Selective beta1-blocker without its own sympathomimetic activity, has no membrane stabilizing action. It reduces plasma renin activity, reduces myocardial oxygen demand, reduces heart rate (HR) (at rest and during exercise). It has antihypertensive, antiarrhythmic and antianginal effects. Blocking in low doses of beta1-adrenergic receptors of the heart, reduces the formation of catecholamines stimulated cAMP from ATP, reduces intracellular calcium ion current, has a negative chrono-, Drome, BATM and inotropic effect, depresses conduction and excitability, reduces myocardial contractility.
With increasing doses has beta2-adrenoceptor blocking activity.
The total peripheral vascular resistance at the beginning of the drug in the first 24 hours, is increased (as a result of reciprocal increase in the activity of alpha-adrenoceptor stimulation and removal of beta2-adrenoceptor), which is 1-3 days returns to the original, and prolonged appointment reduced.
The hypotensive effect associated with a decrease in cardiac output, sympathetic stimulation of peripheral vascular disease, decreased activity of the renin-angiotensin system (is more important for patients with initial hypersecretion of renin), restoration of sensitivity (there is no baroreceptors of the aortic arch to increase their activity in response to the decline blood pressure (BP) and the influence on the central nervous system (CNS). When hypertension effect occurs within 2-5 days, stable operation – through 1-2 months.
Antianginal effect is due to a decrease in myocardial oxygen demand as a result of deceleration in heart rate and decrease contractility, lengthening of diastole, improving myocardial perfusion. By increasing end-diastolic pressure in the left ventricle and increase the tension of the muscle fibers of the ventricles can increase oxygen demand, especially in patients with chronic heart failure.
The antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP levels, hypertension ), reduction of the spontaneous excitation rate sinus and ectopic pacemaker and deceleration of the atrioventricular (AV) of the (preferably antegrade and to a lesser degree, in the retrograde direction through the AV node), and additional routes.
When used in high therapeutic doses, unlike nonselective beta-blockers, has a less pronounced effect on the organs containing beta2-adrenergic receptors (pancreas, skeletal muscle, smooth muscle of the peripheral arteries, bronchi and uterus) and carbohydrate metabolism, does not cause a delay of sodium ions (Na +) in the body; atherogenic action expression is not different from that of propranolol. When used in large doses (200 mg or more) has a blocking effect on both beta-adrenergic receptor subtypes, primarily bronchial and vascular smooth muscle.
Absorption – 80-90%, does not affect food intake on absorption. The maximum plasma concentration observed after 2-4 hours, the connection with plasma proteins – 26-33%. The permeability of the blood-brain barrier and the placental barrier – low secretion of breast milk – is low.
It is metabolized in the liver, elimination half-life -. 9-12 hours excreted by the kidneys – 50% in an unmodified form, less than 2% in the bile.
Prevention of angina attacks
Hypersensitivity to buy testosterone propionate or other beta-blockers, shock, collapse, pulmonary edema, congestive heart failure, chronic heart failure decompensation (including cardiogenic shock), AV blockade II-III century., Sinoatrial block, sick sinus syndrome site, bradycardia, Prinzmetal angina, cardiomegaly (with no signs of heart failure), hypotension (systolic blood pressure less than 90 mm Hg, especially myocardial infarction); asthma and chronic obstructive pulmonary disease history; lactation, concomitant use of monoamine oxidase inhibitors (MAOIs) (except MAO-B), the later stages of peripheral circulatory disorders, Raynaud’s disease, pheochromocytoma (without simultaneous use of alpha-blockers), metabolic acidosis, age 18 years (effectiveness and safety set ).
Precautions : hepatic failure, chronic renal failure, myasthenia gravis, thyrotoxicosis, diabetes mellitus, atrioventricular block I degree, psoriasis, depression (including history), advanced age.
Use in pregnancy and lactation is possible if you use to the mother outweighs the risk of side effects in the fetus and child.
Dosing and Administration
Inside, in the morning on an empty stomach, not liquid, 2.5-5 mg once daily. If necessary to increase the dose of 10 mg 1 time per day. The maximum daily dose – 20 mg / day.
In patients with impaired renal function with a creatinine clearance less than 20 mL / min, or with severe liver problems, the maximum daily dose – 10 mg.
CNS: fatigue, weakness, dizziness, headache, sleep disorders, depression, anxiety, confusion, or momentary loss of memory, hallucinations, asthenia, myasthenia gravis, paresthesia in the extremities (in patients with “intermittent” claudication and Raynaud’s syndrome), tremors. From the senses: visual disturbances, reduced secretion of tear fluid, dryness and soreness of eyes, conjunctivitis. cardio-vascular system: sinus bradycardia, heart rate, conduction disturbances infarction, AV block (up to the development of a complete transverse blockade and heart failure ), arrhythmia, weakening of the myocardial contractility and development (worsening) of chronic heart failure (swelling of ankles, feet, shortness of breath), reduced blood pressure, orthostatic hypotension, a manifestation of vasospasm (strengthening of peripheral blood circulation, cooling of the lower extremities, Raynaud’s syndrome), pain in the chest. From the digestive system: dryness of the oral mucosa, nausea, vomiting, abdominal pain, constipation or diarrhea, abnormal liver function (dark urine, yellow skin or sclera, cholestasis), changes in taste, hepatitis. The respiratory system: nasal congestion , shortness of breath when administered at high doses (loss of selectivity) and / or in predisposed patients – laryngo and bronchospasm. from endocrine system: hyperglycemia (in patients with insulin-dependent diabetes), hypoglycemia (in patients receiving insulin), hypothyroid state. Allergic reactions: itching, rash, urticaria. For the skin: increased sweating, flushing of the skin, rash, psoriasiform skin reactions, exacerbation of psoriasis symptoms.Laboratory findings: thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, changes in the activity of liver enzymes (increased AST, ALT), bilirubin, triglycerides. Effects on the fetus: intrauterine growth retardation, hypoglycemia, bradycardia. Other: back pain, arthralgia, weakening of libido, reduced potency, the syndrome of “lifting” (increasing angina attacks, increased blood pressure) .
Symptoms: arrhythmia, ventricular premature beats, bradycardia, AV block, decrease blood pressure, chronic heart failure, cyanosis of nails of fingers or palms, shortness of breath, bronchospasm, dizziness, fainting, seizures. Treatment: gastric lavage and the appointment of absorbent medicines; Symptomatic therapy: which developed at AV blockade – intravenous (I / O) 1-2 mg of atropine, epinephrine or staging a temporary pacemaker; with ventricular arrhythmia – lidocaine (Ia class of drugs does not apply); with a decrease in blood pressure – the patient must be in the Trendelenburg position;if there are no signs of pulmonary edema – intravenous plasma substituting solutions, with inefficiency – the introduction of epinephrine, dopamine, dobutamine (to maintain the chronotropic and inotropic effects and elimination of significant decrease in blood pressure); heart failure – cardiac glycosides, diuretics, glucagon; in convulsions – diazepam intravenously; with bronchospasm – beta2-adrenostimulyatorov inhalation.
Interaction with other drugs
The allergens used for immunotherapy, or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving buy testosterone propionate.
Iodinated radiopaque drugs for intravenous administration increases the risk of anaphylactic reactions.
Phenytoin intravenous administration, drugs for inhalation general anesthesia (derivatives of hydrocarbons) increase the intensity of cardiodepressive action and the likelihood of blood pressure lowering.
Changes of insulin efficiency and oral hypoglycemic drugs, masking the symptoms of developing hypoglycemia (tachycardia, increased blood pressure).
Reduces the clearance of lidocaine and xanthine (except dyphylline) and increases their concentration in plasma, especially in patients with initially increased clearance of theophylline under the influence of smoking.
Antihypertensive effect of weakening non-steroidal anti-inflammatory drugs (delay of Na + ions and blockage of prostaglandin synthesis by the kidneys), corticosteroids, and estrogens (delay of Na + ions).
Cardiac glycosides, methyldopa, reserpine and guanfacine blockers “slow “calcium channel (verapamil, diltiazem), amiodarone or other antiarrhythmic drugs increase the risk of developing or worsening bradycardia, AV blockade of cardiac and heart failure.
Nifedipine can lead to a significant reduction in blood pressure.
Diuretics, clonidine, sympatholytic, hydralazine, and other antihypertensive drugs funds may lead to an excessive reduction in blood pressure.
Extends the action of non-depolarizing muscle relaxants and anticoagulant effect of coumarin.
tri- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedatives and sleeping medications increase CNS depression.
not recommended simultaneous application with MAO inhibitors due to the significant strengthen hypotensive action, a break in treatment between receiving MAO inhibitors and buy testosterone propionate must not be less than 14 days.
Negidrirovannye ergot alkaloids increase the risk of peripheral circulatory disorders.
Ergotamine increases the risk of peripheral circulatory disorders; sulfasalazine increases the concentration of buy testosterone propionate in the plasma; rifampin shortens the half-life.
Monitoring of patients receiving Bisokard should include heart rate and blood pressure measurement (at the beginning of treatment – daily, then 1 every 3-4 months) holding an electrocardiogram, determination of blood glucose in patients with diabetes (1 every 4-5 months). In elderly patients, it is recommended to monitor renal function (1 every 4-5 months).
It is necessary to train the patient’s heart rate calculation method and instruct on the need of medical advice in heart rate less than 50 bpm. / Min.
Before treatment recommended study of respiratory function in patients with a history of bronchial-pulmonary history.
Approximately 20% of patients with angina beta-blockers are ineffective. The main reason – severe coronary atherosclerosis with a low threshold of ischemia (heart rate less than 100 beats / min.) And increased end-diastolic volume of the left ventricle, which violates the subendocardial blood flow.
At the “smokers” the effectiveness of beta-blockers lower.
Patients who use contact lenses, must be taken into account, against the background of treatment may decrease the production of tear fluid.
When used in patients with pheochromocytoma have a risk of paradoxical hypertension (if not previously reached effective alpha adrenoblockade).
When buy testosterone propionate thyrotoxicosis may mask certain clinical signs of hyperthyroidism (eg, tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated because the symptoms can increase.
In diabetes may mask tachycardia caused by hypoglycemia. In contrast, nonselective beta-blockers practically no increase insulin-induced hypoglycemia and delay recovery of blood glucose to normal levels.
At the same time taking clonidine its reception can be terminated only after a few days after discontinuation of buy testosterone propionate.
Perhaps the increased severity of hypersensitivity and lack of response the effect of conventional doses of epinephrine with aggravated allergic history.
In the case of the need for a planned surgical treatment abolition of the drug is carried out for 48 hours before general anesthesia. If the patient took the drug before surgery, he must pick a medicament for general anesthesia with minimal negative inotropic effect.
Reciprocal activation of the vagus nerve can be removed intravenous atropine (1.2 mg).
Drugs that reduce catecholamine stocks (including reserpine) can enhance the action of beta-blockers, so patients taking such drug combinations should be under constant medical supervision in order to identify pronounced lowering of blood pressure and bradycardia.
You can assign cardioselective blocker in case of intolerance and / or ineffectiveness of other antihypertensive drugs patients with bronhospasticheskimi diseases means. Overdosing is dangerous development of bronchospasm.
In the case of elderly patients increasing bradycardia (less than 50 u. / Min), pronounced reduction in blood pressure (systolic blood pressure below 100 mm Hg), AV blockade bronchospasm, ventricular arrhythmias, severe liver dysfunction and kidneys need to reduce the dose or discontinue the treatment.
It is recommended to discontinue therapy in the development of depression.
Do not abruptly discontinue the treatment because of the risk of severe arrhythmias and myocardial infarction. Abolition are gradually reducing the dose for 2 weeks or more (reduce dose by 25% in 3-4 days).It is necessary to cancel prior to the study in blood and urine catecholamines, metanephrines and vanilinmindalnoy acid; titers of antinuclear antibodies.
In the period of treatment must be careful when driving and occupation of other potentially hazardous activities that require high concentration and psychomotor speed reactions.