Enalapril

Enalapril

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Systematic (IUPAC) name
(2S)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]pyrrolidine-2-carboxylic acid
Clinical data
Trade names	Vasotec, Renitec
AHFS/Drugs.com	monograph
MedlinePlus	a686022
Pregnancy category	C,D
Legal status	℞ (Prescription only)
Routes of administration	intravenous and by mouth
Pharmacokinetic data
Bioavailability	60% (oral)
Metabolism	hepatic (to enalaprilat)
Biological half-life	11 hours (enalaprilat)
Excretion	renal
Identifiers
CAS Number	75847-73-3 Y
ATC code	C09AA02 (WHO)
PubChem	CID: 5388962
IUPHAR/BPS	6322
DrugBank	DB00584 Y
ChemSpider	4534998 Y
UNII	69PN84IO1A Y
KEGG	D07892 Y
ChEBI	CHEBI:4784 Y
ChEMBL	CHEMBL578 Y
Chemical data
Formula	C20H28N2O5
Molecular mass	376.447 g/mol
SMILES O=C(O)[C@H]2N(C(=O)[C@@H](N[C@H](C(=O)OCC)CCc1ccccc1)C)CCC2
InChI InChI=1S/C20H28N2O5/c1-3-27-20(26)16(12-11-15-8-5-4-6-9-15)21-14(2)18(23)22-13-7-10-17(22)19(24)25/h4-6,8-9,14,16-17,21H,3,7,10-13H2,1-2H3,(H,24,25)/t14-,16-,17-/m0/s1 Y Key:GBXSMTUPTTWBMN-XIRDDKMYSA-N Y
Physical data
Melting point	143 to 144.5 °C (289.4 to 292.1 °F)
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File:Enalapril 3D animation.gif

Enalapril 3D structure

Enalapril (marketed as Vasotec in the US, Enaladex and Renitec in some other countries, and Enacard for veterinary use) is an angiotensin-converting-enzyme (ACE) inhibitor used in the treatment of hypertension, diabetic nephropathy, and some types of chronic heart failure.

ACE converts the peptide hormone angiotensin I to angiotensin II. One of the actions of angiotensin II is the vasoconstriction of blood vessels, resulting in an increase in blood pressure. ACE inhibitors such as enalapril prevent this effect. Enalapril has been shown to lower the death rate in systolic heart failure. Enalapril was the first member of the group known as the dicarboxylate-containing ACE inhibitors.

It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.

Medical uses

Enalapril is used to treat hypertension, symptomatic heart failure, and asymptomatic left ventricular dysfunction. It has been proven to protect the function of the kidneys in hypertension, heart failure, and diabetes, and may be used in the absence of hypertension for its kidney protective effects. It is widely used in chronic kidney failure.

Cautions and contraindications

Enalapril is pregnancy category D. Some evidence suggests it will cause injury and death to a developing fetus. Patients are advised not to become pregnant while taking enalapril and to notify their doctors immediately if they become pregnant. In pregnancy, enalapril may result in damage to the fetus’s kidneys and resulting oligohydramnios (not enough amniotic fluid). Enalapril is secreted in breast milk and is not recommended for use while breastfeeding.

Side effects

The most common side effects of enalapril include increased serum creatinine (20%), dizziness (2–8%), low blood pressure (1–7%), syncope (2%), and dry cough (1–2%). The most serious common adverse event is angioedema (swelling) (0.68%) which often affects the face and lips, endangering the patient’s airway. Angioedema can occur at any point during treatment with enalapril but is most common after the first few doses. Angioedema and fatality therefrom is reportedly higher among black people.

Mechanism of action

Normally, angiotensin I is converted to angiotensin II by an angiotensin-converting enzyme. Angiotensin II constricts blood vessels, increasing blood pressure. By inhibiting the ACE, enalapril decreases levels of angiotensin II leading to less vasoconstriction and decreased blood pressure.

Pharmacokinetics and pharmacodynamics

Pk and Pd are as follows:

• Onset of action: about 1 hour
• Peak effect: 4–6 hours
• Duration: 12–24 hours
• Absorption: ~60%
• Metabolism: prodrug, undergoes biotransformation to enalaprilat

History

Squibb developed the first inhibitor, captopril, but it had adverse effects such as a metallic taste (which, as it turned out, was due to the sulfhydryl group). Merck & Co. developed enalapril as a competing prodrug.

Enalaprilat, the first dicarboxylate-containing ACE inhibitor, was developed partly to overcome these limitations of captopril. The sulfhydryl moiety was replaced by a carboxylate moiety, but additional modifications were required in its structure-based design to achieve a similar potency to captopril. Enalaprilat, however, had a problem of its own in that it had poor oral availability. This was overcome by the researchers at Merck by the esterification of enalaprilat with ethanol to produce enalapril.

Merck introduced enalapril to market in 1981; it became Merck's first billion-dollar selling drug in 1988.

External links

Package insert at DailyMed: dailymed-nlm-nih.gov