indication

For the treatment of hypertension.

pharmacology

Olmesartan, a specific angiotensin II type 1 antagonist, is used alone or with other antihypertensive agents to treat hypertension. Unlike the angiotensin receptor antagonist losartan, olmesartan does not have an active metabolite or possess uricosuric effects. Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and circulating angiotensin II levels do not overcome the effect of olmesartan on blood pressure.

mechanism of action

Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation and renal reabsorption of sodium. Olmesartan blocks the vasoconstrictor effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT₁ receptor in vascular smooth muscle. Its action is, therefore, independent of the pathways for angiotensin II synthesis. Olmesartan has more than a 12,500-fold greater affinity for the AT₁ receptor than for the AT₂ receptor.

toxicity

Symptoms of overdose include dehydration (dry mouth, excessive thirst, muscle pain or cramps, nausea and vomiting, weakness), dizziness, low blood pressure, and slow or irregular heartbeat.

biotransformation

Olmesartan is rapidly and completely bioactivated by ester hydrolysis to olmesartan during absorption from the gastrointestinal tract. There is virtually no further metabolism of olmesartan.

absorption

Bioavailability is about 26%. Food does not affect the bioavailability of olmesartan.

half life

Approximately 13 hours

drug interactions

Drospirenone: Increased risk of hyperkalemia

Tobramycin: Increased risk of nephrotoxicity

Trandolapril: The angiotensin II receptor blocker, Olmesartan, may increase the adverse effects of Trandolapril.

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.