Vasotec: profile and news






Proteon Therapeutics Hires Veteran Biotechnology Executive Timothy ...  May 10, 2006
...worked for many years with Merck & Co across multiple roles in its hypertension and heart failure group, managed care division, and on its Vasotec and Prilosec ... - Yahoo! News (press release)

Novartis Says FDA Accepts Application For High Blood Pressure ...  Apr 20, 2006
Rasilez will also face competition from AstraZeneca's Zestril, Merck's Vasotec and Prinivil - both of which are off-patent, and Altace, which is marketed by ... - Trading Markets,

Merck Announces Strong Financial Results for the First Quarter ...  Apr 20, 2006
ARCOXIA, CANCIDAS, COSOPT, CRIXIVAN, EMEND, INVANZ, MAXALT, PRIMAXIN, PROPECIA, PROSCAR, STOCRIN, TIMOPTIC/TIMOPTIC XE, TRUSOPT, Vaccines and VASOTEC/VASERETIC ... - Business Wire (press release),


Other information


Indication
For the treatment of hypertension and heart failure. It may be used alone or in combination with thiazide diuretics

Pharmacology
Enalapril, an angiotensin-converting enzyme (ACE) inhibitor, is a prodrug which, when hydrolyzed by estarases to its active Enalaprilat, is used to treat hypertension and heart failure, to reduce proteinuria and renal disease in patients with nephropathies, and to prevent stroke, myocardial infarction, and cardiac death in high-risk patients. Enalapril and Enalaprilat inhibit angiotensin-converting enzyme (ACE) in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex.

Mechanism Of Action
Enalaprilat, the active metabolite of Enalapril, competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. Inhibition of ACE results in decreased plasma angiotensin II. As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin activity, lower concentrations result in a decrease in blood pressure and stimulation of baroreceptor reflex mechanisms, which leads to decreased vasopressor activity and to decreased aldosterone secretion. Enalaprilat may also act on kininase II, an enzyme identical to ACE that degrades the vasodilator bradykinin.

Drug Category
Antihypertensive Agents; Angiotensin-converting Enzyme Inhibitors; ATC:C09AA02

Brand Names/Synonyms
Bonuten; Enalapril; Enalapril Bp; Enalapril Maleate; Enalapril Richet; Enalaprila [Inn-Spanish]; Enalaprilat; Enalaprilum [Inn-Latin]; Gadopril; Kinfil; Vaseretic; Vasotec

Dosage Forms
Tablets; IV injection

Absorption
60%

Interactions
Interactions for Enalapril:

Hypotension: Patients on Diuretic Therapy: Patients on diuretics and especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with enalapril or enalaprilat. The possibility of hypotensive effects with enalapril or enalaprilat can be minimized by either discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with enalapril or enalaprilat. If it is necessary to continue the diuretic, provide close medical supervision after the initial dose for at least two hours and until blood pressure has stabilized for at least an additional hour..

Agents Causing Renin Release: The antihypertensive effect of enalapril and enalapril IV is augmented by antihypertensive agents that cause renin release (e.g., diuretics).

Non-steroidal Anti-inflammatory Agents: In some patients with compromised renal function who are being treated with nonsteroidal anti-inflammatory drugs, the co-administration of enalapril may result in a further deterioration of renal function. These effects are usually reversible.

In a clinical pharmacology study, indomethacin or sulindac was administered to hypertensive patients receiving VASOTEC. In this study there was no evidence of a blunting of the antihypertensive action of VASOTEC. However, reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE inhibitors.

Other Cardiovascular Agents: Enalapril and enalapril IV have been used concomitantly with beta adrenergic-blocking agents, methyldopa, nitrates, calcium-blocking agents, hydralazine, prazosin and digoxin without evidence of clinically significant adverse interactions.

Enalapril IV has been used concomitantly with digitalis without evidence of clinically significant adverse reactions.

Agents Increasing Serum Potassium: Enalapril and enalapril IV attenuate potassium loss caused by thiazide-type diuretics. Potassium-sparing diuretics (e.g., spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium. Therefore, if concomitant use of these agents is indicated because of demonstrated hypokalemia, they should be used with caution and with frequent monitoring of serum potassium. Potassium sparing agents should generally not be used in patients with heart failure receiving enalapril.

Lithium: Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs which cause elimination of sodium, including ACE inhibitors. A few cases of lithium toxicity have been reported in patients receiving concomitant enalapril/enalapril IV and lithium and were reversible upon discontinuation of both drugs. It is recommended that serum lithium levels be monitored frequently if enalapril is administered concomitantly with lithium.



Chemical IUPAC Name
1-[2-(1-ethoxycarbonyl-3-phenyl-propyl)aminopropanoyl]pyrrolidine-2-carboxylic acid

Chemical Formula
C20H28N2O5

Half Life
11 hours

Drug Type
Approved Drug

# Accession No
APRD00510

CAS Registry Number
75847-73-3

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