Class I Antiarrhythmics

Quinidine Sulfate, USP. Quinidine sulfate is the sulfate of an alkaloid obtained from various species of Cinchona and their hybrids. It is a dextrorotatory di-astereoisomer of quinine. The salt crystallizes from water as the dihydrate, in the form of fine, needlelike, white crystals. Quinidine sulfate contains a hydroxy methyl group that serves as a link between a quinoline ring and a quinu-clidine moiety. The structure contains two basic nitrogens, of which the quinuclidine nitrogen is the stronger base (pKa 10). Quinidine sulfate is bitter and light sensitive. Aqueous solutions are nearly neutral or slightly alkaline. It is soluble to the extent of 1% in water and more highly soluble in alcohol or chloroform.

Quinidine (Cardioquin) (Quinora) (Auinidex)

Quinidine sulfate is the prototype of antiarrhythmic drugs and a class IA antiarrhythmic agent according to the Vaughan Williams classification. It reduces Na+ current by binding the open ion channels (i.e., state A). The decreased Na+ entry into the myocardial cell depresses phase 4 dias-tolic depolarization and shifts the intracellular threshold potential toward zero. These combined actions diminish the spontaneous frequency of pacemaker tissues, depress the automaticity of ectopic foci, and, to a lesser extent, reduce impulse formation in the SA node. This last action results in bradycardia. During the spike action potential, quinidine sulfate decreases transmembrane permeability to passive influx of Na+, thus slowing the process of phase 0 depolarization, which decreases conduction velocity. This is shown as a prolongation of the QRS complex of electrocardiograms. Quinidine sulfate also prolongs action potential duration, which results in a proportionate increase in the QT interval. It is used to treat supraventricular and ventricular ectopic arrhythmias, such as atrial and ventricular premature beats, atrial and ventricular tachycardia, atrial flutter, and atrial fibrillation.

Quinidine sulfate is used most frequently as an oral preparation and is occasionally given intramuscularly. Quinidine sulfate that has been absorbed from the gastrointestinal tract or from the site of intramuscular injection is bound 80% to serum albumin.18 The drug is taken up quickly from the bloodstream by body tissues; consequently, a substantial concentration gradient is established within a few minutes. Onset of action begins within 30 minutes, with the peak effect attained in 1 to 3 hours. Quinidine is metabolized primarily in the liver by hydroxylation, and a small amount is excreted by the liver.26 Because of serious side effects and the advent of more effective oral antiar-rhythmic agents, quinidine is now used less, except in selected patients for long-term oral antiarrhythmic therapy.

Quinidine Gluconate, USP. Quinidinium gluconate (Duraquin, Quinaglute) occurs as an odorless, very bitter, white powder. In contrast with the sulfate salt, it is freely soluble in water. This is important because there are emergencies when the condition of the patient and the need for a rapid response make the oral route of administration inappropriate. The high water solubility of the gluconate salt along with a low irritant potential makes it valuable when an injectable form is needed in these emergencies. Quinidine gluconate forms a stable aqueous solution. When used for injection, it usually contains 80 mg/mL, equivalent to 50 mg of quinidine or 60 mg of quinidine sulfate.

Quinidine Polygalacturonate. Quinidine polygalac-turonate (Cardioquin) is formed by reacting quinidine and polygalacturonic acid in a hydroalcoholic medium. It contains the equivalent of approximately 60% quinidine. This salt is only slightly ionized and slightly soluble in water, but studies have shown that although equivalent doses of quinidine sulfate give higher peak blood levels earlier, a more uniform and sustained blood level is achieved with the polygalacturonate salt.

In many patients, the local irritant action of quinidine sulfate in the gastrointestinal tract causes pain, nausea, vomiting, and especially diarrhea, often precluding oral use in adequate doses. Studies with the polygalacturonate salt yielded no evidence of gastrointestinal distress. It is available as 275-mg tablets. Each tablet is the equivalent of 200 mg of quinidine sulfate or 166 mg of free alkaloid.

Procainamide Hydrochloride, USP. Procainamide hydrochloride, p-amino-n-[2-(diethylamino)ethyl]benzamide monohydrochloride, procainamidium chloride (Pronestyl, Procan SR), has emerged as a major antiarrhythmic drug. It was developed in the course of research for compounds structurally similar to procaine, which had limited effect as an antiarrhythmic agent because of its central nervous system (CNS) side effects and short-lived action caused by rapid hydrolysis of its ester linkage by plasma esterases. Because of its amide structure, procainamide hydrochloride is also more stable in water than is procaine. Aqueous solutions of procainamide hydrochloride have a pH of about 5.5. A kinetic study of the acid-catalyzed hydrolysis of procainamide hydrochloride showed it to be unusually stable to hydrolysis in the pH range 2 to 7, even at elevated

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