Magazine article Drug Topics

New Antihypertensive Has Unique Mechanism of Action

Magazine article Drug Topics

New Antihypertensive Has Unique Mechanism of Action

Article excerpt


Patients whose hypertension remains inadequately controlled will soon have a therapeutic option with a unique mechanism of action. On Sept. 30, the Food & Drug Administration granted marketing approval for eplerenone (Inspra, Pharmacia) for the treatment of mild to moderate hypertension alone or in combination with other antihypertensives.

Eplerenone is the first agent that selectively binds to the mineralocorticoid receptor and blocks the binding of aldosterone, said Cynthia Sanoski, Pharm.D., assistant professor of clinical pharmacy, Philadelphia College of Pharmacy.

Spironolactone, which also blocks aldosterone, binds to androgen and progesterone receptors in addition to mineralocorticoid receptors, she said.

Sanoski and Mark Munger, Pharm.D., professor of clinical pharmacology, University of Utah, Salt Lake City, explained that this selectivity for the mineralocorticoid receptor gives eplerenone an improved sideeffect profile compared with spironolactone in terms of endocrine-related adverse effects, such as gynecomastia, in males and abnormal vaginal bleeding in females.

Sanoski also pointed out that angiotensin converting enzyme (ACE) inhibitors do not always completely block the renin-angiotensinaldosterone system (RAAS). With the long-term use of ACE inhibitors, aldosterone escape occurs, Sanoski explained, because non-RAAS pathways for aldosterone production exist. Eplerenone, however, will block aldosterone from binding right at the receptor, so it does not matter how the aldosterone is produced.

Munger and Sanoski agreed that the principal risk of treatment with eplerenone is hyperkalemia. Eplerenone therapy is contraindicated in patients with a serum potassium level > 5.5 mEq/L. Use of eplerenone is also contraindicated in patients with Type 2 diabetes and microalbuminuria, both said.

According to Sanoski and Munger, eplerenone use is contraindicated in male patients with a serum creatinine level > 2.0 mg/dl and in female patients with a serum creatinine level > 1.8 mg/dl. Persons with creatinine clearance < 50.0 ml/min should not take eplerenone, they added.

Eplerenone use is contraindicated in patients treated concomitantly with potassium supplements or potassium-sparing diuretics, said Sanoski and Munger. They explained that use is also contraindicated in patients treated with strong inhibitors of the cytochrome P450 3A4 isoenzyme (CYP3A4), such as ketoconazole and itraconazole (Sporanox, Janssen-Ortho), because metabolism of eplerenone is predominantly mediated by the CYP3A4 isoenzyme. …

Search by... Author
Show... All Results Primary Sources Peer-reviewed


An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.