Mytensa Mechanism of Action

Pharmacological classification: Vasodilators, hypotensive medicines.
Pharmacology: Pharmacodynamics: Losartan: Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues (e.g., vascular smooth muscle, adrenal gland). Both Losartan and its principal active metabolite do not exhibit any partial agonist activity at the AT1 receptor and have much greater affinity (about 1000-fold) for the AT1 receptor than theAT2 receptor.
Amlodipine: Amlodipine inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that Amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.
Pharmacokinetics: Absorption: Amlodipine: Plasma levels peak 6-12 hrs after oral administration; 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.
Losartan: Metabolized to an active carboxylic acid metabolite E-3174 (EXP-3174), which has greater pharmacological activity than losartan; some inactive metabolites are also formed.
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 hrs.
Losartan and its active metabolites: Biliary excretion; terminal half-life: About 2 hrs (Losartan) and 6-9 hrs (metabolites).