Lisinopril pharmacology
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Lisinopril Structure and Mechanism of Action
Lisinopril is a synthetic, orally active angiotensin-converting enzyme (ACE) inhibitor that does not contain a sulfhydryl group and is not an ester prodrug, distinguishing it from other ACE inhibitors like captopril and enalapril Gomez1987De1989Case1989+2 MORE. It works by inhibiting ACE, which reduces the formation of angiotensin II, a potent vasoconstrictor, and decreases aldosterone secretion. This leads to lower blood pressure and increased plasma renin activity Gomez1987Piepho2000Chase1989.
Pharmacokinetics: Absorption, Distribution, Metabolism, and Excretion
Lisinopril is slowly absorbed after oral administration, with peak serum concentrations occurring 6–8 hours post-dose Gomez1987De1989Case1989+1 MORE. Its bioavailability is about 25% and is not significantly affected by food, age, or coadministration with drugs like hydrochlorothiazide, propranolol, digoxin, or glibenclamide Gomez1987Chase1989. However, some studies note a 20–25% reduction in systemic exposure when taken with food compared to fasting . Lisinopril is not metabolized by the liver and is excreted unchanged in the urine, primarily via glomerular filtration Gomez1987De1989Case1989+2 MORE. The elimination half-life is approximately 12–13 hours, supporting once-daily dosing De1989Case1989Chase1989. In patients with severe renal impairment, significant accumulation can occur, so dose adjustments may be necessary Gomez1987Chase1989.
Clinical Effects and Therapeutic Use
Lisinopril is effective in lowering blood pressure in patients with essential and renovascular hypertension, with antihypertensive effects beginning within 2 hours, peaking at 6 hours, and lasting at least 24 hours Gomez1987Chase1989. It produces smooth, gradual blood pressure reduction without affecting heart rate or cardiovascular reflexes . Lisinopril is as effective as hydrochlorothiazide, atenolol, metoprolol, and nifedipine, and combining it with hydrochlorothiazide enhances its antihypertensive effect Gomez1987Chase1989. It also increases cardiac output and decreases pulmonary capillary wedge pressure and mean arterial pressure in patients with congestive heart failure Gomez1987Chase1989.
Safety, Tolerability, and Drug Interactions
Lisinopril is generally well tolerated, with a good safety profile and minimal clinically significant drug interactions reported Gomez1987Chase1989. It does not cause hypokalemia, hyperglycemia, hyperuricemia, or hypercholesterolemia, and has natriuretic properties with stable or increased renal blood flow . The most common adverse effects for ACE inhibitors as a class include hypotension, cough, and hyperkalemia . Caution is advised when lisinopril is used with diuretics, nifedipine, or agents that may increase potassium levels .
Special Populations: Pediatrics and Renal Impairment
Lisinopril pharmacokinetics in children and adolescents with normal to mildly reduced kidney function are being studied, as its use in pediatric populations is often off-label, especially under age 6 Xie2020Sandra2023. In patients with renal impairment, the drug’s elimination is prolonged, requiring lower dosages Gomez1987Chase1989.
Additional Pharmacological Insights
Lisinopril is one of the least lipophilic ACE inhibitors and does not require hepatic metabolism, making it unique among its class . It has also shown potential for rapid mood-elevating effects in animal models, possibly through mechanisms involving the bradykinin system and mTORC1 pathway, suggesting possible antidepressant properties .
Conclusion
Lisinopril is a well-established, once-daily ACE inhibitor with predictable pharmacokinetics, effective antihypertensive and heart failure benefits, and a favorable safety profile. Its lack of hepatic metabolism and minimal drug interactions make it suitable for a wide range of patients, though dose adjustments are needed in renal impairment and special populations such as children Gomez1987De1989Case1989+6 MORE.
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The clinical pharmacology of lisinopril.
Lisinopril is a once-daily oral drug with a slow absorption rate, immediate availability, and a 12-13 hour plasma half-life, making it suitable for treating hypertension and congestive heart failure without complications.
Overview of the angiotensin-converting-enzyme inhibitors.
ACE inhibitors play a crucial role in the renin-angiotensin system, with differences in potency, affinity for ACE, pharmacokinetics, and toxicity affecting their pharmacokinetic and safety profiles.
DOI
Lisinopril: A New Angiotensin‐Converting Enzyme Inhibitor
Lisinopril effectively lowers blood pressure and improves heart function in patients with essential and renovascular hypertension, with potential for combination with hydrochlorothiazide for greater blood pressure reduction.
Population pharmacokinetics of lisinopril in hypertensive children and adolescents with normal to mildly reduced kidney function
Lisinopril is a safe and effective antihypertensive drug for children and adolescents with normal to mildly reduced kidney function.
Pharmacokinetic evaluation of lisinopril-tryptophan, a novel C-domain ACE inhibitor.
Lisinopril-tryptophan (LisW-S) is a novel C-domain ACE inhibitor with a 5.4% oral bioavailability and potential for improved clinical application.
DOI