Amlocor Mechanism of Action

Pharmacology: Amlodipine acts as a calcium ion channel antagonist in peripheral, vascular and coronary smooth muscle cells, thus producing marked vasodilation in peripheral and coronary vascular beds. The reduction in peripheral blood pressure produced by Amlodipine is a result of peripheral arterial vasodilation resulting in a reduction of peripheral vascular resistance. In patients with mild to moderate essential hypertension, Amlodipine has a sustained and gradual onset of antihypertensive effect. Amlodipine, in once daily dosage regimen of 2.5 to 10mg has been shown to produce reductions in mean systolic and diastolic pressure of about 10 to 18% in hypertensive patients. Moreover, in such patients Amlodipine also increased renal blood flow as well as glomerular filtration rate, and reduced renovascular resistance. Urine volume and urinary sodium excretion were unchanged suggesting that Amlodipine has no long-term effect on sodium homeostasis. Plasma renin activity as well as aldosterone and catecholamine levels were not significantly affected. Amlodipine reduces myocardial oxygen demand, increases myocardial oxygen supply and improves exercise capacity in patients with symptomatic myocardial ischaemia. In patients with stable angina pectoris, Amlodipine, through reduction in peripheral vascular resistance, reduces afterload as well as the rate-pressure product, thereby reducing myocardial oxygen demand. Amlodipine also inhibits coronary spasm and restores coronary blood flow in patients of vasospastic (Prinzmetal's) angina.
Amlodipine has no significant effects on the sinoatrial or atrioventricular node. In clinical studies where Amlodipine was administered concomitantly with beta-blockers to patients with either hypertension or angina, no adverse effects on electrocardiographic parameters were observed.
Animal studies have demonstrated a cardioprotective effect for Amlodipine in both in-vivo and in-vitro models of ischaemic reperfusion; reductions in tissue calcium content and increase in shortening fraction have been noted after reperfusion. After oral administration of therapeutic doses, Amlodipine is slowly and almost completely absorbed; peak plasma concentration is attained within 6 to 12 hours with absolute bioavailability between 64 and 90%. The bioavailability of Amlodipine is not altered by the presence of food. Amlodipine has relatively long elimination half-life of 35 to 45 hours, which permits once-daily oral doses, to inactive metabolites with most metabolites excreted in the urine. Amlodipine is more that 95% bound to plasma proteins.