PHARMACOVIGILANCE EVALUATION OF LISINOPRIL: A COMPREHENSIVE REVIEW OF ADVERSE DRUG REACTIONS AND SAFETY PROFILE
AUTHOR(S): Rohan S. Chavan*, Maithili Patil, Sanika Devadkar, Prajkta Aswale, Anuradha Patil, Dr. Shobhraj B. Malavi, Dr. Sandeep Biradar.
Abstract:
Lisinopril is a widely used angiotensin-converting enzyme (ACE) inhibitor used to treat heart failure, hypertension, and the aftermath of a myocardial infraction, and diabetic nephropathy. It exerts its therapeutic effect aldosterone reduces vasoconstriction by preventing angiotensin I from being converted to angiotensin II secretion, and cardiac workload, while also enhancing bradykinin-mediated vasodilation. Although lisinopril is generally well tolerated, it is associated with adverse drug reactions such as dry cough, hypotension, hyperkalaemia, renal impairment, dizziness, and the potentially life-threatening reaction angioedema. This review examines the pharmacological profile, therapeutic applications, pharmacokinetics, adverse effects, drug interactions, contraindications, toxicological concerns, and pharmacovigilance data related to lisinopril. The findings emphasize the importance of monitoring renal function, serum potassium, and blood pressure while receiving treatment, particularly in older people and those with renal impairment or concomitant interacting medications. Overall, lisinopril remains an effective cardiovascular and renoprotective agent, but safe use depends on careful patient selection, adverse event recognition, and ongoing pharmacovigilance.
Keywords:
Hyperkalaemia, Angioedema, Adverse Drug Reaction
Introduction:
Lisinopril is a highly effective, long-acting medication primarily prescribed to manage hypertension, enhance survival by treating heart failure following a heart attack [1]. Angiotensin II normally narrows the coronary blood vessels and increases the force of heart contraction. Because of this, it raises blood pressure, vascular resistance, and the heart’s oxygen demand. If this effect continues for a long time, it can cause enlargement of heart muscle cells and growth of vascular smooth muscle cells[2].
Lisinopril has favourable pharmacokinetic properties, including good oral bioavailability as well as a lengthy duration of action that allows that permits once-daily administration[3]. Due to its therapeutic benefits, lisinopril has become among the most frequently recommended ACE inhibitors in the practice of medicine. However, like other medications, lisinopril may produce certain adverse drug reactions such as dry cough, dizziness, hypotension, hyperkalaemia, and angioedema[4]. Monitoring these adverse effects is important for ensuring patient safety and improving treatment outcomes[5]. Due to its widespread clinical use and proven benefits in cardiovascular and renal protection, lisinopril remains an important drug in modern therapeutics[6].
Therefore, the present study aims to evaluate and analyse the adverse drug reactions associated with lisinopril and assess its safety profile in patients receiving this medication.
Drug Profile (IUPAC Based):
Drug Name: Lisinopril
Name of IUPAC:
2S)-1-[(2S)-6-amino-2-{[(1S)-1-carboxy-3-phenylpropyl] amino} hexanoyl] pyrrolidine-2- carboxylic acid
Molecular Formula:
C₂₁H₃₁N₃O₅
Weight of Molecule:
405.49 g/mol
Chemical Class:
Angiotensin-converting enzyme (ACE) inhibitor
Structural Characteristics:
Lisinopril is a lysine analogue of Enalapril at containing two carboxyl groups and a proline moiety, which enables strong binding to the angiotensin-converting enzyme active site.
Mechanistic Category:
Antihypertensive agent acting through suppression of the renin- angiotensin- aldosterone system (RAAS).
Action Mechanism:
An ACE inhibitor called lisinopril prevents angiotensin I from being converted. Into angiotensin II. By reducing angiotensin II levels, it helps prevent heart muscle enlargement and abnormal thickening of blood vessel walls seen in untreated patients. Additionally, bradykinin levels are raised by ACE inhibitors, which promote vasodilation (widening of blood vessels). In addition, lisinopril reduces the overall activity of the renin-angiotensin system, helping to lower blood pressure[7].
PHARMACOKINETIC:
Lisinopril is absorbed moderately after oral administration with a bioavailability of about 20-30%, with the highest levels of plasma are arrived in six to eight hours[8]. It shows minimal plasma protein binding and is distributed to tissues containing angiotensin-converting enzyme[9]. The drug is not significantly metabolized and is eliminated mainly unaltered through the kidneys, with an elimination half-life of almost twelve hours[10].
PHARMACODYNAMICS:
The pharmacodynamics activity of lisinopril is primarily related to inhibition of Angiotensin-converting enzyme (ACE) is an essential component of the renin-angiotensin-aldosterone pathway[12]. Via blocking ACE, lisinopril stops angiotensin I from becoming angiotensin II, a strong vasoconstrictor. A decrease in angiotensin II cause the relaxation of vascular smooth muscle, decreased peripheral vascular resistance[13].
Reduced secretion of the adrenal cortex’s aldosterone. As a result, retention of water and sodium are decreased, contributing to a lowering of blood pressure. In addition, inhibition of ACE reduces the degradation of the vasodilatory peptide bradykinin, which further improves vasodilation. Through these combined mechanisms, lisinopril improves hemodynamic function and is effective within the management of heart failure, high blood pressure, and certain conditions related to the heart[14].
THERAPEUTIC INDICATION OF LISINOPRIL:
1. Hypertension -
Lisinopril is widely utilized for the administration of essential high blood pressure. By preventing ACE, or angiotensin-converting enzyme decreases the production of angiotensin II, which causes vasodilation and a decrease in peripheral vascular resistance. This effect within lowering blood pressure as well as reducing the risk of cardiovascular complications[15].
2. Heart Failure –
Lisinopril is indicated in individual with symptomatic cardiac failure to improve cardiac function and reduce disease progression. It decreases preload and afterload on the heart, thereby enhancing cardiac outcome and improving clinical outcomes in patients with reduced left ventricular function[16].
3. Acute Myocardial Infarction -
Lisinopril is administered in the early phase of acute myocardial infarction in thermodynamically stable patients. It helps limit ventricular remodeking, improves survival, and reduces the risk of heart failure following myocardial injury[17].
4. Diabetic Nephropathy -
Lisinopril is beneficial in patients with diabetes who have evidence of kidney involvement. It helps lessen proteinuria and delay the development of renal harm by lowering intraglomerular pressure and improving renal Hemodynamic[18].
5. Cardiovascular Event Prevention-
Within high-risk individuals with hypertension or heart disease, lisinopril may help lower the chance of heart attacks, strokes, and other cardvascular events through its blood pressure-lowering and cardio protective effects[19].
DOSE AND ADMINISTRATION OF LISINOPRIL:
Lisinopril is administered orally and is typically given once a day, either with or without food. The ailment being treated determines the dosage. The patient’s age, and kidney function[20].
1. Adult with hypertension
Initial dose: 10 mg once daily
Dosage for maintenance: 20-40 mg once every day
Maximum dose: 80 mg per day
In patients already taking diuretics, therapy to lower the risk of severe hypotension, start with 5 mg once daily[21].
2. Hypertension (Children ≥6 years)
Starting dosage: 0.07 mg/kg once daily (5mg maximum first dose)
Dose may become increased gradually based on the response of blood pressure.
Maximum dose: 40 mg per day[22].
3. Heart Failure
First dose: once daily 2.5- 5 mg
The dosage can be increased slowly based on patient tolerance.
Typical maintenance dose: 5-20 mg once daily[23].
4. Acute Myocardial Infraction
Initial dose: 5 mg within a day after symptoms appear
Second dose: 5 mg following a day
Third dose: 48 hours later, 10 mg
Maintenance dose: 10 mg once a day for at least 6 weeks if tolerated[24].
5. Dose Adjustment in Renal Impairment
Since lisinopril is eliminated mainly through the kidneys, lower starting doses are recommended in individual with reduced renal function. The recommended dosage is adjusted based on creatinine clearance and patient response[25].
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