Makindo Medical Notes

⚡ Bretylium tosylate is a class III antiarrhythmic once used in the management of ventricular tachycardia (VT) and ventricular fibrillation (VF) resistant to defibrillation. It has fallen out of routine use due to severe hypotension and limited evidence of improved outcomes. Now rarely used in modern resuscitation protocols but remains of historical and pharmacological interest.

📘 About

• Always check the drug reference here or the BNF for current formulation and safety advice (availability in the UK is limited).
• Previously used as an adjunct in refractory VT/VF when unresponsive to electrical cardioversion and first-line antiarrhythmics (e.g. amiodarone, lidocaine).
• Acts as both a neuronal adrenergic blocker and a prolonger of cardiac action potential duration.

⚙️ Mode of Action

• Initially releases stored noradrenaline from sympathetic nerve terminals, producing a transient rise in blood pressure and contractility.
• Then produces adrenergic blockade (prevents further noradrenaline release), leading to sympatholytic hypotension.
• At the myocardium, prolongs the cardiac action potential and refractory period by inhibiting potassium efflux — classified as a Class III antiarrhythmic.
• Overall effect: suppression of re-entry circuits and increased ventricular fibrillation threshold.

💊 Indications & Dose

• Reserved for life-threatening ventricular arrhythmias (VT/VF) resistant to defibrillation, adrenaline, amiodarone, and lidocaine.
• Onset of action is slow — usually ≥10 minutes — so it should not delay other definitive interventions.
• Adult dose: 5–10 mg/kg IV infusion, diluted and given over ≥10 minutes.
• Further doses may be given cautiously depending on response and blood pressure.

⚗️ Pharmacokinetics

• Onset: 10–20 minutes after infusion start.
• Elimination half-life: 6–10 hours.
• Renal excretion — adjust dose in renal impairment.

🔄 Interactions

• See BNF or equivalent for details.
• May potentiate hypotension when combined with other antihypertensive or sympatholytic drugs.
• Avoid concurrent use with other class III agents (e.g. amiodarone, sotalol) due to additive QT prolongation and torsades risk.

⚠️ Cautions

• Profound postural hypotension common, especially in elderly or hypovolaemic patients.
• Ensure adequate volume status before administration.
• Can initially cause transient hypertension and tachycardia before onset of sympathetic blockade.
• May exacerbate myocardial ischaemia or heart failure in unstable patients.

🚫 Contraindications

• Severe hypotension or shock states.
• Marked bradycardia or AV block without pacing.
• Uncontrolled heart failure or recent myocardial infarction (relative contraindication).
• See BNF for further details if available.

💥 Adverse Effects

• 🩸 Profound hypotension (most common and limiting effect).
• GI upset: nausea, vomiting.
• Dizziness, light-headedness, vertigo, or syncope due to postural hypotension.
• Transient hypertension or arrhythmia at onset (from noradrenaline release).
• Rare: bradycardia, prolonged QT, or cardiac arrest.

🧠 Teaching Note

Bretylium demonstrates a key principle in antiarrhythmic pharmacology: dual sympatholytic and membrane effects. Its historical role in refractory VT/VF has been replaced by amiodarone and lidocaine, which are safer and more effective. However, its mechanism is still of interest for understanding the evolution of antiarrhythmic therapy and the balance between sympathetic tone and cardiac excitability.

📚 References

• Drugs.com: Bretylium Injection Monograph
• Resuscitation Council UK (2023): Advanced Life Support Guidelines
• BNF Online: Antiarrhythmic Drugs — Class III Agents
• Katzung BG. Basic & Clinical Pharmacology (15th ed.)