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These studies suggest that lisinopril effectively lowers blood pressure, improves congestive heart failure, reduces mortality and left ventricular dysfunction, and is well-tolerated in various patient populations.
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Lisinopril: Pharmacology, Clinical Efficacy, and Safety
Introduction to Lisinopril
Lisinopril is a long-acting angiotensin-converting enzyme (ACE) inhibitor used primarily to treat hypertension, congestive heart failure, and acute myocardial infarction. It is a lysine derivative of enalaprilat and is administered orally once daily.
Efficacy in Elderly Patients with Hypertension
Lisinopril has been shown to be effective in reducing blood pressure in elderly patients with hypertension. Clinical trials have demonstrated that 68.2% to 89.1% of elderly patients responded to lisinopril treatment over a period of 8 weeks, achieving a diastolic pressure of ≤90 mm Hg. The dosage for elderly patients typically ranges from 2.5 to 40 mg/day, with adjustments needed for those with significant renal impairment.
Pharmacokinetics and Bioequivalence
A study on the pharmacokinetics of lisinopril/hydrochlorothiazide tablets in healthy Chinese subjects found no significant differences in pharmacokinetic parameters between test and reference formulations under fasting and postprandial conditions. However, a notable food effect was observed, with a 20%-25% reduction in systemic exposure when administered postprandially. This indicates that lisinopril is bioequivalent to the reference product and well-tolerated under both conditions.
Pediatric Use and Dosage Adjustments
Lisinopril is also used in pediatric patients with hypertension, although it is off-label for children under six years old. A study involving children aged 1.9 to 17.9 years found that lisinopril's pharmacokinetics are influenced by body weight and estimated glomerular filtration rate (eGFR). Dosage adjustments based on these factors are recommended to optimize treatment.
Impact on ACE2 Levels and COVID-19 Implications
Research has shown that oral lisinopril increases tissue levels of ACE2, the receptor for SARS-CoV-2, in healthy mice. This increase was observed across various tissues, including the small intestine, lung, kidney, and brain. Interestingly, the combination of lisinopril and losartan did not increase ACE2 levels, suggesting a complex interaction between ACE inhibitors and angiotensin receptor blockers.
Effects on Hypoxic Pulmonary Vasoconstriction
Lisinopril has been found to attenuate acute hypoxic pulmonary vasoconstriction (HPV) in humans. In a randomized, double-blind study, lisinopril significantly blunted the increase in mean pulmonary artery pressure and total pulmonary vascular resistance induced by hypoxemia, without affecting systemic hemodynamic parameters. This suggests that ACE inhibition may be beneficial in managing hypoxemic pulmonary hypertension.
Comparison with Other ACE Inhibitors
In the treatment of congestive heart failure, lisinopril has been compared to captopril in a randomized trial. Lisinopril was found to be more effective in increasing exercise duration and improving left ventricular ejection fraction, particularly in patients with renal impairment. High doses of lisinopril (32.5 to 35 mg/day) have shown significant advantages over low doses in reducing the risk of major clinical events in heart failure patients.
Post-Myocardial Infarction Benefits
The GISSI-3 trial demonstrated that lisinopril, when administered within 24 hours of acute myocardial infarction symptoms, significantly reduced mortality and severe ventricular dysfunction. The combination of lisinopril and transdermal glyceryl trinitrate further improved survival rates and ventricular function.
Combination Therapy with Hydrochlorothiazide
Lisinopril combined with hydrochlorothiazide has been shown to be highly effective in controlling blood pressure in patients with mild to moderate hypertension. The combination therapy provided better results compared to monotherapy with either drug alone, with minimal metabolic side effects .
Conclusion
Lisinopril is a versatile and effective ACE inhibitor for treating hypertension, heart failure, and post-myocardial infarction. It is well-tolerated across different patient populations, including the elderly and children, and offers significant clinical benefits when used alone or in combination with other medications. Its impact on ACE2 levels and potential implications for COVID-19 warrant further investigation.
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