Captopril

General characteristics. Structure:

Active agent: captopril – 25 mg.

Excipients: cellulose microcrystallic, sugar milk, starch corn, magnesium stearate.

Pharmacological properties:

Pharmacodynamics.
The mechanism of anti-hypertensive action is connected with competitive inhibition of activity of APF which leads to reduction in the rate of transformation of angiotensin I into angiotensin II and eliminates its vasoconstrictive action.
Reduction of concentration of angiotensin II is resulted by secondary increase in activity of a renin of a blood plasma due to elimination of negative feedback at release of a renin and direct decrease in secretion of Aldosteronum. Thanks to vasodilating action, reduces the general peripheric vascular resistance (afterload), jamming pressure in pulmonary capillaries (preloading) and resistance in pulmonary vessels; increases the minute volume of heart and tolerance to loading. Does not influence lipid metabolism.

Pharmacokinetics.
After intake not less than 75% of drug are quickly soaked up and the maximum concentration is observed in blood in 50 minutes. Linkng with proteins, is preferential with albumine, makes 25-30%. Captopril is metabolized in a liver with education disulfide a dimeasure of captopril and captopril of a tsisteindisulfid. Metabolites pharmacological are inactive. The elimination half-life makes about 3 hours. An elimination half-life at a chronic renal failure 3,5-32 hours. Kumuliruyet at a chronic renal failure. More than 95% of drug are removed with urine from which 40-50% in an invariable look, other quantity is removed in the form of metabolites. Duration of effect of drug about 5 hours.

Indications to use:

- Arterial hypertension (including renovascular).
- Chronic heart failure (as a part of a combination therapy).

Route of administration and doses:

Captopril is appointed for an hour to food. The mode of dosing is set individually.

At arterial hypertension drug 2 times a day appoint in an initial dose 25 mg. If necessary the dose gradually (with an interval of 2-4 weeks) is increased before achievement of optimum effect.
At soft or moderate arterial hypertension the usual maintenance dose makes 25 mg 2 times a day; The Maximum dose – 50 mg 2 times a day.
At heavy arterial hypertension the maximum dose – 50 mg 3 times a day. The maximum daily dose – 150 mg.

For treatment of chronic heart failure Captopril is appointed when use of diuretics does not provide adequate effect. The average maintenance dose makes 25 mg 2-3 times a day. Further, if necessary, the dose gradually (with an interval not less than 2 weeks) is increased. The maximum dose – 150 mg a day.

Patients with disturbances of functions of kidneys at moderate extent of disturbances of functions of kidneys (clearance of creatinine not less than 30 ml/min. / 1,73 m 2) Captopril can appoint 75-100 mg/days in a dose. At more expressed extent of disturbances of functions of kidneys (clearance of creatinine less than 30 ml/min. / 1,73 m 2) the initial dose has to make no more than 12,5-25 mg/days; further if necessary, with rather long intervals the Captopril dose is gradually raised, but use smaller, than usually, a daily dose of drug.

Features of use:

Before the beginning, and also regularly in the course of treatment by the drug Captopril it is necessary to control function of kidneys.

At chronic heart failure drug is used on condition of careful medical observation.

With exclusive care appoint captopril to patients with diffusion diseases of connecting fabric or system vasculites; the patient receiving immunodepressants, especially in the presence of disturbances of functions of kidneys (risk of development of the serious infections which are not giving in to therapy by antibiotics). In such cases it is necessary to carry out control of a picture of peripheral blood prior to Captopril use, every 2 week within the first 3 months of therapy and periodically – to the subsequent period of treatment.

Drug with care is used against the background of treatment by Allopyrinolum or procaineamide, and also against the background of treatment by immunodepressants (including, Azathioprinum, cyclophosphamide), especially at patients with renal failures.

The probability of development of arterial hypotension in the course of treatment can be reduced if in 4-7 days prior to treatment by Captopril to stop use of diuretics or it is essential to reduce their dose. In case of emergence after reception of Captopril of symptomatic arterial hypotension the patient should accept horizontal position with the raised legs.

In case of the expressed arterial hypotension the positive effect is noted at intravenous administration of isotonic solution of sodium chloride. In case of development of a Quincke's disease drug is cancelled and carry out careful medical observation. If hypostasis is localized on a face, special treatment usually is not required (for reduction of expressiveness of symptoms antihistaminic drugs can be used); if hypostasis extends to language, a throat or a throat and there is a threat of development of obstruction of respiratory tracts, it is necessary to enter immediately adrenaline subcutaneously (0,5 ml in cultivation 1:1000).

With care apply at patients with instructions in the anamnesis on diseases of kidneys as the risk of development of a proteinuria increases. In such cases within the first 9 months of treatment by Captopril it is necessary to control monthly amount of protein in urine. If protein level in urine exceeds 1 g/days, it is necessary to resolve an issue of expediency of further use of drug. With care appoint Captopril to patients with a stenosis of renal arteries since there is a risk of development of disturbances of functions of kidneys; in case of increase in level of urea or creatinine in blood the dose decline of Captopril or drug withdrawal can be required.

Side effects:

- From cardiovascular system: arterial hypotension, tachycardia.
- From an urinary system: a proteinuria, a renal failure (increase in level of urea and creatinine in blood).
- From water and electrolytic and acid-base balance: hyperpotassemia, acidosis.
- From system of a hemopoiesis: seldom – a neutropenia, anemia, thrombocytopenia, an agranulocytosis.
- From TsNS: dizziness, headache, feeling of fatigue, adynamy.
- From respiratory system: dry cough, bronchospasm.
- Allergic and immunopathological reactions: a Quincke's disease, a serum disease, a limfoadenopatiya, in rare instances – emergence of anti-nuclear antibodies in blood.
- Dermatological reactions: rash, usually makulo-papular character, is more rare than vesicular or violent character, an itch, the increased photosensitivity.
- From a GIT, a liver, a pancreas: nausea, a loss of appetite, it is rare – diarrhea, abdominal pains, increase in activity of enzymes of a liver, signs of hepatocellular damage and a cholestasia (in rare instances).
- Other: paresthesias.

Interaction with other medicines:

Diuretic means and vazodilatator (for example, minoksidit) exponentiate hypotensive effect of Captopril.

At combined use of Captopril with indometacin (and, perhaps, with other non-steroidal anti-inflammatory drugs) decrease in hypotensive action can be noted.

Hypotensive effect of Captopril can be slowed down at appointment to his patients receiving a clonidine.

Simultaneous use with kaliysberegayushchy diuretics or drugs of potassium can lead to a hyperpotassemia.

At simultaneous use of salts of lithium increase in concentration of lithium in blood serum is possible. Use of Captopril for the patients accepting Allopyrinolum or procaineamide increases risk of development of a neutropenia and/or Stephens-Johnson's syndrome.

Use of captopril for the patients accepting immunodepressants (for example, циклофосфацин or Azathioprinum) increases risk of development of hematologic disturbances.

Contraindications:

— hypersensitivity to captopril and other APF inhibitors;
— a Quincke's disease in the anamnesis (including in the anamnesis after use of other APF inhibitors);
— the expressed renal failures, an azotemia,
— a stenosis of the mouth of an aorta, a mitral stenosis, existence of other obstacles to outflow of blood from a left ventricle of heart;
— the expressed abnormal liver functions;
— arterial hypotension;
— cardiogenic shock;
— pregnancy and period of a lactation;
— age up to 18 years (efficiency and safety are not established).

With CARE to apply: a serious autoimmune illness (including a system lupus erythematosus, a scleroderma), oppression of marrowy blood circulation (risk of development of a neutropenia and agranulocytosis), brain ischemia, a diabetes mellitus (the risk of development of a hyperpotassemia), the patients who are on a hemodialysis, a diet with sodium restriction, the coronary heart disease, states which are followed by decrease in volume of the circulating blood (including diarrhea, vomiting is increased), advanced age.

Use at pregnancy and feeding by a breast
Drug is contraindicated at pregnancy and in the period of a lactation (breastfeeding).

Overdose:

Symptoms: the expressed arterial hypotension, up to a collapse, a myocardial infarction, an acute disorder of cerebral circulation, tromboembolic episodes.

Treatment: to lay the patient with the raised lower extremities; the measures directed to recovery of arterial pressure (increase in volume of the circulating blood, including intravenous injection of isotonic solution of sodium of chloride), symptomatic therapy. Use of a hemodialysis is possible; the peritoneal hemodialysis – is inefficient.

Storage conditions:

List B. In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 3 years. Not to use drug after the date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of 25 mg.
On 10 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.
On 10,20,30,40,50 or 100 tablets in a container polymeric for medicines or a bottle from glass melt with the screwed plastic or aluminum covers.
One container (bottle) or 1,2, 4, 6, 8 or 10 blister strip packagings together with the application instruction place in a pack from a cardboard.
On 10 or 20 containers (bottles) or on 20,40, 60, 80 and 100 blister strip packagings together with the corresponding number of application instructions place in a box from a cardboard (for hospitals).