Captopril

Antihypertensive agent, ACE inhibitor. The mechanism of antihypertensive action is associated with competitive inhibition of ACE activity, which leads to a decrease in the rate of conversion of angiotensin I to angiotensin II (which has a pronounced vasoconstrictor effect and stimulates the secretion of aldosterone in the adrenal cortex). In addition, captopril appears to have an effect on the kinin-kallikrein system, preventing the breakdown of bradykinin. The antihypertensive effect does not depend on the plasma renin activity, a decrease in blood pressure is noted with a normal and even reduced hormone concentration, which is due to the effect on the tissue RAAS. Increases coronary and renal blood flow.

Due to the vasodilating action, it reduces the OPSS (afterload), the pressure of wedging in the pulmonary capillaries (preload) and resistance in the pulmonary vessels; increases cardiac output and exercise tolerance. With prolonged use, it reduces the severity of left ventricular myocardial hypertrophy, prevents the progression of heart failure and slows down the development of left ventricular dilatation. Helps reduce sodium in patients with chronic heart failure. Expands arteries more than veins. Improves blood flow to the ischemic myocardium. Reduces platelet aggregation.

Reduces the tone of the efferent arterioles of the kidney glomeruli, improving intraglomerular hemodynamics, and prevents the development of diabetic nephropathy.

From the side of the central nervous system and peripheral nervous system: dizziness, headache, fatigue, asthenia, paresthesia.

On the part of the cardiovascular system: orthostatic hypotension; rarely - tachycardia.

On the part of the digestive system: nausea, decreased appetite, impaired taste; rarely - abdominal pain, diarrhea or constipation, increased activity of hepatic transaminases, hyperbilirubinemia; signs of hepatocellular damage (hepatitis); in some cases, cholestasis; in isolated cases - pancreatitis.

From the hematopoietic system: rarely - neutropenia, anemia, thrombocytopenia; very rarely in patients with autoimmune diseases - agranulocytosis.

From the side of metabolism: hyperkalemia, acidosis.

From the urinary system: proteinuria, impaired renal function (increased concentration of urea and creatinine in the blood).

From the respiratory system: dry cough.

Allergic reactions: skin rash; rarely - Quincke's edema, bronchospasm, serum sickness, lymphadenopathy; in some cases - the appearance of anti-nuclear antibodies in the blood.

With simultaneous use with immunosuppressants, cytostatics, the risk of leukopenia increases.

With simultaneous use with potassium-sparing diuretics (including spironolactone, triamterene, amiloride), potassium preparations, salt substitutes and dietary supplements containing potassium, hyperkalemia may develop (especially in patients with impaired renal function), because ACE inhibitors reduce the content of aldosterone, which leads to a retention of potassium in the body against the background of limiting the excretion of potassium or its additional intake into the body.

With the simultaneous use of ACE inhibitors and NSAIDs, the risk of developing renal dysfunction increases; hyperkalemia is rarely observed.

With simultaneous use with "loop" diuretics or thiazide diuretics, severe arterial hypotension is possible, especially after taking the first dose of a diuretic, apparently due to hypovolemia, which leads to a transient increase in the antihypertensive effect of captopril. There is a risk of developing hypokalemia. Increased risk of developing renal dysfunction.

With simultaneous use with drugs for anesthesia, severe arterial hypotension is possible.

With simultaneous use with azathioprine, anemia may develop, which is due to inhibition of the activity of erythropoietin under the influence of ACE inhibitors and azathioprine. Cases of the development of leukopenia have been described, which may be associated with an additive inhibition of bone marrow function.

With simultaneous use with allopurinol, the risk of developing hematological disorders increases; described cases of severe hypersensitivity reactions, including Stevens-Johnson syndrome.

With the simultaneous use of aluminum hydroxide, magnesium hydroxide, magnesium carbonate, the bioavailability of captopril decreases.

Acetylsalicylic acid in high doses can reduce the antihypertensive effect of captopril. It has not been finally established whether acetylsalicylic acid reduces the therapeutic efficacy of ACE inhibitors in patients with coronary artery disease and heart failure. The nature of this interaction depends on the course of the disease. Acetylsalicylic acid, by inhibiting COX and prostaglandin synthesis, can cause vasoconstriction, which leads to a decrease in cardiac output and worsening of the condition of patients with heart failure receiving ACE inhibitors.

There are reports of an increase in the concentration of digoxin in the blood plasma while using captopril with digoxin. The risk of drug interactions is increased in patients with impaired renal function.

With simultaneous use with indomethacin, ibuprofen, the antihypertensive effect of captopril decreases, apparently due to the inhibition of prostaglandin synthesis under the influence of NSAIDs (which are believed to play a role in the development of the hypotensive effect of ACE inhibitors).

With simultaneous use with insulins, hypoglycemic agents, sulfonylurea derivatives, hypoglycemia may develop due to an increase in glucose tolerance.

With the simultaneous use of ACE inhibitors and interleukin-3, there is a risk of developing arterial hypotension.

With simultaneous use with interferon alfa-2a or interferon beta, cases of severe granulocytopenia have been described.

When switching from taking clonidine to captopril, the antihypertensive effect of the latter develops gradually. In the event of a sudden withdrawal of clonidine in patients receiving captopril, a sharp increase in blood pressure is possible.

With the simultaneous use of lithium carbonate, the concentration of lithium in the blood serum increases, accompanied by symptoms of intoxication.

With simultaneous use with minoxidil, sodium nitroprusside, the antihypertensive effect is enhanced.

With simultaneous use with orlistat, it is possible to reduce the effectiveness of captopril, which can lead to an increase in blood pressure, hypertensive crisis, a case of cerebral hemorrhage has been described.

With the simultaneous use of ACE inhibitors with pergolide, an increase in the antihypertensive effect is possible.

When applied simultaneously with probenecid, the renal clearance of captopril decreases.

With simultaneous use with procainamide, an increase in the risk of developing leukopenia is possible.

With simultaneous use with trimethoprim, there is a risk of hyperkalemia, especially in patients with impaired renal function.

With simultaneous use with chlorpromazine, there is a risk of orthostatic hypotension.

With simultaneous use with cyclosporine, there are reports of the development of acute renal failure, oliguria.

It is believed that it is possible to reduce the effectiveness of antihypertensive drugs when used simultaneously with erythropoietins.

When administered orally, the initial dose is 6.25-12.5 mg 2-3 times / day.

With insufficient effect, the dose is gradually increased to 25-50 mg 3 times / day. In case of impaired renal function, the daily dose should be reduced.

The maximum daily dose is 150 mg.