Nebilet Plus Nebivolol and thiazides tablets 5mg/12.5 №28

Nebilet Plus Nebivolol and thiazides tablets 5mg/12.5 №28

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Composition active ingredients: nebivolol, hydrochlorothiazide; 1 coated tablet contains nebivolol (in the form of nebivolol hydrochloride) 5 mg and hydrochlorothiazide 12.5 mg Auxiliary substances: Polysorbate 80, gipromelloza, lactose, corn starch, sodium croscarmellose, microcrystalline cellulose, silicon colloidal dioxide, magnesium stearate shell: gipromelloza, microcrystalline cellulose, stearate macrogol, titanium dioxide (E 171), Carmine acid (e 120). Dosage form Tablets, film-coated. Basic physico-chemical properties: almost pink, round, a little biconvex tablets covered with a film shell, embossed "5/12.5" on one side and the risk on the other. Risk to separation is only intended to break the tablet in order to facilitate swallowing, not to divide the tablet into equal parts. Pharmacological group Selective blockers of beta-adrenoreceptors with thiazide diuretics. Code ATX C07B B12. Pharmacological properties Pharmacological. Nebilet Plus 5/12.5 is a combination of nebivolol, a selective antagonist of beta-receptors, and hydrochlorothiazide, a thiazide diuretic. The combination of these ingredients has an additive antihypertensive effect and reduces blood pressure to a greater extent than the individual components. Nebivolol is a racemate consisting of two enantiomers: SRRR-nebivolol (d-nebivolol) and RSSS-nebivolol (L-nebivolol). It combines two pharmacological properties: thanks to D-enantiomer, nebivolol is a competitive and selective blocker of ? 1-adrenoreceptors; thanks to L-enantiomer, it has mild vasodilating properties due to metabolic interaction with L-arginine/nitrogen oxide (NO). With a single and repeated use of nebivolol decreases heart rate at rest and under stress as in patients with normal blood pressure, and in patients with hypertension. Antihypertensive effect in long-term treatment is maintained. In therapeutic doses, ?-adrenergic antagonism is not observed. During short-term and long-term treatment of nebivolol in patients with hypertension decreases systemic vascular resistance. Despite the decrease in heart rate, reducing cardiac output at rest and under load is limited due to increased shock volume. The clinical significance of this hemodynamic difference compared to other ?-adrenoreceptor blockers has not yet been sufficiently studied. In patients with arterial hypertension, nebivolol increases vascular response to acetylcholine mediated by nitrogen monoxide in patients with endothelial dysfunction, this reaction is reduced. In experiments of IP vitro and in vivo on animals it is shown that nebivolola is not inherent in sympathomimetic activity. In experiments of IP vitro and in vivo on animals it is shown that at pharmacological doses nebivolol has no membrane-stabilizing activity. In healthy volunteers, nebivolol has no significant effect on the ability to tolerate maximum physical activity or endurance. Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equal amounts. The diuretic effect of hydrochlorothiazide reduces plasma volume, increases plasma renin activity and aldosterone secretion, followed by an increase in potassium and bicarbonate losses in the urine and a decrease in serum potassium levels. When applying hydrochlorothiazide diuresis occurs after about 2:00, and peak effect is achieved after about 4: 00 after taking the drug, whereas the action lasts for about 6-12 hours. Pharmacokinetics. Co-administration of nebivolol and hydrochlorothiazide does not affect the bioavailability of each active substance. The combination tablet is bioequivalent to the joint application of the individual components. nebivolol Suctions. After taking, there is a rapid absorption of both enantiomers of nebivolol. The absorption of nebivolol is not affected by food, so it can be taken with or without food. Bioavailability of orally administered nebivolol is on average 12% in patients with rapid metabolism and is almost complete in patients with slow metabolism. In the equilibrium state and at the same dose level, the maximum concentration in plasma of unchanged nebivolol is approximately 23 times higher in patients with slow metabolism than in patients with rapid metabolism. If we take into account the unchanged drug and active metabolites, the difference in peak plasma concentrations is 1.3-1.4 times. Based on the difference in metabolic rate, the dosage of the drug should be set depending on the individual needs of the patient; patients with slow metabolism require lower doses. Concentration in plasma, which ranges from 1 to 30 mg of nebivolol proportional to the dose. A person's age on the pharmacokinetics of nebivolol is not affected. Distribution. In the plasma of both enantiomer of nebivolol are associated predominantly with albumin. Protein binding is 98.1% for SRRR-nebivolol and 97.9% for rsss-nebivolol. Metabolism. Nebivolol is metabolized to a large extent, partly - to active hydroxymetabolites. Nebivolol is metabolized by alicyclic and aromatic hydroxylation, N-dealkylation and glucuronidation; in addition, glucuronides of hydroxymetabolites are formed. The metabolism of nebivolol by aromatic hydroxylation depends on the genetic oxidative polymorphism CYP2D6. Conclusion. In patients with rapid metabolism, the half-life of the enantiomers of nebivolol is approximately 10:00. In patients with slow metabolism, it is 3-5 times longer. In patients with a rapid metabolism level in the plasma of the RSSS-enantiomer are slightly higher, than for the SRRR-enantiomer. In patients with slow metabolism, this difference increases. In patients with rapid metabolism, the half-life of hydroxymetabolites of both enantiomers is on average 24 hours, and in patients with slow metabolism - is prolonged by almost half. Equilibrium levels in plasma in patients with rapid metabolism are achieved in 24 hours for nebivolol and in a few days - for hydroxymetabolites. A week after administration, 38% of the dose is excreted in the urine and 48% - with feces. The excretion of unchanged nebivolol in the urine is less than 0.5% of the dose. hydrochlorothiazide Suctions. Hydrochlorothiazide is well absorbed after oral administration (from 65 to 75%). Plasma concentrations are linearly dependent on the administered dose. Absorption of hydrochlorothiazide depends on the time of passage through the intestine: increases when the time of intestinal transit is slow, for example, when used with food. When tracking plasma levels for at least 24 hours, the half-life period ranged from 5.6 to 14.8 hours, and the maximum plasma concentration was achieved within 1-5 hours after taking the drug. Distribution. Hydrochlorothiazide binds to the protein in plasma by 68%, and the actual volume of distribution is 0.83-of 1.14 l/kg. Hydrochlorothiazide passes through the placenta but does not cross the blood-brain barrier. Metabolism. Hydrochlorothiazide metabolism is very low. Almost all hydrochlorothiazide is excreted in the urine unchanged. Conclusion. Hydrochlorothiazide is excreted mainly by the kidneys. In 3-6 hours after ingestion more than 95% of hydrochlorothiazide found in the urine in unchanged form. In patients with renal insufficiency hydrochlorothiazide concentration increased, and the half-life period increases. Indications The treatment of hypertension. Contraindications Hypersensitivity to active ingredients or other components of the drug hypersensitivity to other substances-sulfonamide derivatives (since hydrochlorothiazide is a sulfonamide derivative) hepatic insufficiency or impaired liver function anuria, severe renal failure (creatinine clearance less than 30 ml/min); acute heart failure, cardiogenic shock or episodes of decompensated heart failure requiring the introduction of drugs with a positive inotropic effect the syndrome sick sinus, including sinoatrial block blockade II and III extent (without implanted pacemaker) bradycardia (before treatment heart rate less than 60 beats/min); arterial hypotension (systolic blood PRESSURE less than 90 mm Hg. art.) severe violations of peripheral blood circulation history of bronchospasm and bronchial asthma untreated pheochromocytoma; metabolic acidosis, resistant hypokalemia, hypercalcemia, hyponatremia and symptomatic hyperuricemia. Special security measures nebivolol The following warnings apply in General to beta blockers. Anesthesia. Continuation of beta blockade reduces the risk of arrhythmia during induction of anesthesia and intubation. If the pre-op beta-blockade is necessary to stop using beta-blocker should cancel at least 24 hours before. Care should be taken for some anesthetics that cause myocardial depression. The patient can be protected from vaginal reactions by the introduction of atropine. Cardio-vascular disorders. In General, beta-blockers should not be used in patients with untreated congestive heart failure, unless their condition has been stabilized. Patients with cardiac ischemia treatment with beta-blockers should be stopped gradually, that is, within 1-2 weeks. If necessary, at the same time you need to start replacement therapy to prevent exacerbation of angina pectoris. Antagonists of beta-adrenergic receptors can cause bradycardia if the heart rate drops below 50-55 BPM at rest and/or the patient's present symptoms indicative of bradycardia, the dosage should be reduced. Antagonists of beta-adrenergic receptors should be used with caution patients with peripheral circulatory disorders (Raynaud's disease or syndrome, intermittent claudication), because it can cause aggravation of these disorders; patients with AV-blockade of I degree for the negative impact of beta-blockers at the time of AV conduction patients with prinzmetals angina due to spasm of the coronary arteries, which is caused by the activation of alpha receptors on the background of blockade of beta-receptors: beta-blockers can increase the number and duration of angina attacks. In General, a combination of nebivolol with calcium channel blockers such as verapamil and diltiazem with antiarrhythmic drugs of class I and antihypertensive agents of Central action is not recommended. Metabolism/endocrine disorders . Nebivolol does not affect glucose levels in diabetics. However, caution is needed for patients with diabetes because nebivolol can mask symptoms of hypoglycemia (tachycardia, rapid heartbeat). Beta adrenoreceptors can mask the symptoms of tachycardia in hyperthyroidism. Sudden withdrawal may exacerbate the symptoms. Respiratory disorders. Patients with chronic obstructive pulmonary disorders beta-adrenoreceptor antagonists should be administered with caution, as obstruction of the respiratory tract may worsen. Other. Patients with a history of psoriasis should use beta-adrenoreceptor antagonists only after a thorough evaluation of the feasibility. Antagonists of beta-adrenoreceptors may increase sensitivity to allergens and the severity of anaphylactic reactions. hydrochlorothiazide Renal impairment. The maximum effect from the use of thiazide diuretics can be expected only in the absence of renal dysfunction. In patients with renal dysfunction, thiazides can increase nitrogen. Patients with impaired renal function may develop cumulative effects of the active substance. With the obvious progression of renal dysfunction, manifested in the growth of non-protein nitrogen, a thorough reassessment of therapy for the abolition of diuretics is necessary. Metabolism and endocrine effects. Tiazidami therapy may disturb glucose tolerance. It may be necessary to correct the dose of insulin or oral antidiabetic drugs. During therapy with thiazides, latent diabetes mellitus may occur. With the use of therapy to thiazide diuretics is associated with increased levels of cholesterol and triglycerides. Thiazide therapy in some patients may be accelerated by hyperuricemia and/or gout. Violation of the balance of electrolytes. As for any patient, receives therapy with diuretics, it should be from the appropriate periodicity to determine serum electrolytes. Thiazides, including hydrochlorothiazide, can cause imbalance of fluid or electrolytes (hypokalemia, hyponatremia and hypochloremic alkalosis). Signs of fluid or electrolyte imbalance are dry mouth, thirst, weakness, lethargy, dizziness, excitement, pain or muscle cramps, muscle fatigue, arterial hypotension, oliguria, tachycardia, and gastrointestinal disorders such as nausea or vomiting . The higher risk of hypokalemia in patients with cirrhosis, patients with rapid diuresis, patients with inadequate oral intake of electrolytes and in patients receiving concurrent therapy with corticosteroids or ACTH. Particularly high risk of hypokalemia exists in patients with Qt prolongation syndrome, congenital or iatrogenic. Hypokalemia increases cardiotoxicity of digitalis glycosides and the risk of cardiac arrhythmia. For patients at risk of hypokalemia, frequent monitoring of plasma potassium is indicated, starting with the week after the start of therapy. In hot weather in patients prone to edema, can cause mild hyponatremia. Chlorine deficiency is usually weak and does not require treatment. Thiazides can reduce the excretion of calcium in the urine and can cause periodic and mild increase in serum calcium in the absence of established calcium metabolism disorders. Significant hypercalcemia can be a manifestation of latent hyperparathyroidism. Before testing for parathyroid function, use of thiazides should be discontinued. It is shown that thiazides increase the excretion of magnesium in the urine, which can lead to hypomagnesemia. Lupus erythematosus. It was reported that the use of thiazides occurs exacerbation or activation of systemic lupus erythematosus. Anti-doping test . Hydrochlorothiazide contained in this preparation can lead to a positive doping test result. More. Patients with or without a history of allergies or bronchial asthma may experience sensitivity reactions. Occasionally for thiazide diuretics reported photosensitization. If photosensitization occurs during treatment, it is recommended to discontinue therapy. If it is considered necessary to resume treatment, it is recommended to protect the appropriate surface from sunlight or artificial UV light. Iodine is associated with the protein. Thiazides can reduce the level of protein-bound iodine without signs of thyroid disorders. The combination of nebivolol/hydrochlorothiazide In addition to warnings regarding monocomponents, the following statement applies directly to the drug Nebilet Plus. Galactose intolerance, the Lapp lactase deficiency, malabsorption syndrome of glucose-galactose. This medicinal product contains lactose. Patients with rare congenital problems of galactose intolerance, the Lapp lactase deficit or malabsorption syndrome of glucose-galactose should not use this medication. Interaction with other medicinal products and other forms of interaction pharmacodynamic hamodia nebivolol The following interactions relate to the overall antagonists of beta-adrenergic receptors. Combinations are not recommended Antiarrhythmic drugs of class I (guanidin, hydroquinidine, cibenzoline, flecainide, disopyramide, lidocaine, meksiletin, propafenon). May increase effect at the time of AV-conduction and increase the negative inotropic effect. Calcium channel blockers of the type verapamil/diltiazem. Negative influence on contractility and AV-conduction. The administration of verapamil to patients treated with ?-blockers can lead to severe hypotension and AV blockade. Antihypertensives Central action (clonidine, guanfacine, moxonidine, methyldopa, rilmenidine). The simultaneous use of antihypertensive drugs of Central action may worsen heart failure due to the decrease in the Central sympathetic tonus (reduction of heart rate and cardiac output, vasodilation). Sudden cancellation, especially before the termination of beta-blockers can increase the risk of "ricochet" hypertension. Combinations that should be used with caution Antiarrhythmic drugs class III (amiodarone). Can potenzirovti effect at the time of AV conduction. Anesthetics are volatile halogen. Concomitant use of beta-blockers and anaesthetics may attenuate reflex tachycardia and increase the risk of hypotension. As a General rule, should be avoided sudden withdrawal of treatment with beta blockers. It is necessary to inform the anesthesiologist if the patient receives Nebilet Plus. Insulin and oral antidiabetic drugs . Although nebivolol does not affect glucose level, concomitant use may mask certain symptoms of hypoglycaemia (frequent palpitations, tachycardia). Combinations to be taken into account The digitalis glycosides. Concurrent use may increase AV conduction time. In clinical trials of nebivolol not found any manifestations of interaction. Nebivolol does not affect the pharmacokinetics of digoxin. Calcium antagonists of dihydropyridine type (amlodipine, felodipine, lacidipine, nifedipine, nicardipine, nimodipine, nitrendipine). Simultaneous use can increase the risk of arterial hypotension; it is impossible to exclude the increased risk of further deterioration of the pumping function of the ventricles in patients with heart failure. Antipsychotic agents, antidepressants (tricyclic agents, barbiturates and phenothiazines). Simultaneous use can increase the hypotensive effect of beta-blockers (additive effect). Nonsteroidal anti-inflammatory drugs (NSAIDs). Not affect the effect of lowering nebivolol blood pressure. Sympathomimetic agents. Simultaneous use can counteract the effect of beta-blockers. Beta-adrenergic agents can lead to non-resistant alpha-adrenergic activity of sympathomimetics agents with both alpha-and beta-adrenoreceptor effects (risk of hypertension, severe bradycardia and heart block). hydrochlorothiazide Potential interactions related to hydrochlorothiazide. Simultaneous use is not recommended Lithium. Thiazides reduce renal clearance, respectively, while the use of hydrochlorothiazide risk of lithium toxicity may increase. Therefore, the use of the drug Nebilet Plus in combination with lithium is not recommended. If the use of this combination is considered necessary, it is recommended to carefully monitor the level of lithium in the blood serum. Medical preparations affecting the level of potassium. The proper hydrochlorothiazide effect of reducing the potassium content may increase with the simultaneous use of other medical drugs, which are associated with the loss of potassium and hypokalemia (for example, others with the simultaneous appointment of diuretics, laxatives, corticosteroids, ACTH, amphotericin, carbenoxolone, sodium penicillin G or salicylic acid derivatives) . Therefore, such joint application is not recommended. Joint application, which requires caution Nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs (e.g. acetylsalicylic acid (> 3 g/day), COX-2 inhibitors and nonselective NSAIDs) may reduce the antihypertensive effect of thiazide diuretics. Calcium salt. Thiazide diuretics may increase serum calcium levels due to reduced excretion. If you want to use calcium supplements, should monitor the calcium level in the serum and to adjust them accordingly. The digitalis glycosides. Hypokalemia or hypomagnesemia caused by thiazides can contribute to the appearance of cardiac arrhythmia caused by digitalis. Medicals preparations, which are influenced by changes in the content of potassium serum. Periodic monitoring of serum potassium and ECG is recommended when Nebilet Plus 5/12.5 is used with medicines affected by changes in serum potassium content (e.g. digitalis glycosides and antiarrhythmic drugs) , and with medical drugs causing torsades de pointes (ventricular tachycardia) (including some antiarrhythmic drugs), since hypokalemia is a favorable factor for torsades de pointes (ventricular tachycardia): antiarrhythmic drugs Ia class (e.g. quinidin, hydroquinidine, disopyramide) class III antiarrhythmic drugs (e.g. amiodarone, sotalol, dofetilide, ibutilide) some antipsychotic agents (e.g. thioridazine, chlorpromazine, levomepromazine, triptorelin, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pymod, haloperidol, droperidol) other (e.g. bepridil, cisapride, diphemanil, erythromycin, halofantrine, mizolastine, pentamidine, sparfloxacin, terfenadine, vincamine has intravenously). The non-depolarizing skeletal muscle relaxants ( e.g. tubocurarine et al). Hydrochlorothiazide can enhance the effect of non-depolarizing relaxants of skeletal muscles. Antidiabetic drugs (oral drugs and insulin). Treatment with thiazides can affect glucose tolerance. You may need to adjust the dose of antidiabetic drugs. Metformin. Metformin should be used with caution because of the risk of lactic acidosis due to possible renal damage that is associated with the use of hydrochlorothiazide. Beta-blockers and diazoxide. Thiazides may potentiate the hyperglycemic effect of beta-blockers, nebivolol is different from, and diazoxide. Pressor amines (e.g. noradrenaline). The effect of Pressor amines may be decreased. A medicine used to treat gout (probenecid, sulfinpirazon, allopurinol). It may be necessary to correct the dosage of medications that reduce uric acid levels, since hydrochlorothiazide may increase the level of uric acid in the blood serum. It may be necessary to increase the dose of probenecid or sulfinpirazon. The combined use of thiazide may increase hypersensitivity reactions to allopurinol. Amantadine. Thiazides may increase the risk of side effects caused by amantadine. Salicylates. In the case of high doses of salicylates hydrochlorothiazide may increase their toxic effects on the Central nervous system. Cyclosporine. Co-treatment with cyclosporine can increase the risk of hyperuricemia and complications such as gout. Iodine-containing contrast agents. In the case of dehydration caused by diuretic, there is an increased risk of acute renal failure, especially at high doses of iodine preparations. Before use, it is necessary to rehydrate the patient. Potential interactions due to both nebivolol and hydrochlorothiazide Joint application, which must be taken into account Other antihypertensive drugs. In a joint application with other antihypertensive agents may occur additive hypotensive effect or potentiation of their action. Antipsychotics, tricyclic antidepressants, barbiturates, drugs and alcohol . The combined use of the drug Nebilet Plus 5/12,5 with these drugs may increase the hypotensive action and/or lead to postural hypotension. Pharmacokinetic interaction. nebivolol As nebivolol metabolism involves CYP2D6 isoenzyme, concomitant use with drugs that inhibit this enzyme, especially paroxetine, fluoxetine, thioridazine and quinidine may lead to increased levels of nebivolol in plasma at an increased risk of excessive bradycardia and adverse effects. Simultaneous use of cimetidine increases levels of nebivolol in plasma without changing the clinical effect. The combined use of ranitidine does not affect the pharmacokinetics of nebivolol. If Nebilet Plus 5/12.5 is taken with food, and antacid - between meals, you can appoint both drugs. The combination of nebivolol with nicardipine slightly increases the levels of both drugs in plasma without changing the clinical effect. The combined use of alcohol, furosemide or hydrochlorothiazide does not affect the pharmacokinetics of nebivolol. Nebivolol does not affect the pharmacokinetics and pharmacodynamics of warfarin. hydrochlorothiazide The absorption of hydrochlorothiazide is disturbed in the presence of anionic ion exchange resins (e.g. colestiramine resin and colestipol). The cytotoxic agents. When combined use of hydrochlorothiazide and cytotoxic agents (eg cyclophosphamide, fluorouracil, methotrexate) should be expected to increase bone marrow toxicity (in particular the development of neutropenia). Application features Use during pregnancy or breast-feeding. Application during pregnancy There is a lack of sufficient data on the use of the drug Nebilet Plus 5/12.5 pregnant women. Studies on animals of two separate components are insufficient to establish the effect of a combination of nebivolol and hydrochlorothiazide on reproductive function. nebivolol There is insufficient evidence of its use by pregnant women to identify the potential risk of nebivolol. However, nebivolol has such pharmacological effects that may have a dangerous effect on pregnancy and/or fetus/newborn. In General, beta-blockers reduce placental perfusion, which is associated with delayed growth, intrauterine death, miscarriage or premature birth. The fetus/newborn may have side effects (e.g. hypoglycemia and bradycardia). If the treatment of beta-blockers is necessary, it is advisable to use beta1-selective blockers adrenoretseptorov. Nebivolol should not be used by pregnant women without the need. If treatment nebivolol deemed necessary, should be monitored uteroplacental blood flow and fetal growth. In case of threatening effects on the course of pregnancy or fetus, alternative treatment should be used. The newborn should be closely monitored. Symptoms of hypoglycemia and bradycardia in General should be expected in the first 3 days. hydrochlorothiazide Experience in the use of hydrochlorothiazide in pregnant women is limited, especially for use in the first trimester. Animal research is insufficient. Hydrochlorothiazide passes through the placenta. Based on the mechanism of pharmacological action, its use in the second and third trimesters can worsen Feto-placental perfusion and cause the fetus and newborn effects such as jaundice, violation of the balance of electrolytes and thrombocytopenia. Hydrochlorothiazide should not be used in gestational edema, gestational hypertension or late toxicosis pregnant due to the risk of reducing plasma and placental hypoperfusion without beneficial effects on the course of the disease. Hydrochlorothiazide should not be used in essential hypertension in pregnant women, except in rare situations where it is impossible to apply another treatment. Application for lactation Unknown, nebivolol is excreted in breast milk. Studies in animals showed that nebivolol is excreted in breast milk. Most beta blockers, especially lipophilic compounds such as nebivolol, penetrate into breast milk, although in varying degrees. Hydrochlorothiazide is excreted in breast milk in small quantities. High doses of thiazides, causing intense diuresis can inhibit milk production. The use of the drug Nebilet Plus 5/12.5 breast-feeding is not recommended. If Nebilet Plus 5/12.5 is used by women who breastfeed, the dose should be the lowest. The ability to influence the reaction rate when driving motor transport or operating other mechanisms. Research of influence on ability to operate motor transport and to work with other technical means wasn't carried out. However, when driving vehicles and working with technical means, it should be noted that antihypertensive therapy can sometimes cause dizziness and fatigue. Method of application and doses Adults. Nebilet Plus 5/12.5 is intended for patients whose blood pressure is adequately controlled by the combined use of 5 mg of nebivolol and 12.5 mg of hydrochlorothiazide. The dosage is one tablet (5 mg/12.5 mg) per day, preferably at the same time. The drug can be taken with meals. Patients with renal insufficiency. Nebilet Plus 5/12.5 should not be used in patients with severe renal insufficiency. Patients with hepatic insufficiency. The experience of using the drug in such patients is limited, so the use for such patients is contraindicated. Elderly patients. - For insufficient experience of the drug in patients aged 75 years, its use requires caution and careful monitoring. Children. Studies on the use of the drug in children and adolescents were not carried out, so for this age group the drug is not recommended. Overdose Symptoms. There is no evidence of overdose of nebivolol. Symptoms of overdose beta blockers: bradycardia, hypotension, bronchospasm and acute heart failure. With an overdose of hydrochlorothiazide is associated electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration due to excessive diuresis. The most common symptoms of an overdose of hydrochlorothiazide are nausea and drowsiness. Hypokalemia may lead to muscle spasms and/or cardiac arrhythmia associated with the simultaneous use of digitalis glycosides or associated anti-arrhythmic drugs. Treatment. In case of overdose or hypersensitivity, the patient should conduct strict supervision in intensive care. It is necessary to control the level of glucose. Serum electrolytes and creatinine should be monitored regularly. Suction residues of the drug, still remain in the gastrointestinal tract, can be prevented by washing the stomach and the use of activated charcoal and laxative. You may need artificial respiration. Massive bradycardia or vagal reactions should be treated with atropine or methylatropine. Arterial hypotension and shock should be treated with the introduction of plasma/plasma substitutes, and if necessary - catecholamines. It is necessary to correct violations of electrolyte balance. The effects of beta-blockers can be counteracted by the slow introduction of isoprenaline hydrochloride, starting with a dose of 5 µg/min, or dobutamine, starting with a dose of 2.5 µg/min, to achieve the desired effect. In severe cases, difficult to treat, isoprenaline should be combined with dopamine. If this does not give the desired effect, the introduction of 50-100 µg/kg glucagon should be considered. If necessary, the injection should be repeated within an hour, and then (if necessary) to conduct infusion of 70 µg/kg/h glucagon. In extremely severe cases of bradycardia, it is resistant to treatment, you can install an artificial rhythm driver. Adverse reaction Adverse reactions are given separately for each active substance. nebivolol Adverse reactions after monotherapy with nebivolol, which were reported, in most cases, were from mild to moderate severity and are shown in the table below and classified by organ systems and frequency of occurrence. system organochlo (31/100 to <1/10) infrequently (31/1000 to ? 1/100) Very rare (?1/10000)frequency unknown From the immune system Angioedema, hypersensitivity Psychiatric disorders nightmares; depression From the nervous systemically pain, dizziness, paraesthesia syncope From the organs of vision visual impairment Heart problems Bradycardia, heart failure, slow AV conduction/AV-block From the vessels hypotension, increased intermittent claudication The respiratory patellogastropoda From the digestive tract constipation, nausea, diarrhea, flatulence, vomiting From the skin Itching, erythematous skin siphonostegia psoriasis Impotence on the part of the genitals Characterposition disorders common fatigue, oedema In addition, it was reported such adverse reactions caused by some ?-adrenergic receptors: hallucinations, psycho

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