Captopril - instructions for use, dose, side effects, contraindications

Pharmacodynamics:Angiotensin-converting enzyme inhibitor. Reduces the formation of angiotensin II from angiotensin I. Reduction in angiotensin II leads to a direct reduction in the release of aldosterone. This reduces the overall peripheral vascular resistance, blood pressure, post- and preload on the heart. Expands arteries more than veins. It causes a decrease in the degradation of bradykinin (one of the effects of ACE) and an increase in the synthesis of prostaglandin.

The hypotensive effect does not depend on the plasma renin activity, the decrease in arterial pressure is noted at a normal and even lowered level of the hormone, which is due to the effect on tissue renin-angiotensin systems. Strengthens coronary and renal blood flow.

With prolonged use reduces the severity of myocardial hypertrophy and the walls of arteries of resistive type. Improves the blood supply of the ischemic myocardium. Reduces the aggregation of platelets. Helps reduce the content of Na + in patients with heart failure.

Reduction of blood pressure, in contrast to direct vasodilators (hydralazine, minoxidil and others) is not accompanied by reflex tachycardia and leads to a decrease in myocardial oxygen demand. With heart failure in an adequate dose does not affect the value of blood pressure.

The maximum decrease in blood pressure after oral administration is observed after 35-40 minutes. The duration of the hypotensive effect is dose-dependent and reaches optimal values within a few weeks.

Pharmacokinetics:Absorption - 60-75%, with food - 30-55%. Bioavailability - 35-40%. Penetrates through the blood-brain barrier (1%). The connection with plasma proteins is 25-30%. Biotransformation occurs in the liver (CYP2D6). Half-life is less than 3 hours, with chronic renal failure - 3.5-32 hours. A pronounced effect of the first passage through the liver is characteristic.Elimination by the kidneys (95%, 40-50% of them unchanged). Removed during hemodialysis.

Indications:Arterial hypertension, including renovascular; chronic heart failure (in complex therapy); violations of left ventricular function after a myocardial infarction with a clinically stable condition; Diabetic nephropathy against a type 1 diabetes mellitus (for albuminuria more than 30 mg per day).

ICD-10

IX.I10-I15.I10 Essential [primary] hypertension

IX.I10-I15.I15 Secondary Hypertension

IX.I20-I25.I25.2 Postponed myocardial infarction

IX.I30-I52.I42 Cardiomyopathy

IX.I30-I52.I50.9 Heart failure, unspecified

XIV.N00-N08.N08.3 * Glomerular lesions in diabetes mellitus (E10-E14 + with the common fourth sign .2)

Contraindications:

Hypersensitivity (including other ACE inhibitors), angioedema (history of treatment with ACE inhibitors or hereditary).

Severe renal / hepatic insufficiency, hyperkalemia, bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney with progressive azotemia, condition after kidney transplantation, idiopathic hypertrophic subaortic stenosis, diseases and conditions, accompanied by difficulty in the outflow of blood from the left ventricle.

Pregnancy, breast-feeding.

Age to 18 years (effectiveness and safety not established).

Carefully:Severe autoimmune diseases of connective tissue (including systemic lupus erythematosus, scleroderma), oppression of bone marrow hematopoiesis (risk of neutropenia and agranulocytosis), cerebral ischemia, diabetes mellitus (risk of hyperkalemia); persons on hemodialysis; diet with sodium restriction, primary hyperaldosteronism, ischemic heart disease; conditions, accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting); elderly age.

Pregnancy and lactation:Do not use during pregnancy! The action category for the fetus by FDA is D. Lactation: the drug penetrates into breast milk, is prohibited for use during breastfeeding. At the time of treatment, stop lactation.

Dosing and Administration:

Arterial hypertension (including renovascular - 25-150 mg per day inside 1 hour before meals. Begin with the reception of the lowest effective dose of 12.5 mg 2 times a day. If necessary, the dose is gradually increased to the optimal dose with an interval of 2-4 weeks.With mild and moderate arterial hypertension, a maintenance dose of 25 mg 2 times a day; the maximum dose of 50 mg 2 times a day. With severe arterial hypertension, the initial dose of 12.5 mg 2 times a day. It should be gradually increased to a maximum daily dose of 150 mg (50 mg 3 times per day).

Chronic heart failure (in complex treatment) - from 25-150 mg per day. The initial daily dose of 6.25 mg 3 times a day, if necessary, increase the dose (interval - at least 2 weeks). The average maintenance dose of 25 mg 2-3 times a day. The maximum daily dose of 150 mg in 3 divided doses.

Violations of the function of the left ventricle after a previous myocardial infarction in a clinically stable condition - 25-150 mg per day. Admission begins 3 days after myocardial infarction. The initial dose of 6.25 mg per day, then the daily dose can be increased to 37.5-75 mg in 2-3 doses (depending on the tolerability of the drug). The maximum dose is 150 mg per day in 3 divided doses.

Diabetic nephropathy on the background of insulin-dependent diabetes mellitus, diabetic retinopathy - 25-100 mg per day or in a dose of 75-150 mg per day in 2-3 divided doses. With type 1 diabetes mellitus with macroalbuminuria, 50 mg twice a day. With a total protein clearance of more than 500 mg per day - 25 mg 3 times a day.

With a moderate degree of impaired renal function (creatinine clearance of at least 30 ml / min at 1.73 m²surface of the body) the drug is prescribed in a dose of 75-100 mg per day. With a more pronounced degree of impaired renal function (creatinine clearance less than 30 ml / min at 1.73 m²body surface) the initial dose is not more than 12.5 mg twice a day. In the future, if necessary, the dose of captopril is gradually increased (with a long interval) to achieve a therapeutic effect, but the daily dose should be lower than usual.

In elderly patients, the initial dose is 6.25 mg twice a day.

Side effects:Allergic reactions: skin rash, itching, fever, Quincke's edema, Stevens-Johnson syndrome and so on.

From the cardiovascular system and hematopoiesis system: hypotension (including orthostatic), angina pectoris, myocardial infarction, acute cardiac arrhythmias, neutropenia, agranulocytosis, thrombocytopenia, pancytopenia.

From the respiratory system: bronchospasm, shortness of breath, interstitial pneumonitis, bronchitis, attacks of dry cough.

From the side of the central nervous system: fatigue, dizziness, headache, CNS depression, depression, confusion, and so on.

From the skin: redness of the skin of the face, rash, itching, toxic epidermolysis, alopecia, shingles and the like.

From the digestive tract: inflammatory phenomena of the mucous membrane of the digestive tract, diarrhea, constipation, nausea, vomiting, abdominal pain.

Laboratory indicators: increased serum transaminases and alkaline phosphatase.

Genitourinary system: impaired renal function, acute renal failure, oliguria, proteinuria, impotence.

Overdose:Symptoms: a sharp decrease in blood pressure, shock, stupor, bradycardia, water-electrolyte balance disorders, renal failure.

Treatment: gastric lavage, the introduction of adsorbents and sodium sulfate for 30 minutes after administration, the introduction of 0.9% sodium chloride solution or other plasmasubstitutional solutions (pre-patient to lay, raise the legs and then take measures to replenish the volume of circulating blood), hemodialysis. With bradycardia or pronounced vagus reactions - the introduction of atropine. An artificial pacemaker can be considered. Peritoneal dialysis is ineffective for removing captopril from the body.

Interaction:Tetracycline, digoxin, iron preparations - retardation of absorption. It is necessary to observe a two-hour "window" of taking these drugs and captopril.

Thiazide diuretics - increased hypercalcemia.

Calcitonin - a decrease in the effect of calcitonin in hypercalcemia.

Phenytoin - decreased bioavailability.

Strengthens the hypotensive effect of anesthetics.

Drugs that depress the function of the bone marrow - increases the risk of death on the background of developing agranulocytosis and leukopenia.

Special instructions:

The effectiveness of antihypertensive action is equal to enalapril, lisinopril, trandolapril, valsartan.

With heart failure reduces the risk of sudden cardiac death, which is comparable to the effect of losartan.

Has the same effect on heart volume, ejection fraction and area of myocardial infarction, as well as valsartan, as well as a combination captopril + valsartan.

By the ability to improve systolic and overall left ventricular function in patients with acute myocardial infarction superior to losartan.

In people with hypertension captopril reduces the incidence of diabetes mellitus (in comparison with antihypertensive therapy with diuretics or β-adrenoblockers).

Slows the progression of kidney disease in patients with hypertension, not suffering from diabetes.

Reduces left ventricular hypertrophy, including in patients with chronic renal failure.

When taking captopril test for the content of acetone in urine can be false-positive.

Instructions

Captopril (Captoprilum)