[The effect of cardiac insufficiency on pharmacokinetics].
Heart failure may have repercussions on the different stages of pharmacokinetics. Following intramuscular or oral administration, drug absorption may be slowed down by the fall in cardiac output and by peripheral vasoconstriction. Tissue distribution is altered by changes in the plasma protein binding of drugs and by redistribution of cardiac output to the brain and heart, resulting in changes in the apparent volume of distribution. Excretion through the liver is influenced by the decrease of hepatic blood flow and metabolic capacities. Lowering of the renal blood flow alters the glomerular and tubular excretion processes. These hepatic and renal dysfunctions result in a reduction of total plasma clearance. The effects of heart failure on the pharmacokinetics of digitalis compounds seem to consist merely of a delay in digestive tract absorption. More studies have been devoted to the fate of antiarrhythmic agents. Blood concentrations of lidocaine are raised in patients with heart failure; this is accounted for by the redistribution of local blood flows, the increase in plasma protein binding observed after myocardial infarction and the reduced hepatic clearance. A fall in the volume of distribution and total clearance of quinidine has been described. Data concerning disopyramide are discordant, but reduction of the free drug fraction and variations in total clearance have been observed after myocardial infarction. Alterations in the total clearance of prazosin, nitroglycerin and theophylline have been reported by several authors.(ABSTRACT TRUNCATED AT 250 WORDS)
Cheymol
G
G
Service de pharmacologie et d'explorations fonctionnelles cardio-vasculaires, hôpital Saint-Antoine, Paris.
Jaillon
P
P
D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics; D002302:Cardiac Output; D004071:Digitalis Glycosides / Q000493:pharmacokinetics; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D007408:Intestinal Absorption; D010599:Pharmacokinetics; D014018:Tissue Distribution; D014661:Vasoconstriction
D000889:Anti-Arrhythmia Agents; D004071:Digitalis Glycosides
Influence de l'insuffisance cardiaque sur la pharmacocinétique.