The medicinal effects of the bark of the cinchona tree have been known for over 350 years. The tree is indigenous to South America and is known as Peruvian, Jesuit's, or Cardinal Bark. During the 1600s and 1700s, Jesuit priests imported cinchona bark from South America to Europe where it was used as a powder, extract, or infusion to treat fevers as well as “rebellious palpitation.”1,2 In the early 1800s, Pelletier and Caventou worked to isolate the more than 20 structurally related alkaloids found in the bark of the cinchona tree, quinine and quinidine being the most important ones.1, 2, and 3 Pelletier and Caventou successfully isolated quinine in 1820 (see Figure 18-1).2,3
Chemical structure of quinine.
In 1918, Walter von Frey of Berlin reported that quinidine was the most effective of the four principal cinchona alkaloids in controlling atrial arrhythmias.2, 3, and 4 Quinidine, the d-isomer of quinine, is both more potent and more toxic than quinine (see Figure 18-2).5 By the 1920s, quinidine became the drug of choice for maintaining normal sinus rhythm (NSR) in patient with atrial fibrillation or atrial flutter (Afib/flutter) and to prevent the recurrence of ventricular tachycardia (VT) or ventricular fibrillation; albeit, quinidine was known to produce a potentially lethal idiosyncratic pro-arrhythmic effect.4 In 1998, quinidine was the most frequently prescribed antiarrhythmic agent to maintain NSR in after conversion from Afib/flutter.4 Today, quinidine is used infrequently because studies show that quinidine therapy is associated with a threefold increase in the risk of sudden cardiac death when compared with placebo or other antiarrhythmic agents, especially in patients with structural heart disease, including left ventricular dysfunction.6,7
Quinidine is an intraerythrocytic schizonticide; it is gametocidal to Plasmodium vivax and P. malariae, but not to P. falciparum.9,10 Quinidine has minimal effects on sporozites or preerythrocytic parasites.
Quinidine is a Class 1A antiarrhythmic agent that is devoid of negative inotropism. In cardiac muscle and in Purkinje fibers, quinidine depresses the rapid inward depolarizing sodium current, thereby slowing phase-0 depolarization and reducing the amplitude of the action potential without affecting the resting potential.10 In normal Purkinje fibers, it reduces the slope of phase-4 depolarization, shifting the threshold voltage upward toward zero. The result is slowed conduction and reduced automaticity in all parts of the heart, with increase of the effective refractory period relative to the duration of the action potential in the atria, ventricles, and Purkinje tissues. Quinidine also raises the fibrillation ...