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|Drug Toxicity - clinical assessment
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|Drug Toxicity with Specific Antidotes
💡 Key Point: Hyperkalaemia is a hallmark of severe Digoxin toxicity and correlates with mortality.
Consult the National Poisons Information Service (NPIS) early. Digoxin-specific antibody fragments (Digoxin immune Fab / Digibind) are expensive and may be stocked only in tertiary centres.
💊 About
- Origin: Digoxin is derived from the Digitalis purpurea (foxglove) plant and is also present in oleander and lily of the valley.
- Therapeutic use: Rate control in atrial fibrillation and for symptomatic heart failure in selected patients.
- Therapeutic index: Very narrow - small changes in dose or renal function can cause toxicity.
⚙️ Mechanism & Pathophysiology
- Digoxin inhibits the Na⁺/K⁺-ATPase pump in cardiac myocytes → ↑ intracellular Na⁺ → reduced Na⁺/Ca²⁺ exchange → ↑ intracellular Ca²⁺ → enhanced contractility.
- It also ↑ vagal tone → slowed AV nodal conduction and bradycardia.
- Excess inhibition causes electrical instability and automaticity → arrhythmias of any type.
- Lethal dose: ≈10× daily dose (≈10 mg in adults, ≈4 mg in children).
- T½: 30–40 h (longer if renal impairment). Toxicity peaks at ~6 h post-ingestion; death may occur within 6–12 h.
⚠️ Factors Increasing Toxicity
- Electrolytes: ↓ K⁺, ↓ Mg²⁺, ↑ Ca²⁺ enhance binding to Na/K-ATPase.
- Renal impairment: Reduces clearance → accumulation.
- Drug interactions: Amiodarone, verapamil, macrolides, quinidine increase serum levels.
- Age/frailty: Lower volume of distribution → toxicity at “therapeutic” levels.
🩺 Clinical Presentation
- Gastrointestinal: Anorexia, nausea, vomiting, abdominal pain (early clues).
- Visual: Blurred or yellow vision (xanthopsia), “halo” effect.
- Cardiac: Bradycardia, AV block, sinus arrest, SVT with AV block, VT, or VF.
- Neurological: Confusion, weakness, delirium, lethargy.
- Electrolyte: Hyperkalaemia in acute toxicity (poor prognostic sign).
🧪 Investigations
- FBC, U&E, Mg, Ca, renal function.
- Serum digoxin level (≥ 4 h post ingestion for accuracy).
- ECG: “Reverse tick” ST depression, prolonged PR, frequent ectopics, AV block, or bidirectional VT.
- Continuous cardiac monitoring (CCU/HDU).
🚫 Management Principles
❗ Do NOT give IV calcium unless under senior/NPIS guidance - may precipitate fatal “stone heart” contraction.
| Management Step |
Key Actions & Rationale |
| 1️⃣ Stop Digoxin & Decontaminate |
Discontinue digoxin immediately.
If ingestion < 1 h: consider gastric lavage and/or activated charcoal (single or multiple doses for sustained release).
Monitor airway if vomiting or reduced GCS. |
| 2️⃣ Assess & Correct Electrolytes |
Check K⁺, Mg²⁺, Ca²⁺.
• Correct hypokalaemia and hypomagnesaemia.
• Treat hyperkalaemia (K⁺ > 6 mmol/L) with insulin-glucose ± sodium bicarbonate. Avoid calcium unless absolutely indicated. |
| 3️⃣ Cardiac Monitoring & Arrhythmia Control |
- Bradyarrhythmia: IV Atropine 0.6–1.2 mg; consider temporary pacing if refractory.
- Tachyarrhythmia (VT/VF): Lidocaine or Phenytoin IV.
Avoid Amiodarone or Procainamide (exacerbate toxicity).
- Defibrillation: use low-energy shocks (≈25 J) if needed.
|
| 4️⃣ Antidote – Digoxin Immune Fab (Digibind® / DigiFab®) |
Indications (per BNF/NPIS):
- Life-threatening arrhythmia or cardiac arrest.
- Serum digoxin > 15 nmol/L (acute ingestion) or > 10 nmol/L (delayed).
- Ingested dose > 10 mg (adult) or > 4 mg (child).
- Hyperkalaemia (K⁺ > 5 mmol/L).
Dose: Each vial binds ≈ 0.5 mg digoxin; large overdoses may need 10–20 vials.
Monitor for rebound heart failure once digoxin effect reversed. |
| 5️⃣ Supportive Care |
High-flow O₂, IV fluids (avoid overload), antiemetics, and correction of precipitating factors (renal impairment, drug interactions). |
| 6️⃣ Monitoring & Follow-up |
Repeat electrolytes and ECG frequently.
Digoxin level becomes unreliable after Fab therapy (immunoassay interference).
Observe ≥ 24 h post-antidote for recurrent bradyarrhythmia or hypokalaemia. |
📈 Prognosis
- With early Fab administration, survival exceeds 90% even in severe overdose.
- Mortality correlates with initial serum potassium and delay to antidote therapy.
- Chronic low-level toxicity (in elderly or renally impaired) often presents subtly with GI upset, confusion, or visual change.
📚 References
Summary: Digoxin toxicity produces a distinctive triad - gastrointestinal upset, visual changes, and any arrhythmia.
Hyperkalaemia marks severe poisoning.
Management centres on stopping the drug, correcting electrolytes, controlling arrhythmias, and giving Digoxin Immune Fab early in life-threatening cases.
