Long-acting calcium-channel blocker.
Pharmacology: Amlodipine is a dihydropyridine calcium antagonist that inhibits the transmembrane influx of calcium ions into the vascular smooth muscle and cardiac muscle. The mechanism of the antihypertensive action is due to a direct relaxant effect on vascular smooth muscle. The precise mechanism by which amlodipine relieves angina may be due to the following 2 actions: Amlodipine dilates peripheral arterioles thus, reduces the total peripheral resistance against which the heart works. Since there is no associated reflex tachycardia, this unloading of the heart reduces myocardial energy consumption and oxygen requirements and probably accounts for the effectiveness of amlodipine in myocardial ischaemia.
The mechanism of action of amlodipine probably involves dilation of the main coronary arteries and coronary arterioles, both in normal and ischaemic regions.
Pharmacokinetics: After oral administration of the therapeutic doses, amlodipine is well absorbed with peak blood levels between 6-12 hrs post-dose. The volume of distribution was approximately 20 L/kg. The terminal elimination half-life is about 35-50 hrs and is consistent with once-daily dosing, steady-state plasma levels are reached after 7-8 days of consecutive dosing. Amlodipine is extensively metabolised to inactive metabolite with 10% of the parent compound and 60% of metabolites excreted in the urine. Bioavailability following oral administration approximates 60-65%. Approximately 97.5% of amlodipine is bound to plasma proteins.