Pharmacology: Pharmacodynamics: Amlodipine is classified as calcium ion influx inhibitor (slow channel blocker or calcium ion antagonist). It inhibits an influx of calcium ions across cell membrane into cardiac and vascular smooth muscles.
Amlodipine produces arteriolar vasodilation by acting directly on vascular smooth muscle. This mechanism results in a reduction of blood pressure. The precise mechanisms by which amlodipine relieves angina have not been fully delineated, but are thought to include the two categories as follows: Amlodipine is a peripheral arteriolar vasodilator, thus it reduces total peripheral resistance (afterload) against which the heart works. Due to static heart rate, reduction in heart work causes reduction in myocardial energy and oxygen demand.
Mechanism of action of amlodipine may be related to blocking constriction and restoring blood flow in coronary arteries and arterioles. This inhibition of coronary spasm is responsible for the effectiveness in vasospastic (Prinzmetal's variant angina).
Pharmacokinetics: Absorption: After oral administration of therapeutic doses, amlodipine is well absorbed. It reaches peak plasma concentration within 6-12 hours after intake. The absolute bioavailability is approximately 64-90% while the distribution volume is equivalent to 21 litres/kg. Amlodipine can be taken either before or after meals as food has no effect on its absorption.
Metabolism and Elimination: Plasma elimination terminal half life of amlodipine is 30-50 hours making it suitable to be given as once daily dosage. The plasma level reaches steady state and remains consistent when taking consecutive doses for 7-8 days. Amlodipine is generally metabolized into inactive form at the liver, where 10% remains unchanged, and 60% of the metabolites will be excreted in the urine.