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Lisinopril



Lisinopril Drug
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 . 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 kidney 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

Pregnancy

Category D
When lisinopril therapy in women of child-bearing age is started pregnancy must be excluded and effective contraceptive methods used.

Lisinopril is teratogenic and can cause birth defects and even death of the developing fetus.

When pregnancy is detected, Lisinopril should be discontinued as soon as possible.

Lactation
In rats Lisinopril is excreted in the milk during lactation. No data on human breastfeeding mothers exist. Therefore, mothers should terminate breastfeeding, if Lisinopril is given during that period.

Side effects
As with all angiotensin converting enzyme (ACE) inhibitors


Interactions
As with all angiotensin converting enzyme (ACE) inhibitors

Dosing
Lisinopril can be given once a day to improve patient compliance. The usual daily dose in all indications ranges from 2.5mg in sensitive patients to 40mg. Some patients have been treated with 80mg daily and have tolerated this high dose well.

Downward adjustments need to be made in patients with higher grade renal impairment (glomerular filtration rate lower than 30ml/min). Particular schedules exist designed for physician's use.

History/Brand Names
Lisinopril was developed by Merck & Co. and is marketed worldwide by Merck with the brand name Prinivil and by AstraZeneca with the brand name Zestril. In Australia it is marketed by AlphaPharm with the brand name Lisodur. In most countries generics are available.

Other useful drug information: Flexeril | Effexor | Alprazolam | Crestor | Zantac | Allopurinol | Coreg

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Regulatory or medical requirements may wary in different countries, this information is intended for U.S. citizens.

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