Amvasc BE Mechanism of Action

Pharmacology: Pharmacodynamics: Amlodipine, a dihydropyridine calcium antagonist (slow channel blocker or calcium ion antagonist), inhibits the transmembrane influx of calcium ions into cardiac muscle and vascular smooth muscle. Its antihypertensive action is due to a direct relaxant effect on vascular smooth muscle resulting in decreased peripheral vascular resistance and blood pressure.
Amlodipine's exact mechanism in relieving angina has not been fully established; however, amlodipine decreases total ischemic burden by dilating peripheral arterioles thereby reducing total peripheral resistance (afterload) against which the heart works. The unloading of the heart decreases myocardial energy consumption and oxygen requirements as the heart rate remains stable; and dilating the main coronary arteries and arterioles, both in normal and ischemic areas. This dilatation increases myocardial oxygen delivery in patients with coronary artery spasm (Prinzmetal's or variant angina).
Pharmacokinetics: After oral administration of therapeutic doses of amlodipine, peak plasma concentrations are reached between 6 and 12 hours. Amlodipine's absolute bioavailability is between 64 and 90%; its bioavailability is unaffected by food. Amlodipine's volume of distribution is about 20 L/kg.
About 90% of amlodipine is converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine. Studies have shown that about 93% of the circulating drug is bound to plasma proteins in hypertensive patients. Plasma elimination is biphasic with a terminal elimination half-life of 30 to 50 hours. Steady state plasma amlodipine concentrations are reached after 7 to 8 days of consecutive dosing.
The pharmacokinetics of amlodipine is not significantly influenced by renal impairment. Thus, the usual initial dose may be given to patients with renal failure.
Amlodipine's clearance is decreased and the AUC increased (by 40 to 60%) in elderly patients and patients with hepatic impairment. Plasma amlodipine elimination half-life (t_1/2) is prolonged (56 hours) in patients with hepatic impairment. Thus, a lower initial dose may be given in these patients. A comparable increase in AUC was seen in patients with moderate to severe heart failure.