Hydrochlorothiazide, enalapril

Pharmacological properties

Berlipril plus 10/25 is a combination drug, which includes an apf inhibitor, enalapril and an antihypertensive diuretic, hydrochlorothiazide.

Enalapril. Enalapril maleate is a salt of maleic acid and enalapril, a derivative of two amino acids - L-alanine and L-proline. ACE is a peptidyldipeptidase and catalyzes the conversion of angiotensin I to angiotensin II, which has a vasopressor effect. After absorption, enalapril is hydrolyzed to form enalaprilat, which in turn inhibits ACE. This leads to a decrease in the level of angiotensin II in blood plasma and a further increase in plasma renin activity (due to the blocking of the negative feedback mechanism with renin release) and a decrease in aldosterone secretion. The structure of ACE does not differ from kininase II, so enalapril can block the breakdown of bradykinin, a powerful vasodilator. However, the clinical significance of this effect has not yet been elucidated. The antihypertensive effect of enalapril is primarily associated with inhibition of the activity of the renin-angiotensin-aldosterone system (RAAS), but the drug also lowers blood pressure in patients with low-corinine hypertension. The use of enalapril in patients with hypertension is accompanied by a decrease in blood pressure in the horizontal and vertical position of the body without a significant increase in heart rate. In rare cases, this is accompanied by orthostatic hypotension. In some patients, an optimal decrease in blood pressure is noted only after a few weeks of treatment. The sudden cessation of enalapril therapy is not accompanied by a sharp increase in blood pressure. Sufficient inhibition of ACE activity is usually observed after 2–4 hours with the use of enalapril 1 time per day orally. The antihypertensive effect is manifested within an hour after administration, but the maximum blood pressure decreases after 4-6 hours. The duration of the drug depends on its dose. However, when used in recommended doses, the hypotensive and hemodynamic effects persist for at least 24 hours. When assessing hemodynamics in patients with essential hypertension, a decrease in blood pressure was accompanied by a decrease in peripheral vascular resistance and an increase in cardiac output with a minimal change in heart rate. After the use of enalapril, an increase in renal blood flow was noted, while the glomerular filtration rate remained unchanged. Delays in sodium and water when using enalapril were not noted. However, in patients with an initially low glomerular filtration rate, this indicator may increase during treatment. In short-term clinical trials in patients with impaired renal function and concomitant diabetes mellitus, a decrease in albuminuria, proteinuria, and urinary IgG excretion after enalapril was used. With simultaneous use with diuretic agents of the thiazide group, the antihypertensive effect of enalapril is enhanced. Enalapril can prevent or reduce the manifestations of hypokalemia associated with the use of diuretic agents of the thiazide group.

The simultaneous use of ACE inhibitors and angiotensin II receptor blockers has been studied in two large-scale randomized controlled trials ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in Diabetes).

The ONTARGET study was performed among patients with a history of cardiovascular or cerebrovascular disease or type II diabetes mellitus, accompanied by signs of damage to the target organ. The VA NEPHRON-D study was performed in patients with type II diabetes mellitus and diabetic nephropathy. These studies did not reveal a significant positive effect on the outcome of renal and / or cardiovascular diseases and the mortality associated with them, while compared with monotherapy, there was an increased risk of developing hyperkalemia, acute kidney damage and / or hypotension. Given the similar pharmacodynamic properties, these results are also applicable to other ACE inhibitors and angiotensin II receptor blockers. The simultaneous use of ACE inhibitors and angiotensin II receptor blockers is contraindicated in patients with diabetic nephropathy.

An ALTITUDE study (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) was performed to identify the beneficial effects of adding aliskiren to standard therapy with ACE inhibitors or angiotensin II receptor blockers in patients with type 2 diabetes and chronic kidney disease, cardiac vascular diseases or those who have both diseases. This study was interrupted earlier due to an increased risk of adverse reactions. Mortality from cardiovascular diseases and cases of stroke were more often recorded in the aliskiren group than in the placebo group, and serious adverse reactions (hyperkalemia, hypotension, and renal dysfunction) were reported more often in the aliskiren group compared with the placebo group.

Hydrochlorothiazide. Hydrochlorothiazide is a diuretic agent of the thiazide series, which has a diuretic effect due to inhibition of sodium reabsorption in the cortical segment of the renal tubules. It enhances the excretion of sodium and chlorine, and to a lesser extent potassium and magnesium, increasing the volume of urine and contributing to a decrease in blood pressure. The diuretic effect of the drug usually manifests itself 2 hours after oral administration, reaches its maximum value after 4 hours and lasts for 6-12 hours. When a certain dose is reached, the increase in the severity of the therapeutic effect of diuretic agents of the thiazide series ceases, while the severity of undesirable reactions increases. In the absence of effect, increasing the dose of the drug above the recommended does not give the desired result and is accompanied by numerous undesirable reactions.

Enalapril / hydrochlorothiazide. Clinical studies have shown that the simultaneous use of enalapril and hydrochlorothiazide has a more pronounced antihypertensive effect than monotherapy with the components of the drug. Enalapril can prevent or reduce the manifestations of hypokalemia due to hydrochlorothiazide.

Pharmacokinetics Enalapril. Absorption. After oral administration, enalapril is rapidly absorbed, its C_max serum is reached within an hour.Based on the content of enalapril in the urine, its absorption after oral administration in tablet form is about 60%. Eating does not affect the absorption of enalapril. After absorption, enalapril is rapidly and in significant quantities hydrolyzed to enalaprilat, a potent ACE inhibitor. The maximum level of enalaprilat in serum is achieved 4 hours after oral administration of enalapril in tablet form. Effective T_½ for enalaprilat after repeated use of enalapril is 11 hours. With normal renal function, the equilibrium concentration of enalaprilat in serum is reached 4 days after the start of its use.

Distribution. In the range of therapeutic concentrations, the degree of binding of enalaprilat to human plasma proteins does not exceed 60%.

Biotransformation. Enalapril does not undergo significant metabolic transformations, with the exception of conversion to enalaprilat.

Excretion. Enalaprilat is excreted mainly by the kidneys. In urine, enalaprilat is determined, the proportion of which is 40% of the applied dose, and unchanged enalapril (about 20%).

Impaired renal function. The exposure of enalapril and enalaprilat increases with renal failure. In mild or moderate renal failure (creatinine clearance of 40-60 ml / min), AUC of enalaprilat in equilibrium at a dose of 5 mg once a day is approximately 2 times higher than with normal renal function. In severe renal failure (creatinine clearance ≤30 ml / min), AUC increases by approximately 8 times. In such patients, with repeated use of enalapril maleate, the effective T is lengthened_½ enalaprilat and increases the time to reach equilibrium.

Lactation. For 4–6 hours after oral administration at a dose of 20 mg by five women in the postpartum period C_max enalapril maleate in mothers milk averaged 1.7 μg / L (peak range 0.54–5.9 μg / L). Average c_max enalaprilat - 1.7 μg / l (1.2–2.3 μg / l); C_max fixed at different times for 24 hours. According to C_max in breast milk, it is believed that an infant who consumes only mother’s milk receives ≤0.16% of the substance of the dose taken by the mother and selected per 1 kg of body weight. In a woman who used 10 mg of enalapril per day for 11 months, C_maxcomponent of 2 μg / l, was observed approximately 4 hours after taking the drug, and C_max enalapril, reaching 0.75 mcg / l, approximately 9 hours after administration. The total daily content of enalapril in mothers milk was 0.63 μg / L, and the total daily content of enalapril was 1.44 μg / L. 4 hours after taking a single dose of 5 mg of enalapril by one patient and a single dose of 10 mg of enalapril by two patients, the level of enalaprilat in milk was below the detection limit (0.2 μg / l); the content of enalapril has not been established.

Hydrochlorothiazide. After oral administration, hydrochlorothiazide is rapidly absorbed in an amount of 80% of the dose taken. Eating does not affect its absorption. C_max in blood plasma is reached after 2-5 hoursAbout 50-60% of hydrochlorothiazide binds to albumin, but most of it accumulates in red blood cells. Medium T_½ 5–15 hours. Hydrochlorothiazide is excreted by the kidneys almost unchanged (95%).

Preclinical safety data. Standard preclinical studies of pharmacological safety, toxicity with repeated use, genotoxicity, carcinogenicity and reproductive toxicity did not reveal a specific risk to humans. Data from reproductive toxicity studies suggest that enalapril maleate does not affect the fertility and functioning of the reproductive system in rats and does not have a teratogenic effect. In a study in which the drug was administered to rats before mating and during pregnancy, as well as lactation, increased mortality of the offspring was established. It is proven that the drug passes through the placenta and is excreted in milk. The fetotoxic effect (harmful effect on the fetus and / or fetal death) of drugs belonging to the class of ACE inhibitors, if they are prescribed in the II and III trimester of pregnancy, is also proven.

Indications

Essential Ag.

Berlipril plus 10/25 is indicated when the decrease in blood pressure is insufficient with the use of enalapril maleate monotherapy.

This drug can be used to replace the combination therapy of enalapril with 10 mg maleate and 25 mg hydrochlorothiazide if the patient is at a stable condition at these doses.

Application

This drug is not indicated for the initial treatment of essential ag. at the first stages, it is necessary to select the optimal dose of its individual components. if necessary, the patient is prescribed a combined drug with fixed doses of active substances instead of monotherapy.

The standard daily dose of the drug is 1 tablet per day. The tablet is taken regardless of the meal in the morning and washed down with a sufficient amount of liquid, for example a glass of water.

When transferring patients with enalapril monotherapy to Berlipril plus 10/25, especially patients with water-electrolyte disorders (for example, after vomiting, diarrhea, treatment with diuretics), with severe heart failure, severe form of hypertension, including renal origin, significant a decrease in blood pressure, therefore, such patients should be monitored for 8 hours after applying the first dose.

Renal failure (creatinine clearance 30–80 ml / min). Berlipril plus 10/25 is contraindicated in patients with severe renal failure. Its purpose is possible for patients with creatinine clearance of 30, but 80 ml / min, and only after the selection of active substances separately. In such patients, the initial recommended dose of enalapril maleate with monotherapy is 5-10 mg.

Patients of advanced age. There are no data on the relationship between the effectiveness and safety of the drug with the age of the patient. When using the drug, kidney function must be considered.

Contraindications

Hypersensitivity to enalapril or other apf inhibitors, thiazide diuretics, sulfa drugs / sulfonylureas or other components of the drug; angioneurotic edema as a result of therapy with APF inhibitors in history, as well as hereditary angioedema; severe renal failure (creatinine clearance ≤30 ml / min) and hemodialysis, anuria; renal artery stenosis; severe liver dysfunction; the simultaneous use with drugs containing aliskiren is contraindicated in patients with diabetes mellitus or impaired renal function (glomerular filtration rate of 60 ml / min / 1.73 m2); pregnant women or women planning to become pregnant (see use during pregnancy and lactation); lactation period.

Side effects

During clinical trials or after the drug was placed on the market, the following adverse reactions of the drug berlipril plus 10/25 were reported, separately for enalapril or hydrochlorothiazide.

To assess the incidence of side effects, the following classification is used: very often: 1/10; often: 1/100, 1/10; sometimes: 1/1000, 1/100; rarely: 1/10 000, 1/1000; very rarely: 1/10 000; the frequency is unknown (according to the available data, the frequency cannot be set).

Infections and infestations: rarely - sialadenitis.

On the part of the blood and lymphatic system: sometimes - anemia, including aplastic and hemolytic; rarely neutropenia, decreased hemoglobin, decreased hematocrit, thrombocytopenia, agranulocytosis, inhibition of bone marrow function, pancytopenia, lymphadenopathy, autoimmune diseases.

From the endocrine system: the frequency is unknown - syndrome of impaired secretion of antidiuretic hormone (SIADH).

From the digestive system and metabolism: often - hypokalemia, hypercholesterolemia, hypertriglyceridemia, hyperuricemia; sometimes - hypoglycemia, hypomagnesemia, gout; rarely - hyperglycemia, glucosuria; very rarely - metabolic alkalosis, hypercalcemia.

From the side of the nervous system and mental disorders: often - headache, depression, loss of consciousness, changes in taste perception; sometimes - confusion, drowsiness, insomnia, irritability, paresthesia, dizziness, decreased libido; rarely - unusual dreams, sleep disturbances, paresis (due to hypokalemia).

From the side of the organ of vision: very often - blurred vision; sometimes - xantopsia; the frequency is unknown - an acute attack of angle-closure glaucoma.

On the part of the organ of hearing and the labyrinth: sometimes - tinnitus.

From the cardiovascular system: very often - dizziness; often - arterial hypotension, including orthostatic, cardiac arrhythmias, angina pectoris, tachycardia; sometimes - hot flashes, palpitations, myocardial infarction or cerebrovascular accident, probably due to severe arterial hypotension in patients at risk; rarely - Raynauds syndrome, necrotizing angiitis (vasculitis, cutaneous vasculitis).

On the part of the respiratory system, chest and mediastinum: very often - cough; often shortness of breath; sometimes - rhinorrhea, sore throat or hoarseness, bronchospasm / BA; rarely, pulmonary infiltrates, respiratory distress syndrome (including pneumonitis and pulmonary edema), rhinitis, allergic alveolitis / eosinophilic pneumonia.

From the digestive system: very often - nausea; often - diarrhea, abdominal pain; sometimes - intestinal obstruction, pancreatitis, vomiting, dyspeptic disorders, constipation, stomach irritation, dry mouth, peptic ulcers, flatulence; rarely - stomatitis / aphthous stomatitis, glossitis; very rarely - angioedema of the intestine.

From the hepatobiliary system: rarely - liver failure, liver necrosis (sometimes fatal), hepatitis (hepatocellular or cholestatic), jaundice, cholecystitis (in particular in patients with diagnosed cholelithiasis).

On the part of the skin and subcutaneous tissue: often - rashes (exanthema), hypersensitivity / angioedema (there have been reports of angioedema of the face, limbs, lips, tongue, epiglottis and / or larynx); sometimes - increased sweating, skin itching, urticaria, alopecia, photosensitivity; rarely - polymorphic erythema, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, purpura, skin form of systemic lupus erythematosus and lupus-like reactions, pemphigus, erythroderma, anaphylactic reactions.

A symptom complex is described, which includes the following phenomena: fever, serositis, vasculitis, myalgia / myositis, arthralgia / arthritis, a positive titer of antinuclear antibodies, increased ESR, eosinophilia, leukocytosis. Rashes, photosensitization and other skin reactions are also possible.

From the musculoskeletal system: often - muscle cramps; sometimes arthralgia.

From the kidneys and urinary tract: sometimes - impaired renal function, renal failure, proteinuria; rarely - oliguria, interstitial nephritis.

From the reproductive system and mammary glands: sometimes - impotence; rarely - gynecomastia.

Systemic disorders and complications at the injection site: very often - asthenia; often - increased fatigue, chest pain; sometimes - general malaise, fever.

Additional research methods: often - hyperkalemia, increased serum creatinine; sometimes - an increase in the level of urea in the blood, hyponatremia; rarely - increased activity of liver enzymes, increased serum bilirubin level.

special instructions

Enalapril

Stenosis of the aortic orifice and mitral valve / hypertrophic cardiomyopathy. Like other vasodilators, ACE inhibitors should be used with caution in patients with impaired blood outflow from the left ventricle, as well as with cardiogenic shock and stenosis, which causes a significant effect on hemodynamics.

Impaired renal function.The development of renal failure has been reported with enalapril treatment, mainly in patients with severe heart failure or kidney disease, including renal artery stenosis. With timely diagnosis and adequate treatment, this renal failure is reversible.

Vasorenal hypertension. When using ACE inhibitors in patients with bilateral renal artery stenosis or with renal artery stenosis of a single functioning kidney, the risk of arterial hypotension and renal failure increases. In this case, impaired renal function can be accompanied by only minor changes in the concentration of creatinine in the blood serum. In such patients, the drug is used under constant medical supervision in a low dose, which is gradually carefully increased under the control of renal function.

Kidney transplantation. There is no clinical experience with the use of the drug Berlipril plus 10/25 in patients who have recently undergone kidney transplantation; therefore, the drug is not recommended for this category of patients.

Hemodialysis. Enalapril is not indicated for patients with renal failure requiring dialysis. There have been reports of the development of anaphylactic reactions during hemodialysis with high-throughput membranes (for example AN 69) in patients taking ACE inhibitors. If such a procedure is necessary, it is recommended to use a different type of dialysis membrane or to use a drug of a different antihypertensive class.

Liver failure. In rare cases, the use of ACE inhibitors was accompanied by a syndrome that began with cholestatic jaundice or hepatitis and ended with fulminant liver necrosis, sometimes fatal. The mechanism of development of such a syndrome has not been elucidated. Patients who develop jaundice during treatment with ACE inhibitors or significantly increase the level of liver enzymes should stop using the ACE inhibitor and begin appropriate treatment.

Neutropenia / agranulocytosis. There have been reports of the development of neutropenia / agranulocytosis, thrombocytopenia and anemia in patients using ACE inhibitors. With normal kidney function and the absence of other triggering factors, neutropenia occurs quite rarely. Enalapril is used with caution in patients with vascular damage on the background of collagen diseases, in the treatment of immunosuppressive drugs, allopurinol, procainamide or in combination of these factors, especially in patients with previous kidney damage. Some patients developed severe infectious processes resistant to antibiotic therapy. During the use of enalapril in such patients, it is necessary to periodically monitor the leukocyte formula, while all patients are advised to inform the doctor about any signs of the infection process.

Hyperkalemia In some patients using ACE inhibitors, including enalapril, an increase in serum potassium levels was noted.Risk factors for developing hyperkalemia are renal failure, impaired renal function, patient age (over 70 years), diabetes mellitus, intercurrent diseases and conditions, including such as dehydration, acute decompensation of cardiac activity, metabolic acidosis and the concomitant use of potassium-sparing diuretics ( e.g. spironolactone, eplerenone, triamteren, amiloride), potassium supplements or salt substitutes containing potassium, as well as other agents leading to an increase in potassium levels in cr ova (e.g. heparin). When using potassium preparations, potassium-sparing diuretics, potassium supplements or salt substitutes containing potassium, in patients with impaired renal function, a significant increase in the level of potassium in the blood is possible. Hyperkalemia can cause the development of severe arrhythmias, including fatal ones. If the use of the above funds with enalapril is advisable, treatment should be carried out with caution, regularly monitoring the level of potassium in the blood.

Double blockade of RAAS. Clinical studies indicate that the simultaneous use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren increases the risk of hypotension, hyperkalemia, and decreased kidney function (including acute renal failure). Therefore, the double blockade of RAAS against the background of the simultaneous use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended. If therapy with double blockade of RAAS is absolutely advisable, then it should be carried out only under the supervision of a specialist, as well as against the background of careful monitoring of renal function, electrolytes in the blood and blood pressure. The simultaneous use of ACE inhibitors and angiotensin II receptor blockers is contraindicated in patients with diabetic nephropathy.

Patients with diabetes. Patients with diabetes taking oral antidiabetic drugs or insulin, before using ACE inhibitors, should be warned about the need for careful monitoring of blood sugar levels to avoid the development of hypoglycemia, especially in the first month of simultaneous use.

Hypersensitivity Reactions / Angioedema. When using ACE inhibitors, including enalapril, there have been reports of the development of angioedema of the face, limbs, lips, tongue, epiglottis, and larynx. Such edema can develop at any time during treatment. In this case, you should immediately stop using the drug Berlipril plus 10/25, the patient should be under medical supervision until all symptoms disappear completely. Even if angioedema affects only the tongue, without concomitant respiratory failure, prolonged monitoring of the patients condition is necessary, since the use of antihistamines and corticosteroids may not be enough. Rarely reported death due to angioedema of the larynx and tongue.With swelling of the tongue, epiglottis or larynx, the risk of airway obstruction is increased, especially in patients who have recently undergone surgery on the airways. In such cases, it is necessary to take immediate measures, including sc injection of epinephrine solution 1: 1000 (0.3-0.5 ml) and / or airway patency may be necessary.

In representatives of the Negroid race, cases of angioedema were more often observed in relation to patients of the Caucasian race who took ACE inhibitors. In general, it is believed that representatives of the Negroid race have a higher risk of developing angioedema.

Patients with a history of angioedema of a different etiology with a history of ACE inhibitors are in another high-risk group with respect to this complication.

Anaphylactic reactions during desensitization by insect venom. Rarely, anaphylactic life-threatening reactions were detected in patients using ACE inhibitors during desensitization with insect venom. Such reactions can be avoided by temporarily stopping the use of an ACE inhibitor before each desensitization procedure.

Anaphylactic reactions in LDL apheresis. Rarely, anaphylactic life-threatening reactions were detected in patients using ACE inhibitors during LDL apheresis with dextrin sulfate. Such reactions can be avoided by temporarily stopping the ACE inhibitor before each apheresis procedure.

Cough. A persistent unproductive cough was reported with the use of an ACE inhibitor, which stopped after its withdrawal, which should be taken into account when conducting differential diagnosis of the cause of cough.

Surgery / Anesthesia When performing surgical interventions or using anesthesia with drugs that lower blood pressure, enalapril blocks the formation of angiotensin II due to the compensatory release of renin. In the case of the development of arterial hypotension caused by this mechanism, it is eliminated with the help of infusion therapy.

Pregnancy. Berlipril plus 10/25 should not be used in pregnant women or women planning a pregnancy. If pregnancy is confirmed during treatment with Berlipril plus 10/25, its use should be stopped immediately and replaced with another drug approved for use in pregnant women.

Ethnic differences. As with other ACE inhibitors, in patients of the Negroid race, the antihypertensive effect of enalapril may be less pronounced than in other patients, possibly due to the greater prevalence of low levels of renin in individuals of this race.

Hydrochlorothiazide

Impaired renal function. The use of diuretics of the thiazide group is not always advisable in the treatment of patients with impaired renal function. They are ineffective when creatinine clearance is ≤30 ml / min (for example, in patients with moderate or severe renal failure).

Liver failure.Preparations of the thiazide group should be used with caution in patients with impaired liver function or its progressive disease, since minor changes in the fluid content and water-salt balance in the body can cause hepatic coma.

Metabolic and endocrine effects. Thiazide drugs may impair glucose tolerance. In patients with diabetes, dose adjustment of hypoglycemic agents, including insulin, is allowed. The use of thiazide group diuretics can lead to an increase in the level of cholesterol and triglycerides in the blood serum, and some patients may develop hyperuricemia or gout. This effect of hyperuricemia is probably dose dependent. In addition, enalapril can increase the level of uric acid in the blood and thus enhance the hyperuricemic effect of hydrochlorothiazide. As with any diuretics, periodic monitoring of serum electrolytes is necessary.

Preparations of the thiazide group, including hydrochlorothiazide, can cause a violation of the water-electrolyte balance (hypokalemia, hyponatremia, hypochloremic alkalosis). Symptoms that foreshadow the occurrence of water-electrolyte imbalance are dry mouth, thirst, weakness, drowsiness, dizziness, anxiety, muscle pain or cramps, muscle weakness, hypotension, oliguria, tachycardia, and gastrointestinal disorders such as nausea and vomiting. . Although hypokalemia may occur with hydrochlorothiazide, concomitant use of enalapril reduces this effect. The risk of hypokalemia is more significant in patients with cirrhosis, with significantly increased diuresis, with insufficient intake of electrolytes in patients with corticosteroids or ACTH. In patients with edema in hot weather, hyponatremia may occur. Chloride deficiency is usually mild and does not require therapeutic intervention. Preparations of the thiazide group can reduce urinary calcium excretion and cause a reversible and slight increase in serum calcium levels in the absence of relevant diseases that affect its metabolism. With latent hyperparathyroidism, severe hypercalcemia may occur. The use of thiazide drugs must be discontinued before parathyroid function tests. Preparations of the thiazide group can increase the excretion of magnesium in the urine, which can lead to hypomagnesemia.

Anti-doping test. The hydrochlorothiazide contained in this preparation may cause a false positive anti-doping test result.

Hypersensitivity. In patients with AD in history or without it, hypersensitivity reactions may occur. There have also been reports of an increased risk of increased severity or activation of systemic lupus erythematosus.

An acute attack of angle-closure glaucoma. Hydrochlorothiazide, which is a sulfonamide, has been associated with an idiosyncrasy reaction leading to acute transient myopia and an acute attack of angle-closure glaucoma.Symptoms include an acute decrease in visual acuity or the appearance of pain in the eyes. They usually occur within a period of time from several hours to 1 week after the start of treatment. An attack of acute angle-closure glaucoma can lead to permanent loss of vision if left untreated.

Priority measures: discontinue hydrochlorothiazide as soon as possible. If intraocular pressure is not controlled, it may be necessary to decide on immediate therapeutic or surgical treatment. A risk factor for the development of angle-closure glaucoma may be a history of allergies to sulfonamides or penicillins.

The combined preparation of enalapril and hydrochlorothiazide

Arterial hypotension and an imbalance in the electrolyte / fluid balance in the body. Symptomatic arterial hypotension rarely occurs in patients with uncomplicated hypertension. With the use of enalapril, the risk of its development increases with a violation of water-electrolyte metabolism, a diet with limited salt intake, dialysis, diarrhea or vomiting. In such patients, regular monitoring of serum electrolyte concentrations should be carried out. Particular attention should be paid to patients with coronary heart disease or cerebrovascular disease, in which an excessive decrease in blood pressure can lead to myocardial infarction or the development of acute cerebrovascular accident. Symptomatic arterial hypotension was detected in patients with heart failure with concomitant renal failure or without it. With the development of arterial hypotension, the patient should be given a horizontal position and, if necessary, infuse a physiological solution. Transient arterial hypotension is not a contraindication to further treatment, which can be prolonged after the normalization of blood pressure during infusion therapy.

Impaired function