MedUSER

Medicine Update, Safety, Ethics and Research September 2013, Volume 1, Issue 5
International Quality - Reach - Scale - Godly Compassion
Poisoning by drug overdose constitutes a large fraction of accidental deaths
around the world. These drugs may be drugs of abuse or therapeutic
medication. Whatever the case, if the victim receives prompt medical attention
and good supportive care, the prognosis is a good one.
An understanding of the common mechanisms of death due to poisoning by
drugs can help health professionals in diagnosis & management of the patient.
Some of the main systems affected and mechanisms are mentioned here:
The central nervous system - CNS depressant drugs not only impair
consciousness and lead to coma but may also lead to loss of protective reflexes
and respiratory drive of the patient. Cause of death can be airway obstruction
by flaccid tongue, aspiration of gastric contents into the tracheobronchial tree
or respiratory arrest. These are seen in an overdose of narcotics, barbiturates,
alcohol and other sedative-hypnotic drugs.
Seizures can be a cause of death by causing pulmonary aspiration, hypoxia
and brain damage. These often result from overdose of amphetamine, cocaine,
antipsychotic, anti depressants, diphenhydramine, theophylline, isoniazid etc.
These drugs can also cause muscular hyperactivity and rigidity, which may in
turn lead to complications of hyperthermia, muscle breakdown,
myoglobinuria, renal failure, lactic acidosis and hyperkalemia.
The cardiovascular system Overdose of cardio-active drugs such as
ephedrine, amphetamine, cocaine, tricyclic antidepressants, digitalis and
theophylline, can cause death by altering cardiac contractility, lead to
hypotension, or cause arrhythmias. Hypotension may be caused by depression
of cardiac contractility; peripheral vascular collapse is due to blockade of -
adrenoceptor mediated vascular tone; hypovolemia maybe due to vomiting,
diarrhea, fluid sequestration or due to temperature deregulating effects leading
to hypothermia or hyperthermia. Arrhythmias like ventricular tachycardia or
fibrillation, commonly caused by these drugs, may also prove to be lethal.
Cellular hypoxia- Drugs that interfere with the transport or utilization of
oxygen may cause cellular hypoxia in spite of adequate ventilation and oxygen
administration. These drugs such as cyanide clinically present with
tachycardia, hypotension, severe lactic acidosis and signs of ischemia on ECG.
Other systems - Other organ system damage may occur due to drug poisoning
but may be delayed in onset. A few examples are that of paraquat affecting
lung tissue, resulting in pulmonary fibrosis, which begins several days after
ingestion. A similar example is that of massive hepatic necrosis due to
poisoning by paracetamol, which may result in hepatic encephalopathy and in
death two to three days later after ingestion.
Certain behavioral effects of drugs may be a cause of death in an indirect
manner. For example, alcohol or sedative-hypnotic drugs can cause motor
vehicle accidents; patients under the influence of hallucinogens like
phencyclidine or LSD may die in fights or falls from high places.

Toxicological Diagnosis
To proceed for making a toxicological diagnosis for the patient, the history,
physical findings and lab results have to be noted. Oral statements should be
substantiated with any articles recovered from the patients side, like empty
bottles, vials, syringes or drug strips, in order to quantify the drug ingestion.
Clinical Examination
Certain clues from physical examination of the patient can help in arriving at
the diagnosis. A few examples are as follows:
a) Vital signs:
1) Blood pressure Hypertension and tachycardia are typical with
amphetamines, cocaine and anti-cholinergic drugs.
Hypotension and bradycardia are characteristic features of overdose with
calcium channel blockers, -blockers, clonidine and sedative-hypnotics.
Hypotension and tachycardia is common with tricyclic anti-depressants,
phenothiazines, vasodilators and theophylline.
2) Respiration: Rapid respiration is typical of salicylates, carbon monoxide and
others producing metabolic acidosis or cellular hypoxia.
3) Temperature Hyperthermia is associated with sympathomimetics,
anticholinergics, salicylates and drugs producing seizures and muscular
rigidity.
Hypothermia can be produced by CNS depressants.
b) Eyes: Miosis constriction of pupils, is typical of opioids, clonidine,
phenothiazines, cholinesterase inhibitors and sedative drugs
Mydriasis- dilatation of pupils is common with amphetamines, LSD, atropine
and other anticholinergic agents.
Horizontal nystagmus is characteristic of intoxication with alcohol, phenytoin,
barbiturates and other sedatives. Presence of both vertical and horizontal
nystagmus is suggestive of poisoning with phencyclidine.
c) Skin: It may appear flushed, hot and dry in poisoning with atropine and other
antimuscarinics. Excessive sweating occurs with sympathomimetics, nicotine
and anti-cholinesterases. Cyanosis may be due to hypoxemia or
methemoglobinemia. Icterus may suggest hepatic necrosis due to paracetamol
toxicity.
d) Nervous system: Nystagmus, dysarthria and ataxia are typical of phenytoin,
carbamazepine, alcohol and other sedative intoxication. Twitching and
muscular hyperactivity are common with atropine, cocaine and other
sympathomimetics. Muscular rigidity is seen under effect of haloperidol and
other anti psychotics.
Continued on page 3.

Theme Topic Theme Topic Theme Topic Theme Topic Drug Poisoning Drug Poisoning Drug Poisoning Drug Poisoning Part 1 Part 1 Part 1 Part 1









































Drug Research





Dengue Vaccine
With nearly half the worlds population at risk of dengue infection
and an estimated 400 million people getting infected per year, the
need for a safe and long-lasting vaccine is acute. A new strategy that
cripples the ability of the dengue virus to escape the host immune
system has been discovered by Singapore Immunology Network
(SIgN). Dengue virus requires the enzyme called MTase to
chemically modify its genetic material to escape detection. By
introducing a genetic mutation to deactivate the MTase enzyme of
the virus, initial cells infected by the weakened MTase mutant virus
is immediately recognised as foreign. This results in a strong
protective immune response.
Malarial Vaccine
An experimental vaccine against malaria that was delivered via the
bloodstream offered 100 per cent protection to a dozen human
volunteers in a phase 1 study that was described in the journal
Science. The vaccine, known as PfSPZ, contains live malaria
parasites collected through a painstaking process of dissecting the
salivary glands of mosquitoes. It might need four years to get the
vaccine to market.
Clinical Updates
Probiotics and diarrhoea
A study published in The Lancet has found that antibiotic-induced
diarrhea is not prevented in the elderly by a daily dose of probiotics.
Earlier research had shown potential and prompted doctors to routinely
prescribe antibiotics and probiotics together. The probiotic market had
been estimated to reach $2.07 billion by 2015. In the study 10.8% of
people in the probiotic group got antibiotic-associated diarrhea, compared
to 10.4% of the control group. Researcher Stephen J. Allen concluded,
Our findings should discourage the use of microbial preparations for the
prevention of Antibiotic Associated Diarrhoea and C. difficile diarrhea.
He believes previous research was flawed because of microbial variation,
small sample sizes, erroneous reporting, and poor trial designs.
Broad Spectrum Antibiotics
Recent studies have found doctors are prescribing too many antibiotics
and too often turning to broad-spectrum antibiotics when narrow-
spectrum varieties will often be effective. The American Academy of
Pediatrics and the Center for Disease Control and Prevention both caution
that overuse can lead to antibiotic-resistant infections and diminish the
bodys supply of good bacteria. Journal of Antimicrobial Chemotherapy
found that broad-spectrum antibiotics are chosen 60% of the time by
doctors, and a pediatric study in the journal Pediatrics found broad-
spectrum products chosen about 50% of the time.
Finasteride lowers prostate cancer risk
A study funded by the National Cancer Institute and published in NEJM
found that participants taking finasteride had a 43% lower risk of being
diagnosed with a low-grade prostate cancer.








Fluoroquinolones and Nerve Damage
US FDA is mandating an update to medication labels for all
systemic fluoroquinolones warning of quick and potentially
permanent nerve damage. The peripheral neuropathy problems seem
to occur in oral or injectable variants, but not topical formulations.
The FDA finds that nerve damage problems can exist for over a year
after patients stop using fluoroquinolones.
Calcium Channel Blockers and Breast Cancer
New research published in JAMA Internal Medicine found that
taking calcium channel blockers for years may raise a womans risk
for breast cancer. Women who took amlodipine besylate for 10 years
or longer had a 2.5 times higher risk of developing breast cancer
than those who never took the medicine or who used other blood
pressure treatments.

Medication Caution
Fluoroqiunolones and Blood Sugar
A study reported in CID on 78,000 people with diabetes finds that
fluoroquinolone antibiotics are associated with an increased risk of blood
glucose swings in patients with diabetes. Investigators looked at data on
approximately 78,000 people with diabetes. The level of risk varied
according to the specific fluoroquinolone.


Medical Technology
Fusion of MRI and Ultrasound








potential tumors. This technology is part of an overall approach to
first use MRI scans to best determine when prostate biopsies are
necessary and then use the MRI/ultrasound fusion to increase the
efficiency of the biopsy.
First Rapid Diagnostic test to detect HIV-1 antigen and
HIV-1/2 antibodies
The USFDA has approved the first rapid HIV test for the
simultaneous detection of HIV-1 p24 antigen as well as antibodies to
both HIV-1 and HIV-2 in human serum, plasma, and venous or
fingerstick whole blood specimens. The Alere Determine HIV-1/2
Ag/Ab Combo test is also the first FDA-approved test that
independently distinguishes results for HIV-1 p24 antigen and HIV
antibodies in a single test. The test does not distinguish between
antibodies to HIV-1 and HIV-2, and is not intended to be used for
screening of blood donors.

Drug Poisoning continuation (from page 1)
Laboratory Tests for Drug Poisoning
Laboratory tests usually required to arrive at a diagnosis or for confirmation are
ABG Arterial Blood Gas, serum electrolytes, serum osmolality, renal function
tests and ECG.
Table 1: Drugs that may induce an elevated anion gap acidosis
Type of elevation of the
Anion gap
Agents
Organic acid metabolites Methanol, ethylene glycol
Lactic acidosis
Cyanide, carbon monoxide, ibuprofen, isoniazid,
metformin, salicylates, valproic acid, any drug
induced seizures, hypoxia or hypotension

Table 2: Drugs that cause alteration in serum potassium levels
Type Agents
Drugs that may cause
hyperkalemia
Potassium itself, -blockers, digitalis glycosides,
potassium sparing diuretics and fluoride
Drugs that may cause
hypokalemia
Barium, antagonists, caffeine, theophylline,
thiazide and loop diuretics

Drugs that cause alteration in serum potassium levels are hazardous as they may
lead to cardiac arrhythmias. Clinical examination and laboratory tests are usually
sufficient to generate a tentative diagnosis and an appropriate treatment plan.
Quantitative tests are indicated when a specific antidote or other treatment is
under consideration.
Part 2 of this article, looking at Management of Drug Poisoning will be
continued in the October issue of MedUSER.


LaughterThe Safest Medicine
Is he feeling better?
Senior Doctor: How is that boy who swallowed the 100 rupiah coin?
Junior Doctor: No change yet!

What should I do?
Patient: Doctor, what should I do if the temperature rises by 5 points?
Doctor: Sell!

The Prison Hospital
Prisoner: Look here doctor! You have already removed my tonsils,
spleen and one of my kidneys! I only came to see whether you could get
me out of this place.
Doctor: I am, part by part.

W We e w we el lc co om me e a an ny y f fe ee ed db ba ac ck k. . P Pl le ea as se e e em ma ai il l u us s a at t C CP PM MM M@ @s si il lo oa am mh ho os sp pi it ta al ls s. .c co om m
An innovative fusion of MRI
and ultrasound is being
studied that might be a better
way to detect and assess
prostate cancer. The new
technology blends real-time
imaging from both MRI and
ultrasound devices and lets
physicians more accurately
direct the biopsy needle that
draws cell samples from