Adverse cardiovascular effects of anti-arrhythmia drugs. Part II: Inotropic effects and specific pharmacokinetic properties.
The antiarrhythmic drugs are unfortunately not devoid of adverse effects. A good watching of their safety is necessary, according to their cardiovascular adverse effects which are the most dreaded. Among these and beside the proarrhythmic effects, the negative inotropic effects can impair cardiac function. Different mechanisms could explain the negative inotropic effects of antiarrhythmic drugs: reduction of adrenergic sensitivity, decrease of calcium concentration in the cardiac cells. Pharmacokinetic properties of antiarrhythmic drugs can modulate their cardiovascular adverse effects. As a matter of fact the plasmatic concentration of the unbound drug, which could be correlated to the adverse effects, fluctuates according to the protein binding of the drug. In an other way the first pass hepatic effect of a drug can be saturable so that the resulting dose-concentration curve becomes exponential. Drug disposition might also be very different from one patient to another depending on kidney and/or hepatic function and genetically determined metabolic pathways.
Libersa
C
C
Service de Pharmacologie Hospitalière, Faculté de Médecine, CHRU, Lille.
Caron
J
J
Guedon-Moreau
L
L
Adamantidis
M
M
Nisse
C
C
D000889:Anti-Arrhythmia Agents / Q000009:adverse effects* / Q000493:pharmacokinetics*; D003864:Depression, Chemical; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents