Amlosar Mechanism of Action

Pharmacological classification: Angiotensin II receptor blocker/calcium channel blocker.
Pharmacology: Amlodipine inhibits the movement of Ca ions across the cell membrane into vascular smooth muscles and myocytes. Action is greater in the arterial resistant vessels causing peripheral vasodilatation and reduction in afterload. Losartan is an angiotensin II receptor (type At1) antagonists antihypertensive which acts by blocking the actions of angiotensin II of renin-angiotensin-aldosterone system. The drug and its active metabolite selectively block the vasoconstrictor and aldosterone secreting effects of angiotensin II by selectively antagonising the binding of angiotensin II to At1 receptors.
Pharmacokinetics: Absorption: Amlodipine: Plasma levels peak 6-12 hr after oral admin; absolute bioavailability is estimated to be 64-90%. Losartan: Well absorbed; undergoes substantial 1st pass metabolism by CYP450 enzymes; systemic bioavailability is about 33%; about 14% of an oral dose is converted to active metabolites.
Distribution: Amlodipine: 93% bound to plasma proteins.
Losartan and its active metabolites: Highly bound to plasma proteins, mainly albumin.
Metabolism: Amlodipine: About 90% converted to inactive metabolites hepatically.
Excretion: Amlodipine: 10% of parent compound and 60% of the metabolites are removed in the urine; elimination from the plasma is biphasic with terminal half-life of about 30-50 hr.
Losartan and its active metabolites: Biliary excretion; terminal half-life: About 2 hr (losartan) and 6-9 hr (metabolites).