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What is Bretylium?

Bretylium (bretylium tosylate, brand name Bretylol) is a Class III antiarrhythmic drug approved by the FDA for short-term prevention and treatment of ventricular fibrillation and life-threatening ventricular arrhythmias unresponsive to first-line agents like lidocaine. 1

Pharmacological Mechanism

Bretylium has a unique and complex mechanism of action that distinguishes it from other antiarrhythmic agents:

  • It is an adrenergic neuronal blocking agent that is selectively taken up at peripheral adrenergic nerve terminals, where it initially releases norepinephrine (producing a sympathomimetic effect) and then causes adrenergic neuronal blockade. 2

  • Direct cardiac membrane effects include prolonging action potential duration and effective refractory period, but unlike other membrane-active antiarrhythmics, bretylium does not depress conduction velocity or automaticity. 2

  • It increases ventricular fibrillation threshold and prevents the decrease in this threshold associated with myocardial ischemia. 2

  • Bretylium does not depress myocardial contractility, which is an important safety advantage. 2

Clinical Indications

The FDA-approved indications are specific and limited:

  • Short-term prevention and treatment of ventricular fibrillation (VF). 1

  • Treatment of life-threatening ventricular arrhythmias, including ventricular tachycardia (VT) that is unresponsive to adequate doses of first-line antiarrhythmic agents such as lidocaine. 1, 2

Metabolism and Drug Interactions

  • Bretylium is not metabolized and is excreted unchanged in the urine. 3

  • Drug interactions are primarily pharmacodynamic rather than pharmacokinetic, meaning bretylium interacts with other drugs (including other antiarrhythmics) through its pharmacological effects rather than through metabolic pathways. 3

Historical Context and Current Availability

  • Originally approved in 1986, bretylium was withdrawn from the US market in 2011 due to unavailability of raw materials required for production. 1

  • Removed from ACLS Guidelines in 2000 for VF/pulseless VT due to manufacturing challenges. 1

  • Recently reintroduced to the US market by a generic pharmaceutical company with the same indications as its original approval. 1

Clinical Efficacy

  • Clinical studies have demonstrated effectiveness in suppressing ventricular arrhythmias, particularly recurrent, drug-resistant ventricular tachycardia or ventricular fibrillation. 2

Important Clinical Caveat

Bretylium should be reserved for life-threatening ventricular arrhythmias that have failed to respond to first-line agents, as it is not a first-line therapy and has a complex biphasic effect (initial sympathomimetic followed by adrenergic blockade). 1, 2 Close monitoring is essential when using bretylium, particularly given its unique mechanism and the potential for interactions with other antiarrhythmic drugs through pharmacodynamic mechanisms. 3

References

1
Research

Bretylium, a Class III Antiarrhythmic, Returns to the Market.

The American journal of cardiology, 2020

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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