Lisinopril mode of action
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Lisinopril Mode of Action
Angiotensin-Converting Enzyme (ACE) Inhibition
Lisinopril is a potent angiotensin-converting enzyme (ACE) inhibitor that functions by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This inhibition leads to a reduction in plasma levels of angiotensin II and aldosterone, while increasing plasma renin activity. The reduction in angiotensin II results in vasodilation, decreased blood pressure, and reduced workload on the heart .
Pharmacokinetics and Bioavailability
Lisinopril is an orally active, nonsulfhydryl ACE inhibitor that is not metabolized or bound to proteins. It reaches peak serum concentrations 6-8 hours after oral administration and has a bioavailability of approximately 25%, which is not significantly affected by food intake or coadministration with other drugs like hydrochlorothiazide (HCTZ), propranolol, digoxin, and glibenclamide. The drug is excreted unchanged in the urine, and steady-state levels are achieved within 2-3 days.
Antihypertensive Effects
Lisinopril produces a smooth and gradual reduction in blood pressure without significantly affecting heart rate or cardiovascular reflexes. The antihypertensive effect begins within 2 hours, peaks around 6 hours, and lasts for at least 24 hours. It is effective in reducing both systolic and diastolic blood pressure and is comparable to other antihypertensive agents like nifedipine and atenolol . The addition of HCTZ enhances its antihypertensive effects.
Cardioprotective Properties
Lisinopril has been shown to improve cardiac output and reduce pulmonary capillary wedge pressure and mean arterial pressure in patients with congestive heart failure who are refractory to conventional treatments. It also accelerates the recovery of cardiomyocytes during reoxygenation and mitigates the effects of oxidative agents, suggesting a protective role in myocardial reoxygenation and oxidative damage.
Pulmonary Effects
Lisinopril significantly attenuates the pulmonary pressor response to hypoxemia, indicating that angiotensin II may play a modulatory role during hypoxic pulmonary vasoconstriction (HPV). This suggests that ACE inhibition could be a useful adjunctive treatment in hypoxemic pulmonary hypertension.
Interaction with Serum Proteins
Lisinopril binds to bovine serum albumin (BSA) primarily through van der Waals forces and hydrogen bonding, forming a stable lisinopril-BSA complex. This interaction induces slight conformational changes in BSA but retains its α-helical structure.
Effects on ACE2 Levels
Oral administration of lisinopril increases tissue levels of ACE2, the cellular receptor for SARS-CoV-2, in various tissues including the small intestine, lung, kidney, and brain. This increase is significant and persists even after cessation of the drug. However, the combination of lisinopril with losartan prevents this increase in ACE2 levels.
Conclusion
Lisinopril is a well-tolerated and effective ACE inhibitor that provides significant antihypertensive and cardioprotective benefits. Its mode of action involves the inhibition of ACE, leading to reduced levels of angiotensin II and aldosterone, and increased plasma renin activity. Additionally, lisinopril has beneficial effects on myocardial recovery, pulmonary hypertension, and proteinuria, making it a versatile agent in the management of cardiovascular and renal conditions.
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