Medical Toxicology
Medical Toxicology
Medical Toxicology
Ministry of Health
Medical Toxicology Guide. /Ministry of Health .-
Riyadh , 2016
615.908 dc
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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
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AUTHORS
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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.
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PREFACE 2
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.
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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
Toxidromes 10
Dr. ISLAM GAMALEDDIN MD, MSc, PhD (CAN), CISAM.
Investigations 13
Dr. ALI GADO MD, MSc, PhD.
Decontamination 14
Dr. ISLAM GAMALEDDIN MD, MSc, PhD (CAN), CISAM.
Enhancement of elimination 19
Dr. HANY GOUDA MD, MSc, PhD.
Admission criteria for a poisoned patient 22
Dr. HANY GOUDA MD, MSc, PhD.
SYSTEMIC TOXICOLOGY
Iron 53
Dr. ALI GADO MD, MSc, PhD.
Food Poisoning 59
Dr. ALI GADO MD, MSc, PhD.
Botulism 65
Dr. ISLAM GAMALEDDIN MD, MSc, PhD (CAN), CISAM.
PHARMACEUTICALS
Antidiabetic Drugs 70
Dr. ALI GADO MD, MSc, PhD.
Anticholinergics 77
Dr. ISLAM GAMALEDDIN MD, MSc, PhD (CAN), CISAM.
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CARDI0PULMONARY MEDICATIONS
Beta-blockers 81
Dr. ALI GADO MD, MSc, PhD.
Calcium Channel Blockers 87
Dr. ALI GADO MD, MSc, PhD.
Cardiac Glycosides 93
Dr. ALI GADO MD, MSc, PhD.
Theophylline 101
Dr. HANY GOUDA MD, MSc, PhD.
PSYCHOTROPIC MEDICATIONS
Lithium 109
Dr. HANY GOUDA MD, MSc, PhD.
Tricyclic Antidepressants 113
Dr. ALI GADO MD, MSc, PhD.
Antipsychotic Drugs 119
Dr. AHMED REFAT MD, MSc, PhD.
Benzodiazepines 125
Dr. AHMED REFAT MD, MSc, PhD.
SUBSTANCE OF ABUSE
Amphetamines and Cathinones 130
Dr. ISLAM GAMALEDDIN MD, MSc, PhD (CAN), CISAM.
Cocaine 135
Dr. ISLAM GAMALEDDIN MD, MSc, PhD (CAN), CISAM.
Opiates 138
Dr. ISLAM GAMALEDDIN MD, MSc, PhD (CAN), CISAM.
Cannabis 146
Dr. AHMED REFAT MD, MSc, PhD.
Ethanol 152
Dr. AHMED REFAT MD, MSc, PhD.
HOUSEHOLD PRODUCTS
Caustics 158
Dr. ISLAM GAMALEDDIN MD, MSc, PhD (CAN), CISAM.
Hydrocarbons 164
Dr. HANY GOUDA MD, MSc, PhD.
Methanol 170
Dr. HANY GOUDA MD, MSc, PhD.
Paraphenylenediamine 176
Dr. ALI GADO MD, MSc, PhD.
PESTICIDES
Aluminum and Zinc Phosphide 179
Dr. ISLAM GAMALEDDIN MD, MSc, PhD (CAN), CISAM.
Organophosphates and Carbamates 183
Dr. HANY GOUDA MD, MSc, PhD.
Pyrethrins and Pyrethroids 189
Dr. AHMED REFAT MD, MSc, PhD.
Warfarin and Related Rodenticides 194
Dr. AHMED REFAT MD, MSc, PhD.
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GASEOUS POISONS
Carbon Monoxide 199
Dr. AHMED REFAT MD, MSc, PhD.
ANTIDOTES 244
list of antidotes 261 -262
Dr. ALI GADO MD, MSc, PhD.
Dr. HANY GOUDA MD, MSc, PhD.
Dr. ISLAM GAMALEDDIN MD, MSc, PhD (CAN), CISAM.
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LIST OF CHARTS
LIST OF FORMS
SNAKE BITE OBSERVATION FORM P. 212
MEDICAL TOXICOLOGY HISTORY INTAKE FORM P. 240
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LIST OF ABBREVIATIONS
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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".
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GENERAL APPROACH TO
POISONED PATIENTS
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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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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
Mental status Pupils Vital signs Other manifestations Examples of toxic agents
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
Mental status Pupils Vital signs Other manifestations Examples of toxic agents
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
Mental status Pupils Vital signs Other manifestations Examples of toxic
agents
CNS Miosis Hypothermia Hyporeflexia Benzodiazepines,
depression, (usually) bradycardia, barbiturates,
confusion, hypotension, carisoprodol,
stupor, coma apnea & meprobamate,
bradypnea glutethimide,
alcohols, zolpidem
Withdrawal Toxidrome
Mental status Pupils Vital signs Other manifestations Examples of toxic
agents
Alter mental Mydriasis Hyperthermia, tremors, Withdrawal (EtOH,
status tachycardia, hyperreflexia, BDZ, opiates)
hypertension & seizures, nausea,
hyperventilation vomiting
Serotonin Toxidrome
Examples of toxic
Mental status Pupils Vital signs Other manifestations
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
Mental status Pupils Vital signs Other manifestations
agents
Hallucinations, Mydriasis Hyperthermia, Nystagmus Phencyclidine, LSD,
perceptual (usually) tachycardia, mescaline,
distortions, hypertension psilocybin, designer
depersonalization, & tachypnea amphetamines (e.g.,
synesthesia, MDMA ["Ecstasy"])
agitation
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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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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.
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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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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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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
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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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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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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MECHANISM OF TOXICITY:
- 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.
CLINICAL MANIFESTATIONS:
- 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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- 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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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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CLINICAL MANIFESTATIONS:
- 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.
- Supportive treatment:
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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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.
MECHANISM OF TOXICITY:
- 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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DISCHARGE CRITERIA/INSTRUCTIONS
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.
MECHANISM OF TOXICITY:
- 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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INCUBATION
LIKELY MICROBES LIKELY FOOD SOURCES
PERIOD
Prepared Food, E.G., Salads,
S. aureus 1 to 6 hr.
Dairy And Meat
Vomiting
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
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:
- Airway, breathing, and circulation (ABC) should be evaluated and
stabilized as necessary.
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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MECHANISM OF TOXICITY:
- After entering the cell's cytoplasm, the toxin causes an irreversible
modulation in stimulation-induced acetylcholine release in the same
presynaptic nerve terminal.
CLINICAL MANIFESTATIONS:
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.
DIFFERENTIAL DIAGNOSIS:
- 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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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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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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MECHANISM OF TOXICITY:
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CLINICAL MANIFESTATIONS:
- 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.
DIFFERENTIAL DIAGNOSIS:
- 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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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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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
Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg
Med 2005; 23:589.
4. Litovitz TL, Klein-Schwartz W, Rodgers GC Jr, et al. 2001 Annual report of the American
Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg
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.
DRUG AND DISEASE INTERACTIONS
- 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.
MECHANISM OF TOXICITY:
- 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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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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- 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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DISCHARGE CRITERIA/INSTRUCTIONS
- 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 β-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.
DRUG AND DISEASE INTERACTIONS
- 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.
MECHANISM OF TOXICITY:
- Inhibition of the Na-K ATPase-dependent myocardial sarcolemmal pump.
The increase in intracellular sodium prevents the sodium-calcium
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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.
DIFFERENTIAL DIAGNOSIS:
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.
- Arterial blood gases or oximetry.
- EKG monitoring.
- Pregnancy test in all women of childbearing age.
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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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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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
- Toxic manifestations following exposure are typically mild to moderate
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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DIFFERENTIAL DIAGNOSIS:
- 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.
- Pregnancy test in all women of childbearing age.
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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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.
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DISCHARGE CRITERIA/INSTRUCTIONS
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.
MECHANISM OF TOXICITY:
- 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.
CLINICAL MANIFESTATIONS:
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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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.
MECHANISM OF 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.
CLINICAL MANIFESTATIONS:
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.
- Pregnancy test in all women of childbearing age.
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.
DIFFERENTIAL DIAGNOSIS:
- 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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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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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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CLINICAL MANIFESTAIONS
- 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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- 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.
Expected course and prognosis
- 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
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
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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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CLINICAL MANIFESTAIONS
- 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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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
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MECHANISM OF TOXICITY:
- 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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COMMON PITFALLS:
- In case of agitation, DO NOT give butyrophenones (e.g., haloperidol)
and 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.
MECHANISM OF TOXICITY:
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.
DIFFERENTIAL DIAGNOSIS:
- 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.
- Serum Paracetamol, Salicylates.
- 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.
- 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:
- Persistent severe intolerable pain (e.g., severe toothache or headache)
may predispose to overuse.
DRUG AND DISEASE INTERACTIONS:
- 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.
MECHANISM OF TOXICITY:
- 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.
CLINICAL MANIFESTATIONS:
- 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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DIFFERENTIAL DIAGNOSIS:
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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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.
EXPECTED COURSE AND PROGNOSIS
- 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.
DISCHARGE CRITERIA/INSTRUCTIONS
- 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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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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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.
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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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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.
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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.
EXPECTED COURSE AND PROGNOSIS
- 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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DISCHARGE CRITERIA/INSTRUCTIONS
- 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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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.
MECHANISM OF TOXICITY:
- 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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INVESTIGATIONS:
Routine:
- Bed Side RBS.
- ABGs, Electrolytes.
- 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:
- Airway, breathing, and circulation (ABC) should be evaluated and
stabilized as necessary.
- 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.
Supportive treatment:
- 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 ·
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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
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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;37:119–124.
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.
MECHANISM OF TOXICITY:
- 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.
CLINICAL MANIFESTATIONS:
- 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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clothing and thoroughly washing the skin with soap and water.
- Don’t use syrup of ipecac, gastric lavage or activated charcoal.
Supportive treatment:
- 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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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.
11. Goldfrank, L. R., & Flomenbaum, N. (2010). Goldfrank's toxicologic emergencies. New York:
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.
MECHANISM OF TOXICITY:
- 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.
CLINICAL MANIFESTATIONS:
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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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.
Supportive treatment:
- 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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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.
MECHANISM OF TOXICITY:
- 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.
CLINICAL MANIFESTATIONS:
- 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.
- ABGs, Electrolytes.
- CBC, BUN, Creatinine, ALT, AST, Creatine Kinase.
- EKG.
- Pregnancy test for females at childbearing period.
- 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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- Supportive treatment:
- 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
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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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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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Supportive treatment:
- 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.
4. Goldfrank, L. R., & Flomenbaum, N. (2010). Goldfrank's toxicologic emergencies. New York:
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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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
CLINICAL MANIFESTAIONS
- 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.
Expected course and prognosis
- 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.
Discharge criteria/instructions
- 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
2. Soderlund DM, Clark JM, Sheets LP, Mullin LS, Piccirillo VJ, et al.
(2002) Mechanisms of pyrethroid neurotoxicity: implications for cumulative risk
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Discharge criteria/instructions
- 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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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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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.
MECHANISM OF TOXICITY:
- 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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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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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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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.
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-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).
MECHANISM OF TOXICITY:
- 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.
CLINICAL MANIFESTATIONS:
- 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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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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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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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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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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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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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.
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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**
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
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Not P**
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- 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.
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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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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Child 1 to 17 years: 20 to 100 % of the adult
Botulism
antitoxin
dose.
lism IG (BIG)
(BabyBIG) for infant awaiting results of diagno-
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
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
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Antidote Toxin Dose AR* NOTES
eMedical
Not P**
- 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
(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.
Dicobalt edetate
available and institute supportive
measures immediately.
* (AR) Availability requirements - ** Purchasable By MOH (P by MOH) Or Not Purchasable By MOH (Not NP by MOH)
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eMedical
Antidote Toxin Dose AR* NOTES
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.
Fomepizole
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P or
Antidote Toxin Dose AR* NOTES
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.
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
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* (AR) Availability requirements - ** Purchasable By MOH (P by MOH) Or Not Purchasable By MOH (Not NP by MOH)
sic
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eMedical
Not P**
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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P or
Antidote Toxin Dose AR* NOTES
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
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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P or
Antidote Toxin Dose AR* NOTES
Not P**
diuG ygoToxicology
Dabigatran etexilate 5 g idarucizumab iv as 2 consecutive infusions of 2.5
B -it binds specifically to dabigatran
NP
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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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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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