Mechanism of Action

Benicar blocks the vasoconstrictor effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in vascular smooth muscle. Angiotensin II is a potent vasoconstrictor that increases blood pressure in the body.

Benicar HCT is a combination of Benicar and hydrochlorothiazide (HCTZ) that works by blocking angiotensin II receptors in the blood vessels and increasing excretion of sodium and chloride in approximately equivalent amounts, resulting in lower systolic and diastolic blood pressure.

Angiotensin II increases blood pressure by causing the constriction of blood vessels, while sodium and chloride cause retention of water, increase in blood volume, and ultimately an increase in blood pressure. Therefore Benicar HCT reduces blood pressure by two complementary methods of action.

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Benicar pharmacodynamics and pharmacokinetics
Benicar mechanism of action
Benicar HCT mechanism of action
Reference

Benicar pharmacodynamics and pharmacokinetics

The clinical significance of pharmacodynamic and pharmacokinetic data is unknown

Benicar 40 mg inhibited 74% of the BP-raising effect of angiotensin II at the 24th hour.^1-5

The clinical significance of pharmacodynamic and pharmacokinetic data is unknown

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Benicar 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.

An AT2 receptor is found also in many tissues, but this receptor is not known to be associated with cardiovascular homeostasis. Olmesartan has more than a 12,500-fold greater affinity for the AT1 receptor than for the AT2 receptor.

Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is a mechanism of many drugs used to treat hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because olmesartan medoxomil does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known.

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.

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Benicar HCT mechanism of action

Along with the active ingredient in Benicar, olmesartan medoxomil, Benicar HCT also contains hydrochlorothiazide, a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so co-administration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with these diuretics.

The mechanism of the antihypertensive effect of thiazides is not fully understood.

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