Enalaprilat

Absorption

Enalaprilat is poorly absorbed following oral administration, and is therefore only available as an intravenous injection.

Toxicity

Adverse experiences occurring in 0.5 to 1.0 percent of patients in controlled clinical trials included: myocardial infarction, fatigue, dizziness, fever, rash and constipation. Angioedema has also been reported in patients receiving enalaprilat, with an incidence higher in black than in non-black patients. Angioedema associated with laryngeal edema may be fatal. If angioedema of the face, extremities, lips, tongue, glottis and/or larynx occurs, treatment with enalaprilat should be discontinued and appropriate therapy instituted immediately .
Rarer adverse effects that are less likely, but should be monitored for, include development of anaphylaxis, hypotension, agranulocytosis, hepatic failure, hyperkalemia, and persistent cough.
Furthermore, ACE inhibitors should be avoided during pregnancy as they can cause fetal and neonatal morbidity and death. When pregnancy is detected, ACE inhibitors should be discontinued as soon as possible. Use during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death.

Description

Enalaprilat is the diacid active metabolite of enalapril. As an injectable ACE inhibitor, it is reportedly useful in the treatment of uncomplicated accelerated hypertension and hypertensive emergencies. Enalaprilat is more effective in reducing blood pressure in the elderly than in the young, despite the fact that renin activity is lower in old age.

Chemical properties

White Crystalline Solid

Originator

Merck (USA)

The Uses of Enalaprilat

Enalapril is a ACE (angiotensin-converting enzyme) inhibitor, suggested to be more potent than Captopril (sc-200566). Studies indicate that Enalapril downregulates the expression of IL-β, IL-6, and NF-κB. Further studies show that Enalapril upregulates the expression of VEGF and heme oxygenase-1. Enalaprilat reports demonstrate that the compound has some antioxidant activity, which does not include the PKC-NADPH oxidase pathway.

The Uses of Enalaprilat

Active metabolite of Enalapril. A nonsulfhydryl dipeptide angiotensin converting enzyme (ACE) inhibitor

The Uses of Enalaprilat

primary hypertension

Background

Enalaprilat is the active metabolite of the orally available pro-drug, enalapril. Used in the treatment of hypertension, enalapril is an ACE inhibitor that prevents Angiotensin Converting Enzyme (ACE) from transforming angiotensin I into angiotensin II. As angiotensin II is responsible for vasoconstriction and sodium reabsorption in the proximal tubule of the kidney, down-regulation of this protein results in reduced blood pressure and blood fluid volume. Enalaprilat was originally created to overcome the limitations of the first ACE inhibitor, captopril, which had numerous side effects and left a metallic taste in the mouth. Removal of the problematic thiol group from captopril resulted in enalaprilat, which was then modified further with an ester to create the orally available pro-drug enalapril.
Enalaprilat is poorly orally available and is therefore only available as an intravenous injection for the treatment of hypertension when oral therapy is not possible.

Indications

Enalaprilat injection is indicated for the treatment of hypertension when oral therapy is not practical.

What are the applications of Application

Enalaprilat is an active metabolite of Enalapril

Definition

ChEBI: Enalapril in which the ethyl ester group has been hydrolysed to the corresponding carboxylic acid. Enalaprilat is an angiotensin-converting enzyme (ACE) inhibitor and is used (often in the form of its prodrug, enalapril) in the treatment of hypertension an heart failure, for reduction of proteinuria and renal disease in patients with nephropathies, and for the prevention of stroke, myocardial infarction, and cardiac death in high-risk patients. Unlike enalapril, enalaprilat is not absorbed by mouth but is g ven by intravenous injection, usually as the dihydrate.

brand name

Vasotec (Biovail);Renitec.

Pharmacokinetics

Enalaprilat injection results in the reduction of both supine and standing systolic and diastolic blood pressure, usually with no orthostatic component. Symptomatic postural hypotension is therefore infrequent, although it might be anticipated in volume-depleted patients. The onset of action usually occurs within fifteen minutes of administration with the maximum effect occurring within one to four hours. The abrupt withdrawal of enalaprilat has not been associated with a rapid increase in blood pressure. The duration of hemodynamic effects appears to be dose-related. However, for the recommended dose, the duration of action in most patients is approximately six hours. Following administration of enalapril, there is an increase in renal blood flow; glomerular filtration rate is usually unchanged. The effects appear to be similar in patients with renovascular hypertension.

Metabolism

Both enalapril and enalaprilat undergo renal excretion without further metabolism.