Pharmacological properties
Pharmacodynamics. Captopril inhibits the activity of ACE, which converts angiotensin I to angiotensin II. The result of inhibition of ACE activity is a decrease in the concentration of angiotensin II, an increase in renin activity in the blood plasma and a decrease in aldosterone secretion. The maximum effect on the renin-angiotensin system is observed within 1 hour and lasts 6-8 hours; while the activity of ACE in the blood serum is 12-14 hours. In patients with AG, captopril dilates the resistance vessels and reduces the OPSS. In addition, there is a decrease in pulmonary wedge pressure against the background of the absence of changes in pulmonary vascular resistance.
Captopril reduces resistance in the renal vascular system, increases renal blood flow, glomerular filtration, and sodium and water excretion; maintains potassium levels, reduces protein excretion and accumulation of mesangial macromolecules, and therefore prevents mesangial damage and the development of glomerulosclerosis.
Pharmacokinetics. Captopril is rapidly absorbed from the gastrointestinal tract. Absorption is 70%. In patients with hypertension, the average half-life is 0.45 h. Bioavailability is 60%. C max in serum is reached after 1 h, when the drug is taken under the tongue, absorption is accelerated compared to oral administration. Metabolized in the liver. Captopril is rapidly excreted from the body by the kidneys, mainly in unchanged form. The main mechanism of excretion is tubular secretion and, to a lesser extent, glomerular filtration. The average total clearance from the body is 0.8 l/kg/h, and the average renal clearance is 0.4 l/kg/h.
Indication
Treatment of all forms of AG, congestive heart failure, left ventricular dysfunction after myocardial infarction, prevention of renal failure in patients with diabetic nephropathy or other kidney diseases (in the presence or absence of AG).
Application
The doses are prescribed by the doctor individually for each patient, depending on his condition and the course of the disease. The tablets are swallowed whole, washed down with water, on an empty stomach, 1 hour before meals or 2 hours after. The drug should be taken regularly at the same time every day. 2 doses of captopril should not be used at the same time.
AH. The recommended initial dose is 12.5 mg 2-3 times a day. Doses are selected depending on the degree of decrease in blood pressure, which is observed after 2-4 weeks of treatment. As a rule, a dose of 25 mg 2-3 times a day is sufficient. If a satisfactory response is not observed even at a dose of 50 mg 2-3 times a day, a diuretic is added. The maximum daily dose of Captopril is 150 mg. Patients with hypovolemia and hyponatremia are initially prescribed 6.25 mg of Captopril 2-3 times a day.
Patients with malignant hypertension are initially prescribed doses of 12.5 to 25 mg of Captopril 2-3 times a day. The doses are increased every 24 hours (or more often) until an adequate reduction in blood pressure is observed.
A dose of 25 mg is recommended for the treatment of acute increases in blood pressure (hypertensive crises). Patients should chew the tablet and leave it under the tongue until completely dissolved. The effect can be expected after 15-30 minutes. The same dose can be taken after 1 hour if there is no sufficient effect.
In case of renovascular hypertension or suspicion of such treatment should be carried out by an experienced specialist.
Congestive heart failure. The usual initial dose of Captopril is 6.25-12.5 mg 2-3 times a day. Doses are adjusted according to the patient's condition and needs after 2-4 weeks of treatment. A dose of 25-50 mg 2-3 times a day is sufficient.
The maximum daily dose is 150 mg of Captopril.
Left ventricular dysfunction. The initial dose is 6.25 mg of Captopril; this dose is increased to 12.5 mg 3 times a day the next day. In the absence of contraindications, the dose is gradually increased to 50 mg 3 times a day over several weeks.
Diabetic nephropathy. The recommended initial dose is 6.25 mg of Captopril 3 times a day. The maintenance dose is 25 mg of Captopril 3 times a day.
Impaired renal function. The dose of captopril is determined individually, based on the state of renal function, i.e. creatinine clearance and blood pressure. The usual initial dose is 6.25 mg 2 times a day. It is increased every 7-14 days until a satisfactory clinical effect is achieved. During treatment with captopril, it is recommended to monitor renal function and serum potassium levels.
Hemodialysis: The dose of Captopril should be reduced by 50% after 4 hours of hemodialysis.
The recommended initial dose for newborns is 0.01 mg/kg body weight 2-3 times a day. For children, a dose of 0.3 mg/kg body weight 3 times a day is recommended. The maximum daily dose for children should not exceed 6 mg/kg body weight. Children with hypovolemia and hyponatremia, taking diuretics, and renal failure are prescribed half the initial dose (0.15 mg/kg body weight). Newborns and children are prescribed Captopril only when treatment with other antihypertensive drugs has not helped to reduce blood pressure and maintain it at the desired level.
Contraindication
Hypersensitivity to the active substance, other components of the drug or to other ACE inhibitors, patients with edema as a result of the use of ACE inhibitors in history or with edema in history; with pronounced bilateral renal artery stenosis or hemodynamically significant stenosis of the artery of a single kidney; porphyria, during pregnancy and breastfeeding.
The most common side effects are skin rash (which may be accompanied by itching or fever, eosinophilia and muscle and joint pain), loss or change in taste, and dry cough, which usually disappear a few weeks after stopping treatment with captopril.
Possible arterial hypotension (dizziness, vertigo, headache, weakness and fatigue), tachycardia, palpitations, angina pectoris, impaired renal function, proteinuria, decreased or increased diuresis, renal failure, hyperkalemia, decreased appetite, gastrointestinal disorders (nausea, vomiting, abdominal discomfort, diarrhea, constipation, dry mouth), facial flushing, pallor, insomnia, hair loss, paresthesia; very rarely - neutropenia, agranulocytosis and angioedema.
During treatment with Captopril, slight liver dysfunction may occur, very rarely jaundice. These disorders usually disappear after discontinuation of therapy. Lupus-like syndromes (fever, muscle and joint pain, serositis, vasculitis, leukocytosis and eosinophilia) have been reported.
Special instructions
It is necessary to monitor the patient's blood pressure, respiration, concentration of urea, creatinine and potassium in the patient's serum, as well as diuresis. In patients with severe heart failure or impaired renal function, arterial hypotension (excessive decrease in blood pressure) may occur, accompanied by weakness, increased heart rate and dizziness, even after a considerable period of time after the first dose of captopril. Excessive decrease in blood pressure may also occur in a patient with impaired water and electrolyte metabolism due to a low-salt diet, dehydration associated with treatment with drugs that lead to diuresis, diarrhea, vomiting, excessive sweating or hemodialysis.
Hypotension and its serious consequences are rare and transient. If possible, diuretics and a low-salt diet should be discontinued before starting treatment with Captopril in order to avoid these effects. If diuretic treatment is necessary, it is recommended to start with the lowest dose of Captopril (6.25 mg).
Since there is a risk of developing arterial hypotension and impaired blood supply to vital organs, Captopril should be prescribed with caution to patients with severe coronary artery disease, severe cerebral vascular disease, and patients with valvular stenosis or aortic stenosis of any type.
Due to vasodilation of the glomerular efferent arterioles in patients with impaired renal function and in patients with bilateral renal artery stenosis affecting hemodynamics or stenosis of the artery to a solitary kidney, transient renal dysfunction or acute renal failure may occur. Renal function should be monitored before and during therapy with Captopril.
Elderly patients are at increased risk of side effects, so they should be prescribed Captopril with caution.
During treatment with Captopril, the level of potassium in the blood may increase, especially in patients with chronic renal failure and diabetes mellitus, as well as in patients who are simultaneously taking diuretics that contribute to potassium retention in the body (spironolactone, amiloride and triamterene), or which contain potassium. Therefore, the simultaneous use of Captopril and these drugs should be avoided. Captopril should be prescribed with caution to patients with diabetes mellitus. For some patients, it is necessary to reduce the dose of insulin or oral antidiabetic drugs.
During treatment with Captopril, neutropenia may occur (more often in patients with connective tissue diseases: systemic lupus erythematosus, progressive systemic sclerosis), in patients with renal failure and in patients taking immunosuppressants in combination. Reactions similar to hypersensitivity reactions have been observed during hemodialysis or other blood separation procedures (apheresis) using special dialysis membranes in patients treated with ACE inhibitors.
Adverse hypersensitivity reactions have been observed during desensitization treatment with bee or snake venom.
The effectiveness and safety of using Captopril for the treatment of children has not yet been established, therefore it can be prescribed to children, including newborns, only when other blood pressure-lowering drugs have proven ineffective.
Pregnancy and breastfeeding. You should not take Captopril during this period.
Taking Captopril during pregnancy can cause serious fetal abnormalities. Women should use contraception during treatment with the drug.
Captopril during pregnancy (especially in the II and III trimesters) is used only in emergency cases, when the benefits of such treatment for the mother outweigh the potential risk to the fetus (with frequent ultrasound of the fetus and / or when oligohydramnios is excluded).
Despite the insignificant amount of captopril in milk, this should be taken into account when choosing an antihypertensive agent for a nursing mother. Therefore, breastfeeding is not recommended during treatment with Captopril. In the absence of another method of feeding, careful monitoring of blood pressure, serum potassium and renal function in the child is necessary.
Therefore, until the drug's effects on the body are known, caution should be exercised when driving vehicles and operating other mechanisms.
Interactions
Simultaneous intake of food or antacids slows down the absorption of captopril.
During treatment with Captopril, you should not drink alcoholic beverages, as alcohol enhances the blood pressure-lowering activity of Captopril.
The antihypertensive effect of Captopril is enhanced by concomitant administration of alprostadil, anesthetics, β-adrenergic blockers, α 1 -receptor blockers, central α 2 -agonists, diuretics, dopaminergic drugs, calcium antagonists, minoxidil, muscle relaxants, nitrates and vasodilators.
Antidepressants, antipsychotics, anxiolytics, and hypnotics may also enhance the antihypertensive effect of Captopril.
Concomitant administration of potassium-sparing diuretics (spironolactone, amiloride, triamterene) or potassium preparations may lead to hyperkalemia. In the presence of hypokalemia, treatment with the above drugs is necessary, therefore it is recommended to carry out therapy with special caution with frequent determination of serum potassium levels.
No clinically significant adverse reactions were observed with the simultaneous administration of Captopril and digitalis glycosides.
The antihypertensive effect of Captopril is enhanced by the simultaneous use of analgesics, epoetins, estrogens or a combination of oral contraceptives, carbenoxolones, corticosteroids and naloxone.
The simultaneous use of Captopril and nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid (as a result of inhibition of prostaglandin synthesis), may reduce the effectiveness of Captopril and increase the risk of renal dysfunction.
Probenecid reduces the renal clearance of Captopril and increases its concentration in the blood serum.
Concomitant use of Captopril and drugs containing lithium may increase the risk of developing lithium side effects.
The risk of bone marrow depression is increased in patients receiving concomitant therapy with Captopril and immunosuppressants or allopurinol. In the literature, there have been reports of dangerous anaphylactoid reactions (Stevens-Johnson syndrome, arthralgia, myalgia and fever) in patients receiving concomitant allopurinol and Captopril.
Captopril increases insulin sensitivity. Therefore, some patients may need to reduce the dose of insulin or oral hypoglycemic agents.
During elective surgeries, it is necessary to inform the doctor about taking Captopril if there is an increased risk of lowering blood pressure during general anesthesia.
In patients undergoing major surgery or anesthesia with drugs that cause hypotension, Captopril may inhibit the formation of angiotensin II. If hypotension occurs due to these events, volume loading should be performed.
Overdose
The main manifestation is arterial hypotension. In case of taking a large number of tablets, it is recommended to do gastric lavage (if poisoning has occurred recently) and administer activated charcoal. If signs of hypotension appear, the patient should be placed in a horizontal position and put his head on a small pillow. If necessary, correction of blood plasma volume can be carried out by infusion of 0.9% sodium chloride solution.
In more severe cases, captopril can be removed from the blood by hemodialysis. The hemodialysis clearance is 4.8/h and 7.2/h, depending on the hemodialyzer used.
Storage conditions
In a dry place protected from light at a temperature not exceeding 25 °C.
