Q-Pid Mechanism of Action

Pharmacology: Pharmacodynamics: Losartan is a synthetic oral angiotensin-II receptor (type AT1) antagonist. Angiotensin II, a potent vasoconstrictor, is the primary active hormone of the renin/angiotensin system and an important determinant of the pathophysiology of hypertension. Angiotensin II binds to the AT1 receptor found in many tissues (e.g. vascular smooth muscle, adrenal gland, kidneys and the heart) and elicits several important biological actions, including vasoconstriction and the release of aldosterone. Angiotensin II also stimulates smooth muscle cell proliferation.
Pharmacokinetics: Losartan is readily absorbed from the gastrointestinal tract after oral doses, but undergoes substantial first pass metabolism resulting in a systematic bioavailability of about 33%. It is metabolized to an active carboxylic acid metabolite E-3174 (EXP-3174), which has greater pharmacological activity than Losartan; some inactive metabolites are also formed. Metabolism is primarily by cytochrome P450 isoenzymes CYP2C9 and CYP3A4. Peak plasma concentrations of Losartan and E-3174 occur about 1 hour and 3 to 4 hours, respectively, after morning oral dose. Both Losartan and E-3174 are more than 98% bound to plasma proteins. Losartan is excreted in the urine, and in the faeces via bile, as unchanged drug metabolites. About 4% of an oral dose is excreted unchanged in the urine and about 6% is excreted as active metabolite. The terminal elimination half-lives of Losartan and E-3174 are about 1.5 to 2.5 hours and 3 to 9 hours, respectively.