|Trade names||Vasotec, Renitec, Enacard, others|
|ATC code||C09AA02 (WHO)|
|Bioavailability||60% (by mouth)|
|Metabolism||liver (to enalaprilat)|
|Biological half-life||11 hours (enalaprilat)|
|Chemical and physical data|
|Molar mass||376.447 g/mol|
|3D model (Jmol)||Interactive image|
|Melting point||143 to 144.5 °C (289.4 to 292.1 °F)|
Enalapril, sold under the brand name Vasotec among others, is a medication used to treat high blood pressure, diabetic kidney disease, and heart failure. For heart failure it is generally used with a diuretic such as furosemide. It is given by mouth or injection into a vein. Onset of effects are typically within an hour when taken by mouth and last for up to day.
Common side effects include headache, feeling tired, lightheadedness with standing, and cough. Serious side effects include angioedema and low blood pressure. Use during pregnancy is believed to result in harm to the baby. Enalapril is in the angiotensin-converting-enzyme inhibitor (ACEi) family of medications.
Enalapril was patented in 1978 and came into medical use in 1984. It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system. The wholesale cost in the developing world is about 0.08 to 0.80 USD per month. In the United States it costs about 25 to 50 USD per month.
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. Furthermore, enalapril is an emerging treatment for psychogenic polydipsia. A double-blind, placebo-controlled trial showed that when used for this purpose, enalapril lead to decreased water consumption (determined by urine output and osmality) in 60% of patients.
Pregnancy and breastfeeding
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.
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 (ACE). Angiotensin II constricts blood vessels, increasing blood pressure. By inhibiting the ACE, enalaprilat, the active metabolite of 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
Squibb developed the first ACE 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.:12–13
Enalaprilat 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 potency similar 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.:13
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Two large trials showed that when patients with NYHA class II, III, or IV heart failure were treated with enalapril, as compared with placebo, in addition to diuretics and digoxin, the rates of admission to the hospital were reduced, and there was a relative risk reduction for death of 16 to 40%.
- He YM et al. Enalapril versus losartan for adults with chronic kidney disease: a systematic review and meta-analysis. Nephrology (Carlton). 2013 Sep;18(9):605-14. doi: 10.1111/nep.12134. PMID 23869492
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