Lisinopril is a medication belonging to the drug class of ACE inhibitor and is used to treat hypertension (high blood pressure), heart failure, and heart attacks.[ For high blood pressure it is usually a first-line treatment. It is also used to prevent kidney problems in people with diabetes mellitus.][ Lisinopril is taken orally (swallowed by mouth).][ Full effect may take up to four weeks to occur.][
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Common side effects include headache, dizziness, feeling tired, cough, nausea, and rash.[ Serious side effects may include low blood pressure, liver problems, hyperkalemia (high blood potassium), and angioedema.][ Use is not recommended during the entire duration of pregnancy as it may harm the baby.][ Lisinopril works by inhibiting the renin–angiotensin–aldosterone system.][
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Lisinopril was patented in 1978 and approved for medical use in the United States in 1987.[ In 2022, it was the third most commonly prescribed medication in the United States, with more than 82million prescriptions.]
Medical uses
Lisinopril is typically used for the treatment of hypertension, congestive heart failure, and diabetic nephropathy and after acute myocardial infarction (heart attack).
Contraindications
Lisinopril is contraindicated in people who have a history of angioedema (hereditary or idiopathic) or who have diabetes and are taking aliskiren.
Adverse effects
Common side effects include headache, dizziness, feeling tired, cough, nausea, and rash.[ Serious side effects may include low blood pressure, liver problems, hyperkalemia, and angioedema.][ Use is not recommended during the entire duration of pregnancy as it may harm the baby.][
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Pregnancy and breastfeeding
Animal and human data have revealed evidence of harm to the embryo and teratology associated with ACE inhibitors.
Interactions
Dental care
ACE-inhibitors like lisinopril are considered to be generally safe for people undergoing routine Dentistry, though the use of lisinopril prior to dental surgery is more controversial, with some dentists recommending discontinuation the morning of the procedure.
Pharmacology
Lisinopril is the lysine-analog of enalaprilat, the active metabolite of enalapril.
Mechanism of action
Lisinopril is an ACE inhibitor, meaning it blocks the actions of angiotensin-converting enzyme (ACE) in the renin–angiotensin–aldosterone system (RAAS), preventing angiotensin I from being converted to angiotensin II. Angiotensin II is a potent direct vasoconstrictor and a stimulator of aldosterone release. Reduction in the amount of angiotensin II results in relaxation of the arterioles. Reduction in the amount of angiotensin II also reduces the release of aldosterone from the adrenal cortex, which allows the kidney to excrete sodium along with water into the urine and increases the retention of potassium ions.
Pharmacokinetics
Absorption
Following oral administration of lisinopril, peak serum concentrations of lisinopril occur within about seven hours,
Studies in rats indicate that lisinopril crosses the blood-brain barrier poorly. Multiple doses of lisinopril in rats result in little or no accumulation in brain tissue.
Distribution
Lisinopril does not bind to proteins in the blood.
Elimination
Lisinopril leaves the body completely unchanged in the urine.
Lisinopril is the only water-soluble member of the ACE inhibitor class and thus has no metabolism by the liver.
Chemistry
Pure lisinopril powder is white to off-white in color.
History
Captopril, the first ACE inhibitor, is a functional and structural analog of a peptide derived from the venom of the jararaca, a Brazilian pit viper ( Bothrops jararaca).[Jenny Bryan for The Pharmaceutical Journal, 17 April 2009 "From snake venom to ACE inhibitor – the discovery and rise of captopril"]
Enalapril is actually a prodrug; the active metabolite is enalaprilat.
The di-acid metabolite of enalapril, enalaprilat, and its lysine analogue lisinopril are potent inhibitors of angiotensin-converting enzyme (ACE); they do not contain sulphydryl groups. Both drugs can be assayed by high-pressure liquid chromatography and by radioimmunoassay and plasma ACE inhibition remains stable under normal storage conditions. It is therefore possible to study their pharmacokinetics as well as their pharmacodynamic effects in humans. Enalaprilat and lisinopril as well as ACE activity have been measured in blood taken during the course of two studies of the effects of these drugs on blood pressure and autonomic responsiveness.
Lisinopril is a synthetic peptide derivative of captopril.
The discovery posed a problem, since sales of enalapril were strong for Merck, and the company did not want to diminish those sales. Merck ended up entering into an agreement with Zeneca under which Zeneca received the right to co-market lisinopril, and Merck received the exclusive rights to an earlier stage aldose reductase inhibitor drug candidate, a potential diabetes treatment. Zeneca's marketing and brand name, "Zestril", turned out to be stronger than Merck's effort.
The US patents expired in 2002.[Express Scripts. Patent expirations] Since then, lisinopril has been available under many brand names worldwide; it is also available in with diuretic hydrochlorothiazide (as lisinopril/hydrochlorothiazide), and with calcium channel blocker amlodipine (as lisinopril/amlodipine).
Society and culture
Legal status
In July 2016, an oral solution formulation of lisinopril was approved for use in the United States.
Further reading
