It has antihypertensive, antianginal and antiarrhythmic action. Reduces high blood pressure (BP) at rest, exertion and stress. Competitive and selectively blocks the synaptic testosterone enanthate vs cypionate and post-synaptic beta-1-adrenergic receptors. making them inaccessible to catecholamines modulate release factor endotedialnogo vasodilator nitrogen oxide.
The antihypertensive effect develops in 2-5 days of treatment, stable effect observed after 1 month. This effect is maintained during long-term treatment. Antihypertensive action also caused a decrease in activity rsnii aldostsronovoy-angiotensin system (not directly correlated with the change in renin activity in blood plasma).
The use of Nebivolol improves system and intracardiac hemodynamics. Nebivolol slows the heart rate (HR) and blood pressure at rest and during exercise, reduces end-diastolic left ventricular pressure, reduces the total peripheral vascular resistance, improves diastolic cardiac function (reduced filling pressure) increases the ejection fraction.
By reducing myocardial oxygen demand (slowing of heart rate. Reduction in preload and afterload) reduces the number and severity of attacks of angina and improve exercise tolerance.
Antiarrhythmic effect is due to the suppression of automaticity of the heart (including in the pathological focus) and slowing of atrioventricular (AV) conduction.
Gidrohlorogiazid – thiazide diuretics. It reduces the reabsorption natriya ions in the cortical segment of the loop of Henle, without affecting its portion extending into the renal medulla. Blocks carbonic anhydrase in the proximal convoluted tubule. enhances renal excretion of potassium ions, phosphates and bicarbonates. Virtually no effect on acid-base status. It enhances the excretion testosterone enanthate vs cypionate of kidney machines ions: a delay in the body of calcium ions and inhibits the excretion of urate.
The diuretic effect develops in 1-2 hours, reaches a maximum after 4 hours, continues until 10-12 hours. The diuretic effect decreases with a decrease in glomerular filtration rate, and it stops at the value of less than 30 ml / min. (Volume of urine and reduces its concentration increases).
After oral administration of nebivolol is rapidly absorbed from the gastrointestinal tract. Food intake has no effect on the absorption, so nebivolol can irinimag regardless of the meal. Bioavailability is an average of 12% from the Nazis with “fast” metabolism, and is almost complete in patients with a “slow” metabolism. Efficacy nebivolol metabolism is independent of speed. Plasma Clearance in most patients (with “fast” metabolism) is achieved within 24 hours and to gidroksimetabolitov – after several days. Plasma concentrations of 1-30 mg / l dose proportional.
Communication with the plasma proteins (mainly albumin) for D-isbivolola is 98.1% and L-nebivolol 97.9%.
Nebivolol actively metabolized to form the active part gidroksimetabolitov. It is metabolized by acyclic and aromatic hydroxylation, N-dealkylation partial. Nebivolol metabolic rate by aromatic hydroxylation oxidative polymorphism genetically determined and depends on isozyme CYP2D6.
After the introduction of 38% (the amount of the unchanged active substance is less than 0.5%) of the dose excreted by the kidneys and 48% – in the intestine.
Patients with “fast” metabolic half-life value (T 1/2 ) enantiomers of nebivolol plasma averages 10 hours. In patients with the “slow” metabolism of these values are increased by 3-5 times. Patients with “fast” metabolism values of T 1/2 gidroksimetabolitov both enantiomers from plasma averages 24 hours, in patients with “slow” metabolism, these values were approximately 2 fold increase. Pharmacokinetics nebivolol does not affect the age and sex of patients.
If ingestion is rapidly absorbed, but incomplete. The time to reach maximum concentration in plasma is about 4 hours. Hydrochlorothiazide bioavailability of 60-80%. Communication to plasma proteins is 40%.
It penetrates through the placental barrier and is excreted in breast milk. Do not metabolized.
It reports the news, largely unaltered by glomerular filtration and active tubular secretion. The half-life of about 8h.
Arterial ginertenziya (patients who shook combination therapy).
- Hypersensitivity to Nebivolol or one of the components of the drug, as well as to other beta-blockers. hypersensitivity to hydrochlorothiazide or other sulfonamide derivatives;
- severe liver function;
- congestive heart failure;
- cardiogenic shock;
- Chronic heart failure decompensation (requires inotronnoy therapy);
- sick sinus syndrome fragile, including sinoatrial block;
- agrioventrikulyarnaya block II and III degree (without pacemaker);
- severe bronchial asthma and chronic disease obstruktivioy such (COPD);
- pheochromocytoma (without simultaneous application of alpha-adrenoblokayurov);
- metabolic acidosis;
- bradycardia (heart rate less than 60 bpm..);
- severe hypotension (systolic blood pressure less than 90 mm PT .st.);
- Serious disturbances of peripheral circulation ( “intermittent” claudication, Raynaud’s syndrome);
- age of 18 years (effectiveness and safety have been established);
- lactose intolerance, lactase deficiency or glucose-galactose malabsorption (product contains lactose);
- simultaneous reception floctafenine. sulpiride (it see Interactions with other drugs.);
- unmanageable diabetes;
- acute renal failure;
- Addison’s disease;
- anuria, chronic renal insufficiency (creatinine clearance (CC) of less than 30 ml / min);
- Refractory hypokalaemia, hyponatraemia, hypercalcaemia.
Pregnancy and lactation
In pregnancy, the drug is prescribed only under strict indications, where the benefits to the mother outweighs the risk to the fetus (in connection with the testosterone enanthate vs cypionate possible development of the newborn bradycardia, hypotension, hypoglycemia and respiratory paralysis).
must be interrupted for 48-72 hours before delivery. In cases where this is not possible, it is necessary to ensure strict monitoring of the newborn for 48-72 hours after delivery.
No data on the allocation of nebivolol in human milk. Therefore, the drug is not recommended for women during lactation. Veli nebivolol application during lactation is necessary, breast-feeding should be discontinued.
Hydrochlorothiazide crosses the placental barrier.
Do not use this drug in the first trimester of pregnancy. In the second and third trimesters of pregnancy, the drug can be administered only in case of urgent need when the benefit to the mother outweighs the potential risk to the fetus and / or the child.
There is a risk of fetal or neonatal jaundice, platelet persecution and other consequences.
Hydrochlorothiazide passes into breast milk; therefore, if the use of the drug is absolutely necessary, breast-feeding should be discontinued.
Dosing and Administration
Inside, it is desirable to take one and the same time, 1 time a day, regardless of meal times, with liquid squeezed enough liquid kolichestvo. At the beginning of therapy should take 1 tablet per day.
With insufficient expression of therapeutic effect after 2 weeks of dose can be increased up to 2 tablets.
The maximum daily dose is 2 tablets per day.
Patients with severe hepatic impairment and renal impairment (creatinine clearance less than 30 ml / min) use of the drug is not recommended (see. “Contraindications”).
The frequency of side effects is presented in the following grading: very often (10%), frequent (more than 1% and less than 10%), rare (more than 0.1% and less than 1%), rare (0.01% and more than 0 , 1%), very rare (less than 0.01%), including isolated reports.
From the nervous system:
Common: headache, dizziness, fatigue, weakness, paresthesias;
Uncommon: depression, vivid dreams, confusion, insomnia
Very rare: syncope, hallucinations, amnesia.
From the gastrointestinal tract:
Common: nausea, constipation, diarrhea
Uncommon: flatulence, dyspepsia, and vomiting.
Uncommon: bradycardia, heart failure, atrioventricular block, orthostatic giiotenziya, peripheral circulatory disorders (feeling of “cold” in the extremities, cyanosis), shortness of breath, heart rhythm disorders, Raynaud’s syndrome, peripheral edema, false angina, worsening trends chronic heart failure, marked reduction in blood pressure.
With the Skin:
Uncommon: rash erythematous character, itchy skin. flushing of the skin;
Very rare: aggravation of current psoriasis, alopecia;
in some cases: angioedema.
Uncommon: bronhosnazm (including the absence of lung diseases obegruktivnyh history), bronhosnazm in patients with bronchial asthma or airway obstruction in history.
Other: photodermatosis, rash, visual disturbances (dry eyes), sexual dysfunction.
Violation of water and electrolyte balance
hypokalemia, hypomagnesemia, hypercalcemia and alkalosis gipohloremichesky: dryness of the oral mucosa, thirst, irregular heart rhythm. lability of mood or psyche, cramps and muscle pain, nausea, vomiting. unusual tiredness or weakness. Gipohloremichesky alkalosis may cause hepatic encephalopathy or hepatic coma.
Hyponatremia: confusion, seizures, slow thought process. fatigue, irritability, convulsions, lethargy.
Metabolic effects: hyperglycemia, glycosuria, hyperuricemia with gout exacerbation.
Thiazide treatment can decrease glucose tolerance and flowing latent diabetes may manifest. At high doses may be increased lipid concentration in the blood serum.
On the part of the digestive tract:
cholecystitis, or pancreatitis, cholestatic jaundice, diarrhea, sialadenitis, constipation, anorexia.
arrhythmia, testosterone enanthate vs cypionate orthostatic hypotension. vasculitis.
From the nervous system:
dizziness, temporary blurred vision. headache, paresthesia.
From the side of hematopoiesis:
(very rare): leukopenia, agranulocytosis. thrombocytopenia, hemolytic anemia, aplastic anemia.
urticaria, purpura, necrotizing vasculitis, Stevens-Johnson syndrome, respiratory distress (including pneumonitis and non-cardiogenic pulmonary edema), photosensitivity, anaphylactic reactions up to shock.
decreased potency, renal dysfunction, nephritis interstinialny.
Symptoms: marked reduction of blood pressure, bradycardia. severe violation of intracardiac conduction, shock, asystole, respiratory arrest, bronchospasm, unconsciousness, convulsions, coma, nausea, vomiting, cyanosis, hypoglycaemia, ginerkaliemiya.
Treatment: gastric lavage, activated charcoal. In the case of a pronounced decrease in the AL must be given to a patient horizontal position with legs raised, if necessary, on / in a fluid and vasopressors.
If bradycardia is introduced into / in the 0.5-2 mg atropine, with no positive effect can be staged or transvenous intracardiac pacemaker.
When AV block (II-III cent.) recommended that intravenous administration of beta-agonists.
If their inefficiency should consider setting an artificial pacemaker. In heart failure, treatment is initiated with the introduction of cardiac glycosides and diuretics, with no effect expedient administration of dopamine, dobutamine or vasodilators. When bronchospasm injected beta-2-agonists.
In convulsions intravenous diazepam.
When ventricular arrhythmia lidocaine (antiarrhythmic agents should not be administered 1A class).
The most visible manifestation of an overdose of hydrochlorothiazide is acute loss of fluid and electrolytes, which is expressed in the following signs and symptoms: tachycardia, marked reduction in blood pressure, shock. weakness, confusion. dizziness and cramping of the calf muscles, paresthesia, disturbance of consciousness, fatigue, nausea, vomiting, thirst, polyuria, oliguria or anuria (due to hemoconcentration), hypokalemia, hyponatremia, hyposalemia, alkalosis, increased blood urea nitrogen (especially in patients renal failure).
Treatment: No specific antidote.
The induction of vomiting, gastric lavage, charcoal activated. In the case of significant decrease in blood pressure or shock should compensate for blood volume (CBV) and electrolytes (potassium, sodium).Necessary to control fluid and electrolyte balance (especially potassium content in blood serum) and nochek function.
Interaction with other drugs
Floctafenine in case of shock or hypotension induced by administration floctafenine, beta-blockers attenuate compensatory mechanisms of the cardiovascular system.
Sultopirid: increased risk of ventricular arrhythmias, especially type “pirouette”.
With simultaneous use of beta-blockers blockers “slow” calcium channels (BCCI) (verapamil and diltiazem) amplifies a negative effect on myocardial contractility and AV conduction. Contraindicated in / with the introduction of verapamil in patients receiving nebivolol. In an application with antihypertensive drugs, nitroglycerin or BCCI can rachvitsya severe hypotension (special caution is needed in combination with prazosin).
While the use of antiarrhythmic drugs increase the risk of bradycardia cardiodepressive action and in combination with any antiarrhythmic agent. Since amiodarone and also increases the risk of atrioventricular block. The risk of ventricular arrhythmia, called sotalol, amiodarone increases, dronedarone, procainamide, and quinidine (to avoid joint application).
With simultaneous use of nebivolol with cardiac glycosides have been identified gain influence pas slow AV conduction.
Concomitant use of drugs for nebivolol and sheathe anesthesia can cause suppression of the reflex tachycardia and increase the risk of hypotension.
Clinically significant interactions of nebivolol and nonsteroidal anti-inflammatory drugs (NSAIDs) is not established, acetylsalicylic acid simultaneously with nebivolol can be used as an antiplatelet agent.
Glucocorticosteroids and estrogens, progestins weaken the antihypertensive effect of beta-blockers.
The simultaneous use of tricyclic aitidepressantov, barbiturates and phenothiazines derivatives, ethanol, anxiolytics, hypnotics may enhance the antihypertensive deistvie nebivolol.
The allergens used for immunotherapy, or allergen extracts for skin tests increase the risk of severe systemic anaphylactic allergic reactions in patients receiving nebivolol.
Iodine-containing X-ray contrast agent for the on / in the increase the risk of anaphylactic reactions. Pharmacokinetic interactions
In an application with drugs that inhibit the reuptake of serotonin, or other means, with the participation of isoenzyme Biotransformiroetsa SYP2D6, nebivolol testosterone enanthate vs cypionate metabolism slows down, which can lead to the risk of bradycardia.
With simultaneous use of nebivolol had no effect on the pharmacokinetic parameters of digoxin. In an application with cimetidine concentration in blood plasma nebivolol increases (on the impact of the data on the pharmacological effects of the drug available). pharmacokinetic parameters of nebivolol.
When applied simultaneously with nebivolol nicardipine concentration of active substances in the blood plasma increased somewhat, but it has no clinical significance.
Simultaneous treatment with ethanol, furosemide or hydrochlorothiazide did not affect the pharmacokinetics of nebivolol.
No clinically significant interaction found nebivolol and warfarin.
With simultaneous use of sympathomimetic agents inhibit the activity of nebivolol.
In a joint application with nebivolol insulin and hypoglycemic agents for oral administration, may mask the symptoms of hypoglycaemia (tachycardia, tremor).
Avoid the simultaneous application with:
- lithium salts (renal clearance of lithium is reduced, it increases the toxicity).
Be wary of the following medications:
- antihypertensive drugs (potentiated their action may be necessary to dose adjustment)
- cardiac glycosides (hypokalemia and hypomagnesemia. associated with the effect of thiazide diuretics may increase the toxicity of cardiac glycosides)
- amiodarone (its use in conjunction with thiazide diuretics can lead to increased risk of arrhythmias associated with hypokalemia)
- hypoglycemic agents for oral administration (reduced their effectiveness, hyperglycemia may develop)
- corticosteroids, calcitonin (increase the level of potassium excretion)
- NSAIDs (may weaken the diuretic effect of thiazides and antigipertenzivnos)
- nedepolyariziruyuschimi muscle relaxants (their effect can be amplified)
- amantadine (amantadine hydrochlorothiazide clearance may be reduced, resulting in increased plasma concentrations of amantadine and possible toxicity)
- colestyramine, which reduces the absorption of hydrochlorothiazide
- ethanol, barbiturates and narcotics, which increase the risk of orthostatic hypotension.
Abolition of beta-blockers should be carried out gradually, within 10 days (up to 2 weeks in patients with coronary heart disease patients). Monitoring of blood pressure and heart rate at the start of drug administration should be daily.
In elderly patients, renal function should be monitored (1 every 4-5 months).
When angina selected dose should provide a resting heart rate in the range of 55-60 bpm. / Min., With a load of less than 110 bpm. / Min.
Patients who use contact lenses should bear in mind that during treatment with beta-blockers may reduce the production of tear fluid.
Nebivolol has no effect on plasma concentrations of glucose in patients with diabetes. However, caution should be exercised when treating these patients, as nebivolol may mask certain symptoms of hypoglycemia (eg, tachycardia) caused by the use of hypoglycemic agents.
Controlling the glucose concentration in the blood plasma should be one every 4-5 months. (In patients with diabetes).
Beta-blockers should be used with caution in patients with COPD, since it may worsen bronchospasm.
When hyperthyroidism drug eliminates tachycardia.
The effectiveness of beta-blockers in smokers is lower than that of non-smokers.
The therapy beta adrenoblokagorami possible exacerbation of psoriasis flow. Patients with this disease Nebilong N should be used with caution.
During therapy with H Nebilong need to monitor the performance of acid-base status and electrolytes (potassium, sodium »calcium).
In long-term treatment should be carefully monitored clinical symptoms of disorders of water and electrolyte balance, especially in high-risk groups of patients: patients with diseases of the cardiovascular system and liver dysfunction; in the case of severe vomiting or signs of fluid and electrolyte balance, such as dryness of the oral mucosa, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscle weakness, hypotension oliguria, tachycardia, complaints of the gastrointestinal -kishechnogo tract.
Hypokalemia can be avoided by using potassium-containing medications or foods rich in potassium (fruits, vegetables), particularly in the case of enhanced potassium loss (enhanced diuresis, long-term treatment) or concurrent treatment with cardiac glycosides or corticosteroids.
It is shown that thiazides increase the renal excretion of magnesium: it may cause hypomagnesemia.
With reduced kidney function should be monitored creatinine clearance. In such patients, the drug can cause azotemia and cumulative effects may develop. If renal function is obvious, upon the occurrence of oliguria should weigh the possibility of withdrawal of the drug. Patients with impaired hepatic function or progressive liver disease, thiazides administered with caution as a small violation of water-electrolyte balance, as well as the ammonium content in blood serum can cause hepatic coma.
In patients with peripheral circulatory disorders caution should be exercised when administering the drug Nebilong N.
Alcohol, barbiturates, narcotics enhance orthostatic hypotensive effect of thiazide diuretics. Thiazides may reduce the amount of iodine binding to serum proteins, without showing signs of thyroid dysfunction (due to hydrochlorothiazide).
Patients with pheochromocytoma should not be given Nebilong H as long as the prescribed treatment of alpha-blockers. It is necessary to control blood pressure. It is recommended to discontinue therapy with Nebilong H in the development of depression caused by the intake of beta-blockers (due to content in the nebivolol). Particular attention is required in cases of surgery under general anesthesia in patients taking beta-blockers. Such patients should be abolished Nebilong H 48 hours before surgery, warn the anesthesiologist that the patient takes the drug Nebilong N. As a means for general anesthesia should choose the drug with minimal negative inotropic effect.
When specifying a history of anaphylactic reactions, regardless of their causes, especially during desensitizing therapy, treatment with Nebilong H (due to content in the nebivolol) may increase the risk of allergic reactions and contribute to the development of resistance to treatment with epinephrine (adrenaline) in normal doses.
In patients with hyperuricemia increased risk of acute gout attacks. In this case, H Nebilong dose should be selected individually controlled by the concentration of uric acid in serum. Before examining the function of the parathyroid glands treatment with Nebilong H must stop, as the background of his admission may occur transient hypercalcemia.
Influence pas ability to drive vehicles and management mechanisms
During the period of treatment must be careful when driving and occupation of other potentially hazardous activities that require high concentration and psychomotor speed reactions. where to buy anabolic steroids online forum roidsseek review how to buy anabolic steroids online