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|Drug Toxicity with Specific Antidotes
Quinine is a medication used mainly for chloroquine-resistant malaria and occasionally nocturnal leg cramps. β At higher doses it is toxic, producing the syndrome of cinchonism β a combination of auditory, visual, neurological, and cardiovascular disturbances. Prompt recognition and management are vital, as toxicity can progress to blindness, arrhythmias, or death.
About
- Quinine (a natural alkaloid from the cinchona tree π³) was the first effective anti-malarial; still used against chloroquine-resistant Plasmodium falciparum.
- Sometimes prescribed (though controversial) for nocturnal leg cramps; carries significant risk of hypersensitivity and toxicity.
- Structurally and pharmacologically related to quinidine, hence significant cardiac sodium channel blocking effects.
Pathophysiology π§¬
- Neuro-ototoxicity: Direct effects on auditory & optic nerves β tinnitus, hearing loss, blurred vision, blindness (vasospasm of retinal arterioles, retinal oedema, optic atrophy).
- Cardiotoxicity: Class Ia antiarrhythmic effect (NaβΊ channel block + KβΊ channel block) β widened QRS, prolonged QTc, torsades de pointes, VF. β‘
- Metabolic effects: Stimulates pancreatic insulin release β profound hypoglycaemia, especially in children and pregnant women. π¬β¬οΈ
- Haematological: Quinine hypersensitivity can trigger haemolysis, thrombocytopenia, and DIC (βBlackwater feverβ). β οΈ
Clinical Presentation π©Ί
- Cinchonism: Tinnitus, hearing loss, headache, dizziness, nausea, visual disturbances (blurred vision, photophobia, blindness). π§ποΈ
- Neurological: Confusion, delirium, tremor, seizures, coma, respiratory depression.
- Cardiac: Hypotension, bradycardia or tachyarrhythmias, wide QRS, prolonged QT, torsades de pointes, VF. β€οΈ
- Metabolic: Hypoglycaemia (may be recurrent and prolonged).
- Other: Fever, tachypnoea, acute renal injury, hypersensitivity reactions (rash, haemolysis).
Investigations π¬
- ECG: Widened QRS (>120 ms), prolonged QTc, risk of torsades/VF.
- Blood glucose: Monitor frequently β hypoglycaemia may recur despite treatment.
- U&E, renal function: To detect AKI and electrolyte derangements.
- LFTs & FBC: To assess haemolysis, thrombocytopenia, or DIC in hypersensitivity cases.
- Quinine levels: Rarely available, not essential to management.
Management π
- Immediate decontamination: Activated charcoal (50 g, repeated doses for large ingestion). Gastric lavage if very early & airway protected.
- Cardiac support:
- Atropine 0.6 mg IV for symptomatic bradycardia; pacing if refractory.
- If QRS >120 ms β IV sodium bicarbonate (target pH 7.45β7.55). π§ͺ
- Magnesium sulfate for torsades de pointes. β‘
- Neurological: Benzodiazepines (e.g. lorazepam, diazepam) for seizures.
- Hypoglycaemia: IV dextrose; repeated boluses or infusion as quinine stimulates recurrent insulin release.
- Haemodialysis: Limited role (quinine is highly protein bound) but may help in massive overdose with renal failure.
- Supportive: IV fluids, electrolyte correction, continuous cardiac monitoring, early ITU involvement.
Prognosis π
- Mortality is dose-dependent; survival possible with aggressive support if detected early.
- Visual loss is often permanent due to retinal artery spasm and optic atrophy. ποΈβ
- Hypoglycaemia and arrhythmias are the main causes of death.
Clinical Pearls β¨
- π Classic triad in exams: Visual disturbance + Tinnitus/hearing loss + Arrhythmias β think Quinine (cinchonism).
- π¬ Hypoglycaemia is common, prolonged, and may require continuous glucose infusion β especially in pregnant women.
- β€οΈ ECG resembles TCA/quinidine poisoning β sodium bicarbonate is lifesaving.
- π©ββοΈ Visual loss often irreversible β emphasise early recognition and prevention.