1. Paracetamol (acetaminophen) toxicity results from formation of a reactive metabolite which causes liver and occasionally renal failure. Acetylcysteine treatment within 8 hours of overdose is highly effective at replenishing glutathione reserves and preventing toxicity. 2. Salicylate poisoning causes respiratory alkalosis, metabolic acidosis, and organ dysfunction. Treatment involves correcting dehydration and acidosis with sodium bicarbonate, and hemodialysis for severe or refractory cases. 3. Tricyclic antidepressant overdose can cause life-threatening arrhythmias, hypotension, and seizures due to sodium channel blockade and anticholinergic effects. Treatment involves

1. Poisoning by specific
pharmaceutical agents
Dr. Mohamed shekhani

2. Paracetamol
• Acetaminophen) is the drug most commonly used in overdose.
• Toxicity results from formation of an intermediate reactive
metabolite which binds covalently to cellular proteins, causing cell
death , results in hepatic& occasionally renal failure.
• In therapeutic doses, the toxic intermediate metabolite is
detoxified in reactions requiring glutathione, but in overdose,
glutathione reserves become exhausted.

3. Management
• Activated charcoal used in patients presenting within 1 hour.
• Antidotes act by replenishing hepatic glutathione.
• Acetylcysteine IV (or orally in some countries) is highly
efficacious if administered within 8 hours of the overdose.
• The efficacy declines thereafter, administration should not be
delayed in patients presenting after 8 hours to await a
paracetamol blood concentration result.
• The antidote can be stopped if the paracetamol concentration is
shown to be below the appropriate treatment line.
• The most important adverse effect is related to dose-related
histamine release, the ‘anaphy-actoid’ reaction, with itching /
urticaria,in severe cases, bronchospasm/ hypotension,managed by
temporary discontinuation & an antihistamine.
• An alternative antidote is methionine 2.5 g orally 4-hourly to a
total of four doses, less effective, especially if delayed.

4. Management
• If a patient presents >15 hours after ingestion, liver function
tests, PT(or INR), renal function tests& a venous bicarbonate
should be measured, the antidote started& a poisons information
centre or local liver unit contacted for advice if results are
abnormal.
• ABG should be taken in patients with severe liver function
abnormalities; as metabolic acidosis indicates severe poisoning.
• Liver transplantation should be considered in individuals who
develop life- threatening liver failure.
• If multiple ingestions of paracetamol have taken place over several
hours or days (i.e. a staggered overdose), acetylcysteine should
be given when the paracetamol dose exceeds 150 mg/kg /any
one 24-hour period or 75 mg/kg in ‘high-risk groups’

7. (Salicylates (aspirin
• Commonly causes nausea, vomiting, sweating, tinnitus ,
deafness.
• Direct stimulation of the respiratory centre produces
hyperventilation &respiratory alkalosis.
• Peripheral vasodilatation with bounding pulses& profuse sweating
occurs in moderately severe poisoning.
• Serious salicylate poisoning is associated with metabolic acidosis,
hypoprothrombinaemia, hyperglycaemia, hyperpyrexia, renal
failure, pulmonary oedema, shock &cerebral oedema.
• Agitation, confusion, coma&fits may occur, especially in children.
• Toxicity is enhanced by acidosis, which increases salicylate transfer
across the BBB.

8. Management
• Activated charcoal should be administered if presents early.
• Multiple doses of activated charcoal may enhance salicylate
elimination but currently are not routinely recommended.
• The plasma salicylate concentration should be measured at
least 2 (in symptomatic patients) or 4 hours (asymptomatic
patients) after overdose&repeated in patients with suspected
serious poisoning, since it may continue to rise some hours after .
• In adults, concentrations >500 -700 mg/L suggest serious & life-
threatening poisoning respectively, but clinical status is more
important assessing severity.
• Dehydration should be corrected carefully, as there is a risk of
pulmonary oedema.
• Metabolic acidosis should be identified and treated with iv sodium
bicarbonate (8.4%), once plasma potassium has been corrected.
• Urinary alkalinisation is indicated for adults if salicylate >500 mg/L.

9. Management
• Haemodialysis is very effective at removing salicylate
&correcting acid–base & fluid balance abnormalities& should be
considered when :
• Serum concentrations >700 mg/L in adult patients with severe
toxic features
• Or when there is renal failure
• Pulmonary oedema,
• Coma
• Convulsions
• Refractory acidosis

10. (Tricyclic antidepressants (TCAs
• TCAs used frequently in overdose
• It carries a high morbidity/mortality relating to their sodium
channel-blocking, anticholinergic &α-adrenoceptor-blocking effects

11. Clinical features
• Anticholinergic effects are common .
• Life-threatening complications are frequent, including convulsions,
coma, arrhythmias (ventricular tachycardia, ventricular fibrillation
, less commonly, heart block) & hypotension, which results from
inappropriate vasodilatation or impaired myocardial contractility.
• Serious complications appear to occur more commonly with
dosulepin &amitriptyline.

12. Management
• Activated charcoal should be given if presents sufficiently early.
• All patients with possible TCAD overdose should have a 12-lead ECG
& ongoing cardiac monitoring for at least 6 hours.
• Prolongation of the QRS interval (especially if > 0.16 s) indicates
severe sodium channel blockade associated with an increased
risk of arrhythmia .
• ABGs be measured in patients with suspected severe poisoning.
• In patients with arrhythmias, severe ECG effects or acidosis, IV
sodium bicarbonate (50 mL of 8.4% solution) should be
administered &repeated to correct pH.
• The correction of the acidosis &sodium loading that result is
often associated with rapid improvement in ECG & arrhythmias.
• Hypoxia &electrolyte abnormalities should also be corrected.
• Anti-arrhythmic drugs should only be given on specialist advice.
•

13. :Cardiotoxic drugs

14. Antipsychotics
• Often prescribed for patients at high risk of self-harm or suicide,
&commonly encountered in overdose.

15. Clinical features
• Drowsiness, tachycardia,hypotension are frequently found.
• Anticholinergic features& acute dystonias (e.g. oculogyric crisis,
torticollis &trismus) may occur after overdose with typical
antipsychot-ics such as haloperidol or chlorpromazine.
• QT interval prolongation &torsades de pointes may occur with
some antipsychotics, either typical (e.g. thioridazine,
haloperidol) or atypical (e.g. quetiapine, ziprasidone).
• Convulsions may occur.

16. Management
• Activated charcoal may be of benefit if given sufficiently early.
• Cardiac monitoring should be undertaken for at least 6 hours.
• Management is largely supportive, with treatment directed at
complications

17. Antidiabetic agents
• Commonly causing toxicity in over-dose include the sulphonylureas
(chlorpropamide, glibenclamide, gliclazide, glipizide, tolbutamide),
biguanides (metformin and phenformin)& insulins.

18. Clinical features
• Sulphonylureas &parenteral insulin cause hypoglycaemia when
taken in overdose, but insulin is non-toxic if ingested.
• The duration of hypoglycaemia depends on the half-life or release
characteristics of the preparation& may be prolonged over
several days with long-acting agents such as chlorpropamide,
insulin zinc suspension or insulin glargine.
• Features of hypoglycaemia include nausea, agitation, sweating,
aggression, behavioural disturbances, confusion, tachycardia,
hypothermia, drowsiness, coma or convulsions .
• Permanent neurological damage can occur if hypoglycaemia is
prolonged.
• Hypoglycaemia can be diagnosed using bedside glucose strips but
venous blood should also be sent for laboratory confirmation.

19. Clinical features
• Metformin is uncommonly associated with hypoglycaemia.
• Its major toxic effect in overdose is lactic acidosis, which can be
associated with a high mortality, particularly common in elder
&those with renal or hepatic impairment, or ethanol
coingestion.
• Other featuresare nausea ,vomiting, diarrhoea, abdominal pain,
drowsiness, coma, hypotension &CV collapse.

20. Management
• Activated charcoal should be considered for all patients who
present within 1 hour of ingestion of a substantial overdose of an
oral hypoglycaemic agent.
• Venous blood glucose, urea, electrolytes should be measured
&repeated regularly.
• Hypoglycaemia should be corrected using oral or IV glucose (50
mL of 50% dextrose); an infusion of 10–20% dextrose may be
required to prevent recurrence.
• Intramuscular glucagon can be used as an alternative, especially if
IV access is unavailable.
• Failure to regain consciousness within a few minutes of
normalisation of the blood glucose can indicate (CNS) depressant
has also been ingested, the hypoglycaemia has been prolonged,
or there is another cause for the coma (e.g. cerebral haem-orrhage
or oedema).

21. :Management
• ABG should be taken after metformin overdose to assess the
extent of acidosis.
• If present, plasma lactate should be measured &acidosis should be
corrected with intravenous sodium bicarbonate (e.g. 250 mL 1.26%
solution or 50 mL 8.4% solution, repeated as necessary).
• In severe cases haemodialysis or haemo-diafiltration is used.

22. Organophosphorus (op) insecticides/ nerve agents
• Widely used as pesticides, especially in developing countries.
• The case fatality rate following deliberate ingestion of OP pesticides
in devel-oping countries in Asia is 5–20%.
• Nerve agents developed for chemical warfare are derived from
OP insecticides but are much more toxic.
• ‘G’ agents are volatile, are absorbed by inhalation or via the
skin&dissipate rapidly after use.
• ‘V’ agents are contact poisons unless aerosolised,contaminate
ground for weeks or months.
• The toxicology and management of nerve agent&pesticide
poisoning are similar.

23. Mechanism of toxicity
• OP compounds phosphonylate the active site of
acetylcholinesterase (AChE), inactivating the enzyme,leading to the
accumulation of acetylcholine (ACh) in cholinergic synapses.
• Spontaneous hydrolysis of the OP-enzyme complex allows
reactivation of the enzyme.
• Loss of a chemical group from the OP-enzyme complex prevents
further enzyme reactivation‘ageing’),after which,
praladoxime(enzyme reactivator will not be effective) & new
enzyme needs to be synthesised before function can be restored.
The rate of ageing is is more rapid with dimethyl compounds (3.7
hours) than diethyl compounds (31 hours),especially rapid after
exposure to nerve agents (soman in particular), which cause
ageing within minutes.

24. Clinical features
• OP poisoning causes an acute cholinergic phase, occasionally
followed by the intermediate syndrome or organophosphate-
induced delayed polyneuropathy (OPIDN).
• The onset, severity and duration of poisoning depend on the
route of exposure & agent involved.

25. Clinical features
• Acute cholinergic syndrome
• Usually starts within a few minutes of exposure.
• Nicotinic or muscarinic features may be present.
• Vomiting ,profuse diarrhoea are typical following oral ingestion.
• Bronchoconstriction, bronchorrhoea and salivation may cause
severe respiratory compromise.
• Miosis is characteristic &muscle fasciculations strongly suggests
the diagnosis, although often absent, even in serious poisoning.
• Subsequently, generalised flaccid paralysis which can affect
respiratory & ocular muscles &result in respiratory failure.
• Ataxia, coma,convulsions may occur.
• In severe poisoning, cardiac repolarisation abnormalities& torsades
de pointes may occur.
• Other early complications include extrapyramidal features,

26. Management
• If external contamination, further exposure should be prevented,
contaminated clothing&contact lenses removed, the skin washed
with soap and water& the eyes irrigated.
• The airway should be cleared of excessive secretions & high-flow
oxygen administered.
• Intravenous access should be obtained.
• Gastric lavage or activated charcoal may be considered within 1
hour of ingestion.
• Convulsions should be treated
• The ECG, oxygen saturation, blood gases, temperature, urea ,
electrolytes, amylase, glucose should be monitored closely.
• Early use of sufficient doses of atropine is potentially lifesaving in
patients with severe toxicity.
• Atropine reverses ACh-induced bronchospasm

27. Management
• Atropine reverses ACh-induced bronchospasm,bronchorhea,
bradycardia ,hypotension.
• A marked increase in heart rate associated with skin flushing
after a 1 mg intravenous dose makes OP poisoning unlikely.
• In OP poisoning, atropine should be administered in doses of 0.6–2
mg i.v., repeated every 10–25 mins until secretions are
controlled, the skin is dry and there is a sinus tachycardia.
• Large doses may be needed but excessive doses may cause
anticholinergic effects.
• In patients requiring atropine, an oxime such as pralidoxime
chloride (or obidoxime), if available, should also be administered,
as this may reverse or prevent muscle weakness, convulsions or
coma, especially if administered rapidly after exposure.
• The dose for an adult is 2 g i.v. over 4 mins, repeated 4–6-hourly.

28. Management
• Oximes re-activating AChE that has not undergone ‘ageing’ &are
less effective with dimethyl compounds &nerve agents,
especially soman.
• Oximes may provoke hypotension, especially if rapidly.
• Ventilatory support should be instituted before the patient
develops respiratory failure .
• Benzodiazepines may be used to reduce agitation,fasciculations,
&treat convulsions&sedate patients during mechanical ventilation.
• Exposure is confirmed by measurement of plasma
(butyrylcholinesterase) or red blood cell cholinesterase activity.
,correlate poorly with the severity of clinical features, although
values are usually less than 10% in severe poisoning, 20–50% in
moderate poisoning ,> 50% in subclinical poisoning.
• The acute cholinergic phase usually lasts 48–72 hours, with most
patients requiring intensive cardiorespiratory support& monitoring.

29. Ethylene glycol/Methanol
• Found in antifreeze, brake fluids and, in lower concentrations,
windscreen washes.
• Methanol is present in some antifreeze products& commercially
available industrial solvents, methylated spirits,illi-citly produced
alcohol.
• Both are rapidly absorbed after ingestion.
• They are converted via alcohol dehydrogenase to toxic metabolites
largely responsible for their clinical effects.
• are no longer detectable.

30. Clinical features
• Early feature: ataxia, drowsiness, dysarthria and nystagmus, often
associated with vomiting.
• As the toxic metabolites are formed, metabolic acidosis,
tachypnoea, coma,seizures may develop.
• Toxic effects of ethylene glycol toxicity include :
• ophthalmoplegia, cranial nerve palsies, hyporeflexia ,myoclonus.
• Renal pain / acute tubular necrosis occur because of renal
precipitation of calcium oxalate .
• Hypocalcaemia, hypomagnesaemia,hyperkalaemia are common.
• Methanol poisoning features:
• headache, confusion , vertigo.
• Visual impairment & photophobia develop.
• Blindness may be permanent, although some recovery may occur
• Pancreatitis & abnormal liver function reported.

31. Management
• Urea, electrolytes, chloride, bicarbonate, glucose, calcium,
magnesium, albumin&plasma osmolarity,ABG, should be measured
in all patients.
• The osmolal & anion gaps should be calculated.
• Initially, poisoning is associated with an increased osmolar gap, but
as toxic metabolites are produced, an increased anion gap
associated with metabolic acidosis will develop.
• The diagnosis can be confirmed by measurement of ethylene glycol
or methanol concentrations,but not widely available.
• An antidote, either ethanol or fomepizole, should be
administered to all patients with suspected significant exposure
while awaiting the results of laboratory investigations.
• These block alcohol dehydrogenase&delay the formation of toxic
metabolites until the drug is eliminated naturally or by dialysis.

32. Management
• The antidote should be continued until ethylene glycol or methanol
concentrations are undetectable.
• Metabolic acidosis should be corrected with sodium bicarbonate
• (e.g. 250 mL of 1.26% solution, repeated as necessary).
• Convulsions should be treated with an IV benzodiazepine.
• In ethylene glycol poisoning, hypocalcaemia should only be
corrected if there are severe ECG features or seizures occur, since
this may increase calcium oxalate crystal formation.
• Haemodialysis or haemodiafiltration should be used in severe
poisoning, especially if renal failure is present or there is visual
loss in the context of methanol poisoning.
• It should be continued until acute toxic features are no longer
present and ethylene glycol or methanol concentrations are not
detectable.

33. CO poisoning
• CO is a colourless / odourless gas produced by faulty appliances
burning organic fuelsvehicle exhaust fumes,house fires smoke.
• It causes toxicity by binding with haemoglobin &cytochrome
oxidase, which reduces tissue oxygen delivery&inhibits cellular
respiration.
• It is a common cause of death by poisoning& most patients who die
before reaching hospital.

34. CO poisoning: Clinical features
• Early clinical features : headache, nausea, irritability, weakness&
tachypnoea, are non- specific, so correct diagnosis will not be
obvious if the exposure is occult, e.g. faulty domestic appliance.
• Subsequently, ataxia, nystagmus, drowsiness and hyperreflexia
may develop, progressing to coma, convulsions, hypotension,
respiratory depression, cardiovascular collapse &death.
• Myocardial ischaemia may result in arrhythmias or AMI.
• Cerebral oedema is common &rhabdomyolysis may lead to
myoglobinuria &renal failure.
• In those who recover from acute toxicity, longer-term
neuropsychiatric effects are common,as personality change,
memory loss , concentration impairment,extrapyramidal effects,
urinary or faecal incontinence, gait disturbance.
• Poisoning during pregnancy may cause fetal hypoxia& intrauterine
death.

35. CO poisoning: Management
• Patients should be removed from exposure as soon as possible
&resuscitated as necessary.
• Oxygen should be administered in as high a concentration as
possible via a tightly fitting facemask, as this reduces the half-
life of carboxyhaemoglobin from 4–6 hours to about 40
minutes.
• Measurement of carb-oxyhaemoglobin is useful for confirming
exposure, but results do not correlate well with the severity of
poisoning, partly because concentrations fall rapidly after removal
of the patient from exposure, especially if supplemental oxygen has
been given.
• An ECG should be performed in all patients with acute
poisoning, especially those with pre-existing heart disease.
• Arterial blood gas analysis should be checked in those with serious
poisoning.

36. CO poisoning: Management
• Oxygen saturation readings by pulse oximetry are misleading
since both carboxyhaemoglobin &oxyhaemoglobin are measured.
• Excessive IVF should be avoided, particularly in the elderly,
because of the risk of pulmonary & cerebral oedema.
• Convulsions should be controlled with diazepam.
• Hyperbaric oxygen therapy is controversial.
• In theory, at 2.5 atmospheres, it reduces the half-life of
carboxyhae-moglobin to 20 minutes& increases the amount of
dissolved oxygen by a factor of 10.

37. Single-best choice MCQs:
• 1.The antidote of paracetamol can be only be given:
• A.Oraly alone.
• B. IV alone.
• C.Rectally.
• D.IM.
• E. IV / or orally.

38. Single-best choice MCQs:
• 2. The antidote of paracetamol:
• A.Replenishes glutathione liver stores.
• B. Activates drug metabolizing enzymes.
• C. Inhibits drug metabolizing enzyme.
• D.All.
• E.None.

39. Single-best choice MCQs:
• 3. The paracetamol antidote should be given within:
• A. 16 hours.
• B. 4 hours.
• C. 8 hours.
• D. 24 hours.
• E.35 hours.

40. Single-best choice MCQs:
• 4.Paracetamol drug level in paracetamol poisoning is best
measured after ingestion of:
• A. 16 hours.
• B. 4 hours.
• C. 8 hours.
• D. 24 hours.
• E.35 hours.

41. Single-best choice MCQs:
• 5.Paracetamol poisoning causes:
• A.Heopatic failure alone.
• B. Renal failure.
• C. Both.
• D. Neither.
• E. Respiratory failure.

42. Single-best choice MCQs:
• 6.High risk for paracetamol poisoning with lower doses include all
the following except:
• A. Chronic alcoholics.
• B. Eating disorders patients.
• C. Epileptics on treatment.
• D. Asthmatics.
• E. Maluarished persons.

43. Single-best choice MCQs:
• 7. In symptomatic aspirin poisoning patients drug level is best taken
after ingestion of:
• A. 2 HOURS.
• B.4 hours.
• C.6 hours.
• D.8 hours.
• E.10 hours.

44. Single-best choice MCQs:
• 8. In symptomatic aspirin poisoning patients, hemodialysis is
indicated if blood level is above:
• A. 400 mgm/l.
• B. 300 mgm/l.
• C 200 mgm/l.
• D. 600 mgm/l.
• E. 700 mgm/l.

45. Single-best choice MCQs:
• 9. The most serious effects of aspirin poisoning is:
• A. Hypoglycemia.
• B.Hypocalcemia.
• C. Metabolic acidosis.
• D. Respiratory alkalosis.
• E.Bleeding tendencies.

46. Single-best choice MCQs:
• 10.All these drugs are cardiotoxic if taken in overdose except:
• A.Trcyclic antidepressants.
• B.Antipsychotics.
• C. CO.
• D.Paracetamol.
• E.SSRI.

47. Single-best choice MCQs:
• 11.Oximes are least effects in organophosphorous poisoning with:
• A. Soman.
• B.Dimethyl compounds.
• C. Diethyl compounds.
• D. All.
• E.None.

48. Single-best choice MCQs:
• 12.CO poisoning is best diagnosed by:
• A.Pulseoximetry.
• B. Carboxyhemoglobin blood level.
• C. Clinical features.
• D.All.
• E.Neither.

49. Single-best choice MCQs:
• 13. CO poisoning is best treated by:
• A. Usual ward oxygen.
• B. Hyperbaric oxygen.
• C. Only supportive measures.
• D. All.
• E. None.