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Lisinopril is a drug of the angiotensin-converting enzyme (ACE) inhibitor class used primarily in treatment of high blood pressure, heart failure, and after heart attacks. It is also used for preventing kidney and eye complications in people with diabetes. Its indications, contraindications, and side effects are as those for all ACE inhibitors.
Lisinopril was the third ACE inhibitor (after captopril and enalapril ) and was introduced into therapy in the early 1990s. A number of properties distinguish it from other ACE inhibitors: It is hydrophilic, has a long half-life and tissue penetration, and is not metabolized by the liver.
Contents
1 Medical uses
1.1 Specific populations
1.1.1 Kidney problems
1.1.2 Pregnancy and breastfeeding
2 Contraindications
3 Adverse effects
4 Overdose
5 Interactions
5.1 Dental care
6 Pharmacology
6.1 Mechanism of action
6.2 Pharmacokinetics
6.2.1 Absorption
6.2.2 Distribution
6.2.3 Metabolism
6.2.4 Elimination
7 Chemistry
8 History
9 References
10 Further reading
11 External links
Medical uses
Lisinopril is typically used for the treatment of high blood pressure, congestive heart failure, acute myocardial infarction (heart attack), and diabetic nephropathy.
A systematic review concluded that lisinopril was highly effective for treatment of proteinuric kidney disease, including diabetic proteinuria.
Specific populations
Caution should be used in the following populations, as dose adjustments may be required.
Kidney problems
The dose must be adjusted in those with poor kidney function. Dose adjustments may be required when creatinine clearance is less than or equal to 30mL/min. Since lisinopril is removed by dialysis, dosing changes must also be considered for people on dialysis.
Pregnancy and breastfeeding
Lisinopril has been assigned to pregnancy category D by the FDA. Animal and human data have revealed evidence of lethal harm to the embryo and teratogenicity associated with ACE inhibitors. No controlled data in human pregnancy are available. Birth defects have been associated with use of lisinopril in any trimester. However, there have been reports of death and increased toxicities to the fetus and newly born child with the use of lisinopril in the second and third trimesters. The label states, “When pregnancy is detected, discontinue Zestril as soon as possible.” The manufacturer recommends mothers should not breastfeed while taking this medication because of the lack of safety data that currently exists.
Contraindications
Treatment with lisinopril should be avoided for people who have a history of angioedema ( hereditary or idiopathic ) or who have diabetes and are taking aliskiren.
Adverse effects
The incidence of adverse effects varies according to which disease state the patient is being treated for.
People taking lisinopril for the treatment of hypertension may experience the following side effects:
Headache (3.8%)
Dizziness (3.5%)
Cough (2.5%)
Difficulty swallowing or breathing (signs of angioedema ), allergic reaction ( anaphylaxis )
Hyperkalemia (2.2% in adult clinical trials)
Fatigue (1% or more)
Diarrhea (1% or more)
Some severe skin reactions have been reported rarely, including toxic epidermal necrolysis and Stevens-Johnson syndrome ; causal relationship has not been established.
People taking lisinopril for the treatment of myocardial infarction may experience the following side effects:
Hypotension (5.3%)
Renal dysfunction (1.3%)
People taking lisinopril for the treatment of heart failure may experience the following side effects:
Hypotension (3.8%)
Dizziness (12% at low dose – 19% at high dose)
Chest pain (2.1%)
Fainting (5-7%)
Hyperkalemia (3.5% at low dose – 6.4% at high dose)
Difficulty swallowing or breathing (signs of angioedema ), allergic reaction ( anaphylaxis )
Fatigue (1% or more)
Diarrhea (1% or more)
Some severe skin reactions have been reported rarely, including toxic epidermal necrolysis and Stevens-Johnson syndrome ; causal relationship has not been established.
Lisinopril 40-mg oral tablet
Overdose
In one reported overdose, the half-life of lisinopril was prolonged to 14.9 hours.
Interactions
Dental care
ACE-inhibitors like lisinopril are considered to be generally safe for people undergoing routine dental care, 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 enalapril. Unlike other ACE inhibitors, it is not a prodrug and is excreted unchanged in the urine.
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), keeping angiotensin I from being converted to angiotensin II. This prevents the release of aldosterone from the adrenal cortex, which allows the kidney to excrete sodium along with water into the urine, and retention of potassium ions.
Pharmacokinetics
Absorption
Lisinopril has a poor bioavailability of 25% (reduced to 16% in people with NYHA Class II-IV heart failure).
Distribution
Lisinopril does not bind to proteins in the blood.
Metabolism
Lisinopril is the only water-soluble member of the ACE inhibitor class, with no hepatic metabolism.
Elimination
Lisinopril leaves the body completely unchanged in the urine.
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 ). : 12–13
Enalapril is actually a prodrug ; the active metabolite is enalaprilat.
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 treatment for diabetes. Zeneca’s marketing and brand name, “Zestril”, turned out to be stronger than Merck’s effort.
The US patents expired in 2002.

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