Description and Composition of Linopril
Linopril is a drug that contains Lisinopril as its active pharmaceutical ingredient. It also contains inactive ingredients called excipients in sufficient quantities. It is a drug used in the treatment of high blood pressure otherwise known as hypertension. It is a third generation Angiotensin Converting Enzyme Inhibitor. Linopril can be used either alone or in combination with other antihypertensive drugs. It represents a lysine analog of the enalapril, and unlike it, it is directly active. With such action, it interferes with any component of the renin-angiotensin-aldosterone system separately.
Uses and Indications of Linopril
- Linopril is indicated in the treatment of mild to moderate hypertension. It may be used alone or concomitantly with other classes of antihypertensive agents.
- Lisinopril is indicated in the management of congestive heart failure as an adjunctive treatment with diuretics and, where appropriate, digitalis
- Lisinopril is indicated for the treatment of haemodynamically stable patients, within 24 hours after acute myocardial infarction, to prevent the subsequent development of left ventricular dysfunction or heart failure and to improve survival. Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, aspirin and beta-blocker
Dosage and Method of Administration of Linopril
- Absorption of Linopril tablets is not affected by food, and tablets may be administered before, during or after meals.
- Lisinopril should be administered in a single daily dose.
- Lisinopril should be taken at approximately the same time each day
Mild to Moderate Hypertension
- The recommended starting dose is 10 mg.
- The usual effective maintenance dosage is 20 mg administered in a single daily dose
- Dosage should be adjusted according to blood pressure response.
- A maximum dose of 40 mg a day in hypertension is recommended
Contraindications of Linopril
- Breast-feeding mothers: The safety of Linopril has not been established in breast-feeding mothers.
- Lisinopril is contraindicated in patients who are hypersensitive to any components of the product and in patients with a history of angioneurotic oedema relating to previous treatment with angiotensin-converting enzyme inhibitor and in patients with hereditary or idiopathic angioedema
- Lisinopril should not be given to patients with aortic stenosis or hypertrophic cardiomyopathy.
Special warnings and precautions for use
- ACE-inhibitors can cause foetal and neonatal morbidity when administered to pregnant women during the 2nd and 3rd trimesters.
- ACE inhibitors pass through the placenta and can be presumed to cause disturbance in foetal blood pressure regulatory mechanisms Oligohydramnios, which may result in limb contractures, cranofacial deformities and hypoplastic lung development, as well as hypotension, renal failure, hyperkalaemia, oliguria and anuria in new-borns have been reported after administration of ACE-inhibitors in the second and third trimesters.
- Cases of defective skull ossification have been observed Prematurity and low birth mass can occur. The adverse effects to the embryo and foetus do not appear to have resulted from intra-uterine ACE-inhibitor exposure limited to the first trimester Infants whose mothers have taken lisinopril should be closely observed for hypotension, oliguria and hyperkalaemia
- Lisinopril crosses the human placenta.
Interaction of Linopril with other Medicinal Products and Other Forms of Interaction
When a diuretic is added to the therapy of a patient receiving Linopril, the antihypertensive effect is additive. Patients already on diuretics and especially those, in whom diuretic therapy was recently instituted, may experience an excessive reduction of blood pressure when lisinopril is added.
Serum potassium tends to rise but usually remains within normal limits, however hyperkalaemia may occur. Risk factors for the development of hyperkalaemia include renal insufficiency, diabetes mellitus and concomitant use of potassium-sparing diuretics (e.g. spironolactone, triamterene or amiloride), potassium supplements, or potassium-containing salt substitutes. The use of potassium supplements, potassium sparing diuretics or potassium containing salt substitutes, particularly in patients with impaired renal function, may lead to a significant increase in serum potassium
The lithium elimination may to be reduced. Therefore the lithium levels of serum should be carefully compared if lithium salte are administered.
Linopril Use in Pregnancy and lactation
Linopril tablets should not be used during the first trimester of pregnancy. When pregnancy is planned or confirmed, the switch to an alternative treatment should be initiated as soon as possible.
It is not known whether Lisinopril tablets are excreted into human breast milk.
Lisinopril is excreted into the milk of lactating rats.
The use of Lisinopril tablets is not recommended in women who are breast-feeding
Side Effects of Linopril
The following side-effects may occur more frequently
- Nauses and
Other side-effects include:
- Orthostatic effects (including hypotension)
Overdose of Linopril
The symptoms of over-dosage of Linopril may include severe hypotension, electrolyte disturbances and renal failure. Treatment is symptomatic and supportive.
Pharmacology Properties of Linopril
Linopril is a peptidyl dipeptidase inhibitor. It inhibits the angiotensin converting enzyme (ACE) that catalyses the conversion of angiotensin I to the vasoconstrictor peptide angiotensin IL Angiotensin II also stimulates aldosterone secretion by the adrenal cortex Inhibition of ACE results in decreased concentrations of angiotensin 11 which results in decreased vasopressor activity and reduced aldosterone secretion. The latter decrease may result in an increase in serum potassium concentration. While the mechanism through which lisinopril lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, lisinopril is also antihypertensive in patients with low-renin hypertension.ACE is identical to kininase II, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodilatory peptide, play a role in the therapeutic effects of lisinopril remains to be elucidated.
Pharmacokinetic Properties of Linopril
Peak serum concentrations occurred within 6 to 8 hours, although there was a trend to a small delay in time taken to reach peak plasma concentrations in acute myocardial infarction patients. Upon multiple dosing, lisinopril exhibits an effective half-life of accumulation of 12.6 hours. The extent of absorption of lisinopril was approximately 25%, with interpatient variability (6-60%) at all doses tested (5-80 mg) Declining serum concentrations exhibit a prolonged terminal phase which does not contribute to drug accumulation. This terminal phase probably represents saturable binding to ACE and is not proportional to dose Lisinopril is excreted unchanged in the urine Impaired renal function decreases elimination of lisinopril, which is excreted via the kidneys but this decrease becomes clinically important only when the glomerular filtration rate is below 30 mL/min. Older patients have higher blood levels and higher values for the area under the plasma concentration time curve than younger patients, Lisinopril can be removed by dialysis.
Special precaution for storage
Store below 30°C. Protect from light. Keep out of reach of children.