J Clin Pharmacol
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Losartan: first of a new class of angiotensin antagonists for the management of hypertension

AA Carr and LM Prisant

Angiotensin receptor antagonists represent a new class of drugs for the treatment of patients with hypertension. Reduction of blood pressure in patients with essential hypertension requires increased activity of the renin-angiotensin system. Losartan, the first orally active, nonpeptide angiotensin antagonist, specifically competes with angiotensin II (Ang II) for the AT1 receptor and reversibly alters the receptor. Maximum blood pressure reductions occur after doses of approximately 50 mg, although some patients will require 100 mg; the parent compound and a metabolite are responsible for a smooth 24-hour effect on blood pressure. Once-daily dosing with losartan has been documented to be safe. The drug's safety has been evaluated in 4,058 patients; of these patients, more than 1,200 were treated for longer than 6 months and more than 800 were treated for longer than 1 year with doses of 10 mg to 150 mg. Overall, no hypertensive patients were withdrawn from treatment because of elevated serum creatinine or potassium levels, and there were no reports of angioedema. In addition, some reductions in plasma uric acid levels were noted. Cough occurred significantly less often in patients treated with losartan than in those treated with hydrochlorothiazide or lisinopril. In contrast to angiotensin-converting enzyme (ACE) inhibitors, losartan does not activate bradykinin-nitric oxide-prostanoid vasodilation.
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