Mechanism of action

The ACE inhibitor is a hypotensive drug, the mechanism of action is associated with a decrease in the formation of angiotensin I angiotensin II, a decrease in the content of which leads to a direct decrease in the release of aldosterone. At the same time, OPSS, systolic and diastolic blood pressure, post- and preload on the myocardium decrease. Expands the arteries to a greater extent than the veins, while the reflex increase in heart rate is not observed. Reduces the degradation of bradykinin, increases the synthesis of Pg. The hypotensive effect is more pronounced with a high level of plasma renin than with its normal or reduced level. Reducing blood pressure in therapeutic limits does not affect the cerebral circulation, the blood flow in the vessels of the brain is maintained at a sufficient level and against the background of reduced pressure. Enhances coronary and renal blood flow. With prolonged use, left ventricular myocardial hypertrophy and myocytes of resistive-type artery walls are reduced, prevents progression of heart failure and slows down the development of left ventricular dilatation. Improves blood supply to ischemic myocardium. Reduces platelet aggregation. Lengthens life expectancy in patients with heart failure, slows the progression of left ventricular dysfunction in patients after myocardial infarction, without clinical manifestations of circulatory failure. It has some diuretic effect. Reduces intraglomerular hypertension, slowing the development of glomerulosclerosis and the risk of CRF. Enalapril is a "prodrug": as a result of its hydrolysis, enalaprilat is formed, which inhibits ACE. The time of onset of the hypotensive effect when taken orally is 1 hour, it reaches a maximum after 4-6 hours and lasts up to 24 hours. Some patients need therapy for several weeks to achieve an optimal level of blood pressure. In case of heart failure, a noticeable clinical effect is observed with prolonged treatment - 6 months or more.

After ingestion absorption - 60%. Food intake does not affect absorption. In the liver it is metabolized to form the active metabolite enalaprilat, which is a more active ACE inhibitor than enalapril. Communication with plasma proteins enalaprilat - 50-60%. TCmax enalapril - 1 h, enalaprilat - 3-4 h. Enalaprilat easily passes through the histohematic barriers, excluding the BBB, a small amount passes through the placenta and into breast milk. T1 / 2 enalaprilat - 11 h. Excreted mainly by the kidneys - 60% (20% - as enalapril and 40% - as enalaprilat), through the intestine - 33% (6% - as enalapril and 27% - as enalaprilat). It is removed during hemodialysis (speed 62 ml / min) and peritoneal dialysis.

Indications and usage

Arterial hypertension (symptomatic, renovascular, including with scleroderma, etc.), chronic heart failure I-III stage; prevention of coronary ischemia in patients with left ventricular dysfunction, asymptomatic dysfunction of the left ventricle.

Inside, regardless of the meal. With monotherapy of hypertension - the initial dose of 5 mg 1 time per day. In the absence of a clinical effect, after 1-2 weeks, the dose is increased by 5 mg. After the initial dose, patients should be under medical supervision for 2 hours and an additional 1 hour, until blood pressure stabilizes. If necessary, and fairly well tolerated, the dose can be increased to 40 mg / day for 1-2 doses. After 2-3 weeks, switch to a maintenance dose of 10-40 mg / day, divided into 1-2 doses. In moderate hypertension, the average daily dose is about 10 mg. The maximum daily dose of the drug is 40 mg / day. If prescribed to patients receiving diuretics at the same time, diuretic treatment should be stopped 2–3 days before enalapril is prescribed. If this is not possible, the initial dose of enalapril should be 2.5 mg / day. Patients with hyponatremia (the concentration of Na + in the serum is less than 130 mmol / l) or the concentration of creatinine in the serum of more than 0.14 mmol / l, the initial dose is 2.5 mg 1 time per day. Renovascular hypertension: the initial dose is 2.5-5 mg / day. The maximum daily dose is 20 mg. In severe form of arterial hypertension, it is possible in / in the introduction (see Enalaprilat), carried out only in the hospital.In chronic heart failure, the initial dose is 2.5 mg once, then the dose is increased by 2.5-5 mg every 3-4 days in accordance with the clinical response to the maximum tolerated dose (depending on blood pressure), but not more than 40 mg / day once or in 2 doses. In patients with low systolic pressure (less than 110 mm Hg), therapy should be started with a dose of 1.25 mg. Selection of the dose should be carried out within 2-4 weeks or in a shorter time. The average maintenance dose is 5-20 mg / day for 1-2 doses. Older people are more likely to have a more pronounced hypotensive effect and lengthening the time of action of the drug, which is associated with a decrease in the rate of enalapril excretion, therefore the recommended initial dose for the elderly is 1.25 mg. With asymptomatic dysfunction of the left ventricle - 2.5 mg 2 times a day. The dose is adjusted with regard to tolerance up to 20 mg / day, divided into 2 doses. With CRF cumulation occurs when filtration decreases below 10 ml / min. With a CK of 80–30 ml / min, the dose is usually 5–10 mg / day, with a CK of 30–10 ml / min - 2.5–5 mg / day, less than 10 ml / min - 1.25–2.5 mg / day only on dialysis days. The duration of treatment depends on the effectiveness of the therapy. With too pronounced decrease in blood pressure, the dose of the drug is gradually reduced.

Adverse reactions

On the part of the cardiovascular system: excessive reduction in blood pressure, orthostatic collapse, rarely - chest pain, angina, myocardial infarction (usually associated with a pronounced decrease in blood pressure), arrhythmias (atrial brady or tachycardia, atrial fibrillation), heartbeat, thromboembolism of pulmonary artery, areas of the heart, fainting. Nervous system disorders: dizziness, headache, weakness, insomnia, paresthesias, anxiety, depression, confusion, fatigue, drowsiness (2-3%), very rarely with high doses - nervousness, depression, paresthesias. On the part of the senses: disorders of the vestibular apparatus, impairment of hearing and vision, tinnitus. On the part of the digestive system: dry mouth, anorexia, dyspeptic disorders (nausea, diarrhea or constipation, vomiting, pain in the abdomen), intestinal obstruction, pancreatitis, abnormal liver function and biliary excretion, hepatitis, jaundice. On the part of the respiratory system: non-productive dry cough, interstitial pneumonitis, bronchospasm, shortness of breath, rhinorrhea, pharyngitis.Allergic reactions: skin rash, angioedema of the face, extremities, lips, tongue, glottis and / or larynx, dysphonia, polymorphic erythema, exfoliative dermatitis, malignant exudative erythema (syndrome of Stevens-Johnson), toxic epidermal necrolysis (malignant erythema (erectile Johnson syndrome), toxic epidermal necrolysis) (pemphigus), pruritus, urticaria, photosensitivity, serositis, vasculitis, myositis, arthralgia, arthritis, stomatitis, glossitis. From the laboratory parameters: hypercreatininemia, increased urea, increased activity of liver transaminases, hyperbilirubinemia, hyperkalemia, hyponatremia, decreased Hb and hematocrit, increased ESR, thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmuno-erythrocytosis, thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmuno-erythrocytosis, thrombocytopenia, neutropenia, agranulocytosis (in patients with autoimmuno-erythrocytosis, thrombocytopenia, neutropenia, agranulocytosis) On the part of the urinary system: renal dysfunction, proteinuria. Other: alopecia, decreased libido, hot flashes. Overdose. Symptoms: an excessive decrease in blood pressure up to the development of collapse, myocardial infarction, acute cerebrovascular accident or thromboembolic complications, convulsions, stupor. Treatment: the patient is transferred to a horizontal position with a low head. In mild cases, gastric lavage and ingestion of a saline solution are shown, in more serious cases, measures aimed at stabilizing blood pressure: IV injection of saline, plasma substitutes, if necessary IV injection of angiotensin II, and hemodialysis (enalaprilat-62 ml / min).

Hypersensitivity to enalapril or other ACE inhibitors, pregnancy, lactation. With caution - angioedema in the history of ACE inhibitor therapy, hereditary or idiopathic angioedema, aortic stenosis, cerebrovascular diseases (including cerebrovascular insufficiency), coronary artery disease, coronary insufficiency, severe autoimmune systemic diseases of the connective disease, coronary insufficiency, severe autoimmune systemic diseases of the connective disease, coronary insufficiency, severe autoimmune systemic diseases of the connective disease, coronary insufficiency, severe autoimmune systemic diseases of the connective disease, coronary insufficiency, severe autoimmune systemic diseases of the connective disease, coronary insufficiency, severe autoimmune systemic diseases of the connective disease, adrenal glands, coronary insufficiency, severe autoimmune systemic diseases. h. SLE, scleroderma), inhibition of bone marrow hematopoiesis, diabetes mellitus, hyperkalemia, bilateral stenosis of the renal arteries, stenosis of the artery of the only kidney, the state after tra splantatsii kidney, renal and / or liver failure, diet sodium restriction, a condition associated with decreased bcc (includingdiarrhea, vomiting), old age, children under 18 years of age (safety and efficacy have not been studied).

Care must be taken when prescribing patients with reduced BCC (as a result of diuretic therapy, while limiting salt intake, hemodialysis, diarrhea and vomiting) - the risk of sudden and pronounced decrease in blood pressure after even the initial dose of ACE is increased. Transient hypotension is not a contraindication to continue treatment with the drug after stabilization of blood pressure. In the case of repeated pronounced decrease in blood pressure, reduce the dose or discontinue the drug. With the development of an excessive decrease in blood pressure, the patient is transferred to a horizontal position with a low headboard, if necessary, injected with saline and plasma-substituting drugs. The use of high-flow dialysis membranes increases the risk of an anaphylactic reaction. Correction of the dosing regimen in the days free from dialysis should be carried out depending on the level of blood pressure. Before and during treatment with ACE inhibitors, monitoring of blood pressure, blood parameters (Hb, K +, creatinine, urea, activity of "liver" enzymes), and protein in the urine is necessary. It should be carefully monitored for patients with severe heart failure, coronary artery disease and vascular diseases of the brain, in which a sharp decrease in blood pressure can lead to myocardial infarction, stroke or impaired renal function. Sudden cancellation of treatment does not lead to the syndrome of "cancellation" (a sharp rise in blood pressure). Patients with an indication of the development of angioedema in the history, there is an increased risk of its development when taking ACE inhibitors. Newborns and infants who have been exposed to intrauterine effects of ACE inhibitors are recommended to be closely monitored to timely detect a pronounced decrease in blood pressure, oliguria, hyperkalemia and neurological disorders, possibly due to a decrease in renal and cerebral blood flow while reducing blood pressure caused by ACE inhibitors. In oliguria, it is necessary to maintain blood pressure and renal perfusion by injecting appropriate fluids and vasoconstrictor agents. In patients with reduced kidney function, a single dose should be reduced or intervals between doses should be increased.Before the study of the functions of the parathyroid glands, enalapril should be abolished. During the period of treatment, it is necessary to refrain from driving vehicles and practicing potentially hazardous activities that require increased concentration and psychomotor speed, since dizziness is possible, especially after the initial dose of an ACE inhibitor in patients taking diuretics. Caution should be exercised when performing physical exercises or hot weather (the risk of dehydration and excessive blood pressure reduction due to lower BCC). Before surgery (including dentistry), it is necessary to warn the surgeon / anesthesiologist about the use of ACE inhibitors.

Antihypertensive effect reduces NSAIDs, estrogens; diuretics, other antihypertensive drugs (beta-blockers, methyldopa, nitrates, BMCC, hydralazine, prazosin), general anesthesia, ethanol. Immunosuppressants, Allopurinol, cytotoxic drugs enhance hematotoxicity. Potassium-sparing diuretics and potassium-containing drugs increase the risk of hyperkalemia. Enhances the effect of ethanol, slows down the elimination of Li +. Drugs that cause bone marrow depression increase the risk of developing neutropenia and / or agranulocytosis, or even death. Weaken the effect of drugs containing theophylline.