Lisinopril expected pharmacological action
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Pharmacological Action of Lisinopril
Introduction to Lisinopril
Lisinopril is a widely used angiotensin-converting enzyme (ACE) inhibitor, primarily prescribed for the treatment of hypertension and congestive heart failure. It is a lysine derivative of enalaprilat and is known for its long-acting properties, allowing for once-daily dosing 110.
Mechanism of Action: ACE Inhibition
Lisinopril functions by inhibiting the activity of the angiotensin-converting enzyme (ACE). This inhibition leads to a reduction in the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. Consequently, plasma levels of angiotensin II and aldosterone decrease, while plasma renin activity increases 14. This cascade of effects results in vasodilation, reduced blood pressure, and decreased workload on the heart.
Pharmacokinetics: Absorption, Distribution, and Elimination
Lisinopril is orally active and does not require biotransformation for its pharmacological activity. After oral administration, approximately 25-29% of the dose is absorbed, with peak serum concentrations occurring 6-8 hours post-dosing 110. The drug is not metabolized and is excreted unchanged in the urine. Its elimination half-life is about 12.6 hours in normotensive individuals, but this can be prolonged in patients with impaired renal function, necessitating dose adjustments 1410.
Blood Pressure Reduction
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 hydrochlorothiazide, nifedipine, and beta-blockers 110.
Effects on Heart Failure
In patients with congestive heart failure, lisinopril increases cardiac output and decreases pulmonary capillary wedge pressure and mean arterial pressure. It has been shown to improve exercise duration and left ventricular ejection fraction, making it comparable to other treatments like captopril and digoxin 68. High doses of lisinopril have demonstrated significant reductions in the risk of major clinical events in heart failure patients .
Renal Considerations
Lisinopril is particularly effective in patients with normal renal function, but significant accumulation can occur in those with severe renal impairment (creatinine clearance ≤30 ml/min). Therefore, dose adjustments are crucial in such patients to avoid potential side effects 14.
Pediatric Use
Lisinopril is also used in pediatric populations for hypertension, although it is often prescribed off-label for children under six years of age. Dose adjustments based on body weight and estimated glomerular filtration rate (eGFR) are recommended to optimize its efficacy and safety in children .
Additional Effects
Lisinopril has been found to attenuate acute hypoxic pulmonary vasoconstriction, suggesting a potential role in managing hypoxemic pulmonary hypertension . Moreover, it does not produce common metabolic side effects such as hypokalemia, hyperglycemia, hyperuricemia, or hypercholesterolemia, making it a well-tolerated option for long-term use 15.
Conclusion
Lisinopril is a potent ACE inhibitor with a well-established profile for treating hypertension and heart failure. Its pharmacological actions include significant blood pressure reduction, improved cardiac output, and favorable renal effects. With a good safety profile and minimal metabolic side effects, lisinopril remains a cornerstone in the management of cardiovascular diseases.
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