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Lisinopril

A drug of the angiotensin-converting enzyme (ACE) inhibitor class used primarily in treatment of hypertension, congestive heart failure, heart attacks and diabetic nephropathy.

 It is a competitive inhibitor of angiotensin-converting enzyme (ACE) and prevents the conversion of angiotensin I to angiotensin II, which is a potent vasoconstrictor. 

 

 

A decrease in angiotensin II subsequently causes a reduction in aldosterone secretion.

 

 

Aldosterone secretion causes decrease sodium reabsorption in the collecting duct and decreases potassium excretion that may result in a small increase in serum potassium with lisinopril use. 

 

 

By removing the negative feedback of angiotensin II, lisinopril leads to increased serum renin activity.

 

 

In patients with hypertension the inhibitory effects in the renin-angiotensin-aldosterone system (RAAS), resulting in decreased vasopressor and aldosterone activity even in low-renin patients. 

 

It is among the recommended first-line agents for the management of hypertension.

It is one of the first-line agents for hypertension in patients with diabetes and urinary albumin–to–creatinine ratio greater than or equal to 300 mg/g creatinine or 30 to 299 mg/g creatinine.

It is indication for proteinuric chronic kidney disease.

The goal for treating proteinuria is less than 1 g/day.

It has some key features that make it different from enalapril and captopril; 1) it has a long half-life 2) it is hydrophilic, and 3) it is not broken down by the liver.

 

 

Approved for the management of hypertension in adult and pediatric patients six years and older and as adjunctive therapy in the treatment of heart failure. 

 

ACE inhibitors are recommended in all patients with heart failure with reduced ejection fraction (HFreEF) to reduce morbidity and mortality.

It is also strongly recommended within the first 24 hours to all patients with STEMI with the anterior location, heart failure or those with reduced Ejection Fraction (EF) less than or equal to 40%, unless contraindicated. 

 

Approved for the treatment of ST-segment elevation myocardial infarction (STEMI) within 24 hours in hemodynamically stable patients to improve survival.

 

 

 It has a role in proteinuric chronic kidney disease. 

 

 

In IgA nephropathy, adequate control can be achieved with the use of lisinopril. 

 

 

It is used in diabetic nephropathy.

Also used in preventing renal and retinal complications of diabetes.

Its indications, contraindications and side effects are as those for all ACE inhibitors.

It is contraindicated in patients with hyperkalemia, a history of angioedema, renal failure with prior lisinopril use, bilateral renal artery stenosis, and during coadministration with a neprilysin inhibitor or within 36 hours of taking one.

Trade names Prinivil, Tensopril, Zestril, Hipril

Lisinopril absorption is unchanged by food.

 

 

Lisinopril is excreted unchanged in the urine. 

 

 

Bioavailability after oral intake – ranging from 10-30%. 

 

 

Peak concentration can vary from 6-8 hours after ingestion.

 

 

It does not bind to albumin or other proteins.

 

 

Distribution in patients with heart failure is poor.

 

 

Dosing adjustments are necessary in patients in whom the glomerular filtration rate (GFR) is less than or equal to 30 mL/min.

 

 

The usual dosage for adults ranges from 2.5 to 40 mg per day, depending on the indication.

 

For adolescents and children greater than or equal to 6 years, the initial dose is 0.07 to 0.1 mg/kg once daily with a maximum initial dose of 5 mg/day.

The maximum recommended dose is 0.6 mg/kg/day or 40 mg/day. 

Oral agent with bioavailability of approximately 25%, but with a wide range between individuals from 6 to 60%.

The half-life is 12 hours and elimination is unchanged in urine.

A hydrophilic agent.

It is the lysine-analog of enalapril.

Unlike other ACE inhibitors, it is not a prodrug.

It can be removed from circulation by dialysis in cases of overdose.

The dose must be adjusted in those with poor kidney function.

Side-effects may include: oliguria, anaphylaxis, difficulty in swallowing, difficulty in breathing, hoarseness, itching, jaundice, abdominal pain, bloating, vomiting, chest pain or tightness, dizziness, lightheadedness, syncope, dry cough, fever, arthralgias, rash, nausea, diarrhea, dry mouth, drowsiness, headache, tiredness, muscle cramps, hepatotoxicity, and impotence,

The primary adverse effects of ACE inhibitors like lisinopril include hyperkalemia, dry cough, angioedema, hypotension, dizziness, and renal insufficiency.

 

 

Adverse effects of ACE inhibitors may be more common in patients with renal, autoimmune, or collagen vascular diseases. 

 

First-dose hypotension is an uncommon adverse effect.

Serum potassium, blood pressure, and serum creatinine in patients taking lisinopril after 2 to 3 weeks of starting therapy.

The drug might exacerbate hypotension and hyperkalemia, such as antihypertensive agents, or aldosterone antagonists.

There is no antidote available for lisinopril. 

Can be associated with deterioration of renal functions in patients whose glomerular function is dependent on arteriolar vasoconstriction by angiotensin II. 

Mild increases in serum creatinine may occur at the beginning of therapy.

 

 

Use in patients with cardiomyopathy and outflow obstruction may lead to exacerbation of symptoms.

 

 

ACE inhibitors have correlated with an increase in morbidity and mortality in patients with aortic stenosis. 

 

 

Can induce ACE inhibitor-induced cough.

 

 

Cough is a dry, nonproductive, hacking cough that  begins in the first few months of treatment and resolves within 1 to 4 weeks after discontinuation of the medication.

May cause the kidneys to retain potassium, which may lead to hyperkalemia.

Hyperkalemia may occur more frequently in older male users.

Angioedema may occur rarely.

((Angioedema)) is asymmetric swelling of subcutaneous tissue without itching or urticaria involving the face, mouth, and upper airway, that can be 

 

induced by lisinopril angioedema anytime during the therapeutic course starting from hours to years.

 

 

Angioedema  most commonly occurs within the first three months of therapy.  

 

 

Angioedema is secondary to elevated bradykinin levels by inhibition of the angiotensin-converting enzyme, causing vasodilatation and extravasation of plasma into the submucosal tissue leading to angioedema. 

ACE also degrades bradykinin, and it may predispose to angioedema.

Assigned to pregnancy category D use during the second and third trimesters and to category C during the first trimester.

Data suggest embryo death and teratogenicity associated with angiotensin-converting enzyme inhibitors, and this drug is contraindicated during pregnancy.

Pregnancy category Class D due to its teratogenic effects.

 

 

Contraindicated in pregnant women and/or fertile women without proper contraception. 

 

 

Recommend against its use in breastfeeding.

Following oral administration, peak serum concentrations occur within about seven hours.

Does not appear to be bound to other serum proteins, and does not undergo metabolism and is excreted unchanged entirely in the urine.

Lisinopril absorption is not altered by the presence of food in the gastrointestinal tract.

No contraindications with hepatic impairment.

In patients with congestive heart failure, its bioavailability is reduced to about 16%.

Upon multiple dosing, it has a half-life of accumulation of 12 hours.

Impaired renal function decreases elimination of lisinopril, as it is excreted principally through the kidneys, but this decrease becomes clinically important only when the glomerular filtration rate is below 30 ml/min.

Older patients have higher blood levelsthan younger patients.

Can also be used in conjunction with the diuretic hydrochlorothiazide.

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