Enap-N pills 10mg 25mg N20
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Active ingredients
Enalapril + Hydrochlorothiazide
Release form
Pills
Composition
Active ingredient: Enalapril maleate, Hydrochlorothiazide Concentration of active ingredient (mg): 35
Pharmacological effect
Combined drug, whose action is due to the properties of the components included in its composition. has antihypertensive effect. enalapril inhibits apf, which promotes the conversion of angiotensin i to angiotensin ii, reduces aldosterone concentration in the blood, increases the release of renin by juxtaglomerular cells in the walls of the arterioles of the glomeruli, improves the function of kallinrein-kinin, stimulates the level of the program, promotes the release of the current level, stimulates the release of the program, promotes the release of the program, promotes the release of the program, promotes the release of the source, improves the release of the kinikrein-kinin system, stimulates the release of stimuli depresses the sympathetic nervous system. Together, these effects eliminate spasm and dilate peripheral arteries, reduce opss, systolic and diastolic hell, post- and preload on the myocardium. dilates the arteries to a greater extent than the veins, while reflex increase in the heart rate is not observed. hypotensive effect is more pronounced with a high concentration of renin in the blood plasma than with normal or reduced. The reduction of hell within the therapeutic limits does not affect cerebral circulation. improves blood supply to ischemic myocardium. increases the renal blood flow, while the glomerular filtration rate does not change. in patients with initially reduced glomerular filtration, its rate usually increases. The maximal effect of enalapril develops after 6–8 hours and lasts up to 24 hours. Hydrochlorothiazide is a moderately strong thiazide diuretic. reduces the reabsorption of sodium ions at the level of the cortical segment of the loop of Henle, without affecting its portion passing in the medulla of the kidney. blocks carbonic anhydrase in the proximal convoluted tubule, enhances kidney excretion of potassium ions, bicarbonates and phosphates. practically does not affect the acid-base state. increases the excretion of magnesium ions. retains calcium ions in the body. the diuretic effect develops after 1-2 hours, reaches a maximum after 4 hours, lasts 10-12 hours. the effect decreases with a decrease in the glomerular filtration rate and stops when its value is less than 30 ml / min.reduces hell due to a decrease in ock, changes in the reactivity of the vascular wall. The combination of enalapril and hydrochlorothiazide leads to a more pronounced decrease in hell in comparison with monotherapy for each of the drugs separately and allows you to maintain the hypotensive effect of the drug Enapn for at least 24 hours .
Pharmacokinetics
Enalapril Absorption After oral absorption - 60%. Food intake does not affect absorption. In the liver, it is metabolized to form the active metabolite of enalaprilat, which is a more effective ACE inhibitor than enalapril. The time to reach Cmax enalapril is 1 hour, enalaprilat is 3-4 hours. DistributionEnalaprilat easily passes through histohematogenous barriers, excluding BBB, a small amount passes through the placenta and into breast milk. The link with plasma proteins enalaprilat - 50-60%. Metabolism In liver, enalapril is hydrolyzed to the active metabolite - enalaprilat, which is further metabolized. Extraction The renal clearance of enalapril and enalaprilat is 0.005 ml / s (18 l / h) and 0.00225-0.00264 ml / s (8.1-9.5 l / h), respectively. 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) Removed during hemodialysis (38-62 ml / min) and peritoneal dialysis, the serum enalaprilat concentration after 4-hour hemodialysis is reduced by 45-57%. Pharmacokinetics in special clinical cases in patients with reduced renal function slows down, requiring a dose reduction impaired renal function, especially in patients with severe renal failure. In patients with hepatic insufficiency, enalapril metabolism can be slowed down without changing its pharmacodynamic effect. In patients with chronic heart failure, enalaprilat absorption and metabolism slows down, Vd decreases. Hydrochlorothiazide absorption . Absorption is 70% and increases by 10% when taken with food. Cmax in serum is reached in 1.5-5 hours. Bioavailability is 70%. The distribution of Vd is about 3 l / kg.Binding to plasma proteins - 40%. In the therapeutic range of doses, the average AUC increases in direct proportion to the increase in dose, with the appointment of 1 time / day cumulation is negligible. Penetrates through the placental barrier and into breast milk. It accumulates in the amniotic fluid. Serum concentration of hydrochlorothiazide in the blood of the umbilical vein is almost the same as in maternal blood. The concentration in the amniotic fluid exceeds that in the serum from the umbilical vein (19 times). Metabolism Hydrochlorothiazide is not metabolized in the liver. ExcretionHydrochlorothiazide is excreted mainly with urine - 95% unchanged and about 4% as 2-amino-4-chloro-hydrolyzate m-benzedisulfonamida by glomerular filtration and active tubular secretion in the proximal nephron. The renal clearance of hydrochlorothiazide in healthy volunteers and patients with arterial hypertension is approximately 5.58 ml / s (33 5 ml / min. Hydrochlorothiazide has a biphasic elimination profile. T1 / 2 in the initial phase is 2 hours, in the final phase (10-12 hours after administration) - about 10 hours. Pharmacokinetics in special clinical situations In elderly patients, hydrochlorothiazide does not adversely affect the pharmacokinetics of enalapril, but the serum concentration of enalaprilat is higher When administering hydrochlorothiazide to patients with chronic heart failure, it has been established that its absorption decreases in proportion to the extent of the disease by 20–70%. T1 / 2 hydrochlorothiazide is increased to 28.9 h. Renal clearance is 0.17–3.12 ml / s (10-187 ml / min), average values 1.28 ml / s (77 ml / min). In patients undergoing intestinal bypass surgery for obesity , hydrochlorothiazide absorption can be reduced by 30%, and serum concentration by 50% than in healthy volunteers. Simultaneous use of enalapril and hydrochlorothiazide does not affect the pharmacokinetics of each of them.
Indications
Arterial hypertension (in patients for whom combination therapy is indicated).
Contraindications
Anuria; severe renal dysfunction (CK - angioedema in the history of, associated with the use of previously ACE inhibitors; hereditary or idiopathic angioedema; bilateral renal artery stenosis, arterial stenosis of the only kidney; lactose intolerance,lactase deficiency or glucose / galactose malabsorption; children and adolescents under 18 years of age (efficacy and safety have not been established); Hypersensitivity to the components of the preparation Enap or sulfonamide derivatives.
Precautionary measures
The drug should be stored in a dry place inaccessible to children at a temperature not higher than 25 ° C.
Use during pregnancy and lactation
The drug Enap-N is contraindicated during pregnancy. The effect of ACE inhibitors on the fetus in the first trimester of pregnancy has not been established. The use of ACE inhibitors in the II and III trimesters of pregnancy was accompanied by a negative effect on the fetus and newborn. Newborns developed arterial hypotension, renal failure, hyperkalemia, and / or hypoplasia of the cranial bones. Perhaps the development of oligohydramnios, apparently due to impaired renal function of the fetus. This can lead to contracture of the limbs, deformation of the bones of the skull, including its facial part, and lung hypoplasia. The use of diuretics during pregnancy is not recommended, as it can cause fetal and newborn jaundice, thrombocytopenia, and possibly other undesirable reactions observed in adults. Enalapril and hydrochlorothiazide enter breast milk. Therefore, when prescribing the drug Enap-N in the period of lactation, it is necessary to refuse breastfeeding.
Dosage and administration
Enap-N should be taken regularly at the same time, preferably in the morning, during or after a meal, without chewing, with a small amount of liquid. The recommended dose is 1 tablet / day. In patients on diuretic therapy, it is recommended to cancel treatment or reduce the dose of diuretics at least 3 days before the start of treatment with Enap-N to prevent the development of symptomatic hypotension. Renal function should be examined before starting treatment. The duration of treatment is determined by the doctor individually. In patients with renal insufficiency with CK 30-75 ml / min, the drug Enap-N should be used only after preliminary titration of the doses of enalapril and hydrochlorothiazide separately, respectively, the doses in the combined preparation Enap-N.
Side effects
On the part of metabolism: infrequently - gout.From the side of the central nervous system: very often - dizziness, weakness; often - headache, asthenia; infrequently - insomnia, drowsiness, paresthesia, irritability, tinnitus. Since the cardiovascular system: often - orthostatic hypotension; infrequently - fainting, pronounced decrease in blood pressure, palpitations, tachycardia, chest pain. On the part of the respiratory system: often - cough; infrequently - shortness of breath. On the part of the digestive system: often - nausea; infrequently - diarrhea, vomiting, dyspepsia, abdominal pain, flatulence, constipation, dry mouth; rarely - cholestatic jaundice, fulminant necrosis. Allergic reactions: Infrequently - Stevens-Johnson syndrome; rarely, angioedema; very rarely - intestinal angioedema. Dermatological reactions: infrequently - skin rash, itching, increased sweating, skin necrosis, alopecia. From the genitourinary system: infrequently - renal dysfunction, acute renal failure. Reproductive system: infrequently - impotence, decreased libido. On the part of the musculoskeletal system: often - muscle spasms; infrequently - arthralgia. From the laboratory parameters: rarely - hyperglycemia, hyperuricemia, hypokalemia, hyperkalemia, hyponatremia, increased concentration of urea and creatinine in the blood serum, increased activity of hepatic transaminases and bilirubin. Others: a symptom complex has been described, which may include fever, myalgia and arthralgia, serositis, vasculitis, increased ESR, leukocytosis and eosinophilia, skin rash, positive test for antinuclear antibodies.
Overdose
Symptoms: increased diuresis, marked reduction in blood pressure with bradycardia or other heart rhythm disorders, convulsions, impairment of consciousness (including coma), acute renal failure, violation of CShR and water-electrolyte balance of blood. Treatment: the patient is transferred to a horizontal position with raised legs. In mild cases, gastric lavage and ingestion of activated carbon are shown, in more serious cases - measures aimed at stabilizing blood pressure - in / in the introduction of plasma substitutes, infusion of 0.9% sodium chloride solution. The patient needs to control the level of blood pressure, heart rate, respiratory rate, serum concentration of urea, creatinine, electrolytes and diuresis, if necessary in / in the introduction of angiotensin II, hemodialysis (enalaprilat excretion rate - 62 ml / min).
Interaction with other drugs
The use of potassium supplements, potassium-sparing agents or preparations containing potassium, salt substitutes, especially in patients with renal insufficiency, can lead to a significant increase in serum potassium. The loss of potassium during the administration of thiazide diuretics, as a rule, is reduced by the action of enalapril. The content of potassium in the blood serum usually remains within the normal range. When used simultaneously with lithium preparations, lithium is slowed down (increased cardiotoxic and neurotoxic effect of lithium). Thiazide diuretics can enhance the effect of tubocurarine chloride. to orthostatic hypotension. Consistent with enalapril use of beta-blockers, alpha-blockers, ganglioblokiruyuschih with food, methyldopa or slow calcium channel blockers may further reduce blood pressure. Simultaneous use of allopurinol, cytotoxic drugs and immunosuppressants with ACE inhibitors may increase the risk of leukopenia. increase the risk of hyperkalemia. Simultaneous use of NSAIDs (including selective COX-2 inhibitors) may weaken the antihypertensive effect of ACE ghibitory. NSAIDs and ACE inhibitors have an additive effect on the increase in serum potassium, which can lead to a deterioration in renal function, especially in patients with impaired renal function. This effect is reversible. NSAIDs can reduce the diuretic and antihypertensive effects of diuretics. Antacids can reduce the bioavailability of aphphphidia. Epidemiological studies suggest that the simultaneous use of ACE inhibitors and hypoglycemic cf. Food may cause hypoglycemia.More often, hypoglycemia develops in the first weeks of therapy in patients with impaired renal function. Long-term and controlled clinical studies of enalapril do not confirm these data and do not limit the use of enalapril in patients with diabetes mellitus. However, such patients should be under regular medical supervision. The use of hypoglycemic agents for ingestion and insulin with thiazide diuretics may require correction of their doses. Taking Kolestiramine or Colestipol once a day reduces the absorption of hydrochlorothiazide in the gastrointestinal tract by 85% and 43%, respectively. When using simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate) in / c, a symptom complex is described, including facial flushing, nausea, vomiting, and arterial hypotension.
special instructions
Hypotension with all clinical consequences can be observed after the first dose of Enap-N pills in patients with severe heart failure and hyponatremia, severe renal failure, hypertension or left ventricular dysfunction and, in particular, in patients who are in a state of gilovolemia, as a result of therapy diuretics, salt-free diets, diarrhea, vomiting, or hemodialysis. In the event of arterial hypotension, it is necessary to lay the patient on his back with a low headboard and The need to adjust the volume of the BCC by infusion of 0.9% sodium chloride solution. Hypotension that occurred after taking the first dose is not a contraindication for further treatment. Patients with coronary artery disease, severe cerebrovascular disease, aortic stenosis or idiopathic hypertrophic obstructive subaortic stenosis, which prevents the outflow of blood from the left ventricle, severe atherosclerosis, and caudal obstruction, must be observed. as a result of the risk of hypotension and deterioration of the blood supply to the heart, brain, and kidneys. th control serum electrolytes during treatment to detect possible imbalance, and the timely adoption of necessary measures. Determination of serum electrolyte concentration is mandatory for patients with prolonged diarrhea, vomiting. In patients taking the drug Enap-N,it is necessary to identify signs of impaired water and electrolyte balance, such as dry mouth, thirst, weakness, drowsiness, irritability, myalgia and cramps (mainly calf muscles), decreased blood pressure, tachycardia, oliguria, and gastrointestinal disturbances (nausea, vomiting) .The preparation of Enap-N in patients with renal insufficiency (CK 30-75 ml / min) should be used only after preliminary titration of the doses of enalapril and hydrochlorothiazide separately, according to the doses in the combined preparation Enap-N. Preparat Enap-N is necessary It should be used with caution in patients with liver failure or progressive liver disease, as hydrochlorothiazide can cause hepatic coma even with minimal disruption of water and electrolyte balance. It was reported on several cases of acute liver failure with cholestatic jaundice, fulminant necrosis of the liver and fatal outcome (rarely) during treatment with ACE inhibitors. If jaundice occurs and liver transaminases increase, Enap-N treatment should be stopped immediately, patients should be monitored. Caution is necessary in all patients receiving treatment with hypoglycemic oral or insulin, as hydrochlorothiazide can weaken and enalapril strengthen them action. Thiazide diuretics can reduce calcium excretion by the kidneys and cause a slight and transient increase in serum calcium. Severe hypercalcaemia may be a sign of hidden hyperparathyroidism. Thiazide diuretics need to be canceled before conducting a study of the function of the parathyroid glands. Against the background of treatment with thiazide diuretics, serum cholesterol and triglyceride concentrations may increase. Some patients may increase their hyperuricemia and / or aggravate the course of gout with thiazide diuretics. However, enalapril increases the excretion of uric acid by the kidneys, thereby counteracting the hyperuricemic effect of hydrochlorothiazide. In the event of angioedema of the face, it is usually enough to cancel the therapy and prescribe antihistamines to the patient.In case of angioedema of the tongue, pharynx or larynx, which can lead to obstruction of the respiratory tract, it is necessary to immediately administer epinephrine (0.3-0.5 ml of epinephrine (adrenaline) solution in the ratio 1: 1000) and maintain the airway patency (intubation or tracheostomy) . Among the patients of the Negroid race, receiving therapy with an ACE inhibitor, the incidence of angioedema is higher than among patients of a different race. Patients with a history of angioedema, not associated with inhibitors ACE, have an increased risk of developing angioedema when taking any ACE inhibitor. In patients taking thiazide diuretics, hypersensitivity reactions can develop with or without allergic reactions. It reported worsening of systemic lupus volchanki.Vsledstvie increased risk of anaphylactic reactions should not be administered the drug Enap-H patients on hemodialysis using vysokoprotochnyh polyacrylonitrile membranes (AN 69) undergoing apheresis LDL with dextran sulfate and immediately prior to the procedure desensitization or wasp bee venom. Before surgery (including dentistry), an anesthesiologist should be warned about the use of an inhibitor moat APF.Vo time of surgery or general anesthesia using a means causing hypotension, ACE inhibitors can block the formation of angiotensin II in response to compensatory renin release. If this develops a pronounced decrease in blood pressure, explained by a similar mechanism, it can be adjusted by increasing the BCC. When using ACE inhibitors, cough was noted. The cough is dry, long-lasting, which disappears after stopping the use of ACE inhibitors. In the differential diagnosis of cough, it is necessary to take into account cough caused by the use of ACE inhibitors. Influence on the ability to drive vehicles and control mechanisms At the beginning of treatment with Enap-N, a pronounced decrease in blood pressure, dizziness and drowsiness can occur, which can decrease the ability to drive vehicles, engaging in other potentially hazardous activities that require increased concentration of attention and quickness of psychomotor reactions.Therefore, at the beginning of treatment, it is not recommended to drive vehicles or engage in other potentially dangerous activities that require increased concentration and psychomotor speed.