POISONING AND TOXICOLOGY DR ABD. HALIM BIN MANSAR

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

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.

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.

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

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)

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

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.

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

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.

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.

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.

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

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

Paracetamol Accidental and suicidal poisonings Accidental in children Suicidal in adults In overdose can cause acute centrilobular hepatic necrosis which is often fatal 24 - 48 hours = palor, nausea and vomiting Hepatic failure appears 4 - 6 days after ingestion. Treatment: intravenous N-acetylcysteine.

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.

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.

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

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

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

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.

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

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.

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.

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)

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.

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

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.

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

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)

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