ACE inhibitor · Antihypertensive

Enalaprilat

Reviewed by Alex G, BSN, RN, CEN, CCRN, CMC, NREMT-P · From the Reference tab of the app

Indications

Hypertension when oral therapy is not practical, such as NPO patients on a home ACE inhibitor
Adjunct in hypertensive urgency or emergency; its slow onset and 6-h action make it poor for fine titration
Afterload reduction in acute heart failure (off-label)

Dosing

Where	Dose
Blood pressure boluses	Enalaprilat: 1.25 mg IV every 6 h

Mechanism of action

Enalaprilat competitively inhibits angiotensin-converting enzyme (ACE, or kininase II), a zinc metallopeptidase on vascular endothelium, abundant in the lungs. Its carboxylate binds the active-site zinc, so angiotensin I is not converted to angiotensin II and bradykinin is not broken down. Less angiotensin II means less AT1-mediated vasoconstriction, aldosterone and sympathetic drive, and extra bradykinin adds NO- and prostaglandin-mediated vasodilation; without that feedback, renin and angiotensin I rise.

Pharmacology

Cardiovascular: lowers SVR and BP without reflex tachycardia; in heart failure it lowers preload and afterload and raises cardiac output
Renal: efferent arteriolar dilation lowers glomerular pressure; GFR can fall with bilateral renal artery stenosis, volume depletion or heart failure
Metabolic: aldosterone falls, so potassium rises; renin and angiotensin I climb
Respiratory: bradykinin can cause a dry cough

Pharmacokinetics

Onset	Within 15 min IV
Peak	1–4 h
Duration	About 6 h at usual doses; longer with larger doses
Half-life	Initial 2–6 h (renal filtration); a 36-h terminal phase from drug bound to ACE; effective half-life for accumulation about 11 h
Distribution	Binds saturably to ACE in plasma and tissue; crosses the placenta
Protein binding	About 50%
Metabolism	None; it is the active drug
Elimination	Over 90% unchanged in urine within 24 h
Organ failure	Accumulates when GFR is 30 mL/min or less: the label starts lower
Dialysis	Removed by hemodialysis at about 62 mL/min

Chemistry

The diacid form of enalapril: enalapril is its monoethyl ester prodrug, hydrolyzed in the liver after absorption
A carboxyalkyl dipeptide (N-(1-carboxy-3-phenylpropyl)-L-alanyl-L-proline); a single S,S,S stereoisomer
Two carboxylic acids and a secondary amine (pKa about 7.8) leave it charged at body pH (log P below 0), so it is poorly absorbed by mouth and is given IV
Injection 1.25 mg/mL with benzyl alcohol 9 mg/mL; stable 24 h in D5W, saline or lactated Ringer's

Adverse effects and cautions

Safety

Boxed warning: fetal toxicity in the second and third trimesters (renal failure, oligohydramnios, skull hypoplasia, death); not for use in pregnancy
Angioedema, sometimes fatal and more common in Black patients; contraindicated after prior ACE inhibitor angioedema or with hereditary angioedema; keep 36 h from sacubitril-valsartan
First-dose hypotension when volume-depleted, on diuretics, hyponatremic or in heart failure: lay the patient flat and give saline
Hyperkalemia with kidney disease, potassium supplements, potassium-sparing diuretics or other RAAS blockers
AKI with bilateral renal artery stenosis or volume depletion: follow creatinine and potassium
Rare neutropenia or agranulocytosis, mostly with kidney or collagen vascular disease
Raises lithium levels; NSAIDs blunt its effect and worsen kidney function

In the algorithms

Flash Pulmonary Edema (SCAPE)

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Sources

FDA label: enalaprilat injection, Hikma (2024)
MacFadyen 1993 (enalapril kinetics)
PubChem: enalaprilat

For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.