Brands, Medical Use, Clinical Data
- Antihypertensive Agents
- Angiotensin-converting Enzyme Inhibitors
Brands / Synonyms
Bonuten; Enalapril; Enalapril and Hydrochlorothiazide; Enalapril Bp; Enalapril Maleate; Enalapril Richet; Enalaprila [Inn-Spanish]; Enalaprilat; Enalaprilum [Inn-Latin]; Gadopril; Kinfil; Lexxel; Vaseretic; Vasotec; Vasotec
For the treatment of hypertension and heart failure. It may be used alone or in combination with thiazide diuretics.
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.
Biotrnasformation / Drug Metabolism
Tablets and IV Injection
VASOTEC is contraindicated in patients who are hypersensitive to this product and in patients with a history of
angioedema related to previous treatment with an angiotensin converting enzyme inhibitor and in patients with
hereditary or idiopathic angioedema
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
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
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