Lisinopril

Lisinopril is an antihypertensive agent belonging to ACE inhibitors.

Lisinopril is approved for the treatment of heart failure, Hypertension, and Acute Myocardial Infarction. It is also used to treat Migraine, prevention; Non-ST-elevation acute coronary syndrome; Posttransplant erythrocytosis, kidney transplant recipients; Proteinuric chronic kidney disease, diabetic or nondiabetic; Stable coronary artery disease

Following oral administration of the Lisinopril, peak serum concentrations of lisinopril occur within about 7 hours. Lisinopril does not bind to the other serum proteins. It does not undergo metabolism and is excreted unchanged entirely in the urine. The effective half-life of lisinopril is 12 hours. Approximately 25% percent of the dose is recovered unchanged in the urine.

Lisinopril is available in the form of dosage forms such as tablets and oral solutions.

Lisinopril is available in India, France, Japan, and the USA.

Lisinopril belonging to ACE inhibitors acts as an Antihypertensive agent. Lisinopril acts by inhibiting the Angiotensin-converting enzyme (ACE). The beneficial effects of the Lisinopril in Hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system.

The onset of action is achieved in about 1 hour.

The Cmax for lisinopril is 64 +/- 16 ng/mL.

The tmax for lisinopril is 7.5 +/- 1.5 hr

Lisinopril is available in the form of tablets.

Lisinopril tablets are to be swallowed whole with water.

Lisinopril comes as a tablet to be taken by mouth. It is usually taken two times a day

Lisinopril is an antihypertensive agent belonging to ACE inhibitors.

Lisinopril is approved for the treatment of heart failure, Hypertension, and Acute Myocardial Infarction. It is also used to treat Migraine, prevention; Non-ST-elevation acute coronary syndrome; Posttransplant erythrocytosis, kidney transplant recipients; Proteinuric chronic kidney disease, diabetic or nondiabetic; Stable coronary artery disease

Angiotensin-converting enzyme (ACE) inhibitors are widely used in the treatment of heart failure. These agents decrease the formation of angiotensin II, thereby decreasing both arteriolar and venous resistance

Lisinopril is approved for use in the following clinical indications

Hypertension

Lisinopril is indicated for the treatment of Hypertension. It may be used alone as the initial therapy or concomitantly with other classes of antihypertensive agents.

Heart failure

Lisinopril is indicated as adjunctive therapy in the management of heart failure in patients who are not responding adequately to diuretics and digitalis.

Acute Myocardial Infraction

Lisinopril is indicated for the treatment of hemodynamically stable patients within 24 hours of the acute myocardial infarction, to improve survival rate. Patients should receive, as appropriate, standard recommended treatments such as thrombolytics, aspirin, and beta blockers.

Lisinopril is available in the form of tablets and oral solutions.

Lisinopril is available in various dosage strengths as 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg, 40 mg, 1 mg/mL.

Lisinopril is available in the form of tablets and oral solutions.

Dose Adjustment in the pediatric patient:

Hypertension:

Children <6 years: Limited data available: Oral: Initial: 0.07 mg/kg/dose once daily; maximum initial daily dose: 5 mg/day; maximum daily dose: 0.6 mg/kg/day or 40 mg/day. Children ≥6 years and Adolescents: Oral: Initial: 0.07 mg/kg/dose once daily; maximum initial daily dose: 5 mg/day; maximum daily dose: 0.6 mg/kg/day or 40 mg/day

Proteinuria (eg, mild IgA nephropathy, focal segmental glomerulosclerosis [FSGS]):

Children ≥2 years and Adolescents:

Oral: Initial: 0.1 to 0.2 mg/kg/dose once daily; increase at 1- to 2-week intervals to target dose of 0.4 mg/kg/dose once daily; maximum dose: 40 mg/day. Dosing based on a prospective study (total patients: n=138; pediatric patients: n=93, age range: 2 to 17 years) in patients with steroid-resistant FSGS comparing mycophenolate to cyclosporine in which most patients received lisinopril (n=118) for protein sparing effects. Lisinopril was initiated at 0.1 mg/kg/dose and increased every 2 weeks to target dose of 0.4 mg/kg/dose (maximum dose: 40 mg/dose) . In pediatric patients with mild IgA nephropathy (n=40, mean age: 11.4 years; range: 4.4 to 15.4 years), a similar protocol was used, with an initial dose of 0.2 mg/kg/dose increased after 7 days to 0.4 mg/kg/dose (maximum dose: 20 mg/dose)

Lisinopril is approved for the treatment of Hypertension.

Hypertension: It has been observed that the low-salt Dietary Approach to Stop Hypertension (DASH) diet lowers blood pressure. Sometimes after a few weeks, its effects on blood pressure become noticeable.

The food limitation should be tailored to the patient's needs.

Lisinopril may be contraindicated in the following

● Abrupt discontinuation

Abrupt discontinuation of any ACE inhibitor, including Lisinopril, can result in the development of myocardial ischemia, myocardial infarction, ventricular arrhythmias, or severe Hypertension, particularly in patients with preexisting cardiac disease.

Lisinopril is contraindicated in patients who are allergic to the product and in patients with a history of angioedema related to the previous treatment with an ACE inhibitor and in patients with hereditary or idiopathic angioedema.

The treating doctor must preserve pharmacovigilance as follows and continuously monitor the patient.

• Head and Neck Angioedema

Angioedema of the face, extremities, lips, tongue, glottis, and/or larynx has been reported in patients treated with ACE inhibitors, including Lisinopril. This may occur at any time during the treatment. In such cases, Lisinopril should be discontinued.

• Intestinal angioedema

Intestinal angioedema has been reported in patients treated with Lisinopril. These patients presented with abdominal pain with or without nausea and vomiting.

• Hypotension

Excessive hypotension is rare in patients treated with Lisinopril. Patients with heart failure experience these side effects.

• Hepatic failure

Rarely ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to hepatic necrosis and sometimes death.

PRECAUTIONS

• Impaired Renal or Hepatic Function

Patients having compromised renal or hepatic function should use ACE inhibitors with care. Lisinopril clearance is only marginally impacted by poor renal function, but poor hepatic function may cause blood levels of Lisinopril to increase substantially

Drinking alcohol while taking the Lisinopril can increase drowsiness and dizziness, which in turn increases the risk of accidental injury.

Lisinopril use in breast feeding patients is not recommended.

Potassium-Rich Foods: Bananas, sweet potatoes, nuts, and other foods rich in potassium when taken along with Lisinopril, can be led to an increase in blood potassium levels.

Pleurisy Root: Pleurisy roots are not recommended with most heart medications due to the cardiac glycoside content of the root.

The adverse reactions related to the molecule Lisinopril can be categorized as

• Common Adverse effects:

Insomnia, Muscle pain, Dizziness, fatigue, etc.

• Less Common adverse effects:

Nervousness, Elevated liver enzymes, joint pain, edema, vivid dreams, abdominal discomfort, nausea, muscle cramps, paresthesias, bradycardia, cold extremities, hypotension, palpitations, syncope, Tachycardia, Anxiety, lethargy, diarrhea, vomiting, Impotence/reduced libido.

• Rare adverse effects:

Heart failure, tachyarrhythmia, bronchospasm, depression, decreased exercise tolerance, Raynaud's phenomenon, etc.

The clinically relevant drug interactions of Lisinopril are briefly summarized here

● When used with ACE inhibitors, catecholamine-depleting medications (such as reserpine) may have an additional impact. Therefore, patients using Lisinopril together with a catecholamine-depleting medication should be carefully monitored for any signs of hypotension and/or significant bradycardia that might result in vertigo, syncope, or orthostatic hypotension.

● Lisinopril has been used with a variety of antihypertensive agents, including hydrochlorothiazide, hydralazine, and guanethidine without unexpected adverse interactions.

● Lisinopril has been shown to increase serum thioridazine levels when both drugs are coadministered. Lisinopril levels may also be increased with this combination.

The common side of Lisinopril includes the following

Cold hands or feet, Eye irritation, upset stomach, headache, depression, dizziness, nausea, etc.

The use of Lisinopril should be prudent in the following group of special populations:

Pregnancy

Pregnancy Category (FDA): D

The use of drugs that act on the renin-angiotensin system during the 2 and 3 trimesters of pregnancy reduces fetal renal function and increases neonatal morbidity and death. When pregnancy is detected, discontinue Lisinopril

Labor and Delivery

There is no FDA guidance on the use of Lisinopril during labor and delivery.

Nursing Mothers

Since Lisinopril is secreted in human milk, nursing should not be undertaken by the mothers receiving the drug.

Geriatric Use

There is no FDA guidance on the use of Lisinopril in geriatric settings.

No specific information on the emergency treatment of overdosage is available. Therefore, on the basis of the pharmacologic actions of Lisinopril, the following general measures should be employed as appropriate in addition to the gastric lavage:

● Excessive Bradycardia:

Administer atropine; if there is no response to the vagal blockade, administer isoproterenol cautiously.

● Cardiac Failure:

Digitalize the patient and/or administer a diuretic. It has been reported that glucagon may be useful in this situation.

● Hypotension:

Administer vasopressors like epinephrine or norepinephrine, with serial monitoring of blood pressure. (There is evidence that epinephrine may be the drug of choice.)

● Bronchospasm:

Administration of beta2 stimulating agents like isoproterenol and a theophylline derivative.

A case of an acute overdosage has been reported with an intake of 500 mg of Lisinopril by a hypertensive patient. Blood pressure increased, and the heart rate was ≥ 80 beats/min. Recovery was uneventful. In another case, 250 mg of Lisinopril was taken with 150 mg of diazepam and 50 mg of nitrazepam, producing coma and hypotension. The patient recovered in 24 hours.

Pharmacodynamics:

Competitive inhibitor of angiotensin-converting enzyme (ACE); prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor; results in lower levels of angiotensin II which causes an increase in plasma renin activity and a reduction in aldosterone secretion; a CNS mechanism may also be involved in hypotensive effect as angiotensin II increases adrenergic outflow from CNS; vasoactive kallikreins may be decreased in conversion to active hormones by ACE inhibitors, thus reducing blood pressure.

Pharmacokinetics:

• Absorption

Following oral administration of Lisinopril peak serum concentrations occur within an hour after taking Lisinopril. Lisinopril is absorbed to a degree of around 25%, according to urine recovery.

• Distribution

The volume of distribution in the healthy subjects is about 124 L. Lisinopril undergoes extensive metabolism in animals and man.

• Metabolism

Lisinopril has not been demonstrated to bind to serum proteins. Lisinopril is not metabolized and is excreted as an unchanged drug.

• Elimination

Lisinopril is excreted via urine or feces.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019777s054lbl.pdf
• https://go.drugbank.com/drugs/DB00722
• Simpson K, Jarvis B. Lisinopril. Drugs. 2000 May;59(5):1149-67.