Of selective beta 1 adrenoblokator without its own sympathomimetic activity, has no membrane stabilizing action. It lowers blood plasma renin activity, reduces myocardial oxygen demand, slows the heart rate (HR) (at rest and during exercise). It has antihypertensive, antiarrhythmic and antianginal effects. Blocking in low doses of beta 1 -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.
With increasing doses above the therapeutic beta has 2 adrenoblokiruyuschee action.
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 beta 2 – adrenergic receptors), which is 1-3 days returned to baseline, and at long-term administration is reduced.
Hypotensive effect associated with decreased cardiac output, sympathetic stimulation of peripheral blood vessels, reduction in activity of the renin-angiotensin system (important for patients with initial hypersecretion renin) sensitivity reduction in response to the decrease in 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 ), a decrease of spontaneous excitation rate of the sinus and ectopic pacemakers and slowing of the atrioventricular (AV) of (mainly in the antegrade and to a lesser extent, in the retrograde direction through the AV node) and on additional routes.
When used in medium-therapeutic doses, unlike nonselective beta-blockers, has a less pronounced effect on the organs containing the beta 2 -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 (of Na + ) in the body; atherogenic action expression is not different from that of propranolol.
Absorption – 80-90%, it does not affect food intake on absorption. The maximum plasma concentration observed after 1-3 hours, connection with blood plasma proteins for about 30%. The permeability of the blood-brain barrier and the placental barrier – low secretion of breast milk – low.
50% of the dose is metabolized in the liver to inactive metabolites, 50% is excreted by the kidneys unchanged. The half-life of 10-12 hours.
- arterial hypertension;
- Coronary heart disease: prevention of angina attacks.
Hypersensitivity to the drug and other beta-blockers, shock (including cardiogenic), collapse, pulmonary edema, acute Heart Failure, Chronic heart failure in the stage of decompensation, atrioventricular (AV) block II- III st., Cinoatrialnaya blockade syndrome sinus, bradycardia, Prinzmetal angina, cardiomegaly (with no signs of heart failure), hypotension (systolic blood pressure less than 100 mm rt.ct., especially myocardial infarction); severe forms of asthma and other obstructive airway disease; 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, depression, age 18 years (effectiveness and safety have not been established ).
Precautions : hepatic failure, chronic renal failure, myasthenia gravis, thyrotoxicosis, diabetes mellitus, atrioventricular block I Degree, depression (including history), psoriasis, allergic reactions (in history), advanced age.
Use in pregnancy and lactation is possible if the benefit 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, 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 creatine clearance less than 20 mL / min or with severe hepatic impairment, the maximum daily dose -. 10 mg
dose adjustment in elderly patients is not required.
On the part of the central nervous system: 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, convulsions. From the senses: visual disturbances, reduced secretion of tear fluid, cuhost and soreness of eyes, conjunctivitis. cardio-vascular system: sinus bradycardia, heart rate, conduction disturbances infarction, AV-block (up to the development of full transverse blockade and heart failure), the weakening of myocardial contractility, the development of (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 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. The respiratory system: nasal nose, difficulty breathing 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, alopecia. Laboratory findings: thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, change activity of liver enzymes (increased ALT, AST), bilirubin, triglycerides.Effects on the fetus: intrauterine growth retardation, hypoglycemia, bradycardia. Other: back pain, arthralgia, cramps in the calf muscles, weakening of libido, reduced potency, “cancellation” syndrome (increasing angina attacks, increased blood pressure).
Symptoms: ventricular premature beats, bradycardia, AV block, marked reduction in 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 infusion of 1-2 mg of atropine, epinephrine or staging a temporary pacemaker; with ventricular arrhythmia – lidocaine (Class IA drugs are not used); 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 -serdechnye glycosides, diuretics, glucagon; in convulsions – diazepam intravenously; with bronchospasm – beta 2 adrenostimulyatory 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 testosterone propionate results.
Iodine 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 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 + and prostaglandin synthesis kidney blockage), corticosteroids, and estrogens (delay ions Na + ).
cardiac glycosides, methyldopa, reserpine and guanfacine blockers “slow” calcium channel blockers (verapamil, diltiazem) amiodoron other antiarrhythmic drugs increase the risk of developing or worsening bradycardia, AV-blockade, heart failure and heart failure.
Nifedipine can lead to a significant reduction in blood pressure.
Diuretics, clonidine, sympatholytic, hydralazine, and other antihypertensive drugs may cause an excessive decrease of blood pressure.
Extends non-depolarizing muscle relaxant effect and anticoagulant effect of coumarins.
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 increase in the hypotensive action, a break in treatment between receiving MAO and testosterone propionate results inhibitors should 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 testosterone propionate results in the plasma; rifampin shortens the half-life.
Monitoring of patients receiving testosterone propionate results should include measurement of heart rate and blood pressure (at the beginning of treatment – daily, then 1 every 3-4 months) holding an electrocardiogram, determination of blood glucose levels in diabetic patients (1 every 4-5 months ).. In elderly patients, it is recommended to monitor renal function (1 time in 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, it is recommended to carry out research in respiratory function patients with a history of bronchopulmonary history.
Approximately 20% of patients with angina beta-blockers are ineffective. The main reasons -. Severe coronary atherosclerosis with a low threshold of ischemia (. Heart rate less than 100 beats / min) and a higher end-diastolic volume of the left ventricle, which violates the subendocardial blood flow
. The “smoking” 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 testosterone propionate results 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 testosterone propionate results.
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 has taken the drug before surgery, he should choose the drug for general anesthesia with minimal negative inotropic effect.
Reciprocal activation of the vagus nerve can be eliminated by intravenous administration of atropine (1-2 mg).
Drugs that reduce stocks of catecholamines (including reserpine) may 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.
patients with bronhospasticheskimi diseases can assign cardioselective blocker in case of intolerance and / or ineffectiveness of other antihypertensive drugs . 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),
the AV-blockade, it is necessary to reduce the dose or discontinue 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 and Normetanephrine vanilinmindalnoy acid, antinuclear antibody titers.
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. esteroides anabolicos comprar mejores bcaa comprar esteroides bodybuilding ab workout levive red bodybuilding.com tricep workout