Enalapril

General characteristics. Structure:

International name: enalapril, 1 - [-1 - carboxy - 3 - fenilpropit N-[S]] - L - alanyl] - L - proline - 1 '-ethyl ether a maleate;
Main physical and chemical properties: tablets of white or almost white color, a round form with risky and a facet;
Active agent: 1 tablet contains maleate enalapril - 10 mg;
Excipients: sugar milk (lactose), potato starch, polyvinylpirrolidone, calcium stearate.

Pharmacological properties:

Pharmacodynamics. Enalapril belongs to the class of inhibitors of an angiotensin-converting enzyme. The mechanism of pharmacological effect of drug consists in blockade of APF with the subsequent delay of transformation of inactive angiotensin І in its active form - angiotensin ІІ. Besides, it slows down degradation of vasodepressor peptides – bradikinin and E2 prostaglandin causing a relaxation of unstriated muscles of vessels promotes a producing vazodilatiruyushchy prostanoid and release of nitrogen oxide. Pathological vasoconstriction, proliferation and a hypertrophy of cells of a myocardium is as a result oppressed, activation of a sympathetic nervous system is weakened. Drug promotes pressure decrease in the right auricle and in a small circle of blood circulation, reduces a possibility of development of a hypertrophy of a left ventricle. Reduces: an afterload on heart, disintegration of bradikinin, arterial pressure, the general peripheric resistance of vessels, severity of heart failure. Stimulates synthesis of prostaglandins, increases tolerance to an exercise stress. Strengthens a renal blood stream, improves function of kidneys and interferes with development of a diabetic nephropathy. Does not influence metabolism of glucose, lipoproteins. Gets through a placental barrier, it is allocated with breast milk.

Pharmacokinetics. Enalapril pharmacological малоактивен is also pro-medicine. Getting into a liver, it is hydrolyzed in enalaprilat – the APF active inhibitor. Bioavailability - 60%. Meal does not influence absorption. About 50% of drug can contact proteins of plasma. 1 tablet of drug allows to reach uniform effect for days. It is metabolized in a liver. The maximum concentration of enalaprilat is observed for the 4th hour after acceptance orally. It is brought out of an organism in two ways: 10% liver and 90% kidneys. Time of semi-removal of enalaprilat makes 11 hours.

Indications to use:

Arterial hypertension, including renovascular, chronic heart failure and systolic dysfunction of a left ventricle, diabetic nephropathy.

Route of administration and doses:

Appoint irrespective of meal. The initial dose makes 2,5 mg of 1 times a day. If necessary the single dose is gradually increased to 20 mg by 1-2 times a day. A maintenance dose, usually, 10-20 mg a day. The highest daily dose no more than 40 mg once or in 2 receptions.
Congestive heart failure. The recommended initial dose – 2,5 mg of 1 times a day. The dose is gradually raised to achievement of the maximum clinical effect which is observed usually in 2-4 weeks. The usual maintenance dose makes 2,5-10 mg 2 times a day, maximum – 20 mg 2 times a day. Symptomless dysfunction of a left ventricle. An initial dose – 5 mg/days; supporting – 10 mg 2 times a day. Secondary arterial hypertension at diseases of kidneys. The dose is defined taking into account a condition of kidneys and clearance of creatinine. For patients, the clearance of creatinine at whom exceeds 30 ml/min., the initial dose makes 5 mg/days; to patients, clearance of creatinine at whom less than 30 ml/min., appoint 2,5 mg/days which is gradually raised to achievement of satisfactory effect in a dose. To patients who are on a hemodialysis appoint 2,5 mg in day of the procedure; in all other days the dose is established depending on the level of arterial pressure.

Features of use:

At prolonged use control of indicators of peripheral blood is necessary. At patients with heavy heart failure or with heavy renal failures, and also with disturbance of water and electrolytic balance, the diuretics connected with treatment, an electrolyte-deficient diet, diarrhea, vomiting, a hemodialysis arterial hypotension can be observed. Drug is appointed with care to patients at a hyperpotassemia, at collagenoses and autoimmune diseases, at patients to whom carrying out surgical intervention is planned.

In case of development of a Quincke's disease or allergic reactions it is necessary to cancel administration of drug. The positive effect is rendered by antihistaminic drugs. In case of localization of hypostasis in the field of language or a throat it is necessary to enter quickly subcutaneously adrenaline 1:1000 solution (0,3-0,5 ml).

It is recommended to be careful in case of use of drug for patients with a liver failure. Use of APF inhibitors during pregnancy can lead to death of a fruit. For newborns and babies who were exposed to pre-natal influence of APF inhibitors it is recommended to conduct careful observation for early detection of the expressed lowering of arterial pressure, oligurias, a hyperpotassemia and neurologic frustration, possible owing to reduction of the renal and brain blood-groove at a lowering of arterial pressure caused by APF inhibitors. At an oliguria maintenance of arterial pressure and renal perfusion by administration of the corresponding liquids and vasoconstrictors is necessary.

Care is necessary during the work with transport and other potentially dangerous technical means because of a possibility of emergence of dizziness, especially in an initiation of treatment enalapril. During use of drug it is not recommended to take alcoholic beverages, it is necessary to be careful when performing physical exercises in hot weather as there is a risk of development of dehydration and excessive lowering of arterial pressure because of decrease in volume of the circulating blood. Enalapril is removed from an organism at a hemodialysis; in day of holding a procedure it is appointed in a daily dose 2,5 mg. In need of surgical intervention it is necessary to inform the anesthesiologist that the patient receives therapy by enalapril.

Side effects:

At use are possible: dry cough, a headache, is more rare – arterial hypotension (especially after reception of the first dose of drug), the orthostatic reactions which are followed by dizziness, weakness, a vision disorder, a collapse; tachycardia and other disturbances of a cordial rhythm, stethalgia, stenocardia, feeling of fatigue, sleep disorder, nervousness, depression, spasms, sonitus, taste disturbance, nausea, vomiting, diarrhea, anorexia, pancreatitis, stomatitis; a glossitis, feeling of dryness in a mouth; thrombocytopenia, leukopenia, agranulocytosis; short wind, dystonia, infiltrates in lungs, bronchitis; allergic reactions, including skin rashes, Quincke's disease, including eosinophilia, fever, arthralgia; Stephens-Johnson's syndrome, epidermal necrolysis. Skin reactions can be followed by a mialgiya, a miositis, arthritis, a vasculitis, a serositis, an eosinophilia, a leukocytosis.

Interaction with other medicines:

At use of enalapril and thiazide diuretics there is a reduction of expressiveness of symptoms of the hypopotassemia induced by diuretic. Potentiation of effect is observed at a concomitant use with diuretic and antihypertensives, opioid analgetics, anesthetics and alcohol. Joint reception of enalapril with hypnotic drugs, narcotic, anesthetics promotes a lowering of arterial pressure. Joint purpose of enalapril and kaliysberegayushchy diuretics (Spironolactonum, Triamterenum, amiloride), the nutritional supplements and salts containing potassium, especially at treatment of patients with impaired renal functions can lead to a hyperpotassemia. Enalapril can reduce clearance of lithium in blood. At the patients with an impaired renal function receiving non-steroidal anti-inflammatory drugs after the beginning of use of enalapril decrease in their effect and further deterioration in function of kidneys is possible. Cimetidinum increases duration of effect of enalapril. Enalapril weakens effect of theophylline. At combined use with immunodepressants the risk of influence on marrow increases.

Contraindications:

Hypersensitivity to drug components, to APF inhibitors; pregnancy, a lactation, children's and teenage age up to 18 years; a Quincke's disease in the anamnesis, the progressing azotemia at a bilateral stenosis of renal arteries or a renal artery stenosis of the only kidney, a state after renal transplantation; primary diseases of a liver or a liver failure, a hyperpotassemia, performing desensitization to poison of insects, a stenosis of the arterial or mitral valve with the expressed disturbances of a hemodynamics.

Overdose:

At overdose hypotension in combination with blockade a system renin-angiotenzinovoy, dizziness, development of acute insufficiency of coronary and/or cerebral circulation can develop. In case of hypotension the prone position and intravenous infusion of normal saline solution is recommended. In hard cases, at the use of drug the hemodialysis helps removal of enalaprilat from general circulation with the dose which is repeatedly surpassing recommended.

Storage conditions:

To store in the dry, protected from light place at a temperature not higher than + 25 ºС. A period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister. On 2 blisters in a pack.