1. POISONING AND TOXICOLOGY
DR ABD. HALIM BIN MANSAR

2. Routes of administration Tolerance, Idiosyncracy & Drug interaction
POISONING
Definition
Types of poison
Routes of administration
Tolerance, Idiosyncracy & Drug interaction
Poisoning by common drugs and toxic substances
Doctor’s role in poisoning
Alcohol, accidents and the law
Postmortem detection of toxic substances

3. POISONING Definition:
Poison - any substance taken into the body that interferes with normal physiological functions.
Poisoning - the state produced by introduction of a poison into the body.

4. Poisoning
Poisoning is very common, most poisonings being accidental or suicidal in nature (homicidal is now rare)
Majority of the accidental group = children
Two main types of poisoning;
those in the home from medicinal substances and domestic chemicals
those in agriculture and industry from a wide range of toxic substances.

5. Poisoning Definition Types of poisons Routes of administrations
Tolerance, Idiosyncrasy & Drug Interaction
Poisoning by common drugs and toxic substances
Doctor’s Role in poisoning
Alcohol, accidents and the law
Posmortem detection of toxic substances

6. POISONING Types of poison
target organ (liver, kidney, haematopoietic system, etc)
use (pesticide, solvent, food additive, etc.)
source (animal and plant toxin)
effects (cancer, mutation, liver injury, etc)
chemistry (aromatic amine, halogenated hydrocarbon)

7. Poisoning Definition Types of poisons Routes of administrations
Tolerance, Idiosyncrasy & Drug Interaction
Poisoning by common drugs and toxic substances
Doctor’s Role in poisoning
Alcohol, accidents and the law
Posmortem detection of toxic substances

8. Routes Of Administrations
Ingestion (gastrointestinal tract)
Inhalation (lungs)
Topical (skin)
parenteral (intravenous)
Toxic agents elicit greatest effect and produce most rapid response when given by the intravenous route.

9. Poisoning Definition Types of poisons Routes of administrations
Tolerance, Idiosyncrasy & Drug Interaction
Poisoning by common drugs and toxic substances
Doctor’s Role in poisoning
Alcohol, accidents and the law
Posmortem detection of toxic substances

10. Tolerance
Definition: a state of decrease responsiveness to a toxic effect of a chemical resulting from prior exposure to that chemical or to a structurally related chemical.
Example: carbon tetrachloride produces tolerance to itself by decreasing formation of the reactive metabolite that produces liver injury.

11. Idiosyncrasy
Definition: a genetically determined abnormal reactivity to a chemical. The response observed is usually similar to that observed in all individuals (may take the form of extreme sensitivity to low doses or extreme insensitivity to high doses of the chemical).
Example: Prolonged muscular relaxation and apnoea after a standard dose of succinylcholine.

12. Drug Interactions
Mechanism of drug interaction: alterations in absorption, protein binding and biotransformation or excretion of one or both of the interacting drugs.
The response may be increased or decreased because of the toxicological responses at the site of action.
Example: carbon tetrachloride and ethanol are hepatotoxic compounds, but together they produce much more liver injury than their individual effects on the liver.

13. Poisoning Definition Types of poisons Routes of administrations
Tolerance, Idiosyncrasy & Drug Interaction
Poisoning by common drugs and toxic substances
Doctor’s Role in poisoning
Alcohol, accidents and the law
Posmortem detection of toxic substances

14. Poisoning by common drugs and toxic substances
Paracetamol
Salicylates
Paraquat
Organophosphate
Carbon Monoxide

15. Paracetamol Accidental and suicidal poisonings Accidental in children
Suicidal in adults
In overdose can cause acute centrilobular hepatic necrosis which is often fatal
hours = palor, nausea and vomiting
Hepatic failure appears days after ingestion.
Treatment: intravenous N-acetylcysteine.

16. Salicylates Aspirin & methyl salicylate
Mild toxicity: vertigo, tinnitus, nausea and vomiting
Ingestion of greater than 400 mg/kg causes severe vomiting, hyperventilation, confusion, coma, convulsions, hyper or hypoglycaemia and respiratory alkalosis or metabolic acidosis.

17. Paraquat Accidental or suicidal ingestion
1-3 days = intense pain in the mouth and pharynx, with inflammation / ulceration of the mucous membrane.
2-4 days = symptoms of renal and hepatic failure
3-14 days = paraquat is specifically taken by lung tissue. Intra-alveolar oedema and haemorrhage followed by epithelial proliferation, focal atelactasis and massive alveolar fibrosis.

18. Paraquat Treatment: immediate gastric lavage
Fuller’s earth (300 gm in tha stomach)
forced diuresis (intravenous frusemide)

19. Organophosphate Toxic effects results in build up of acetylcholine
Clinical features:
symptoms developed within 12 hours
headache, blurred vision, tremor, twitching, convulsions and coma
urinary incontinence, diarrhoea and vomiting
excessive salivation, lacrimation and sweating
cough, wheezing and sometimes pulmonary oedema

20. Organophosphate Treatment: maintain patient’s airway
control convulsions
intravenous atropine
antidote = pralidoxime

21. Carbon Monoxide Commonly suicidal
CO = 300 times affinity for Hb (replaces oxygen from Hb)
symptoms= headache, nausea, vomiting, convulsions, coma and death.
Suicide : tube leading from exhaust pipe into the car passenger compartment.

22. Poisoning Definition Types of poisons Routes of administrations
Tolerance, Idiosyncrasy & Drug Interaction
Poisoning by common drugs and toxic substances
Doctor’s Role in poisoning
Alcohol, accidents and the law
Posmortem detection of toxic substances

23. The Doctor’s Role In Poisoning
The recognition or suspicion of the fact of poisoning
The early diagnosis, where possible, of the nature of the poison
Emergency primary treatment and admission to hospital where necessary
The identification and retention of residual poison in the house, for transmission to the hospital to confirm the nature of the poison
Where death has occurred, full cooperation with the pathologist in providing details of any illness, psychiatric condition and drugs recently prescribed.

24. The Doctor’s Role In Poisoning
Diagnosis:
should be considered in patients with coma, convulsions, acute hepatic, renal and bone marrow failure.
Ask patient, relatives and friends about possible poisons.
Specimens of blood, urine, vomitus and gastric aspirate should be sent immediately for analysis.

25. The Doctor’s Role In Poisoning
Treatment:
Gastric lavage (avoid following ingestion of kerosene)
Minimise absorption (activated charcoal)
Enhance renal excretion (forced diuresis with saline + IV furosemide)

26. The Doctor’s Role In Poisoning
Supportive therapy:
maintenance of ventilation when CNS is depressed
anticonvulsants in patients with convulsions
cerebral oedema treated with IV corticosteroid and/or IV hypertonic mannitol
patients should be evaluated and treated for the effects of poisoning e.g. hypovolemia, hypotension, cardiac arrhythmias, pulmonary oedema, hypoxia, acute renal failure,acute hepatic failure and disturbances of fluid and electrolytes.

27. Poisoning Definition Types of poisons Routes of administrations
Tolerance, Idiosyncrasy & Drug Interaction
Poisoning by common drugs and toxic substances
Doctor’s Role in poisoning
Alcohol, accidents and the law
Posmortem detection of toxic substances

28. Alcohol, accidents and the law
Drunk drivers more prone to RTA
Legal limit
80 mg alcohol per 100 ml of blood
35 microgram alcohol per 100 ml of breath
107 mg alcohol per 100 ml urine
Incoordination, tremor, ataxia, confusion, coma and even death can occur at progressively higher blood alcohol levels.

29. Poisoning Definition Types of poisons Routes of administrations
Tolerance, Idiosyncrasy & Drug Interaction
Poisoning by common drugs and toxic substances
Doctor’s Role in poisoning
Alcohol, accidents and the law
Posmortem detection of toxic substances

30. Postmortem Detection of Toxic Substances
History
External Examination
Internal Examination
Collection of appropriate specimens
blood, urine, stomach contents, liver tissue, lung tissue
Analysis (P.J. Chemistry Lab)

31. THANK YOU