It should be noted that the selective effect of betaxolol on beta1-adrenergic receptors is not absolute, since when it is used at high doses of betaxolol may impact on beta2-adrenergic receptors located primarily in the bronchial smooth muscle and blood vessels (though effects on betaxolol beta2- adrenergic receptors is much weaker than that of the non-selective beta-blockers) in applying betaxolol anavar side effects its blocking beta1-adrenergic receptor activity is shown by the following pharmacodynamic effects:
- a decrease in heart rate (HR) at rest and during exercise (due to the blockade of beta-adrenergic receptors in the sinus node, which in combination with the lack of betaxolol intrinsic sympathomimetic activity slows down the automaticity of sinus node);
- decrease in cardiac output at rest and during exercise due to competitive antagonism with catecholamines in peripheral (especially cardiac) adrenergic nerve endings;
- reduction in systolic and diastolic blood pressure at rest and during exercise (the mechanism of the antihypertensive action is described below);
- reduction of reflex orthostatic tachycardia.
As a result of these effects, it decreases the load on the heart at rest and during exercise.
The mechanism of antihypertensive effect of beta-blockers are not fully established.
In beta-blockers are assumed to be the following mechanisms of antihypertensive action:
- decreased cardiac output;
- elimination of peripheral artery spasm (due to central action, which leads to a decrease in sympathetic impulses to the periphery, to the vessels, and due to the inhibition of renin activity).
The antihypertensive effect of betaxolol with its chronic administration does not decrease. For a single day during the reception betaxolol (5 to 40 mg) of antihypertensive activity is the same in 3-4 hours (time to reach maximum concentration in the blood betaxolol) and after 24 hours (before the next dose intake). Upon receiving 5 mg and 10 mg of betaxolol its antihypertensive effect is respectively 50% and 80% of the antihypertensive action when receiving 20 mg of betaxolol.
Thus, in the dose range 5-20 mg dose dependency is observed antihypertensive effect, and with increasing doses of 10 mg to 20 mg increment antihypertensive effect is negligible. Increasing the dose from 20 mg to 40 mg has little effect antihypertensive effects of betaxolol. The maximum antihypertensive effect of each dose betaxolol achieved within 1-2 weeks.
In contrast to the antihypertensive effect of betaxolol HR reducing effect by increasing the dose (from 10 mg to 40 mg) is not growing.
In addition, betaxolol can slow down the AV node conduction.
Pharmacokinetics Absorption Betaxolol is rapidly and completely (100%) absorbed from the gastrointestinal tract. Betaxolol has little effect “first pass” through the liver and high bioavailability – about 85%.Betaxolol maximum concentration in plasma is achieved in 2-4 hours. Differences his plasma concentrations in different patients and one patient with prolonged use are subtle differences, which is associated with high bioavailability of betaxolol. Distribution Betaxolol bound to plasma proteins for about 50%. The permeability of the blood-brain and placental barriers – low. The secretion of breast milk -. A smallvolume of distribution -. About 6 L / kg Metabolism In betaxolol body mainly transformed into inactive metabolites. Solubility in fats moderate. Withdrawal excreted by the kidneys as metabolites (80%), 10-15% in unchanged form. The half-life (T1 / 2) of betaxolol is 15-20 hours. T1 / 2 with abnormal liver function is extended by 33%, but the clearance is not changed; in violation of renal function T1 / 2 doubles (required dose reduction). not removed by hemodialysis.
- Arterial hypertension (monotherapy and combination therapy).
- Preventing strokes voltage (monotherapy and combination therapy).
- Hypersensitivity to the excipients and betaxolol formulation.
- Severe forms of asthma and chronic obstructive pulmonary disease.
- Acute heart failure, chronic heart failure decompensation, is not compensated as a result of treatment with diuretics, inotropic agents, ACE inhibitors and other vasodilators.
- Cardiogenic shock.
- Atrioventricular block II and III degree (without pacemaker installed).
- Prinzmetal angina (monotherapy is contraindicated).
- sick sinus syndrome (including sinoatrial block).
- Severe bradycardia (heart rate less than 45-50 beats / min.).
- Severe forms of Raynaud’s disease and peripheral arterial occlusive disease.
- Pheochromocytoma without simultaneous administration of alpha-blockers.
- Arterial hypotension (systolic blood pressure <100 mm Hg. Art.).
- Anaphylactic reactions in the anamnesis.
- Metabolic acidosis.
- In an application with floctafenine (see. “Interaction with other medicinal products” section).
- In an application with sultopride (see. “Interaction with other medicinal products” section).
- At the same time taking monoamine oxidase inhibitors (MAOIs).
- Cardiomegaly (without heart failure).
- Age 18 years (effectiveness and safety have been established).
- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption (due to the presence of lactose in the composition of the drug).
- In bronchial asthma and chronic obstructive pulmonary disease with moderate flow (to start with small doses, and preferably under the control of the parameters of respiratory function, through beta1-selectivity of betaxolol when an asthma attack on the background of his admission may cupping beta2-agonists).
- In chronic heart failure in the stage of compensation, (treatment with betaxolol is possible only under strict medical supervision, treatment should begin with very low doses with their gradual increase).
- When I degree atrioventricular block (requires close monitoring, including ECG monitoring).
- When occlusive peripheral arterial disease, Raynaud’s syndrome (except in severe, see. “Contraindications”) (may increase peripheral circulatory disorders).
- When Prinzmetal angina (possibly more frequent angina, a selective beta1-blocker only possible with the simultaneous use of vasodilators).
- In the treatment of pheochromocytoma (a drug for the treatment of hypertension Lokren® The treatment of pheochromocytoma requires careful monitoring of the blood pressure).
- Elderly patients (treatment should be started with low doses and under close medical supervision).
- In renal insufficiency (with creatinine clearance (CC) more than 20 ml / min – careful observation of the patient during the first 4 days of treatment, with CC less than 20 ml / min and / or hemodialysis requires correction mode dosing, see “section. dosage and administration “).
- When liver failure (requires a careful clinical observation in the beginning of treatment).
- In patients with diabetes mellitus (requires regular monitoring of glucose concentration in the blood, including the active patient self-monitoring at the start of treatment, may decrease the severity of the precursors of hypoglycemia such as tachycardia, palpitations and sweating).
- In psoriasis (beta-blockers may aggravate the course of psoriasis).
- When conducting desensitizing therapy.
Use during pregnancy and lactation Pregnancy In animal experiments have betaxolol has not been found teratogenic effects. To date, no reports of teratogenic effects in humans. In general, beta-blockers reduce blood flow to the placenta and can affect fetal development. It should monitor blood flow in the placenta and uterus, and also to observe the growth and development of the child and in the event of adverse events in respect of pregnancy and / or fetus, alternative therapeutic measures taken. It should be examined carefully newborn after delivery. In the first 3-5 days of life may occur bradycardia symptoms of hypoglycemia, since the action of beta-blockers in newborns whose mothers took them before birth, persists for several days after birth. In the neonatal and postnatal period in newborns have an increased risk of cardiac and respiratory complications. In case of heart failure require hospitalization of the newborn intensive care unit (see. “Overdose” section). Avoid the use of plasma expanders (risk of acute pulmonary edema). Also reported the development of bradycardia, respiratory failure and hypoglycemia. In this regard, during the first 3-5 days of life requires careful observation of such infants in a specialized compartment (heart rate, blood glucose concentration). In connection with this use of the drug during pregnancy Lokren ® is not recommended and is possible only when benefit to the mother outweighs the potential risk to the fetus or child. lactation Beta-blockers, including betaxolol, are excreted in the breast milk (see. “Pharmacokinetics’ section). The risk of hypoglycemia and bradycardia in infants has not been studied, therefore as a precaution breast-feeding during treatment should be discontinued.
Dosing and Administration
The drug is taken by mouth and drink plenty of fluids. Do not chew the tablet.
The initial dose of the drug for both Lokren® indications for use of the drug is generally 10 mg (2.1 mg of 20 tablets). If, within 7-14 days of treatment are not achieved the target values of blood pressure, doubling the dose to 20 mg per day.
Generally not used Lokren® drug dose of more than 20 mg (due to the fact that increasing the dose over 20mg not observed . statistically significant increase in the antihypertensive effect of the drug)
The maximum daily dose of the drug Lokren® -. 40 mg Patients with renal insufficiency . Recommended dose adjustments depending on the functional state of the patient’s kidney When creatinine clearance 20 mL / min dose adjustment is required. However, at the beginning of treatment, a clinical observation is recommended to achieve equilibrium concentration of drug in the blood which is achieved in an average of 4-7 day treatments). In severe renal failure (creatinine clearance less than 20 mL / min), the recommended starting dose is 5 mg / day (regardless of the frequency and the days of hemodialysis in patients on hemodialysis) that the lack of effectiveness can be increased by 2 times every 1-2 weeks. Maximum daily dosage is 20 mg. patients with hepatic impairment in patients with hepatic failure dose adjustment is usually not required. However, at the beginning of therapy, it is recommended more thorough clinical observation of the patient.
The following side effects are given in accordance with the following gradations their frequency of occurrence: very common (> 1/10), common (> 1/100, <1/10); not often (> 1/1000, <1/100); rare (> 1/10000, <1/1000); very rare (<1/10000), (including isolated reports). Violations of the skin and subcutaneous tissue disorders Rare: various skin reactions including rash, pruritus, urticaria, psoriasiform rash or exacerbation of psoriasis flow (see “Precautions” section.) . disorders of the nervous system often:. dizziness, headache Very rare:. paresthesia violations of the organ of vision rare:. dryness of the eyes is very rare: blurred vision. mental disorders Common: asthenia, insomnia. rare:. depression Very rare: hallucinations , confusion, nightmares. Violations of the gastrointestinal tract Common: gastralgia, diarrhea, nausea, vomiting. Violations of the metabolism and nutrition Very rare: hypoglycaemia, hyperglycaemia. Violations of the heart often: bradycardia, possibly severe. rarely : development (or worsening) of symptoms of heart failure (swelling of ankles, feet, legs), marked reduction in blood pressure, slow atrioventricular conduction. Violations of the vessels often: decrease in skin temperature of the upper and lower extremities. rare: symptoms vasoconstriction: Raynaud’s syndrome, increased peripheral circulatory disorders, including “intermittent claudication”, increased frequency of angina attacks.violations of the respiratory system, organs, thoracic and mediastinal disorders rare: bronchospasm. violations of the genital and breast Common: impotence. Laboratory and instrumental data rare: the appearance of antinuclear antibodies, only in exceptional cases, in keeping with the clinical manifestations of the syndrome volchanochnopodobnogo passing after stopping treatment; reduction of intraocular pressure (because of the possibility of its reduction under the influence of beta-blockers). The impact on the fetus Intrauterine growth retardation, hypoglycemia, bradycardia. Other “cancellation” syndrome (increased or increased frequency of angina attacks, increased blood pressure, see. “Special Instructions” section ).
Overdose symptoms of bradycardia, dizziness, atrioventricular block, marked reduction of blood pressure, arrhythmia, ventricular premature beats, fainting, heart failure, shortness of breath, bronchospasm, cyanosis of nails of fingers and palms, cramps. Treatment of gastric lavage, the use of absorbent. In the case of bradycardia It recommended: atropine 1-2 mg intravenously; then (if necessary) 25 mcg slow infusion or an infusion of isoprenaline dobutamina2,5-10 ug / kg / min; may sometimes require temporary staging an artificial pacemaker. In case of excessive reduction of blood pressure is recommended: intravenous plasma-solutions and vasopressor drugs. If bronchospasm: . appointment of bronchodilators, including beta2-agonists and / or aminophylline In the case of heart failure (decompensation) in newborns whose mothers during pregnancy taking beta-blockers are recommended: hospitalization in the intensive care unit; isoprenaline and dobutamine: prolonged and usually in high doses, monitoring specialist.
Interaction with other medicinal products is contraindicated in combination With floctafenine In the case of shock or hypotension due floctafenine, beta-blockers cause a reduction in compensatory cardiovascular reactions. With sultopride Cardiac automatism (severe bradycardia) due to the additional decrease in heart rate. Not recommended combinations With amiodarone Violations contractility, automatism and conduction (suppression of sympathetic compensatory mechanisms). With blockers “slow” calcium channel blockers (bepridil, diltiazem and verapamil) violations of automatism (severe bradycardia, cardiac sinus node), violations of atrioventricular conduction, heart failure [synergistic (mutually reinforcing) effects ]. This combination can only be used under close clinical and electrocardiographic supervision, particularly in elderly patients or in the beginning of treatment. with cardiac glycosides risk of developing or worsening bradycardia, atrioventricular block, cardiac arrest. withMAO inhibitors is not recommended simultaneous application with MAO inhibitors due to the significant enhance antihypertensive effect of betaxolol, a break in treatment between receiving MAO and betaxolol inhibitors should not be less than 14 days. On the iodine-containing contrast media in case of shock and a sharp decline in blood pressure upon administration of iodinated contrast agents, beta-blockers reduce the compensatory cardiovascular reactions. If possible, before performing radiographic studies with iodinated contrast agents should be discontinued the treatment of beta-blocker.Combinations that should be used with caution with inhaled anesthetics galogensoderzhaschichi Beta-blockers have cardiodepressive action (inhibition of beta-adrenergic receptors may be reduced when administered beta- agonists). As a rule, the treatment of beta-blockers is not terminated, and in any case, you should avoid abrupt withdrawal of beta-blockers. Anesthetist must be made aware of the beta-blocker. With drugs capable of causing ventricular cardiac arrhythmias, including ventricular tachycardia type “pirouette”: antiarrhythmics class IA (quinidine, gidrohinidin and disopyramide) and class III (amiodarone, dofetilide, Ibutilide), sotalol, some antipsychotics from the group phenothiazines (chlorpromazine, tsiamemazin, Levomepromazine, thioridazine), benzamides (amisulpride, sulpiride, tiaprid), butyrophenones (droperidol, haloperidol), other neuroleptics (pimozide), and other drugs (cisapride, difemanil introduced intravenous erythromycin, halofantrine, mizolastine, moxifloxacin, pentamidine is administered intravenously spiramycin and injectable vincamine Increased risk of ventricular arrhythmias, particularly ventricular tachycardia type “pirouette”. Requires clinical and electrocardiographic monitoring. With propafenone disturbances of contractility, automatism and conduction (suppression of sympathetic compensatory mechanisms). Requires clinical and electrocardiographic monitoring. With baclofen Increased antihypertensive effect of betaxolol. Requires control of blood pressure and betaxolol dosage adjustment if necessary. With insulin and hypoglycemic agents for oral administration, derivatives of sulfonylurea (see. Forums “with caution”, “Side effects”, “Special Instructions”). All beta-blockers may mask certain symptoms of hypoglycemia, such as palpitations and tachycardia. The patient should be advised of the need to strengthen the regular monitoring of the glucose concentration in the blood, including active self-monitoring by the patient, especially at the beginning of treatment.With the cholinesterase inhibitors (ambenomium, donepezil, galantamine, neostigmine, pyridostigmine, rivastigmine, tacrine) risk enhance bradycardia (additive effect). requires regular clinical monitoring. With antihypertensive drugs central action (clonidine, apraklonidip alpha – methyldopa, guanfacine, moxonidine, rilmenidine) anavar side effects Increased risk of bradycardia, atrioventricular conduction disturbances. significant increase in blood pressure with sharp cancellation antihypertensive agent of central action. It is necessary to avoid abrupt withdrawal of antihypertensive and conduct clinical monitoring. With lidocaine, 10% solution (intravenously as an antiarrhythmic) increase in the concentration of lidocaine in the blood plasma of a possible increase in adverse neurological symptoms and effects of the cardiovascular system (decreased lidocaine metabolism liver). Recommended clinical and ECG monitor and possibly control lidocaine concentration in blood plasma during treatment with beta-blockers and after its termination. If necessary -. Dosage adjustment of lidocaine combinations that should be taken into account with non-steroidal anti-inflammatory drugs (NSAIDs) (drugs with systemic action), including selective cyclooxygenase-2 (COX-2) Reduction of the antihypertensive effect of betaxolol (synthesis inhibition of prostaglandin NSAIDs and delay water and sodium pyrazolone derivatives). with blockers “slow” calcium channels from the group of dihydropyridines mutual reinforcement blocker antihypertensive action “slow” calcium channels and betaxolol, development of heart failure in patients with heart failure latentnoprotekayuschey heart failure or uncontrolled. Treatment of beta-blockers can minimize the reflex activation of the sympathetic nervous system in response to vasodilation influenced blockers “slow” calcium channels from the group of dihydropyridines. With tricyclic antidepressants (such as imipramine), neuroleptics Increased antihypertensive effect of betaxolol and risk of orthostatic hypotension (additive effect). C. mefloquine risk of bradycardia (additive effect). With dipyridamole (intravenous) Increased antihypertensive effect of betaxolol. Since alpha-blockers, including used in urology (alfuzosin, doxazosin, prazosin, tamsulosin, terazosin). Increased antihypertensive effect of betaxolol. Increased risk of orthostatic hypotension. With amifostine Increased antihypertensive effect of betaxolol. Withallergens used for immunotherapy, or allergen extracts for skin samples increased risk of severe systemic allergic reactions or anaphylaxis in patients receiving betaxolol. With phenytoin (intravenous)Increasing severity cardiodepressive actions and the likelihood of blood pressure lowering. with xanthines betaxolol lowers xanthine clearance (except dyphylline) and increases their concentration in the blood plasma, especially in patients with initially increased clearance of theophylline (for example, under the influence of smoking). since estrogen weakening of the antihypertensive effect of betaxolol (sodium and water retention) . Since glucocorticosteroids and tetrakozaktidom weakening of antihypertensive effect of betaxolol (sodium and water retention). With diuretics possible excessive reduction in blood pressure.With the non-depolarizing muscle relaxants betaxolol prolongs the action of non-depolarizing muscle relaxants. With coumarins Strengthening of the anticoagulant effect of coumarins. With alcohol (ethanol), sedative and hypnotic drugs means Increased depression of the central nervous system. with the non-hydrogenated ergot alkaloids Negidrirovannye ergot alkaloids increase the risk of peripheral circulatory disorders while taking betaxolol.
: Do not interrupt treatment with Lokren® sharply and do not change the recommended dose without first consulting your doctor, as this may lead to temporary impairment of the heart. Treatment should not be interrupted suddenly, especially in patients with coronary artery disease: sudden withdrawal may lead to severe cardiac arrhythmias, myocardial infarction, or cardiac arrest. The dose should be reduced gradually, ie, within 2 weeks, and, if necessary, you can simultaneously start replacement therapy other antianginal drugs, to avoid the increased frequency of angina attacks.
Patients taking Lokren® should monitor heart rate and blood pressure (at the beginning of the treatment on a daily basis, then 1 every 3-4 months), the concentration of blood glucose in patients with diabetes mellitus (1 every 4-5 months), renal function in elderly patients (one every 4-5 months).
It should teach the patient heart rate calculation method, and the patient should be instructed about the need to see a doctor with a decrease in heart rate less than 50 beats / min.
Approximately 20% of patients with angina beta-blockers are ineffective.
The main reason – severe coronary atherosclerosis with a low threshold of ischemia (heart rate at the time of development of angina attack at least 100 beats / min.) and increased finite diastolic left ventricular pressure that violates subendocardial blood flow.
at the same time taking clonidine its reception can be terminated only after a few days after discontinuation of the drug Lokren®.
Lokren® should be discontinued prior to assay concentrations of catecholamines, and normetanephrine vanilinmindalnoy acid blood and urine; and antinuclear antibody titers in the blood. Bronchial asthma and chronic lung disease obstruktivpaya Beta-blockers may be administered only in patients with a moderate degree of severity of the disease, with a choice of a selective beta-blocker in a low initial dose.Before treatment, it is recommended to evaluate the respiratory function. With the development of seizures during treatment can be used bronchodilators – (# 946;. 2-agonists Heart Failure In patients with heart failure, a controlled therapeutically, if necessary betaxolol can be used under strict medical supervision in a very low initial doses with their gradual increase, if necessary, in the case of good tolerability (compensated conservation status of chronic heart failure). Bradycardia If the resting heart rate drops below 50-55 beats / min the dose should be reduced Lokren® drug. atrioventricular block I degree view of the negative dromotropic beta-blockers, with the blockade of I degree the drug should be used with caution. Prinzmetal angina beta-blockers may increase the frequency and duration of attacks in patients with Prinzmetal angina. The use of cardioselective beta1-blockers is possible with mild angina severity Prinzmetal or angina mixed type at provided that the treatment is carried out in combination with vasodilators. peripheral circulatory disorders beta-blockers may lead to the deterioration of patients with peripheral circulatory disorders (Raynaud’s disease or Raynaud’s syndrome, arteritis or chronic obliterating leg artery disease). Pheochromocytoma in the case of beta-blockers in the treatment of hypertension caused by pheochromocytoma requires close monitoring of blood pressure. Appointment of the drug Lokren® possible during treatment with alpha-blockers. Elderly patients Treatment of elderly patients should start with low doses and under strict supervision. Patients with renal insufficiency dose must be adjusted depending on the concentration of creatinine in the blood or creatinine clearance (see. “Section dosage and administration “). Patients with diabetes should warn the patient of the need to strengthen the control of blood glucose, including the active self-control by the patient at the beginning of treatment. The patient should be aware that the initial symptoms of hypoglycaemia (especially tachycardia, palpitations and sweating) can be masked with betaxolol. Psoriasis requires careful assessment of the need for the drug, since there have been reports of exacerbation of psoriasis during treatment with beta-blockers. Allergic reactions Beta-blockers including drug anavar side effects may increase the sensitivity to allergens and the severity of anaphylactic reactions due to the weakening of compensatory adrenergic regulation under the effect of beta-blockers. Therapy of anaphylactic reactions, epinephrine (adrenaline) does not always give the expected therapeutic effect. In patients who are prone to severe anaphylactic reactions, particularly involving the use of floctafenine or during desensitisation, beta-blocker therapy may lead to a further strengthening of the reactions and decrease the effectiveness of treatment. General anesthesia With general anesthesia should consider the risk of a beta adrenergic blockade (decrease in heart rate, decreased cardiac output, reduction in systolic and diastolic blood pressure). beta-blockers mask reflex tachycardia and increase the risk of hypotension. Continued therapy Beta blockers reduce the risk of arrhythmia, myocardial ischemia and hypertensive crises. The anesthetist should be informed that the patient is receiving treatment for beta-blockers. If you want to stop therapy with Lokren® before surgery, this should be done gradually and completed within 48 hours prior to general anesthesia, as it is considered that the cessation of therapy, 48 hours can restore sensitivity of receptors to catecholamines. Beta-blockers therapy in some cases it may not be interrupted:
- in patients with coronary insufficiency desirable to continue treatment until surgery, given the risks associated with a sudden cancellation of beta-blockers.
- in the case of emergency surgery or when termination of treatment is not possible, the patient should be protected from the effects of vagal excitation by appropriate premedication with atropine, repeatedly if necessary.
In these patients, general anesthesia is necessary to use a substance, the least depressing the myocardium, and should compensate for blood loss.
I have to take into account the risk of anaphylactic reactions. Hyperthyroidism Symptoms of hyperthyroidism may be masked in the treatment of beta-blockers. Athletes Athletes should be aware that the drug contains the active substance, which may give a positive reaction in tests doping control. at the time of treatment should be deleted alcohol. Patients using contact lenses should bear in mind that during treatment with beta-blockers may reduce the production of tear fluid. The “smokers” the effectiveness of beta-blockers lower. buy anabolic steroids online bruce lee’s workout anabolic steroids online uk ice cream for bodybuilding esercizi per polpacci bodybuilding supplement distributors