Adalat - Nifedipine is a calcium ion influx inhibitor (calcium channel blocker or calcium ion antagonist).
The antianginal and antihypertensive actions of nifedipine are believed to be related to a specific cellular action of selectively inhibiting transmembrane influx of calcium ions into cardiac muscle and vascular smooth muscle. The contractile processes of these tissues are dependent upon the movement of extracellular calcium into the cells through specific ion channels.
Nifedipine selectively inhibits the transmembrane influx of calcium through the slow channel without affecting, to any significant degree, the transmembrane influx of sodium through the fast channel. This results in a reduction of free calcium ions available within the muscle cells and an inhibition of the contractile processes. Nifedipine does not alter total serum calcium.
The specific mechanisms by which nifedipine relieves angina and reduces blood pressure have not been fully determined but are believed to be brought about largely by its vasodilatory action.
Nifedipine dilates the main coronary arteries and coronary arterioles both in normal and ischemic regions resulting in an increase in blood flow and hence in myocardial oxygen delivery.
Nifedipine by its vasodilatory action on peripheral arterioles, reduces the total peripheral vascular resistance. This reduces the workload of the heart and thus reduces myocardial energy consumption and oxygen requirements which probably accounts for the effectiveness of nifedipine in chronic stable angina.
The mechanism by which nifedipine reduces arterial blood pressure involves peripheral arterial vasodilation and subsequent reduction in peripheral vascular resistance. The increased peripheral vascular resistance that is an underlying cause of hypertension results from an increase in active tension in the vascular smooth muscle. Studies have demonstrated that the increase in active tension reflects an increase in cytosolic free calcium.
The negative inotropic effect of nifedipine is usually not of major clinical significance because at therapeutic doses, nifedipine’s vasodilatory property evokes a baroreceptor mediated reflex tachycardia which tends to counterbalance this negative inotropic effect. Continued administration of nifedipine to hypertensive patients has shown no significant increase in heart rate.
Although nifedipine causes a slight depression of sinoatrial node function and AV conduction in isolated myocardial preparations, such effects have not been seen in studies in intact animals or in man. In formal electrophysiologic studies, predominantly in patients with normal conduction systems, nifedipine has had no tendency to prolong AV conduction or sinus node recovery time, or to slow sinus rate.
Nifedipine is extensively metabolized to highly water-soluble, inactive metabolites accounting for 60 to 80% of the dose excreted in the urine. The remainder is excreted in the feces in metabolized form, most likely as a result of biliary excretion. The main metabolite (95%) is the hydroxycarbolic acid derivative, the remaining 5% is the corresponding lactone. Only traces (less that 0.1% of the dose) of unchanged nifedipine can be detected in the urine. Thus, the pharmacokinetics of nifedipine are not significantly influenced by the degree of renal impairment. Patients in hemodialysis or chronic ambulatory peritoneal dialysis have not reported significantly altered pharmacokinetics of nifedipine.
