Quinidine

Quinidine is a class IA antiarrhythmic agent used to treat heart rhythm disturbances.[1] It is a diastereomer of antimalarial agent quinine,[2] originally derived from the bark of the cinchona tree. The drug causes increased action potential duration, as well as a prolonged QT interval. As of 2019, its IV formulation is no longer being manufactured for use in the United States.[3]

Medical uses

Quinidine is occasionally used as a class I antiarrhythmic agent to prevent ventricular arrhythmias, particularly in Brugada Syndrome, although its safety in this indication is uncertain.[1][4]

It reduces the recurrence of atrial fibrillation after patients undergo cardioversion, but it has proarrhythmic effects and trials suggest that it may lead to an overall increased mortality in these patients.[5]

Quinidine is also used to treat short QT syndrome.[6]

Eli Lilly has discontinued manufacture of parenteral quinidine gluconate in the US, and its future availability in many countries is uncertain.[7]

Side effects

Quinidine is an inhibitor of the cytochrome P450 enzyme 2D6, and can lead to increased blood levels of lidocaine, beta blockers, opioids, and some antidepressants. Quinidine also inhibits the transport protein P-glycoprotein and so can cause some peripherally acting drugs such as loperamide to have central nervous system side effects, such as respiratory depression, if the two drugs are coadministered.[11]

Quinidine can cause thrombocytopenia, granulomatous hepatitis, myasthenia gravis, and torsades de pointes (dangerous heart rhythm),[12] and has been largely phased out in favor of other antiarrhythmics. Torsades can occur after the first dose. Quinidine-induced thrombocytopenia (low platelet count) is mediated by the immune system, and may lead to thrombocytic purpura.

Quinidine intoxication can lead to a collection of symptoms collectively known as cinchonism, with tinnitus (ringing in the ears) being among the most characteristic and common symptoms of this toxicity syndrome.

Pharmacology

History

The effects of cinchona bark (the botanical source from which quinidine is extracted) had been commented on long before the understanding of cardiac physiology arose. Jean-Baptiste de Sénac, in his 1749 work on the anatomy, function, and diseases of the heart, had this to say:

"'Long and rebellious palpitations have ceded to this febrifuge'.[20]" "'Of all the stomachic remedies, the one whose effects have appeared to me the most constant and the most prompt in many cases is quinquina [Peruvian bark] mixed with a little rhubarb.'[21]"

Sénac subsequently became physician to Louis XV of France, a counselor of the state, and superintendent of the mineral waters and medicinals in France. As a result of his influence, throughout the 19th century, quinidine was used to augment digitalis therapy. It was described as das Opium des Herzens (the opium of the heart).

However, the use of quinidine to treat arrhythmia really only came into its own because a physician listened to the astute observation of one of his patients. In 1912, Karel Frederik Wenckebach saw a man with atrial fibrillation. He was a Dutch merchant, used to good order in his affairs. He would like to have good order in his heart business, also, and asked, "why there were heart specialists if they could not abolish this very disagreeable phenomenon ... he knew himself how to get rid of his attacks. As I did not believe him, he promised to come back next morning with a regular pulse, and he did."

Chemistry

Quinidine-based ligands are used in AD-mix-β for Sharpless asymmetric dihydroxylation.

Veterinary use

Quinidine sulfate is used in the treatment of atrial fibrillation in horses.[23][24]

External links

• MedlinePlus
• Poisons Information Monograph