial assessment and testing: Outlining the leading margin
of the local swelling with a marker every 15-30 min can help
clinicians assess the progression of the envenomation locally. Bitten
extremity circumference should also be measured upon arrival of
the patient and at regular intervals until local progression subsides.
TREATMENT:
Pre-hospital:
- FIRST AID: Directed towards reducing the spread of the venom and
expediting the transportation of the patient to an appropriate
medical facility.
General principles:
- Keep the patient calm.
- Immobilize the injured part of the body in a functional position using
a light bandage.
- Transfer the patient to the closest medical facility as fast as possible.
- Withhold any drugs that may confound clinical assessment or
interfere with treatment (e.g., anticoagulants, aspirin, NSAIDs, or β blockers).
- Do not remove the immobilization bandage until the patient has
reached the hospital, and a clinical assessment regarding the need
for antivenom has occurred
First Aid for Snake Bite (Do it RIGHT)
*R: Reassure the patient that most of snake bites are
of nonvenomous species.
*I: Immobilize the limb. Use bandage or cloth to hold splints not to
block blood supply or apply pressure.
*GH: Get to the hospital immediately.
*T: Tell the doctor of any symptoms that developed on the way
to the hospital
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Hospital
Stabilization:
- Early care of snake bite victims should focus on supporting patients
with life-threatening respiratory depression or shock. If pressure
immobilization is in place, then it should not be removed until the
initial assessment, stabilization, and if needed, antivenom is
provided.
- Shock: Rapidly administer normal saline or blood (depending upon
the severity of hemorrhage). If shock is not corrected and the CVP
is not low, vasoactive drugs may be indicated.
The anti-snake venom (ASV)
- The most critical decision in the management of a snake bite victim
is whether or not to administer the anti-venom.
Rules for administration of ASV
- The risk of developing a hypersensitivity reaction should always be
considered. Patients having a positive history of atopy (e.g., severe
bronchial asthma and atopic dermatitis) are at a higher risk of
severe hypersensitivity reactions and should be given ASV under
close monitoring during and after treatment.
- Treatment with the antivenom should be administered as soon as it
is indicated. It may reverse systemic complications even after
several days. It should be given as long as coagulopathy persists.
Indications for anti-snake venom administration:
Local indications:
- The presence of a progressive local swelling involving more
than half of the bitten limb (in the absence of a tourniquet)
within 48 hrs of the bite.
- Rapid extension of the swelling within a few hours of the bite
on the hands or feet.
- Development of an enlarged tender lymph node draining the
bitten area.
Systemic indications:
- Clinical indications:
- Spontaneous systemic bleeding.
- Neurotoxic signs: Ptosis, external ophthalmoplegia, paralysis
etc.
- Hypotension, shock, cardiac arrhythmia and /or abnormal EKG.
- Oliguria and/or anuria.
- Rhabdomyolysis.
- Laboratory indications:
- Prolonged PT and thrombocytopenia (<100000).

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- Elevated BUN, creatinine and serum K.

Administration of ASV:
Two methods of administration are recommended:
- Intravenous injection: The physician must remain with the
patient during time of early reactions (up to 180 minutes).
- Intravenous infusion over one hour.
Anti-Snake Venom Doses:
For pit viper envenomation:
- The main course of treatment is the polyvalent antivenom. The
degree of effectiveness of this antivenom is both time and dose
dependent. It has the highest effectiveness in preventing
venom-induced tissue damage when given early. It is less
effective if delayed but can reverse coagulopathies and be
effective even when started 24 hrs after envenomation.
- Administer a loading dose of 5 vials of reconstituted polyvalent
immune Fab diluted in 250 mL of normal saline slowly at 20-50
mL/hr for the first 10 min.
- If no adverse reactions are noted, the remainder of the doses
should be infused over the next hour. The same dose can be
repeated twice every 4-6 hrs until improvement is sufficient to
achieve the initial control of symptoms, reverse coagulopathies,
and correct vital parameters.
- In children, the dose is is the same as in adults. The limb
circumference should be measured at 3 points proximal to the
bite.
- Additonally, the advancing border of the swelling should be
measured every 15-30 min as it can guide decisions about the
need for further administration of additional doses.
For the cobra snake envenomation:
- 5 amp of the bivalent antivenom diluted in 250 ml saline,
infused IV. More antivenom should be administered if severe
signs persist after 1-2 hrs and dose can be repeated every 4-6
hrs until improvement.
N.B. double the dose of the polyvalent antivenom if the bivalent antivenom is not
available.
After Administration of ASV, the victim should be observed for:
- General condition.
- Spontaneous systemic bleeding and decreased blood
coagulability.
- Neurological or cardiovascular symptoms.
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- Urine color due to hematuria.

Criteria for repeating the ASV:
- Uncoagulability after 6 hrs.
- Persistence or recurrence of bleeding after 1-2 hrs.
- Deteriorating neurotoxic or cardiovascular signs after 1-2 hrs.
- Patients should receive tetanus prophylaxis (toxoid). Snakebites
do not usually become infected and antibiotics are indicated
only for patients with clinical evidence of infection.
- Coagulopathy: Blood products (e.g., whole blood, fresh frozen
plasma, or platelets) only if life-threatening bleeding and, when
available, after antivenom administration
- Rhabdomyolysis: Antivenom may attenuate but does not
reverse rhabdomyolysis after a snakebite. Rhabdomyolysis
treated by rapid infusion of isotonic saline.
- Perform proper local wound care after Initial stabilization and
complete assessment, and if needed, intravenous antivenom is
being provided.
COMMON PITFALLS:
- The following methods, while used widely in the past and advocated by
some, cause more harm than good and should be avoided:
- Incision and oral suction.
- Mechanical suction devices.
- Cryotherapy
- Surgery
- Electric shock therapy
- Tourniquets may cut off arterial blood flow and cause significant
ischemic damage, especially when left on for a prolonged period of
time.

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SNAKE BITE OBSERVATION FORM

Patient name: ……………………………. Date & time of bite: …………………..
Date of birth: …………….………………. Number of bite: ….…………………….
ER number: ……………..………………... Type of snake: ……..…………………...
Time After Bite:

Vital signs:
Pulse
Blood pressure
Temperature
Local signs:
Local bite site pain
Local bite site swelling
Reg. lymph node tenderness
General manifestations:
Headache
Nausea
Vomiting
Abdominal pain
Hematological signs:
Persistent blood ooze
Hematuria
Active bleeding
Neurological signs:
Ptosis
Ophthalmoplegia
Fixed dilated pupils
Dysphagia
Dysarthria
Tongue protrusion
Limp weakness
Respiratory weakness
Myolytic signs:
Muscle pain
Myoglobinuria
Renal:
Urine output
Laboratory findings:
PT/INR
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Time After Bite:

aPTT
Hemoglobin count
Platelet count
Fibrinogen
FDP
CK
BUN
Creatinine
K+/Na+
ABG finding
Antivenom:
Type
Amount
Time of administration

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REFERENCES:
1. Chippaux JP, Akaffou MH, Allali BK, Dosso M, Massougbodji A, Barraviera B., 2016: The
6(th) international conference on envenomation by Snakebites and Scorpion Stings in
Africa: a crucial step for the management of envenomation. J Venom Anim Toxins Incl Trop
Dis. Mar 16;22:11.
McGraw-Hill.\
3. Olson, K. R., & California Poison Control System. (2006). Poisoning & drug overdose. New
York: Lange Medical Books/McGraw-Hil.
4. Julian White, j and Cheng A C; 2014: Snakebites worldwide: Management. UPTODATE,:
http://www.uptodate.com/ contents/snakebites-worldwide-management, June, 2014.
5. Isbister GK, Brown SG, Page CB, et al.,2013: Snakebite in Australia: a practical approach to
diagnosis and treatment. Med J Aust; 199:763.
6. Johnston CI, Brown SG, O'Leary MA, et al. .,2013: Mulga snake (Pseudechis australis)
envenoming: a spectrum of myotoxicity, anticoagulant coagulopathy, haemolysis and the
role of early antivenom therapy - Australian Snakebite Project (ASP-19). Clin Toxicol (Phila)
2013; 51:417.
7. Yap MK, Tan NH, Sim SM, Fung SY. .,2013: Toxicokinetics of Naja sputatrix (Javan spitting
cobra) venom following intramuscular and intravenous administrations of the venom into
rabbits. Toxicon; 68:18.
8. Rahmani AH, Jalali A, Alemzadeh-Ansari MH, et al. .,2014: Dosage comparison of snake
anti-venomon coagulopathy. Iran J Pharm Res 2014; 13:283.
9. Cheng AC, Winkel KD. ,2004: Antivenom efficacy, safety and availability: measuring smoke.
Med J Aust; 180:5.
10. Gawarammana IB, Kularatne SA, Dissanayake WP, et al.,2004: Parallel infusion of
hydrocortisone +/- chlorpheniramine bolus injection to prevent acute adverse reactions to
antivenom for snakebites. Med J Aust; 180:20.
11. Bucaretchi F, Hyslop S, Vieira RJ, et al.,2006: Bites by coral snakes (Micrurus spp.) in
Campinas, State of São Paulo, Southeastern Brazil. Rev Inst Med Trop Sao Paulo; 48:141
12. Goldman DR, Seefeld AW. Ocular toxicity associated with indirect exposure to African
spitting cobra venom. Wilderness Environ Med 2010; 21:134.

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SCORPION STING
INTRODUCTION:
- Scorpion venoms are complex and the components are species specific.
(See the Scorpion chart for the common types present in Saudi Arabia).
- The scorpion venom contains varying concentrations of various toxins
e.g., neurotoxin, cardiotoxin, nephrotoxin, hemolytic toxin, phospho-
diesterases, phospholipases, hyaluronidases, glycosaminoglycans,
histamine, serotonin, tryptophan, and cytokine releasing toxins.
- Venom toxins alter sodium channels, leading to prolonged neuronal
excitability.
- Many end-organ manifestations occur secondary to this excessive
excitability. The cardiopulmonary effects observed after some scorpion
envenomations occur as a result of autonomic excitability.
Neuromuscular overstimulation leads to somatic and cranial nerve
hyperactivity.
- Serotonin may be found in the scorpion venom and is thought to
contribute to the pain associated with scorpion envenomations.
- Mild envenomation: Local manifestations only including pain, localized
paresthesias or burning, very mild local oedema, and localized sweating.
- Moderate envenomation: Local manifestations in addition to systemic
manifestations such as sialorrhea, generalized diaphoresis, nausea,
vomiting, abdominal pain, mild tachycardia, hypertension, mild
tachypnea, restlessness, drowsiness, ataxia and priapism.
- Severe envenomation: May present with severe hypertension or
hypotension, pulmonary oedema, myocardial failure.
- EKG may show ST segment or T wave abnormalities, dysrhythmias,
respiratory failure, CNS depression, symptomatic pancreatitis or upper GI
bleeding.
- Children are at a higher risk than adults to develop severe systemic
manifestations, and the majority of mortalities reported are in children
below 10 years of age.
INVESTIGATIONS:
Routine:
- Monitor serum glucose and electrolytes, initiate continuous cardiac
monitoring and obtain an EKG in patients with moderate or severe
manifestations of envenomation.
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- Obtain a chest radiograph and monitor pulse oximetry and/or

arterial blood gases in patients with respiratory signs or symptoms.
Specific:
- Serum lipase (for patients presenting with abdominal pain or
persistent vomiting).
- Follow markers of myocardial injury (troponin, CK-MB or myoglobin)
in patients with severe envenomation.
TREATMENT
Asymptomatic or mild envenomation:
- Most scorpion stings result in mild envenomations (Grade I or II).
- Pain management with oral medications (e.g., NSAIDs).
- Clean the sting site, and tetanus prophylaxis is advised.
- These patients should be observed for 4 hrs to ensure that there is
no further progression of symptoms. The progression of
envenomation grade in children may occur rapidly.
- Prior to discharge, patients should tolerate oral intake, have no
progression of symptoms, and their pain should be adequately
controlled with oral medications.
Moderate and severe envenomation:
Stabilization:
- ABC, administer oxygen and monitor airway carefully in patients
with respiratory signs or symptoms. Excessive secretions and
tachypnea are common, and pulmonary oedema may develop with
severe envenomation. Endotracheal intubation and ventilation may
be necessary in some cases.
- Analgesics may be required for pain control.
- Proper care of respiration, endotracheal intubation in patients with
significant difficulties maintaining their airway or with pulmonary
edema accompanied by hypoxemia.
- Close monitoring for and treatment of myocardial ischemia and/or
acute decompensated heart failure in patients at risk.
- Intravenous fentanyl 1 μg/kg for pain. Fentanyl is preferred if
antivenom administration is planned because, unlike morphine,
fentanyl does not cause histamine release.
- Intravenous benzodiazepines (lorazepam or continuous midazolam
infusion), titrated for sedation and to treat muscle spasticity if
antivenom is not used.

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Antivenom (polyvalent anti scorpion serum)

- It is the treatment of choice. The dose used is determined by the
severity of the clinical manifestations.
- If the patient is asymptomatic, do not give the antivenom and
observe for 6 hrs.
- If the patient presented after 6 hrs and is asymptomatic do not
give anything and discharge.
- If symptomatic, administer an initial dose of 5 amp of the polyvalent
anti scorpion diluted in 20 - 50 ml saline given IV over 20 minutes. If
the systemic manifestations still exist, the same dose can be
repeated q 2 hrs up to 4 doses.
- The antivenom`s main function is to decrease the levels of
circulating unbound venom. In some cases, symptoms may still
persist inspite of the prompt administration of the antivenom. This is
could be attributed to the inability of the antivenom to counteract
the toxins that are already bound to their target receptors.
Therefore, symptomatic and supportive treatment is needed with
immunotherapy.
Summary Scorpion sting evaluation and treatment:
Grade Clinical findings Treatment
I Localized pain or paresthesias at site Symptomatic care, ie,
analgesics, anxiolytics
II Local and remote pain or paresthesias Symptomatic care, ie,
analgesics, anxiolytics
III Localized pain with paresthesias and Symptomatic care and
either: Cranial nerve abnormalities or supportive care, ie,
Somatic skeletal neuromuscular analgesics, anxiolytics; give
dysfunction antivenom if available
IV Localized pain, cranial nerve Symptomatic care and
abnormalities, somatic skeletal supportive care, ie,
neuromuscular dysfunction, and analgesics, anxiolytics; give
airway involvement are all present antivenom if available
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REFERENCES:
1. Chippaux JP, Akaffou MH, Allali BK, Dosso M, Massougbodji A, Barraviera B. The 6(th)
international conference on envenomation by Snakebites and Scorpion Stings in Africa: a
crucial step for the management of envenomation. J Venom Anim Toxins Incl Trop Dis.
2016 Mar 16;22:11.
2. Baykan AO, Gür M, Acele A, Şeker T, Çaylı M. Scorpion envenomation-induced acute
thrombotic inferior myocardial infarction. Turk Kardiyol Dern Ars. 2016 Jan;44(1):82-6
3. Cupo P. Clinical update on scorpion envenoming. Rev Soc Bras Med Trop. 2015
Dec;48(6):642-9.
4. McGhee S, Weiner A, Finnegan A, Visovsky C, Clochesy JM, Graves B. Assessing and
managing spider and scorpion envenomation. Emerg Nurse. 2015 Nov;23(7):32-7; quiz
39.
5. Quan D, LoVecchio F. A clinical score predicting the need for hospitalization in scorpion
envenomation. Am J Emerg Med. 2007 Sep;25(7):856
6. Riley BD, LoVecchio F, Pizon AF. Lack of scorpion antivenom leads to increased pediatric
ICU admissions. Ann Emerg Med. 2006 Apr;47(4):398-9.
7. LoVecchio F, Daniel F Danzl, D F: Scorpion stings in the United States and Mexico,
UPTODATE 2014: http://www.uptodate.com/contents/scorpion-stings-in-the-united-
states-and-mexico.
8. LoVecchio F, McBride C. Scorpion envenomations in young children in central Arizona. J
Toxicol Clin Toxicol 2003; 41:937.
9. Boyer LV, Theodorou AA, Berg RA, et al. Antivenom for critically ill children with
neurotoxicity from scorpion stings. N Engl J Med 2009; 360:2090.
10. Boyer L, Heubner K, McNally J, Buchanan P. Death from Centruroides scorpion sting
allergy. J Toxicol Clin Toxicol 2001; 39:561.
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NON-TOXIC INGESTION:
INTRODUCTION:
Description:
- A case presentation that represents an exposure to a compound thought to be nontoxic.
- A substance should be considered nontoxic category only if the following conditions are met:
- The product has been completely identified.
- Only one compound is involved in the incident.
- The covered label does not contain any warning from the Consumer Product Safety
Manufacture, and the substance in the bottle appears to be the original product (i.e., no
replacement has occurred).
- The amount of substance ingested can be accurately calculated.
- The route of substance exposure can be accurately detected.
- The case is completely free of signs or symptoms of substances effect, both at subjectively
and objectively levels.
- Follow-up procedure must be both easily available and highly reliable (e.g., parent or
guardian).
- If any of these previous mentioned conditions are not met or are questionable, the case
should be managed as an unknown ingestion condition. As Paracelsus stated, "All
substances are poisons; there is none that is not a poison, the right dose differentiates a
poison and a remedy."
Pathophysiology:
- By definition, a nontoxic ingestion should not develop any adverse toxic health effects.
Massive ingestions may produce some mild effects such as GI upset or irritate/obstruct
the airway passage.
Drug interactions:
- Non-toxic substances may interact with drugs that are being taken for therapeutic
purposes.
DIAGNOSIS
Differential Diagnosis
- Following is an alphabetical list of items generally considered to be nontoxic.
Household Items
Ashes Deodorant
Baby Products Erasers
Ballpoint Pen Ink Fabric Softener
Body Conditioner Felt-Tip Pens
Bubble Bath Hand Lotions
Candles Highlighting Markers
Caps For Toy Guns Indelible Markers
Caulk “Accredit Source” Kitty Litter
Charcoal Latex Paint
Clay Laundry Detergent (Liquid)
Cosmetics Lipstick
Crayons “Accredit Source” Magic Markers

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Household Items
Newspapers Produced In The US Shampoos
Pencil Lead (Actually Graphite) Silica Gel
Petroleum Jelly Soaps
Pet Foods Or Chew Toys (Not Including Pet Spackle
Medications)
Photographs Starch
Plastics Sunscreens
Playing Cards Sweeteners
Play-Doh Teething Ring Contents
Rubber Cement Toothpaste
Shaving Cream White Glue
Plant
Many categories of plants are nontoxic. Due to regional variations in names of
plants, a regional poison control center should be contacted if a substantial
amount of any plant is ingested. A partial list of nontoxic plants is as follows:
African Violet Wandering Jew
Aralia Parlor Palm
Baby Tears Peacock Plant
Bird's Nest Fern Piggyback Begonia
Bridal Veil Piggyback Plant
Coleus X Hydrus Prayer Plant
Corn Plant Rubber Tree
Creeping Jenny Snake Plant
Dracaena Indivisa Spider Plant
Dwarf Schefflera String Of Hearts
Emerald Ripple Swedish Ivy
Fiddle-Leaf Fig Velvet Plant
Gardenia Wax Plant
Grape Ivy Zebra Plant
Jade Plant Wandering Jew
Medications
Antacids
Calamine Lotion
Birth Control Pills (If Single Ingestion)
Corticosteroids (If Single Ingestion)
Mineral Oil (Unless Aspirated)
Oral Antibiotics (Some Exceptions)
Water-Soluble Vitamins (Excluding Iron)
Zinc Oxide
Zirconium Oxide
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Signs and Symptoms

- History taking is a main factor in detecting a nontoxic ingestion.
What substances did the case have access to?
What drugs were prescribed to the case or other family members?
When was the last time the case was seen Normally?
Were there initial manifestations that have recovered?
Were substances at the scene of incident brought to the ER for possible
toxicological identification and/or analysis?
- There should be no signs or symptoms at the time of presentation.
- If they do manifestations occur, the case should be managed as an
unknown ingestion.
Laboratory Tests
- If taken history confirms a nontoxic exposure condition, no non-
toxicological or toxicological testing is required. Suicidal attempts should
be treated as unknown ingestions, even if the case claims that only
nontoxic substances were ingested.
TREATMENT
Directing Patient Course
- Dosage and timing should be determined for all compounds that could be
involved. It is important to evaluate the need for toxicological
consultation with a regional poison control center or other concerned
specialists in order to confirm the lack of toxicity of the suspected
ingestion.
Decontamination
- Do not produce any decontamination procedures for a full-ensured
diagnosed nontoxic ingestion.
PITFALLS
- Failure to accurately detecting compound(s) ingested and confirm their
lack of toxicity “non-toxic category”.
REFERENCES:
1. Watson WA, Litovitz TL, Rodgers GC Jr, et al. 2004. Annual report of the American Association of
Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med.;23(5):589–666.
2. Hoffman R, Osterhoudt KC. 2002. Evaluation and management of pediatric poisonings. Pediatr
Case Rev.;2(1):51–63.
3. Barry JD. 2005. Diagnosis and management of the poisoned child. Pediatr Ann.;34(12):937–946.
4. Bar-Oz B, Levichek Z, Koren G. 2004. Medications that can be fatal for a toddler with one tablet
or one teaspoonful: a 2004 update. Paediatr Drugs.;6(2):123–126.

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ROLE OF TOXICOLOGY LABORATORY:

I- Basics:
Description:
- A drug screen tests for a large spectrum of substances. It may be tested
on urine or blood, depending on the particulated drugs and procedures
that are used. Unfortunately, the drugs detected by a drug screen vary
among clinics.
- The drug screen is a close to the history and medical examination in
the evaluation of the intoxicated patient. It rarely gives critical
information but may be helpful to evaluate patients in whom clinical
data fails to give an accurate diagnosis.
Forms:
Urine Drug Screening
- Urine is the specimen of choice for drug screens because most drugs
and their metabolites are excreted in a concentrated forum in the
urine.
- The two major procedures used in drug screens are immunoassay and
chromatography. Mass spectrometry can be utilized in combination
with chromatography to confirm drug detection more accurately.
- Immunoassay
- A drug-specific antibody conjugate to the target substance. The
antibody-drug complex produced is then identified by one of several
procedures (enzymatic immunoassay reaction, fluorescence
immunoassay, or radioisotope immunoassay labeling).
- The advantages of choosing this procedure involve fast turnaround and
the requirement for minimal sample preparation and handling. This
release time and costs approximately low.
- This is the procedure utilized in most laboratories. However, multiple
bedside techniques also use this procedure (e.g., Triage and Verdict).
- T.L.Chromatography:
- The various solubility of substances in polar and nonpolar
compartment is used to separate the different substances in a
specimen. The most common procedure is thin-layer chromatography
(Toxilab), although liquid or gas chromatography columns are indicated
as well, depending on the substances to be detected.
- After separation, the substances are then detected by color
appearance.
- Chromatography can identify a large spectrum of drugs but has
multiple disadvantages. The procedure contains substantial sample
preparation, and interpretation needs experienced technicians. In
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addition, cross-reactivity among substances may locate, thus giving

only probable detection of substances in the urine sample.
- Mass Spectrometry
- Mass spectrometry (MS) is conjugated with gas chromatography
(GC/MS) and is utilized to assure the substances detected by other
procedures.
- The substances molecular structure is bombarded, dividing it into
multiple fragments. These parts are then detected by comparison with
a computer database of parts of known substances.
- The advantage of this procedure is high accuracy in detection.
However, this procedure is relatively time consuming and high cost and
need well-trained technicians.
Serum Drug Screening
- For some drugs (acetaminophen, anticonvulsants, salicylate,
theophylline, ethyl alcohol, ethylene glycol, isopropyl alcohol, lithium,
methanol), screening is best produced on a serum specimen.
Indications
- There are no absolute indications for drug screens. Routine urine
toxicology screening in overdose cases is high-cost and should be
stopped.
Recommended Uses of Drug Screening:
- The patient has a disturbed conscious level of undetected cause. Drug
detecting in this scenario may give data and confirm the cause of
disturbed conscious level.
- Reported suspected ingested substances do not correlated to medical
manifestations. For example, if a case has reportedly exposed a
benzodiazepine medication, but has a heart rate of 130 beats/min,
further investigation must involve a drug screen to evaluate for the
presence of stimulants substances, tricyclic antidepressants
medication, or other drugs.
- Athletics. Substance screening is performed in athletics to discover
illegal procedure of enhancing performance.
- Brain Death. Diagnosis of brain death should not be identified until the
presence of CNS depressant substances has been excluded.
- Intoxication. Substances screens may be helpful if intentional toxicity is
suspected.
- Pregnancy. If substance abuse is suspected, substance testing of
pregnant female at the time of delivery may direct the way for a social
service act.
- Psychiatric. Substance screening in cases with psychiatric symptoms
may indicate a toxic etiology.

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- Treatment Programs. Substance screens may be helpful if

noncompliance with drug treatment protocol is suspected.
- Workplace. Substance screening in the workplace is utilized to identify
high-risk potential employees and to decrease risk of occupational
accidents.
Method of Use
Preparation
- It should be detected how long it will take for investigated test
results to return. In order to have a meaningful effect on immediate
patient medical intervention, test results should be released within
one hour.
- Substance screens should be indicated only after the treating
medical staff has detected what actions will be performed when the
results are appeared. For example, serum drug levels of unusual
substances are rarely of medical value because the correlation of
serum level to poisoning or prognosis is undetectable. Furthermore,
these investigative results may not be ready for several days.
- Contacting a clinical toxicologist for advice relating the usefulness of
substance screening should be involved.
- Prior to collecting the samples, consider contacting the laboratory
technician to assure that the samples is rightly collected and stored.
Collection
Urine
- Sample Collection. A urine specimen of 20-100 cc should be
collected and sent to the laboratory. Be aware to procedure used
to adulterate the presence of drugs in urine sample. Ambulatory
patients giving a specimen for analysis should be observed to
avoid adulterating or replacement of another specimen.
- Specimen Handling. The specific substance being suspected or
the clinical case scenario should be contacted to the laboratory.
This shall allow the technician to better comment the obtained
results or to provide the physician that the specimen may not be
discovered by the procedures that are available at the
laboratory.
Blood
- Sample Collection. Before to collecting the sample, consider
contacting the laboratory technician to confirm that the sutiable
type of collecting tube is utilized.
- Sample Handling. The specific substance being suspected or the
medical situation should be contacted to the laboratory. This will
allow the laboratory technician to better comment the results or
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to support the physician that the specimen may not be identified

by the procedures that are present.
II- Pitfalls
Diagnosis
- Negative" substance screen. The inability to detect a substance
does not equal that it is not situate.
- The substances of interest may not be involved on the panel used.
- The urine sample concentration may be too dilute for detection of
the target substance.
- The urine sample may have been obtained before the substance was
excreted.
- The specimen may have been adulterated with (rare in the acute
disease situation but common in work-related substance screening).
- Detection of a substance in urine does not provide data about the
clinical manifestations of the substance. Most substances assays will
detect substances days after the clinical manifestations are relieved.
Immunoassay
- Immunoassays are limited to detection of the specific substances
involved in the assay spectrum. Other substances with same effects may
not be identified (e.g., opiate immunoassay kit screens panel do not
identify methadone or fentanyl).
- Immunoassay procedure also may cross-react with substances that are
molecular structurally similar but produce other clinical manifestations. If
a substance test is recorded as positive for an illegal substance, it is
critical that the test result is confirmed by GC/MS for medico-legal
indications.
Thin-layer chromatography
- Thin-layer chromatography obtained results are technician dependent,
and a large spectrum of tests are required to maintain proficiency.
Drug screen
- Some substances are not identified by most substance screens. These
include iron, cyanide, hydrocarbons, lithium, heavy metals, toxic
alcohols, LSD, and many rare drugs.
REFERENCES:
1. Brett AS. (1988): Implication disorderance between clinical impression and toxicology
analysis drug in dug overdose. Arch Inter Med: 148:437-441.
2. Institute of Medicine (2004). Forging a poison prevention and control system.
Washington D.C.: National Academy Press;.
3. Klaassen, Curtis (2013). Casarett & Doull's Toxicology: The Basic Science of Poisons,
Eighth Edition: McGraw-Hill Education.

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Substances of Abuse Testing “Specimen Collection”

Overview:
- Toxicology Laboratory provides suggested sample collection guidelines
ONLY. It is the responsibility of individual collection institute to adapt
their own policies and procedures according to their requirement in
accordance with internal authority rules. Laboratory drug and alcohol test
results are usually used in legal issues. The pattern in which samples are
collected and handled is very critical. Samples must be handled and
controlled by collection site personnel throughout the collecting cycle. A
uniform urine and oral fluid obtaining procedure, regardless of the
investigating environment, must be applied.
Site preparations:
Principle:
- Requirements for sample collection vary according to the need for
which the results will be utilized. However, to reach accepted
requirements the sample collection site should be secure in order to
exclude the possibility of sample adulteration or replacement and to
assure the security of the collected sample.
Collection Area Guidelines:
- Secure & Clean Collection Area
- Collection site equipment is secure, well lit, and clear of any
sites where adulterants materials or replaced sample can be
hidden. Furthermore; a clear clean working surface for the
collecting technician to utilize as a sample manipulated area.
- Secure Collection Supplies Source:
- Storage site for collection equipment and related articles is
secure.
- Secure or Eliminated Water Supply Source:
- Exclude all sources of water supply in the site where
urination applies. Bluing substances must be putted in the
toilet tanks and bowls to avoid specimen dilution.
- Secure or Excluded Detergent Source:
- Exclude all soap sources or any other potential adulterants.
- Secure Sample Storage Area:
- A secured collecting site area should be ready to proof
sample security before to carry to the laboratory site.
- Secure Documented Log Book:
- A recorded log book must be ready to report collected
samples.
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Substances of Abuse Testing: (Specimen Collection)

Collection: Urine/Oral Fluid Sample Collection Protocol
Principle:
- The validity of urine sample substance screen results is dependent
on sample integrity level.
- While direct-observation collections technique gives samples of
the highest credibility, non-witnessed collections technique may
be effective if collectors are in site to assure the donor does not
have access to adulterant substances which may change test
results value (tape water, adulterant chemicals substances,
replaced urine, etc.).
Suggested Steps (Before To Collection):
- Ask for the identity of donor :
- e.g. national security card or driver’s license card and photo I.D.
& If using a substance screen test request forum, report the
identity data on the forum.
- Ask the donor case to get ride any unnecessary outer clothing:
- All donor personal belongings (the material may retain a wallet)
must be placed in a secure site outside the collecting site.
- Ask the donor case to empty his/her pockets or to remove articles
of clothing such as shirts, dresses, etc.
- ONLY If a collector repots any abnormal behavior that requires
a donor case may attempt to adulterate a sample (e.g.,
abnormal bulging pockets), the collector personnel may ask
that the donor empty his/her pockets and give the reason of
the requirement for such articles during urine collection
process.
- Ask the donor case to wash his/her hands by soap and water
(before to collecting process):
- To eliminate any possible adulterating materials or
contaminating ingredient from under the suspected fingernails.
Urine Collection Procedure:
- Report the following data on the collecting bottle label:
- Date of urine collection
- Donor’s name and/or identification card numbers
- Collector’s name
- Case reported code number
- Give the donor with:
- A clean, unused urine sample collecting container and
order the donor to fill the collecting container at least half
full (a minimum of 50 mL’).

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-Supervise the unobserved collecting procedure:

- Allow the donor case to enter and maintain privacy within
partitioned collecting site. The collector personnel shall wait
outside the collection site until the donor is finished from
urine collection process. Complete the remaining data of
the test request forum during the donor is obtaining the
sample.
- Accept the sample from the donor.
- The use of disposable plastic gloves is mandatory when
handling samples, so before to accepting the samples from
the donor, be sure to wear plastic gloves.
-Detect urine sample's temperature:
- After accept of the urine sample from the donor,
immediately put the temperature strip (if available) to the
inside of the bottle. If reporting a substance screen
investigating request forum, report the urine temperature
degree on the forum.
NOTE: Urine temperature degree must be detected within (3) three
minutes of collecting process and should read between 32-38 °C
NOTE: Observed Collecting Procedure: Inform the donor that collecting
process shall apply under direct observation protocol. Accompany the
donor into the collection site (the collector must be the same gender).
Direct the donor to urinate into the urine specimen collecting
container with the witness observing urination process direct
protocol. Complete the remainder data of the test request forum
after the donor has completed collecting the urine sample.
Specimen Validity:
Specimen Tampering/Adulteration
- Principle
Techniques to adulterate urine samples for drug abuse testing
procedures generally represent in three procedures:
Urine substitution:
- The replacement of one’s own urine specimen with one which is clean
is a high incidence act. The best procedures to prevent this practice is
to record urine temperature degree, as urine sample even held close
to the body surface for extended durations of time will not give a
physiologically normal temperature-correct sample.
Ingestion of fluids or compounds:
- For flushing out the urinary tract system, diluting the urine sample, or
interfering with the testing procedure. Drinking large amount of
liquid, especially juice of cranberry or pure vinegar is common act.
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Although, procedures revealed these procedures have no action on

testing pathways and may give unexpected informational results.
- Many of the substances being investigated are pH dependent
substances. When large amount of juice of cranberry or pure vinegar
are intake, the urine pH is decreased, and the rate of excretion of
these substances may accelerate. If timed rightly, large volumes of a
substances may excrete rapidly in the urine sample.
- One potentially effective procedure which may negatively affect the
testing procedure is to intake large amount of water, as short term
water loading volume can rise urine amount up to eight time.
Therefore, if the individual‘s drug level is near the cut-off level of an
assay panel, the urine status may be diluted enough so that the urine
sample will detect below the cut-off level. Other reported procedures
of adulteration involve consuming large quantities of vitamin C,
vitamin B, niacin, Golden Seal, etc. All of these substances are useless
acts.
Direct addition of adulterants:
- Direct adding of adulterants materials to the urine sample itself is the
final technique to adulterate the laboratory procedures. Adulteration
of a urine samples with various substances is reported to inactivate
some of the laboratory testing procedures, especially, the enzymatic
immunoassay‘s techniques.
- Adding of material such as alcohols, blood, sodium bicarbonate
various soaps, sodium chloride, hydrogen peroxide, bleach, etc. are
reported to lead to both pseudo negatives and pseudo positives.
- The recent list of adulterating material to urine sample is changing as
the web sites gives an data source, as well as the effect for
commercial products capable of changing the results of some urine
drug testing procedure. Nowadays, nitrites kits (Klear and Whizzies)
and chromates kits (Urine Luck) are two adulterating agents
commonly detected in the field work. Saudi PCCs are capable of giving
testing for these materials.
Adulteration & Dilution Detection:

- Means to identify adulteration techniques by the collector personnel
and/or the laboratory technicians involve the following:
Specimen Temperature:
- Procedure:
- If sample collecting process is not direct observed, the most
effective procedures to detect sample dilution, adulteration,
or replacement is to detect the sample’s temperature degree.

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The collector must measure the temperature degree utilizing

the temperature strip indicator fixed to the sample container
within FOUR minutes of collecting process; it must read
between 32 and 38 ºC.
- Documentation:
- The urine temperature should be reported on Urine Test
Request forum.
- Urine Appearance and Odour:
- From odour:
- Adulterants materials as soaps, bleach, isopropyl
alcohol, and perfumes are readily detected by their
characteristic odor.
- From bubbling:
- Soaps are also detected by marked bubbling
appearance.
- From residues:
- Utilize of solid adulterants materials is identified by the
appearance of residues substitutes in the collecting
container.
- Specific Gravity:
- Normal SGr = 1005 - 1035:
- Normally, a randomly selected urine sample shall have a
specific gravity of ( ) 1.005 & 1.035.
- Low SGr <1.005
- An very low specific gravity (<1.005) revealed a diluting
attempt of urine sample,
- High SGr >1.045
- In the opposite side abnormally increase specific gravity
(>1.045) may direct the collector to the presence of
suspected dissolved solids adulterants as sodium chloride
and sodium bicarbonate.
- pH:
- Normal urine pH = 4.8-7.8:
- Normal randomly selected urine sample pH is 4.8-7.8*.
- Low urine pH < 4.8
- Low urine pH’s revealed possible intake of acidic material
such as juice of cranberry or pure vinegar solution;
condition of starvation ; severe diarrhea; or direct
adulteration attempt of the sample itself with adding
acidic materials.
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- High urine pH > 7.8

- Elevated urine pH’s may indicate the presence of basic
compounds such as sodium bicarbonate, bleach, or
Drano; vegetarian diet; or prolonged vomiting.
- Visible Blood Detection:
- Indication:
- It indicates the presence of blood in the urine sample.
The presence of blood in the urine sample may
adversely affect the testing procedure and, in
addition, material a biohazard for laboratory staff.
- Precaution:
- Collection of clean clear urine sample during
menstruation period should be aimed.
- Urinary Creatinine Level:
- Creatinine is a metabolic end product of muscle catabolism
which normally excrete in urine flow in nearly fixed amounts
over each 24 hour urinary daily excretory duration period.
Therefore, urinary creatinine level can be utilized both as a
indicator marker to specifically detecting a sample as urine
biological sample, and as an indicator value of urinary water
content level (dilution attempt).
- Creatinine urinary level > 20 mg/dl:
- Normal random selected urine sample will have urinary
creatinine concentration of more than 20 mg/dL.
- Creatinine level 10-20 mg/dl:
- Samples with Creatinine concentration between 10
and 20 mg/dL may be rise from increased liquid intake,
physiologically high water content dietary habits, or
high amount of liquid ingestion behavior.
- Creatinine urinary level 2-10 mg/dl:
- Urine sample with creatinine concentration between 2
and 10 mg/dL are usually a result of intake of large
amount of water (or other liquid substances),
identified as short term water/liquid loading
attempted.
- This is a very common act when attempting to dilute a
urinary sample so that any represented drugs in the
urine sample will be diluted below analytical detecting
testing cutoff concentration.
- A critical item to put in mind when comment on dilute
urine samples is that drug use shall be never be

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detected unless specifically detected, and confirmed in

a urine sample. Specifically, a dilute urine sample shall
produce pseudo negative results, as drugs in the urine
at concentrations level near the testing cutoff level or
may be diluted below the testing cutoff concentration,
although, due to the causes documented above it can
be difficult to prove the cause or intent for the urine
sample(s) being dilute.
- Creatinine urinary level <2 mg/dl:
- Urine Creatinine concentration below 2.0 mg/dL are
usually a result of the direct addition attempt of a
water and/or liquid substance to the urine sample.
- Creatinine urinary level 0 mg/dl:
- Creatinine urinary concentration of 0.0 mg/dL mean
the sample is not consistent with normal human urine
sample constitute.
 NB: Urine samples become dilute as a result of the short duration intake of large
volumes of a water and/ or liquid due to an unknown excitatory factors such as a
physiologically response to heat exposure or exercise activities, herbal flushing
effects, diuretics medication prescription, intentional dilution attempts, or
pathological conditions such as diabetes insipidus syndrome.
 NB: The dilution act from taking high volumes of water and/or liquid can present
from two – five hours. Therefore, the raised consuming of water and/or liquid
should have to perform between two – five hours before to the collecting process
of the urine samples.
 NB: For these causes, urine creatinine concentration is recorded in combination
with detecting for drugs of abuse, as an indicator marker of sample validity
condition only, as urine sample with a creatinine concentration below 20 mg/dL
may have a rising attempt of leading a pseudo negative drug testing result.
 NB: Normal mentioned ranges are reported only for freshly voided urine samples.
REFERENCES:
1. Levine B: Principles of Forensic Toxicology, 4th ed. Washington, DC: AACC Press, 2013.
2. Negruz A, Cooper G: Clarke’s Analytical Forensic Toxicology. London: Pharmaceutical
Press, 2013.
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ASYMPTOMATIC PATIENT PRESENTATION:

I- BASICS:
Description:
- Although consuming a life-threatening substances intake, a patient may
be initially asymptomatic or have minimal reported manifestations that
recover and thereby misdirect the physician.
II- DIAGNOSIS:
i- Toxic substances exposure with no initial effects:
Acetaminophen
- 12 - 48 hours: Hepatic impairment associated with gastrointestinal
manifestations as, nausea, vomiting, right upper quadrant pain, and
laboratory finding abnormalities consistent with toxicity of the liver
shall be apparent.
- Renal and pancreatic impairment also may occur.
Anticoagulants
- Anticoagulants (warfarin, pindone, valone, brodifacoum, chlorophacinone,
diphacinone, pivalyn).
- 24 hours to several days: Clinical manifestations of bleeding
(epistaxis, hematemesis, bleeding gums) accompanied with an
increased prothrombin time on laboratory findings may detect.
Arsenic or Thallium
- Days to months: Gastrointestinal upsets usually develop within 1 to
2 hours in acute intoxication. Repeated small arsenic doses
exposures shall lead to delayed manifestations days or weeks later
(water contamination, homicidal attempts).
- Repeated small doses will reveal to delayed toxic manifestations
days or weeks later from the time of onset time of exposure (water
contamination, homicidal acts).
Body Packers
- Hours to days: The category of manifestations depends upon the
substance ingested; heroin and cocaine are the commonest
reported.
- Time of manifestations onset varies with the type packaging
utilized; in cases of body packers, they wrap packed drugs carefully,
but the packets contain huge amounts of addicted substance per
package, resulting in fast and severe development of
manifestations once a package breaks, tear or leaks.
Button (Disk) Battery
- Hours to days: Battery may split or leak during transit pass through
the gastrointestinal tract system.

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- Manifestations may occur suddenly at any time when the battery

breaks and accept the caustic substances contents to release.
Ethylene Glycol
- 8-24 hours: Severe metabolic acidosis condition, tachycardia,
tachypnea, and renal impairment may occur after an initial
asymptomatic stage following exposure of Ethylene Glycol.
- The metabolic acidosis require several hours to start.
- If the patient has exposed to ethanol as well, manifestations may
be postponed further still until the exposed ethanol amount has
been completely metabolized
Hydrofluoric Acid
- Immediate to 12 hours: Low-concentration (6%-8%) cutaneous
hydrofluoric acid damage may locate hours after the onset of
exposure to low-concentration components.
- Dermal Manifestations can appear minimal even when damage and
painful sensation are high.
Lead
- Hours to weeks: Acute exposure by ingestion of lead curtain
weights, sinkers, etc. may develop delayed neurological
manifestation as encephalopathy and death in pediatrics.
Methanol
- 6-24 hours: Severe metabolic acidosis condition with a disturbed
consciousness level, tachycardia, tachypnea, and irreversible
blindness may occur after an initial asymptomatic state following
methanol ingestion.
- The acidosis develops at least 9-12 hours to occur.
- If the patient has co-ingested ethanol with methanol,
manifestations may be postponed more still until the ingested
ethanol amount has been completely metabolized.
Mercury
- Hours to months: A single exposure to mono- or dimethyl mercury
(either cutaneous or through ingestion) has leaded to delayed
neurologic and renal toxic manifestations.
Naphthalene
- 1-7 days: Manifestations of hemolysis with hyperthemia, vomiting,
abdominal pain, diarrhea, lethargy, jaundice, and dark coloured
urine are typically postponed after ingestion as naphthalene is
metabolized to its active hemolytic metabolite ingredients.
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Oral Hypoglycemic
- Oral hypoglycemic agents (glipizide , glyburide, tolazamide
[Tolinase], acetohexamide, chlorpropamide, tolbutamide).
- 2-12 hours: The onset of hypoglycemic manifestations may be
postponed, especially with long-acting medications such as
chlorpropamide, which may have a delayment in peak
concentrations of up to 36 hours.
- It is recommended that the random blood glucose level be
monitored for 12-24 hours following exposure of an unknown oral
hypoglycemic medications.
Snakebite (Coral Snake, Rattlesnake)
- Immediate to 12 hours: Neurologic manifestations following coral
snake bite may be postponed.
- Swelling, edema, tenderness, ecchymotic patches, and
coagulopathy tendency of rattlesnake bite toxicity may be
postponed 4-12 hours.
- Dependent resting positioning of an intoxicated limb may postpone
venom absorption and the onset of toxic manifestations.
Sustained-Release Products
- Includes active ingredients products such as (e.g., aspirin,
theophylline, propranolol, lithium, and verapamil.)
- Up to 24 hours: Postponed absorption and toxic manifestations
may develop due to the constitution of these active ingredients.
- Manifestations vary with the type of intoxicated active ingredient
substances.
ii- Toxic exposure with minimal initial symptoms:
Antineoplastic agents
- Hours to days: Most antineoplastic medication shall lead to some
gastrointestinal upset manifestations within several hours of
intake; however, bone marrow depression, the major toxic
category of most medications, may not occur for several days from
exposure.
Cadmium
- Up to 96 hours: After the recovery of initial manifestations,
including mild cough, precordial and chest pain, dyspnea, shortness
of breath, nausea, malaise and hyperthermia, a patient inhaling
cadmium fumes during welding work may progress to delayed
onset pulmonary edema.

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Carbon Tetrachloride
- 1-3 days: Gastrointestinal upset, nausea and headache may
develop early.
- Hepatic impairment, damage up to necrosis develops 1-3 days after
the onset of carbon tetrachloride exposure.
Cement
- 12-24 hours: Cutaneous exposure to wet form of cement (calcium
hydroxide) may develop in dermal damage and skin ulceration as
cement substance leaks around boots or gloves.
- Manifestations do not start for several hours from the time of
exposure.
Chlorine
- Up to 24 hours: After initial manifestations of respiratory passage
irritation subside, pulmonary edema may occur following high level
inhalation exposure.
- Some manifestations such as an intermittent mild cough are likely
to remain in these patients.
Colchicine
- 2-12 hours: Gastroenteritis usually occurs within hours.
- Bone marrow depression occurs 4-5 days following exposure.
Hydrocarbons
- Up to 6 hours: Aspiration chemical pneumonitis may develop
following hydrocarbon orally exposure.
- The diagnosis of an initial chest radiographic investigations may be
normal with the delayed development of chemical irritant
infiltrates several hours later associated with increasing respiratory
distress signs and symptoms.
- A persistent mild cough episodes may be the only sign of chemical
hydrocarbon aspiration during the otherwise asymptomatic stage.
Iron
- 6-24 hours: Following a gastrointestinal upset stage involving
nausea, vomiting, diarrhea, and abdominal pain, patients may pass
to improve for several hours following orally exposure before
developing systemic toxic manifestations, including hypovolemic
shock, pallor, generalized lethargy, metabolic acidosis, and
coagulopathic manifestations.
Paraquat
- Immediately to days: High-concentration of paraquat ingestion
produces initial caustic gastrointestinal manifestations.
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- Lower concentration of paraquat oral or cutaneous exposure

may occur with renal impairment over 3-5 days and diffuse
pulmonary fibrosis over 1-2 weeks.
Phosgene
- Up to 72 hours: Initial irritant respiratory and neurological
manifestations of cough, dyspnea, irritability, and anxiety may be
delayed following phosgene exposure to concentrations level of
less than 3 ppm.
- Pulmonary imitation and edema may be postponed for as long as
72 hours following inhalation exposure.
III- Treatment:
- A common approach to intoxication includes close patient
observation and performing indicated investigations.
- Knowledge of the specific poison facilitates detecting an
appropriate duration of medical close observation as well as
indicating appropriate laboratory tests panel. (In-dividualialized
Laboratory testing detection)
IV- Pitfalls:
Treatment
- Due to the low incidence of late developed complications of
poisonous ingestion, some physicians have a false sense of security.
- Asymptomatic patient’s presentation may be premature discharged
before more serious manifestations develop.
REFERENCES:
1. Barile FA: Clinical Toxicology(2010): Principles and Mechanisms, 2nd ed. New York:
Informa Healthcare.
2. Hoffman RS, Howland MA, Lewin NA, et al. (eds.)(2014): Goldfrank’s Toxicologic
Emergencies, 10th ed. New York: McGraw-Hill.
3. Tintinalli JE, Stapczynski JS, Ma OJ et al. (eds.)(2010): Emergency Medicine: A
Comprehensive Study Guide, 7th ed. New York: McGraw-Hill,.
4. Klaassen, Curtis; Watkins III, John B. (2015). Casarett & Doull's Essentials of Toxicology,
Third Edition (Lange). McGraw-Hill Education.

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MEDICAL TOXICOLOGY HISTORY INTAKE FORM

PLEASE PRINT
First Name: Last Name: Middle Name: Date:
Street Address: City: Home Phone:
Date of Birth: Marital Status:□M Sex: □M ID/Iqama number
□S □W □D / □F
Name of Primary Care Provider: Phone of Primary Care
Provider:
REASON FOR SEEKING CONSULTATION WITH A MEDICAL TOXICOLOGIST
CURRENT PRESCRIPTION MEDICATIONS / OVER-THE-COUNTER

MEDICATIONS / HERBS & SUPPLEMENTS
List all prescription, non-prescription, herbal medications, and
supplements taken.
Prescription Medication Strength Times per Day When Started
Non-Prescription Strength Times per Day When Started

Medications
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ALLERGIES or REACTIONS TO MEDICINES/FOODS/OTHER AGENTS:

Medication/Food/Other Agent Side Effect
PAST MEDICAL HISTORY:

Please check (√) if YOU have ever seen a physician for or been treated
otherwise for any of the following medical conditions
□ Substance Abuse □ Allergies □ Bleeding Problems
□ Bulimia/Easting Disorder □ Cancer (please specify) □ Depression
□ Diabetes □ Heart Disease □ High Blood Pressure
□ Endocrine/Hormone Disorders (e.g., thyroid, low testosterone) □ Lung Problems
□ Kidney Disease □ Liver Disease □ Hearing impairment
□ Neurological Disorders (e.g., tremor, stroke, blindness, seizures, coma,numbness, weakness, migraine)
□ Chronic Pain □ Psychiatric Problems (e.g., bipolar disorder, schizophrenia)
□ Rash/Allergy □ TB □ Other (Please specify
below)
Please provide details for all checked boxes:
SURGICAL HISTORY
(Please list all prior operations or surgical procedures and dates):

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SOCIAL HISTORY:
Please check (√) all that apply:
SMOKING
□ Current Cigarette Smoker □ Former Cigarette Smoker □ Never Smoked
ALCOHOL USE
□ Currently using □ Used to drink alcohol □ Never drink alcohol
RECREATIONAL DRUG USE
□ Current Drug User □ Former Drug User □ Never Drug User
□ Marijuana □ Cocaine □ Ecstasy □ Methamphetamine
□ Heroin □ Designer Drugs □ LSD □ Glue Sniffing
□ IV Drugs □ Other (Please specify) ……………………………………………………………….
………………………………………………………………………………………………………
EDUCATION COMPLETED:
□ Grade school □ High school □ Univ. □ Post Graduate education.
Total Years of education: ………..
FAMILY HISTORY:
Please check (√) if your (parents, siblings) has a history of any of the
following:
□ Alcohol / Drug Problems □ Allergies □ Bleeding Problems
□ Other blood diseases □ Cancer (please specify type) □ Diabetes
□ Endocrine/hormone (e.g., thyroid) □ Heart Disease □ High Blood
Pressure
□ Kidney Dise □ Liver Disease □ Lung Problems □ Rash
ase
□ Neurological Disorders (e.g.tremor, stroke, coma, blindness) □ TB
□ Psychiatric Problems (e.g., depression, bipolar disorder, schizophrenia)
□ Other (Please specify) ………………………………………………………………….…………………………
……………….………………………………………………………………………………………………………………….
Please provide details for all checked boxes:
……………………………..………………………………………………………………………………………………….
…………..…………………………………....…………………………………………………………………………………………………
……………………………………………………………………………….…..…………………………………………………………………
……………………………………………………………………………………………
OCCUPATIONAL HISTORY
 Any Exposure to Vapors Gas Dusts or Fumes (specify):
………………………………………………………………….……………………………………………
 Is there something you were exposed to that you are concerned about? □
Yes: ………….. □ No: …………..
 Do you use protective equipment such as gloves, masks, respirator, or
hearing protectors in the workplace? □ Yes: ………….. □ No: …………..
If yes, please list the protective equipment used:………………..…………………
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REVIEW OF SYSTEMS:
Please check (√) any current problems you have on the list below.
□ Constitutional □ Fevers/chills/sweats □ Fatigue/weakness □ Allergies
□ Unexplained weight loss/gain □ Eyes
□ Excessive thirst or urination
□ Change in vision (blurry vision or decreased □ Difficult hearing/ringing in ears
vision)
□ Ears/Nose/Throat/Mouth □ Problems with □ Difficulty tasting with food or
teeth/gums drinks
□ Cardiovascular
□ Leg pain with exercise □ Chest pain/discomfort □ Palpitations or irregular heart beat
□ Chest (breast) □ Breast lump/discharge □ Female □ Lactating □ Pregnant
□ Respiratory
□ Cough/wheeze □ Difficulty breathing
□ Gastrointestinal
□ Abdominal pain □ Blood in bowel movement □ Nausea/vomiting/diarrhea
□ Reflux or gastritis □ Ulcer
□ Genitourinary
□ Frequent nighttime urination Leaking urine Unusual vaginal bleeding
□ Discharge: penis or vagina Sexual function problems Musculoskeletal
□ Sexually transmitted disease
□ Muscle/joint pain
□ Joint swelling or inflammation Arthritis Rheumatoid arthritis
Skin
□ Hives / Eczema or Rash □ Chemical Sensitivity □ Abnormal bleeding or bruising
□ Easy bruising/bleeding □ Unexplained lumps
Neurological
□ Headaches □ Dizziness/light-headedness
□ Numbness in hands, feet, fingers or other areas (specify please)
□ Memory loss □ Loss of coordination □ Difficulty walking □ Tremors or shaking
Other “nervous” condition”…………………………………………………………………………………………………………
………………………………………………………………………………………………………………………………...……………………
.
Psychiatric
□ Anxiety/stress □ Hallucinations □ Depression □ Blood/Lymphatic
□ Other (please specify)
Please provide details for all checked boxes:……………………………………………………………………………
………………………………………………………………………………………………………………………………………………………
……………………………………………………………………………………………………………………………………..………………
ENVIRONMENTAL EXPOSURES HISTORY:
Please check (√) If you live or have ever lived next door to or very near
any of the following facilities:
□Industrial Plant □Commercial Business □Waste Dump Site
Have you been out of the country during the past year? □ Yes □ No
If Yes where?........................................................................................
Attending Physician`s Signature..................................................

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REFERENCES:
1. California PCC Antidote Chart (2014), http://www.calpoison.org/hcp/
Antidote_Chart_2014, 1014.
2. Goldfrank, L. R., & Flomenbaum, N. (2010). Goldfrank's toxicologic emergencies. New
York: McGraw-Hill.
3. Olson, K. R., & California Poison Control System. (2006). Poisoning & drug overdose.
New York: Lange Medical Books/McGraw-Hill.
4. Illinois Poison Center Antidote List (2013), http://illinoispoisoncenter.org
/ipc_media/pdf/antidote%20list%202%202011.pdf
5. Poison Information Center of Ireland antidote list (2011), http:// www.poisons.ie/
Downloads/Antidote_Booklet_2011.pdf
6. KSA. MOH Formulary Drug List (2014)
7. Lheureux PE, Zahir S, Gris M, et al. 2006: Bench-to-bedside review: hyper-insulinaemia
/euglycaemia therapy in the management of overdose of calcium-channel blockers.
Crit Care;10 (3):212
8. Young AC, Velez LI, Kleinschmidt KC, 2009: Intravenous fat emulsion therapy for
intentional sustained-release verapamil overdose. Resuscitation; 80 (5):591–3.
9. Buckley NA, Eddleston M, Li Y, et al, 2011: Oximes for acute organophosphate
pesticide poisoning. Cochrane Database Syst Rev Feb 16;(2):CD005085.
260 eMedical
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ANTIDOTES CHART
eMedical
Availability requirements (AR):
(A): Required to be immediately available (within the Emergency Department) ,
diuG ygoToxicology
(B): Required to be available within 1 hour (within the hospital),
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(C): These drugs are rarely used and can be held supra-regionally.
P or
Antidote Toxin Dose AR* NOTES
Not P**
-Acetaminophen - IV NAS 20 hour's course: A - Beware anaphylactic P

Poisoning Loading dose 150 mg/kg over 1 hour followed reaction
-Chloroform by 50 mg/kg over 4 hrs followed by 100 (bronchospasm,
Poisoning mg/kg over 16 hrs. hypotension,
- Carbon - IV NAS 48 hour's course: wheals, and
Tetrachloride Loading dose 140 mg/kg followed by 70 laryngeal edema)
Poisoning mg/kg over 4 hrs. for 12 doses during IV
- Other Hepatotoxins - Oral NAS: administration.
Loading dose 140 mg/kg followed by 70 - IV NAC may be
mg/kg every 4 hrs. for 17 doses. preferable in
Acetylcysteine (NAC)
patients who have
hepatic
encephalopathy or
are pregnant.
- Most poisons. Up to Initial dose: 1 g/kg (adult dose 50–100 g; child A Contraindication in: P
one hr. following < 5 years,10—25 g) orally or by gastric tube alcohols, caustics,
ingestion. - It may Repeated-doses: 15–30 g (0.25–0.5 g/kg) cyanide, iron,
also be considered every 2–4 hours or hourly (adults, average rate hydrocarbons, lithium
more than one hr. of 12.5 g/h; children, rate of 0.2 g/kg/h) is given and coma without
charcoal
Activated
after ingestion in orally or by gastric tube. airway protection
some poi-soning as
Theophylline
- Organophosphate / - In cholinesterase inhibitor poisoning (OPI) A - May require large P
Carbamates adult: 1 to 3 mg IV; children: 0.02 mg/kg IV. amounts in severe
insectcide poisoning Three to five minutes after giving atropine, cholinesterase
& other cholinester- check the pulse, blood pressure, pupil size, inhibitor poisoning
ase inhibitors e.g., sweating and chest sounds. If no response, (oxygen should be
warfare agent double the dose and continue doubling the provided at the first).
- Bradycardia indu- dose q 3 to 5 minutes when the response is - 3 mg is a fully vagolytic
ced by a variety of still absent. Once the parameters have begun dose in adult.
drugs. to improve, cease dose doubling. Similar or
Atropine
smaller dose can be used as required to dry
pulmonary secretions. Once secretions are
dried, maintain with an infusion of 10% to 20%
of the loading dose every hour.
- Drug induced bradycardia: 0.5-1 mg IV for an
G en e r
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Snake envenomation - Haemotoxic: Polyvalent antivenom 5 amp A - Initial sensitivity test. P
diuG ygoToxicology
- Any local or dilutes in 250ml saline given over 60 min - Give antivenin in IV drip
systemic signs are an & can be repeated every 4-6hrs until diluted antivenin 1/1 up
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indication for improvement to 1/10 in isotonic
antivenin admini- - Neurotoxic: Bivalent antivenom 5 amp normal saline.
stration. diluted in 250 ml saline, more antivenom - Be ready to treat
- Polyvalent snake should be given if sever signs persist after anaphylaxis.
antive-nin for 1-2 hrs. and dose can be repeated every - Children dose = adult
Antivenom
heamatotoxic 4-6 hrs. until improvement. dose.
for Snake bite

snakes. N.B. double the dose of the polyvalent
- Bivalent snake antivenom if bivalent not available
(Polyvalent and bivalent)

antivenin for neuro-
toxic snakes.
Scorpion Initial dose: 5 amp polyvalent antiscorpion A - Initial sensitivity test P
envenomation diluted in 20 - 50 ml saline given IV over - Should be given very
20 minutes (min.). early
If systemic manifestations still exists the same - Keep the patient under
dose can be repeated every 2 hrs. up to 4 observation for at least
doses. 24 hrs. after recovery
Antiscorpion
Heavy metals 2.5-3 mg/kg by deep IM every 4-6 hrs for 2 C - IM administration P
poisoning days, 2-4 times daily on the third day and then only
In lead encephalo- 1-2 times daily for 10 days or until recovery - Changing it to oral
pathy: It is used only succimer once patient is
BAL
with conjunction of stable and able to
calcium EDTA absorb. oral formula
(Dimercaprol)
therapy.
-Drugs cause - Diazepam: 0.1-0.3 mg/Kg may repeat if A - Excessive or rapid IV P
convuls-ions, anxiety needed. administration may
and agitation. - Lorazepam: 0.05-0.1 mg/Kg may be cause respiratory
-Treatment chloroq- repeated. arrest.
uine and cocaine - Midazolam: 0.1-0.2 mg/Kg may be repeated.
cardiotoxicity - In Chloroquine toxicity 2 mg/kg IV over 30
- Alcohol or sedative- mins in combination with assisted
Benzodiaze-pines
hypnotics ventilation.
withdrawal.
- Acute dystonic 1-2 mg IV or IM (children 3 years old, 0.02 A - It is an alternative in P
reactions associated mg/kg, maximum 1 mg). Repeat the dose adults to
withof neuroleptics within 15 min if there is no response. Same diphenhydr-amine
or metoclopramide dose may be given orally every 12 hrs. for 2-3 (the drug of choice
days to prevent recurrence of symptoms for children).
Benztropine
- It is not effective for
dyskinesia or NMS. r ec
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Antidote Toxin Dose AR* NOTES etneer sG
eMedical
Not P**
- Botulinum antitoxin, Adult: one vial 10 ml diluted in 0.9% Saline and C - Initial sensitivity test. NP
heptavalent for botulism given by slow IV infusion. A second vial may be - Ready to treat anaphylaxis
diuG ygoToxicology
in child >1 Y & adults. given 2-4 hrs if symptoms worsen. -The antitoxin should be
- Botulism immune given as soon as possible
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loci xoT lacGuide

globulin, human and not delayed while
Botulism
antitoxin
dose.
lism IG (BIG)
(BabyBIG) for infant awaiting results of diagno-
& Baby Botu-

botulism < 1 Y Infant <1 year: 10 % of the adult dose. stic studies
Neuroleptic Adult: 2.5-10 mg orally 2-6 times daily. B - Continue treatment P
malignant syndrome Pediatric dose is unknown. until rigidity ant fev-
(NMS) caused by Use small, frequent dosing to minimize er have completely
riptine
Bromoc
neuroleptic drugs nausea resolved.
Calcium channel blocker Adults: A - Can cause tissue necrosis if P
,ǇƉŽĐĂůĐĞŵŝĂŝŶĚƵĐĞĚ Give 3 g Ca gluconate (30ml of 10% extravasation occurs
ďǇ(fluoride, oxalate solution) or 1g Ca chloride (10ml of 10% - Not used in digoxin
or the IV antic- toxicity.
oagulant citrate, …..)
Solution). This dose may be repeated - Calcium chloride contains
Hydrofluoric acid every 5-10 min., as needed. nearly three times the
toxicity. It can be given as a continuous infusion 20- amount of Ca2+ per mL of
Severe hyperkalemia 50 mg/kg/hr. 10% solution compared
Calcium
with cardiac Children: 60 mg/kg (0.6 ml/kg of 10% with the same concentra-
Gluconate)
manifestations solution) tion of calcium gluconate.
- Use central line for
(not digoxin
Calcium chloride
(Calcium Chloride & Calcium

induced).
Black widow spider.
Hydrofluoric acid 2.5-33 % concentration A - Manufacture of
skin exposure burns topical gel For topical
< 5% of body surface burns
or exposures to
Gel
Calcium
Gluconate
concentrations of <
20%
Hyperammonemia 50–500 mg/kg/d. A Transient nausea and P
from valproic acid - A loading dose equal to the daily dose may be vomiting are the most
toxicity initially given, followed by the daily dose common side effects of
divided into every 4 hrs. doses. L-carnitine
Carnitine
- A maximal daily dose is 3 g/day.
(L-Carnitine)
-Chlorinated - Adult: 4 g three times daily B Rarely used. (Rarely P
hydrocarbons - Children 6-12 years: (Childs weight in kg X prescribed for children).
- Digitoxin adult dose) / 70
- Amiodarone - Children under 6 years: No dosage
- Oral anticoagulants established.
-NSAIDs - ɴ͘ďůŽĐŬĞƌƐ
- Thiazide diuretics
Cholestyr-amine
- Oral hypoglycemic
G en e r
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- Cyanide poisoning Adult: - Amyl nitrite crush ampoule in gauze Kit contains (2-10mL (3%) NP
- Hydrogen cyanide and place under the nose of the victim for 30 amps of sodium nitrite, 2-50
diuG ygoToxicology
(HCN) seconds every min. Use a new ampoule every mL (25%) vials of sodium
- Sodium thiosu-lfate, 12 amyl nitrite
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nitroprusside, Bromates
2-3 min. - Sodium nitrite 300 mg (10 ml of 3% inhalant amps). Stocking
Kit
(thiosulfate only) solution) over 3.5 min. -Sodium thiosulfate this kit may be unnecessary
- Hydrogen sulfide 12.5 g of 25% sol slowly IV if an adequate supply of
Sodium Nitrite &

(H2S) Children: sodium nitrite 0.15-0.33 ml/kg hydroxyl-cobalamin HCl is
(Conventional)
Sodium Thiosulfate A
Cyanide Antidote
(nitrites only) Sodium thiosulfate 1.6 ml/kg of 25% solution. available
- Cyanide & HCN 5 g as intravenous infusion over 15 min. A Newer, safer and easier NP
poisoning Depending on severity of poisoning, to use than the cyanide
- Smoke Inhalation 5 g may be administered as a second dose. kit
PLQ
Victims (CO, H2S)
Cyanokit
+\GUR[\FREDOD
Serotonin syndrome Adults: Initially: 12 mg p.o. and then 2mg every B It is only available in oral NP
caused by: - 2 hrs. if symptoms continue. form, but tablets may be
Monoami-ne oxidase Maintenance: 8mg every 6 hrs. crushed and administer-
dine
inhibitors Children: 0.25 mg/kg/d divided every 6 hrs. ed by nasogastric tube.
- Selective serotonin with a maximum of 12 mg/d.
Cyprohepta
reuptake inhibitors
Hyperthermia from 1mg/kg by rapid IV injection, repeated as B IV administration can P
(malignant hyperther- required to a total dose of 10mg per kg. The cause venous irritation
mia, neuroleptic
average effective dose is about 2.5 mg per kg. and thrsombophlebitis
malign-ant syndrome,
seroton-in syndrome,
Then 1–2 mg/kg IV should be given every 6 hrs.
cocaine and
Dantrolene
amphetamines)
Iron poisoning IV route (15 mg/kg/hrs.). Continue desfe- B Side effect: hypotens- P
rrioxamine until the patient is asymptomatic, ion, auditory, ocular,
resolved anion-gap metabolic acidosis and Iron pulmonary toxicity, and
Defero
xamine
level is <54 micromol/L. infection.
Cyanide toxicity 300 mg by IV injection over about 1 min. A If symptoms of cobalt

The antidote of choice repeated if the dose is inadequate; a further toxicity occur (nausea,
in severe cases when vomiting, urticarial rash,
dose of 300 mg may be given 5 min. later if
there is a high clinical chest pain, bronchospasm,
required. Follow each injection with 50mls of hypotension, co-nvulsions,
suspicion of cyanide
poisoning e.g. after
50% dextrose intravenously. tachycardia, ventricu-lar
cyanide salt exposure. NB. Only one of three cyanide treatment options arrhythmias and periorbital
(Dicobalt edetate/ hydroxocobalamine/ sodium oedema), stop
nitrite, sodium thio-sulphate) is required to be administration of the drug
Dicobalt edetate
available and institute supportive
measures immediately.
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P or
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Not P**
Lipophilic cardiotoxic 1.5 mL/kg of 20% intralipid as an initial bolus A ILE: contraindicated in P
diuG ygoToxicology
agents (Local followed by 0.25 mL/kg/min for 30–60min. patients with known egg
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anesthetics and Depending upon response, bolus could be allergies, disorders of fat
possibly other cardiac repeated 1-2times and infusion rate increased. metabolism, and liver
toxins e.g., CCB, disease.
(Intralipid)
Intravenous
buprop-ion, cocaine,
lipid emulsion
ɴ͕͘͘dͿ
Digoxin poisoning; Acute toxicity: B Consult with poison P
other cardiac Adults (and children > 20kgs): center regarding dosing
No. of vials= Serum Digoxin (ng/mL)× Pt Wt (kg)/100
glycosides (eg,
No. of vials= Amount ingested (mg) × 0,8/0.5
oleander, foxglove) Infants and children <20kgs:
Digoxin
DigiFab®
Digibind or
Dose of digifab (mg) = 0.40 X serum digoxin level
Immune FAB
(ng/ml) X Body weight (kgs)
Heavy metal 10 mg/kg 3 times a day for 5 days followed by C Succimer can be P
poisoning 10 mg/kg twice a day for 14 days. combined with
(Arsenic, Lead , CaNa2EDTA to take
Lewisite, Mercury) advantage of the ability
DMSA
(Succimer)
Heavy metal For patients with lead encephalopathy: C Side effect: Renal NP
poisoning 1500mg/m2/d* by continuous IV infusion toxicity
(Lead toxicity, Zinc ƐƚĂƌƚŝŶŐϰŚƌƐ͘ĂĨƚĞƌƚŚĞĮƌƐƚĚŽƐĞŽĨ>dŚĞŶ The combination of
salts) Concurrent BAL and EDTA therapies are EDTA with succimer
administered for 5 days appears more potent
*M2 is calculated as follows:
EDTA-Calcium
BSA = SQRT(cm*kg)/3600 )
- Methanol toxicity - Loading Dose: 0.8 g/kg of 10% ethanol B IV 10% ethanol product no NP
- Ethylene glycol (infused over 1 hrs. as tolerated) longer manufactured.
toxicity - Maintenance Dose: 110 mg/kg/hr. Fomepizole easier to dose
and monitor than ethanol
Chronic Alcoholic: 150 mg/kg/hr.
Dextrose
Ethanol
IV 10% with 5%
During Hemodialysis: 250 mg/kg/hr.
and Ethanol (oral)

In oral use 20% ethanol
- Methanol toxicity Loading Dose: 15mg/Kg over 30 min, Followed B Fomepizole is the antidote NP
by 10mg/Kg q 12hrs. for 4 doses, then if of choice. Ethanol only
-Ethylene glycol
necessary, 15mg/Kg q 12hrs. until the pH is needs to be held if
toxicity fomepizole is unavailable.
normal and methanol level <20mg/dl.
Fomepizole
* (AR) Availability requirements - ** Purchasable By MOH (P by MOH) Or Not Purchasable By MOH (Not NP by MOH) r ec
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P or
Not P**
diuG ygoToxicology
Benzodiazepine Adults: Initially 0.1-0.2mg IV over 30 seconds. If A Use small initial dose to P
avoid abrupt awakening/
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poisoning: there is no response within 30 seconds, then a 2nd
Reversal of iatrogenic dose of 0.3mg can be administered over 30 sec. delirium. Do not uses in
over-sedation with Further doses of 0.5mg can be given over 30 sec, at cases that are on chronic
benzodiazepines. 60 second intervals, to a total dose of 3mg. If there is BZ therapy as withdrawal
still no response, it is unlikely flumazenil will reverse seizures may occur.
the CNS/resp depression. The infusion rate is 0.1- Should not be used as a
0.5mg/hr.; Adjusted to maintain the desired “diagnostic” agent and is
Flumazenil
response. contraindicated in mixed
Children: A dose has not been recommended in drugs overdoses (e.g. TCA/
children, the following has reversed coma in an BZ) and in cases with
overdose situation: 10mcg/kg IV not more history of epilepsy.
Methanol Toxicity 50 mg of IV folic acid every 6 ŚƌƐ͘ĨŽƌƚŚĞĮƌƐƚ B Should be administered P

-Folic acid antago-nist 24 hrs. and should be continued until the Ăƚ ƚŚĞ ĮƌƐƚ ƐƵƐƉŝĐŝŽŶ ŽĨ
(e.g. Methotrexate, methanol and formate are eliminated. methanol poisoning and
Acid
trimethoprim) In Methotrexate give a dose equal to or within 1 hr. of methotr-
and Folic
greater than the dose of methotrexate given. exate poisoning
(Folinic Acid)
Leucovorin
- Carbon monoxide Indications for HBO: A The optimal dose of HBO, P for
- Cyanide poisoning - Significant CO poisoning with syncope, number of treatments and
for O2
100% treatment pressure, and
- Hydrogen sulĮde seizures, coma, lactic acidosis, myocardial 100%
O2 the time after which it is no
- Carbon tetrachloride ischemia, myocardial infarction, or abnormal longer an effective therapy
- High met Hg level psychometric testing ĂƌĞŶŽƚǇĞƚĐůĞĂƌůǇĚĞĮŶĞĚ͘
unresponsive to - COHb level >25% in non-pregnant patient Consult PCC to determine if
(HBO)
methylene blue - COHb level >20% in pregnant patient HBO treatment is indicated.
100% O2 and
- Evidence of fetal distress due to CO poisoning
Hyperbaric oxygen
during pregnancy.
- Significant cyanide or cyanogenic compound.
Methemoglobinemia 1–2 mg/kg IV given over 5 min., may be A It is ineffective in NP
Methylene repeated Do not exceed total dose of7mg/kg patients with (G6PD)
Blue ĚĞĮĐŝĞŶĐǇ
Reduction of uroth- IV preparation: Adults: Doses are dependent B Urinary output should be P
elial toxicity in anti- on the amount of cyclophosphamide taken. It maint-ained and monitor
neoplastic therapy is 20% of cyclophosphamide taken, in Children for hematuria and
(Cyclophosphamide) or high-risk patients: Doses of up to 40% proteinuria throughout
treatment but frequent
Mesna
Oral preparation: Doses must be doubled bladder emptying should be
avoided
Paracetamol Adult and children <6 Y: 2.5 grams initially No No longer considered
poisoning followed by three doses of 2.5g every 4 hrs. AR* essential because of its
Methionine Child < 6 Y: 1 g initially followed by three short time span of G en e r
al D
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Opioid overdose Adults: 0.05 to 2 mg IV for as bolus dose (0. 01 A Use small initial dose to P
avoid abrupt awakening/
diuG ygoToxicology
mg/kg for children). May be repeated every 2-
withdrawal and
3 min as necessary until the level of
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convulsions. Re-sedation
consciousness and respiratory rate increase can occur within 1-2 hrs.
Narcan
A total dose (10-15 mg) may require.
Naloxone/
Repeated doses of
naloxone may be required
Hypoglycaemia Adults: ϱϬƚŽϭϱϬʅŐ/D͕Žƌ^͕ŝŶũĞĐƚŝŽŶƋϲŚƌƐ͘ B Avoid long-acting depot P
induced by sulphon- Children: 1 - ϭ͘ϱʅŐͬŬŐ;ƵƉƚŽϭϱϬʅŐͿƋϲŚƌƐ͘ products. It may also
ylureas and quinine given IV bolus over
several min. or by
acetate/
continuous IV infusion
Octreotide
Sandostatin
Anticholinergic Adults: 1–2 mg A Give at low dose, over 2- P
poisoning, especially Children: 0.02 mg/kg (maximum: 0.5 mg) 5 min. to avoid severe
antimuscarinic IV infused over at least 5 min. adverse reactions
delirium The dose can be repeated in 10–15 min. including bradycardia, a
Not generally recommended for children. Call systole, and seizures.
PCC due to contraindication with usage. Contraindicated in TCA
Physostigmine
or similar poisoning with
widened QRS intervals
Cholinesterase Pralidoxime: 1-2 grams IV (or 30 mg/kg) over 30 min. C Oximes should be P
Inhibitor poisoning followed by an infusion of 500 to 1000 mg/hr. (or 8 administered slowly,
(organophosphate or mg/kg per hr.). Children loading dose 25 to 50 mg/kg since rapid
“nerve gas”) (2 g maximum) followed by infusion of 10 to 20 mg/kg administration has been
per hr.
Protopam
occasionally associated
Obidoxime
Oximes
Obidoxime (toxogonin): 250 mg amp; with cardiac arrest.
For adult give 1 amp over 15-30 min IV as a loading
Pralidoxime (2-PAM
dose then 30mg/hr.
anticoagulant effects Dose according to quantity of heparin: 1mg of B Slowly IV over at least 1- P
of unfractionated protamine will neutralize approximately 100 3 min., not to exceed 50
heparin (UFH) and for units (1 mg) of UFH mg in a 10 min. period.
some of the effects of If quantity is unknown: give according to (aPTT)
low molecular- or give empiric dose of 25-50mg
Sulphate
Protamine
weight heparin
(LMWH)
Dirty bomb agents: 150–250 mg/kg/d orally or via a nasogastric C Prussian blue is NP
radioactive cesium tube in 2–4 divided doses. dissolved in 50 mL of
and thallium and 15% Mannitol to treat
Blue/
non-radioactive constipation
Prussian
thallium
Radiogardase
* (AR) Availability requirements - ** Purchasable By MOH (P by MOH) Or Not Purchasable By MOH (Not NP by MOH) G en e r
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eMedical
P or
Not P**
diuG ygoToxicology
- Isoniazid (INH) 1 g of pyridoxine for each gram of INH B A benzodiazepine P
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poisoning ingested, to a maximum of 5 g or 70 mg/kg should be used with
- hydrazine, and Unknown amount ingested: 4-5 g pyridoxine in an attempt
derivatives, and For Ethylene glycol poisoning: 100mg/day IV to achieve synergistic
ethylene glycol control of seizures
Pyridoxine
(Vitamin B6)
overdoses
- Cardiotoxicity of xenobio- In TCA and salicylate: 1-2 mEq of NaHCO3 / kg A /ƚ ŝƐ Ă ŶŽŶƐƉĞĐŝĮĐ P
tics that block Na channels IV can be repeated as needed to achieve a antidote effective in the
(TCA)
- Elimination Enhance of blood pH of 7.50–7.55. treatment of a variety of
weak acids (salicylate, Phen- poisonings by means of
obarbiturate , Methotrex- a number of distinct
ate)
Sodium
- Correct life-threatening
mechanisms.
Bicarbonate
acidosis generated from
toxic alcohols
- Rhabdomyolysis
Starch Iodine 15g starch in 500mls water orally. A P

- Every potential Initial therapy: 100 mg daily. Up to 1000 mg of A Given IM or IV P
alcoholic ƚŚŝĂŵŝŶĞ ĐĂŶ ďĞ ƵƐĞĚ ŝŶ ƚŚĞ ĮƌƐƚ ϭϮ ŚƌƐ͘ ŝĨ Ă
- prevent and treat patient demonstrates persistent neurologic
Wernicke abnormalities.
Thiamine
encephalopathy
Hydrochloride
Warfarin, and super- - Oral Vitamin K1: Marked prolongation of PT B - IV Vit K has been P
warfarin rodenticide or INR without bleeding. associated with fatal
- Adult: 50 to 100 mg/day orally initially in anaphylaxis
single or divided doses. - If active bleeding use
- Pediatric: 0.6 mg/kg/day initially in single or 4-factor prothrombin
divided doses. co-mplex concentrate),
- INR or PT should be repeated measurement if available, afresh fro-
daily, and dose increased as needed to zen plasma and Factor
normalize INR or PT. VIIa.
- Parental Vitamin K1: Severe prolongation of - Complete reversal may
PT or INR and frank bleeding. (dŚĞ ƉĂƚŝĞŶƚ not be desired in cases
Vitamin K1
ƐŚŽƵůĚĨŝƌƐƚƌĞĐĞŝǀĞĨƌĞƐŚĨƌŽǌĞŶƉůĂƐŵĂ) with medical indication
- Adult: 25-50 mg vitamin K1 iv infusion (diluted for therapeutic antico-
agulation.
(phytonadione, phylloquinone)
with D5W or 0.9% saline and infused slowly at
a rate not to exceed 1 mg/min).
- Pediatric: initial dose 0.6 mg/kg, titrated to
response. Then, the dose should be repeated r ec
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Poi

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Dabigatran etexilate 5 g idarucizumab iv as 2 consecutive infusions of 2.5
B -it binds specifically to dabigatran
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overdose g/50 ml over 5 to 10 minutes each or as 2 consecutive 2.5 and not to any other anticoagulant
g bolus injections. Administer a second 5 g dose may be -it can be used in conjunction with
Idarucizumab is licensed for standard supportive measures
considered in the following situations: -Hypersensitivity reaction may occur
use in adults when rapid
•Recurrence of clinically relevant bleeding together with -Each 5g Praxbind contains 4 g
reversal of anticoagulant sorbitol excipient, which could cause
prolonged clotting times or
effect of dabigatran etexilate hypoglycemia, hypophosphatemia,
•If potential re bleeding would be life threatening and
is required as in emergency metabolic acidosis, increase in uric
prolonged clotting times are observed or acid, acute liver failure in patients
surgery or urgent proced -
•Patients require a second emergency surgery or urgent with hereditary fructose intolerance
PƌĂǆŝďŝŶĚ
ures or life threatening or
procedure and have prolonged clotting times.
IĚĂƌƵĐŝǌƵŵĂď
uncontrolled bleeding
The safety and efficacy of Praxbind in children below the
age of 18 years have not yet been established
Whole bowel irrigation for The solution is administered as 0.5L/hr in children B Contraindications: P
agents not bound by < 5 years & 1-2 L/hr for adults. Extensive hematemesis, pa
activated charcoal e.g. iron,
- It is administered by nasogastric tube or orally. -ralytic ileus, bowel obst -
lithium, also for body
packers and for slow release
- The end-point is recovery, and return of the drug ruction and, perforation or
preparations. to therapeutic levels peritonitis.
Polyethylene glycol
(Macrogol '3350')
Klean-Prep
ͲĞƚĂďůŽĐŬĞƌŽǀĞƌ ɴďůŽĐŬĞƌƚŽǆŝĐŝƚǇ͗ĂĚƵůƚ͕>ŽĂĚ͗ϯʹϱŵŐ͘,ŝŐŚĞƌ ŶƚŝĐŝƉĂƚĞŶĂƵƐĞĂĂŶĚ W
ĚŽƐĞ ĚŽƐĞƐŵĂǇƵƐĞŝĨƚŚĞŝŶŝƚŝĂůďŽůƵƐŝƐŝŶĞĨĨĞĐƚŝǀĞ ǀŽŵŝƚŝŶŐ͘
ͲŽǀĞƌĚŽƐĞ ;ƵƉƚŽϭϬŵŐͿDĂŝŶƚĞŶĂŶĐĞ͗ϮʹϱŵŐͬŚƌ͘;ƵƉƚŽ
Ͳ,ǇƉŽŐůǇĐĞŵŝĐ ϭϬŵŐͬŚƌͿŚŝůĚ͗Ϭ͘ϭϱŵŐͬŬŐ/sƚŚĞŶ͕Ϭ͘ϬϱͲϬ͘ϭ
ĂŐĞŶƚƐŽǀĞƌĚŽƐĞ ŵŐͬŬŐͬŚ ƵŶƚŝů ŝŵƉƌŽǀĞŵĞŶƚͲ/Ŷ ŚǇƉŽŐůǇĐĞŵŝĐ
ƚŽǆŝĐŝƚǇ͗ ĚƵůƚƐ͗ ϭͲϮŵŐ ŝ͘ŵ͘ ŚŝůĚ͗ ϭŵŐ ŝŶ
'ůƵĐĂŐŽŶ
ĐŚŝůĚхϮϱŬŐ͕Ϭ͘ϱŵŐŝĨфϮϱŬŐ
Ͳ^ĞǀĞƌĞĐĂůĐŝƵŵ ŽůƵƐŽĨZĞŐƵůĂƌ/ŶƐƵůŝŶϭhͬŬŐƚŚĞŶŝŶĨƵƐŝŽŶĂƚ ͲDŽŶŝƚŽƌŐůƵĐŽƐĞ W
ĐŚĂŶŶĞůďůŽĐŬĞƌ Ϭ͘ϱʹϭ͘ϬhͬŬŐͬŚ͘'ŝǀĞϮϱŐŵ;ϱϬĐĐŽĨϱϬtͿ ĨƌĞƋƵĞŶƚůǇƚŽƉƌĞǀĞŶƚ
ƉŽŝƐŽŶŝŶŐ͕ƐĞǀĞƌĞ ŝŶŝƚŝĂůůǇƚŚĞŶĚĞǆƚƌŽƐĞϬ͘ϱŐƌĂŵƐͬŬŐƉĞƌŚ͖ ŚǇƉŽŐůǇĐĞŵŝĂ͘
ͲDŽŶŝƚŽƌƐĞƌƵŵ
ďĞƚĂďůŽĐŬĞƌ dŝƚƌĂƚĞƚŽĞƵŐůǇĐĞŵŝĂ
ƉŽƚĂƐƐŝƵŵĂŶĚƌĞƉůĂĐĞĂƐ
ƉŽŝƐŽŶŝŶŐ ŶĞĞĚĞĚ͘
,ŝŐŚĚŽƐĞ
ŝŶƐƵůŝŶĞƵŐůǇĐĞŵŝĐ
ƚŚĞƌĂƉǇ
,ĞĂǀǇ ŵĞƚĂů ƉŽŝƐŽ ĚƵůƚ͗ ϮϬͲϯϬ ŵŐͬŬŐͬĚ͕ /ŶŝƚŝĂƚŝŶŐ ďǇ Ϯϱй ŽĨ WĞŶŝĐŝůůĂŵŝŶĞƐŚŽƵůĚďĞ W
ƚŚŝƐ ĚŽƐĞ ĂŶĚ ŐƌĂĚƵĂůůǇ ŝŶĐƌĞĂƐĞ ƚŽ ƚŚĞ ĨƵůů ƚĂŬĞŶŽŶĂŶĞŵƉƚǇ
ŶŝŶŐ ;>ĞĂĚ͕ ĐŽƉƉĞƌ
ĚŽƐĞ ŽǀĞƌ Ϯ Ͳϯ ǁĞĞŬƐ͘ DĂǆŝŵƵŵ ĂĚƵůƚ ĚĂŝůǇ ƐƚŽŵĂĐŚ
ĂŶĚĂƌƐĞŶŝĐͿ
ĚŽƐĞŝƐϮŐ͘ŚŝůĚǁŝƚŚŵŝůĚƚŽŵŽĚĞƌĂƚĞůĞĂĚ
ƉŽŝƐŽŶŝŶŐ͕ĚŽƐĞŝƐϮϬŵŐͬŬŐͬĚ
WĞŶŝĐŝůůĂŵŝŶĞ
Ύ;ZͿǀĂŝůĂďŝůŝƚǇƌĞƋƵŝƌĞŵĞŶƚƐͲΎΎWƵƌĐŚĂƐĂďůĞǇDK,;WďǇDK,ͿKƌEŽƚWƵƌĐŚĂƐĂďůĞǇDK,;EŽƚEWďǇDK,Ϳ r ec
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REFERENCES:
1. California PCC Antidote Chart (2014), http://www.calpoison.org/hcp/
Antidote_Chart_2014, 1014.
2. Goldfrank, L. R., & Flomenbaum, N. (2010). Goldfrank's toxicologic emergencies. New
York: McGraw-Hill.
3. Olson, K. R., & California Poison Control System. (2006). Poisoning & drug overdose.
New York: Lange Medical Books/McGraw-Hill.
4. Illinois Poison Center Antidote List (2013), http://illinoispoisoncenter.org
/ipc_media/pdf/antidote%20list%202%202011.pdf
5. Poison Information Center of Ireland antidote list (2011), http:// www.poisons.ie/
Downloads/Antidote_Booklet_2011.pdf
6. KSA. MOH Formulary Drug List (2014)
7. Lheureux PE, Zahir S, Gris M, et al. 2006: Bench-to-bedside review: hyper-insulinaemia
/euglycaemia therapy in the management of overdose of calcium-channel blockers.
Crit Care;10 (3):212
8. Young AC, Velez LI, Kleinschmidt KC, 2009: Intravenous fat emulsion therapy for
intentional sustained-release verapamil overdose. Resuscitation; 80 (5):591–3.
9. Buckley NA, Eddleston M, Li Y, et al, 2011: Oximes for acute organophosphate
pesticide poisoning. Cochrane Database Syst Rev Feb 16;(2):CD005085.
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LIST OF ANTIDOTES
ANTIDOTE PAGE
Acetyl cysteine (NAC) 244
Activated charcoal 245
Anti-scorpion venom 246
Antivenom (Polyvalent and bivalent) for Snake bite 246
Atropine 245
BAL (Dimercaprol 247
Benzodiazepines 247
Benztropine 247
Botulism antitoxin & Baby Botulism IG (BIG) 248
Bromocriptine 248
Calcium Gluconate Gel 249
Calcium Gluconate) 248
Carnitine 249
Cholestyramine 249
Cyanide Antidote Kit (Conventional) 250
Cyanokit Hydroxycobalamin 250
Cyproheptadine 250
Dantrolene 251
Deferoxamine 251
Dicobalt edetate 251
Digoxin Immune FAB Digibind or DigiFab® 252
DMSA (Succimer) 252
EDTA-Calcium 253
Ethanol: IV 10% with 5% Dextrose and Ethanol(oral) 253
Fomepizole 253
Flumazenil 254
Glucagon 261
High dose insulin euglycemic therapy 261
Idarucizumab (praxibind) 260
Intravenous lipid emulsion (Intralipid) 252
Leucovorin (Folinic Acid) and Folic Acid 254
Mesna 255
Methionine 255
Methylene Blue 255
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LIST OF ANTIDOTES cont.
ANTIDOTE PAGE
Naloxone/ Narcan 256
Octreotide acetate/ Sandostatin 256
Oximes :Pralidoxime (2-PAM Protopam Obidoxime 257
Oxygen 100% and Hyperbaric oxygen (HBO) 255
Penicillamine 261
Physostigmine 256
Polyethylene glycol (Macrogol '3350') Klean-Prep 260
Protamine Sulphate 257
Prussian Blue 257
Pyridoxine (Vitamin B6) 258
Sodium Bicarbonate 258
Starch 258
Thiamine Hydrochloride 259
Vitamin K1 (phytonadione, phylloquinone) 259
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© Ministry of Health , General Directorate of Poison Control Centers , 2016

King Fahd National Library Cataloging-in-Publication Data

1- Poisoning 2- Poisoning - Diagnosis

Medical Toxicology Guide

Dr. Ali Gado Dr. Hany Gouda

Dr. Islam Gamaleddin Dr. Ahmed Refat

Dr. Mohamed M. Hosam El-Din Dr. Amir El Seddawy

Dr. Mohamed Siam Dr. Mohamed Khaled

Dr. Hanan Fathy Dr. Essam Hafez

Medical Toxicology Guide

Ph. Raed Abdulaziz Al Khayyal

Medical Toxicology Guide I

Medical Toxicology is a medical subspecialty focusing on the diagnosis, management and

Dr. Fawaz Ali Al Mousa

General approach to acutely poisoned patients 1

ANALGESICS AND ANTIINFLAMMATORY DRUGS

FOODS & DIETARY AGENTS

Medical Toxicology Guide III

NATURAL TOXINS AND ENVONOMENATION

NON-TOXIC INGESTIONS 221

ROLE OF TOXICOLOGY LABORATORY 224

SUBSTANCES OF ABUSE TESTING: (SPECIMEN COLLECTION) 228

Medical Toxicology Guide V

CHART I: GENERAL APPROACH TO POISONED PATIENTS P. 2

ABG Arterial Blood Gases

Medical Toxicology Guide VII

MAJOR PATHOPHYSIOLOGIC TOXIC MECHANISMS:

GENERAL APPROACH TO ACUTELY POISONED PATIENTS

Medical Toxicology Guide 1

Check gag and cough reflexes.

Check by pulse oximetry Assess and treat:

Assess and treat:

Assess and treat:

History Look for:

Skin and ocular decontamination

ANTIDOTES Administer Antidotes if available

Multiple Dose Activated Charcoal

GENERAL PRINCIPLES FOR MANAGEMENT OF ACUTE POISONING:

Medical Toxicology Guide 3

tricyclic anti-depressants and ingestion of toxins while stomach is

EMERGENCY EVALUATION AND LIFE-SAVING TREATMENT

Medical Toxicology Guide 5

- Coma or stupor is the most common serious complications in acute

E = EXPOSURE WITH ENVIRONMENTAL CONTROL

II- SECONDARY ASSESSMENT – DIAGNOSIS OF POISONING

Medical Toxicology Guide 7

- Inquire about liver, renal, cardiac and pulmonary disease,

6) Examine skin for temperature, dry/moist, colour (pale,

Medical Toxicology Guide 9

Medical Toxicology Guide 11

Comparison between anticholinergic and sympathomimetic

Medical Toxicology Guide 13

 Observe for early signs and symptoms) of late onset non-

METHODS OF GIT DECONTAMINATION:

Medical Toxicology Guide 15

nausea, vomiting, constipation, GI obstruction, diarrhea and

2- Multiple-Dose Activated Charcoal (MDAC):

Medical Toxicology Guide 17

4- Whole Bowel Irrigation (WBI):

5- Surgery & Endoscopy: