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Lisinopril

Lisinopril (lye-SIH-no-pril, ATC code C09AA is a drug of the angiotensin converting enzyme (ACE) inhibitor class that is primarily used in treatment of hypertension, congestive heart failure and heart attacks.
Historically, lisinopril was the third ACE inhibitor, after captopril and enalapril that was introduced into therapy in early 1990s . more...

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Lisinopril has a number of properties that distinguish it from other ACE inhibitors: it is hydrophilic, has long half life and tissue penetration and is not metabolized by the liver.

Pharmacology

Chemistry

Lisinopril is chemically described as (S)-1--L-proline dihydrate. Its empirical formula is C21H31N3O5•2H2O. Lisinopril is the lysine-analog of enalapril. Unlike other ACE inhibitors lisinopril is not a prodrug and tablets contain pharamacologically active substance.

Absorption

After oral dosing peak blood levels are reached within ca. 7 hours. The oral bioavailability is approximately 25% according to measurements of the unchanged drug in urine. The interindividual variability is 6 to 60% within the full dose range of 5 to 80 mg. Emptiness of stomach does obviously not influence the extent of gastrointestinal resorption.

Half life

The halflife of Lisinopril under steady-state conditions is 12.6 hours. The terminal phase shows a prolonged terminal phase, but no cumulation of the drug is seen under normal circumstances.

Metabolism

Lisinopril is not metabolized.

Elimination

Lisinopril is solely excreted in urine in the unchanged form. Elimination of the drug depends on glomerular filtration and tubular excretion. Rate of lisinopril elimination decreases with old age and kindney or heart failure. There is a relation between creatinine and lisinopril clearance. With prolonged therapy dose reduction can be necessary to avoid cumulation.

Lisinopril can be removed from circulation by dialysis.

Mode of action

Lisinopril acts by competitive inhibition of Angiotensin Converting Enzyme (ACE), a key enzyme in the renin-angiotensin system (RAS) which plays a crucial role in controlling of blood pressure. Diminished formation of a potent vasocontrictor - Angiotensin II from Angiotensin I leads to lowering of hypertension. Besides it limits degradation of a vasodilator - bradykinin by ACE. Angiotensin II also increases blood pressure by stimulation the production of aldosterone, which promotes sodium and water retention in the body. So the complete action consists of

  • diminished production of angiotensin II
  • diminished degradation of bradykinin
  • diminished production of aldosterone

Indications

  • hypertension
  • congestive heart failure alone or with diuretics
  • acute myocardial infarction
  • renal and retinal complications of diabetes.

Contraindications and Precautions

As with all angiotensin converting enzyme (ACE) inhibitors

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