indication

For the management of hypertension alone or in combination with other classes of antihypertensive agents. Also used as a first-line agent in the treatment of diabetic nephropathy, as well as a second-line agent in the treatment of congestive heart failure (only in those intolerant of ACE inhibitors).

pharmacology

Angiotensin II, the principal pressor agent of the renin-angiotensin system, is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme [kininase II]. It is responsible for effects such as vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Eprosartan selectively blocks the binding of angiotensin II to the AT₁ receptor, which in turn leads to multiple effects including vasodilation, a reduction in the secretion of vasopressin, and reduction in the production and secretion of aldosterone. The resulting effect is a decrease in blood pressure.

mechanism of action

Eprosartan blocks 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). There is also an AT₂ receptor found in many tissues but it is not known to be associated with cardiovascular homeostasis. Eprosartan does not exhibit any partial agonist activity at the AT₁ receptor. Its affinity for the AT₁ receptor is 1,000 times greater than for the AT₂ receptor. In vitro binding studies indicate that eprosartan is a reversible, competitive inhibitor of the AT₁ receptor. Eprosartan has also been shown to bind to AT₁ receptors both presynaptically and synaptically. Its action on presynaptic AT₁ receptors results in the inhibition of sympathetically stimulated noradrenaline release. Unlike ACE inhibitors, eprosartan and other ARBs do not interfere with response to bradykinins and substance P, which allows for the absence of adverse effects that are present in ACE inhibitors (eg. dry cough).

toxicity

There was no mortality in rats and mice receiving oral doses of up to 3000 mg eprosartan/kg and in dogs receiving oral doses of up to 1000 mg eprosartan/kg.

biotransformation

Eprosartan is not metabolized by the cytochrome P450 system. It is mainly eliminated as unchanged drug. Less than 2% of an oral dose is excreted in the urine as a glucuronide.

absorption

Absolute bioavailability following a single 300 mg oral dose of eprosartan is approximately 13%. Administering eprosartan with food delays absorption.

half life

The terminal elimination half-life of eprosartan following oral administration is typically 5 to 9 hours.

drug interactions

Amiloride: Increased risk of hyperkalemia

Drospirenone: Increased risk of hyperkalemia

Lithium: The ARB increases serum levels of lithium

Potassium: Increased risk of hyperkalemia

Spironolactone: Increased risk of hyperkalemia

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

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

Triamterene: Increased risk of hyperkalemia