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 by injection into a vein. Onset of effects are typically within an hour when taken by mouth and last for up to a day.
|Trade names||Vasotec, Renitec, Enacard, others|
|Drug class||ACE inhibitor|
|Bioavailability||60% (by mouth)|
|Metabolism||liver (to enalaprilat)|
|Elimination half-life||11 hours (enalaprilat)|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||376.453 g·mol−1|
|3D model (JSmol)|
|Melting point||143 to 144.5 °C (289.4 to 292.1 °F)|
Common side effects include headache, tiredness, feeling lightheaded 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. It is in the angiotensin-converting-enzyme (ACE) inhibitor 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 safest and most effective medicines needed in a health system. The wholesale cost in the developing world is about US$0.08 to US$0.80 per month. In the United States, it costs about US$25 to US$50 per month. In 2017, it was the 122nd most commonly prescribed medication in the United States, with more than six million prescriptions.
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 led to decreased water consumption (determined by urine output and osmolality) in 60% of patients.
Pregnancy and breastfeedingEdit
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 are reportedly higher among black people.
Mechanism of actionEdit
Normally, angiotensin I is converted to angiotensin II by an angiotensin-converting enzyme (ACE). Angiotensin II constricts blood vessels, increasing blood pressure. Enalaprilat, the active metabolite of enalapril, inhibits ACE. Inhibition of ACE decreases levels of angiotensin II, leading to less vasoconstriction and decreased blood pressure.
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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