Description
Captopril Pharmacodynamics
Captopril is a first generation angiotensin-converting enzyme (ACE) inhibitor containing a sulfhydryl group (SH-group). It has an antihypertensive effect.
By inhibiting ACE, it reduces the conversion of angiotensin I to angiotensin II and eliminates its vasoconstrictor effect on arterial and venous vessels. As a result of decreased concentration of angiotensin II, there is a secondary increase in plasma renin activity (due to elimination of negative feedback of renin release), which leads to a direct reduction of aldosterone secretion by the adrenal cortex. This decreases total peripheral vascular resistance (PPR) and arterial pressure (BP), resistance in the pulmonary vessels, reduces the post- and preload on the heart. Increases cardiac output and exercise tolerance.
Dilates arteries more than veins. Causes a decrease in bradykinin degradation (one of the effects of ACE) and an increase in prostaglandin synthesis.
The antihypertensive effect does not depend on blood plasma renin activity, BP reduction is observed in normal and even reduced activity of the hormone, which is due to the effect on tissue renin-angiotensin-aldosterone system (RAAS).
It enhances coronary and renal blood flow. With long-term use, it reduces the severity of myocardial hypertrophy and arterial wall resistance, prevents the progression of heart failure and slows the development of left ventricular dilatation.
Improves blood supply to ischemic myocardium. Reduces platelet aggregation. Helps reduce sodium ions in patients with heart failure.
Reduces the tone of the renal tubular arterioles, thereby improving intra-column hemodynamics and preventing the development of diabetic nephropathy.
In doses of 50 mg/day it exhibits angioprotective properties against the vessels of the microcircular bed and allows to slow the progression of chronic renal failure in diabetic nephroangiopathy.
BP reduction in contrast to direct vasodilators (hydralazine, minoxidil, etc.) is not accompanied by reflex tachycardia and leads to a decrease in myocardial oxygen demand. In heart failure, an adequate dose has no effect on BP.
Maximum BP reduction after oral administration is observed in 60-90 min. The duration of antihypertensive effect depends on the dose taken and reaches optimal values within a few weeks of therapy.
Discontinuation of captopril should not be abrupt, as it may cause a significant increase in BP.
Indications
– Arterial hypertension, including renovascular;
– Chronic heart failure (as a part of combined therapy);
– Impaired left ventricular function after myocardial infarction in clinically stable condition;
– diabetic nephropathy against the background of diabetes mellitus type 1 (with albuminuria more than 30 mg/day).
Contraindications
– Hypersensitivity to captopril, other drug components or other ACE inhibitors (including history);
– hereditary and/or idiopathic angioedema, history of angioedema (previous therapy with other ACE inhibitors); severe renal dysfunction;
– refractory hyperkalemia, bilateral renal artery stenosis, artery stenosis of the sole kidney with progressive azotemia, conditions after renal transplantation, primary hyperaldosteronism;
– severe hepatic function impairment;
– concomitant use with aliskiren and drugs containing aliskiren in patients with diabetes mellitus and/or moderate or severe renal dysfunction (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m2 body surface area);
– concomitant use with angiotensin II receptor antagonists (ARA II) in patients with diabetic nephropathy;
– concomitant use with neutral endopeptidase inhibitors (e.g., with drugs containing Sacubitril) due to the high risk of angioedema;
– pregnancy;
– Breast-feeding period;
– Under 18 years of age (efficacy and safety have not been established);
– lactose intolerance, lactase deficiency or glucose-galactose malabsorption.
- Dosage and administration
Captopril is prescribed orally one hour before meals. Dosing regimen is set individually.
In arterial hypertension, the drug is prescribed from the lowest effective dose of 12.5 mg twice daily. Attention should be paid to the tolerability of the first dose within the first hour. If arterial hypotension developed, the patient should be transferred to the “lying” position with elevated legs (this reaction should not be an obstacle to further therapy). If necessary, the dose is gradually increased (at intervals of 2-4 weeks) until the optimal effect is achieved. - In mild and moderate degree of arterial hypertension, the usual maintenance dose is 25 mg 2 times per day; the maximum dose is 50 mg 2 times per day. In severe degree the dose is gradually increased to a maximum daily dose of 150 mg (50 mg 3 times daily).
In chronic heart failure, captopril is prescribed together with diuretics and/or in combination with cardiac glycosides (to avoid an initial excessive decrease in BP, the diuretic should be cancelled or the dose reduced before prescribing the drug). The initial daily dose is 6.25 mg 3 times daily. Further, if necessary, the dose is gradually increased (at intervals of at least 2 weeks). The average maintenance dose is 25 mg 2-3 times per day, and the maximum dose is 150 mg per day. In case of symptomatic arterial hypotension in heart failure, the doses of diuretics and/or other simultaneously administered vasodilators may be reduced to achieve a sustained effect. - In patients in clinically stable condition with impaired left ventricular function after myocardial infarction, captopril can be started as early as 3 days after myocardial infarction. The initial dose is 6.25 mg per day, then the daily dose is gradually increased over several weeks to 75 mg in 2-3 doses (depending on tolerance of the drug) up to a maximum daily dose of 150 mg (50 mg 3 times per day).
- In diabetic nephropathy, captopril is prescribed in a dose of 75-100 mg per day, divided into 2-3 doses. In insulin-dependent diabetes (type 1) with microalbuminuria (albumin excretion 30-300 mg per day), the drug dose is 50 mg 2 times per day. If total protein clearance is more than 500 mg per day, the drug is effective in a dose of 25 mg 3 times per day.
- In moderate renal function impairment (FFR not less than 30 ml/min/1.73 m2), captopril can be prescribed in a dose of 75-100 mg daily. If renal function impairment is more severe (GFR less than 30 ml/min/1.73 m2), the starting dose should be no more than 12.5 mg daily; further, if necessary, the captopril dose is gradually increased at long enough intervals, but using a lower daily dose than in the treatment of arterial hypertension.
- If necessary, “loop” diuretics rather than thiazide-type diuretics are prescribed additionally.
Recommended scheme of correction of captopril doses in patients with impaired renal function - Initial daily dose (mg) Maximum daily dose (mg)
40 25-50 150
21-40 25 100
10-20 12,5 75
< 10 6,25 37,5
In elderly patients, the dose of captopril is adjusted individually, and it is recommended that therapy be started with a dose of 6.25 mg twice daily and, if possible, maintained at this level to prevent impaired renal function.
