Effects of quinidine on the cardiac-glycoside sensitivity of guinea-pig and rat heart.
Quinidine causes a marked increase in plasma digoxin concentration in patients receiving the glycoside. Whether the sensitivity of the heart to digoxin is altered by quinidine was examined with rats and guinea pigs. In electrically stimulated rat atrial preparations, quinidine failed to affect digoxin-induced inhibition of ouabain-sensitive 42K+ uptake, an estimate of sodium pump activity. Effects of quinidine on digoxin binding to Na+, K+-adenosine triphosphatase (ATPase) in intact cells were examined by perfusion guinea-pig Langendorff preparations with digoxin and estimating the occupancy of the glycoside-binding sites on the enzyme from a reduction in the initial velocity of the ATP-dependent [3H]ouabain binding reaction. Quinidine did not alter the initial velocity of [3H]ouabain binding to ventricular homogenates obtained from digoxin-perfused preparations, indicating that digoxin binding to Na+, K+-AtPase during the perfusion was not altered. In isolated rat heart preparations, quinidine failed to affect the positive inotropic action of ouabain. Nor did quinidine modify the inotropic action of digoxin in Langendorff preparations of guinea-pig heart. Concurrent i.v. infusion of quinidine in anesthetized guinea pigs increased the digoxin concentration in plasma. Thus, quinidine does not modify digoxin-Na+, K+-ATPase interactions or the digoxin-sensitivity of the myocardium. Quinidine-induced alterations in apparent volume of digoxin distribution should quantitatively change the response of the animal to digoxin.
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive; D001693:Biological Transport, Active / Q000187:drug effects; D004071:Digitalis Glycosides / Q000494:pharmacology*; D004077:Digoxin / Q000097:blood / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011802:Quinidine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D012964:Sodium / Q000378:metabolism
D004071:Digitalis Glycosides; D004077:Digoxin; D012964:Sodium; D011802:Quinidine