Bretylium (also bretylium tosylate) is an antiarrhythmic agent. It blocks the release of noradrenaline from nerve terminals. In effect, it decreases output from the peripheral sympathetic nervous system. It also acts by blocking K⁺ channels and is considered a class III antiarrhythmic. The dose is 5–10 mg/kg and side effects are

high blood pressure Hypertension, also known as high blood pressure, is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms itself. It is, however, a major ri ...

followed by low blood pressure and ventricular ectopy. Originally introduced in 1959 for the treatment of hypertension. Its use as an antiarrhythmic for

ventricular fibrillation Ventricular fibrillation (V-fib or VF) is an abnormal heart rhythm in which the Ventricle (heart), ventricles of the heart Fibrillation, quiver. It is due to disorganized electrical conduction system of the heart, electrical activity. Ventricula ...

was discovered and patented by Marvin Bacaner in 1969 at the

University of Minnesota The University of Minnesota Twin Cities (historically known as University of Minnesota) is a public university, public Land-grant university, land-grant research university in the Minneapolis–Saint Paul, Twin Cities of Minneapolis and Saint ...

. The American Heart Association removed bretylium from their 2000 ECC/ACC guidelines due to its unproven efficacy and ongoing supply problems. Many have cited these supply problems as an issue of raw materials needed in the production of Bretylium. By the release of the AHA 2005 ECC/ACC guidelines there is no mention of Bretylium and it is virtually unavailable throughout most of the world. On June 8, 2011 bretylium tosylate was announced as unavailable in the US after request of Hospira Inc. to withdraw its NDA from the market. Bretylium will remain on the FDA's discontinued drug list since its withdrawal was not the result of a safety or effectiveness concern. In mid 2019, it was reintroduced.

Uses

The drug was used in emergency medicine,

cardiology Cardiology () is the study of the heart. Cardiology is a branch of medicine that deals with disorders of the heart and the cardiovascular system. The field includes medical diagnosis and treatment of congenital heart defects, coronary artery di ...

, and other specialties throughout the 1980s-1990s for the acute management of ventricular tachycardia and

refractory to other first line treatments such as defibrillation or lidocaine. It is contraindicated in patients with AV (atrioventricular) heart block or digoxin

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacteria, bacterium, or plant, as well as the effect o ...

. Bretylium should be used only in an ICU or emergency department setting and should not be used elsewhere due to its dramatic actions and its predominant side effect of

hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

Experimental uses

It is used in physiological and pharmacological research as an inhibitor of sympathetic transmission. Its mechanism of action is the inhibition of neurotransmitter release from sympathetic nerve terminals, both by the inhibition of action potentials in the nerve terminals and by other mechanisms. Its specificity for sympathetic nerves is achieved because it is a substrate for the noradrenaline transporter; hence, it accumulates inside nerve terminals which have this transporter.

References

{{Ion channel modulators Adrenergic release inhibitors Antiarrhythmic agents 2-Bromophenyl compounds Potassium channel blockers Quaternary ammonium compounds