Pharmacodynamics: trenbolone acetate buy belongs to the cardioselective β-adrenergic blockers that do not have intrinsic sympathomimetic activity and membrane stabilizing properties. It has antihypertensive, antianginal and antiarrhythmic action. Blocking in low doses β 1 adrenergic receptors of the heart, reduces the formation of catecholamines stimulated cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), decreases intracellular calcium ion current, has a negative chrono-, Drome, BATM and inotropic effects (heart rate slows rate (hR), depresses conduction, excitability and reduces myocardial contractility).
Total peripheral vascular resistance at the beginning of the use of β-blockers (in the first 24 hours after ingestion) – increases (as a result of retsiproktnogo increasing activity α-adrenoceptor stimulation and removal of .beta. 2 – adrenergic receptors), which after 1-3 days back to the original, but with long-term appointment – is reduced. Hypotensive effect caused by the decrease in cardiac output and synthesis of renin in the kidney, inhibition of the renin-angiotensin system (has a larger value in patients with initial hypersecretion renin) and central nervous system, reduction baroreceptor sensitivity of the aortic arch (not going to increase their activity in response to a decrease in blood pressure) and, ultimately, decreased peripheral sympathetic effects. Reduces high blood pressure (BP) at rest, exertion and stress.
The hypotensive effect develops rapidly (systolic blood pressure decreased after 15 minutes, maximum – 2 hours.) And lasts for 6 hours, diastolic blood pressure changes more slowly: a steady decline observed after a few weeks of regular treatment.
antianginal effect is determined by a decrease in myocardial oxygen demand as a result of shortening of heart rate (lengthening of diastole and improve myocardial perfusion) and contractility, as well as a decrease in the sensitivity of the myocardium to the effects of the sympathetic innervation. It reduces the number and severity of angina attacks and increase exercise tolerance.
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 sinus and ectopic pacemakers and slowing atrioventricular (AV ) conductivity (mainly in the antegrade and to a lesser extent, in the retrograde direction through the AV node and on additional routes).
if supraventricular tachycardia, atrial fibrillation, sinus tachycardia with functional heart disease and hyperthyroidism slows heart rate or may even lead to the restoration of sinus rhythm.
It prevents the development of migraine. When used in medium-therapeutic doses, unlike nonselective β-blockers, it has a less pronounced effect on the organs containing .beta. 2 adrenergic receptors (pancreas, skeletal muscle, smooth muscle of the peripheral arteries, bronchi and uterus), and carbohydrate metabolism. When used in large doses (over 100 mg / day) has a blocking effect on both the p-adrenoceptor subtype.
absorption when administered complete (95%). Maximum plasma concentration is achieved in 1-2 hours after ingestion. The half-life averages 3.5 hours (ranging from 1 hour up to 9 hours). It undergoes extensive first-pass metabolism, bioavailability of 50% at the first ingestion and up to 70% increases with repeated use. Food intake increases the bioavailability of 20-40%. The bioavailability of trenbolone acetate buy increased by cirrhosis of the liver. Contact with blood plasma proteins – 10%. It penetrates the blood-brain and placental barrier. Provided in the breast milk in small quantities. It is metabolized in the liver, the metabolite 2 have β-adrenoblokiruyuschey activity. The metabolism of the drug is involved isozyme CYP2D6. About 5% of the drug is excreted unchanged by the kidneys. Treatment of patients with impaired renal function does not require correction of the dose. Abnormal liver function slows the metabolism of the drug, and in cases of liver failure, the dose should be reduced. Not removed by hemodialysis.
- hypertension (in monotherapy or in combination with other agents);
- functional cardiac abnormalities, accompanied by tachycardia;
- Coronary heart disease: heart attack (secondary prevention – complex therapy), prevention of angina attacks;
- cardiac arrhythmias (supraventricular tachycardia, ventricular premature beats); Hyperthyroidism (complex therapy);
- prevention of migraine attacks.Contraindications
- Hypersensitivity to trenbolone acetate buy or other ingredients, other β-blockers;
- cardiogenic shock;
- AV block II – III degree (without pacemaker);
- sinoatrial (SA) block;
- sick sinus syndrome (SSS);
- sinus bradycardia (heart rate less than 50 beats / min);
- chronic heart failure in the stage of decompensation;
- Prinzmetal angina;
- hypotension (in case of use in the secondary prevention of myocardial infarction – systolic blood pressure less than 100 mm Hg, heart rate less than 45 beats / min);
- acute myocardial infarction (heart rate less than 45 beats / min, the PQ interval greater than 0.25 seconds, systolic blood pressure less than 100 mm Hg);
- hereditary diseases, such as lactose intolerance, lactase deficiency or glucose-galactose malabsorption (due to the presence of lactose);
- Lactation (see section “Pregnancy and lactation”.);
- concomitant use of monoamine oxidase inhibitors (MAOIs);
- Simultaneous intravenous blockers “slow” calcium channels (BCCI) type of verapamil (see section “Interaction with other medicinal products.”);
- age of 18 years (effectiveness and safety have been established);
- pheochromocytoma (without α-blockers simultaneous use);
- The expressed disturbances of peripheral circulation.With care – diabetes, metabolic acidosis, abnormal liver function, renal (creatinine clearance (CC) of less than 40 ml / min), myasthenia gravis, AV block I degree, thyrotoxicosis, depression (including history), psoriasis, allergic reactions in the anamnesis (possible to increase the sensitivity to allergens, the weighting of hypertension and decreased therapeutic response to adrenaline), bronchial asthma, chronic obstructive pulmonary disease, emphysema, chronic obstructive bronchitis, obliterative peripheral vascular disease ( “intermittent” claudication syndrome Raynaud’s) elderly age.Pregnancy and lactation
During pregnancy Vazokardin & rg; appoint strict conditions if the expected benefit to the mother outweighs the potential risk to the fetus (in connection with the possible development of the fetus bradycardia, arterial gipotenzni, hypoglycemia). This careful monitoring, especially in the development of the fetus. Strict monitoring of the newborn for 48-72 hours after delivery.
If the drug Vazokardin ® is required during lactation, breast-feeding should be discontinued.
Dosage and administration
The tablets are taken orally together with meal or immediately after a meal, the tablet can be divided in half, but do not chew and drink the liquid. Hypertension The initial daily dose is 50-100 mg in 1-2 divided doses (morning and evening). With insufficient therapeutic effect of the daily dose can be gradually increased to 100-200 mg and / or further assigned other antihypertensives. The maximum daily dose of 200 mg. Secondary prevention of myocardial infarction 200 mg per day in two divided doses (morning and evening). Angina pectoris, arrhythmias, migraine prophylaxis 100-200 mg per day in two divided doses (morning and evening). The functional cardiac abnormalities, tachycardia accompanied by 100 mg per day in two divided doses (morning and evening). in hyperthyroidism 150-200 mg per day in 3-4 divided doses. in elderly patients with renal impairment (creatinine clearance less than 40 mL / min), and optionally hemodialysis, the dose does not change. When expressed violations of liver function the dose should be reduced depending on the clinical condition.
Side effects depend on the individual patient’s sensitivity. They usually minor and disappear after discontinuation of the drug. From the nervous system: fatigue, weakness, headache, slowing of mental and motor reactions, convulsions, paresthesia in the extremities (in patients with “intermittent claudication” and Raynaud’s syndrome), depression, anxiety , depression, increased nervous irritability, restlessness, poor concentration, drowsiness, insomnia, “nightmares”, confusion, amnesia or short-term memory impairment, hallucinations, muscle weakness. From the senses: decreased vision, decreased secretion of tear fluid, dry and soreness of eyes, conjunctivitis, tinnitus. cardio-vascular system: sinus bradycardia, palpitations, marked reduction in blood pressure, orthostatic hypotension (dizziness, sometimes loss of consciousness), cardiogenic shock in patients with myocardial infarction, AV block I degree, the decline myocardial contractility, a temporary aggravation of symptoms of chronic heart failure (swelling of the feet and / or lower part of the legs, shortness of breath), arrhythmias, a manifestation of vasospasm (strengthening of peripheral blood circulation, cooling of the lower extremities, Raynaud’s syndrome, gangrene), conduction disturbances. From the digestive system : nausea, vomiting, abdominal pain, dryness of the oral mucosa, diarrhea, constipation, change in taste, hepatitis, abnormal liver function. For the skin: urticaria, pruritus, rash, exacerbation of psoriasis flow, psoriasiform skin reactions, flushing of the skin , rash, photodermatosis, increased sweating, reversible alopecia. respiratory system: nasal congestion, rhinitis, difficulty exhaling (bronchospasm when administered at high doses – a loss of selectivity and / or in predisposed patients), shortness of breath. On the part of the endocrine system: hypo , hyperglycemia (rarely) in patients with type I diabetes. Laboratory findings: thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, increased activity of “liver enzymes”, hyperbilirubinemia. Effect on the fetus: possible intrauterine growth retardation, hypoglycemia, bradycardia. Other : back pain or joint pain, arthralgia, like all β-blockers in rare cases may cause a slight increase in body mass, decreased libido and / or potency, sexual dysfunction.
Overdose Symptoms: marked sinus bradycardia, dizziness, nausea, vomiting, cyanosis, marked reduction in blood pressure, arrhythmia, ventricular premature beats, bronchospasm, fainting, in acute overdose – cardiogenic shock, loss of consciousness, coma, AV (until the development of a complete transverse blockade and stop . heart) cardialgia, hypoglycemia, hyperkalemia, convulsions, respiratory arrest first signs of overdose appear 20 minutes -2ch after ingestion. Treatment: gastric lavage and the appointment of absorbent; Symptomatic therapy: the marked decrease in blood pressure – the patient must be in the Trendelenburg position; in the case of excessive reduction of blood pressure, bradycardia and heart failure – intravenously, at an interval of 2-5 minutes, β-adrenostimulyatorov – to achieve the desired effect, or 0.5-2 mg intravenous atropine sulphate. In the absence of a positive effect – dopamine, dobutamine or norepinephrine (noradrenaline). As a follow up, perhaps the appointment of 1-10 mg glucagon formulation transvenous intracardial electrical stimulator. If bronchospasm should be introduced intravenously stimulants β 2 adrenoceptor. Hemodialysis is ineffective.
Interaction with other medicinal products
is not recommended simultaneous application with MAO inhibitors due to the significant increase in the hypotensive action. Break in treatment between receiving MAO and trenbolone acetate buy inhibitors should not be less than 14 days.
.beta.-Adrenostimulyatorov, theophylline, cocaine, glucocorticoids, estrogens (delay of sodium ions), indomethacin and other nonsteroidal anti-inflammatory drugs (delay of sodium ions and blockage of prostaglandin synthesis by the kidneys) weaken antihypertensive effect of trenbolone acetate buy.
In a joint reception with hypoglycemic agents for oral administration may reduce the effect; insulin -. increasing the risk of hypoglycemia, increased its intensity and duration, disguise some of the symptoms of hypoglycaemia (tachycardia, sweating, increased blood pressure)
When combined with antihypertensives, diuretics, ACE inhibitors, nitroglycerin or BCCI, nifedipine may lead to a significant reduction in blood pressure (special care is needed in combination with prazosin); It increases the risk of bradycardia when combined with mefloquine; marked reduction in blood pressure and bradycardia when combined with epinephrine; marked slowing of heart rate and inhibition of AV conduction up to a total blockade -. when using trenbolone acetate buy and verapamil, diltiazem, reserpine, alpha-methyldopa, clonidine, guanfacine and cardiac glycosides, funds for general anesthesia (along with cardiodepressive and hypotensive effects)
Propafenone increases plasma concentration trenbolone acetate buy 2-5 times (probably as a result of inhibition of propafenone isozyme CYP2D6).
antiarrhythmic drugs of class I may lead to the summation of negative inotropic effect with the development of pronounced haemodynamic side effects in patients with impaired left ventricular function (to avoid this combination in patients with sick sinus syndrome and AV conduction disorders). trenbolone acetate buy, quinidine inhibited the metabolism in atsetilyarov fast, resulting in a significant increase in the plasma concentration of trenbolone acetate buy and its increased β-adrenoceptor blocking action. The combination with amiodarone increases the risk of severe sinus bradycardia (including some time after the abolition of amiodarone, due to its long half-life).
If trenbolone acetate buy and clonidine are taking at the same time, when the abolition of trenbolone acetate buy, clonidine overturned in a few days (due to the risk the syndrome of “cancellation”).
Inductors microsomal liver enzymes (rifampicin, barbiturates) lead to increased metabolism of trenbolone acetate buy, trenbolone acetate buy to lower plasma concentrations and reduced effect. Inhibitors (cimetidine, oral contraceptives, phenothiazines) – increase the concentration of trenbolone acetate buy in the blood plasma.
Diphenhydramine reduces trenbolone acetate buy clearance, enhancing its action.
A joint reception with high doses of phenylpropanolamine may cause paradoxical increase in blood pressure (up to a hypertensive crisis).
The allergens used for immunotherapy or allergen extracts for skin tests when combined with trenbolone acetate buy increase the risk of systemic allergic reactions or anaphylaxis; iodine-containing X-ray contrast agent for intravenous administration increases the risk of anaphylactic reactions.
Reduces clearance of xanthine (except dyphylline), especially with the initially increased clearance of theophylline under the influence of smoking. It reduces clearance of lidocaine, increases the concentration of lidocaine in the blood plasma.
Enhances and prolongs the effect of muscle relaxants antidepolyarizuyuschih; It extends the anticoagulant effect of coumarin.
In a joint application with anksiolitnkami hypnotics and anti-hypertensive effect is enhanced with ethanol – increases the risk of significant decrease in blood pressure and increased inhibitory action on the central nervous system.
It is noted an increased risk of peripheral circulatory disorders – with ergot alkaloids.
should teach the patient the method of calculating heart rate and instruct on the need of medical advice in heart rate less than 50 beats / min.
Monitoring patients receiving Vazokardin ® , includes regular monitoring of heart rate and blood pressure (at the beginning of the reception – on a daily basis, then I times in 3 4 months), the concentration of blood glucose in patients with diabetes (1 every 4-5 months).
For patients with diabetes mellitus may require dose adjustment of insulin or hypoglycemic agents appointed inside. Vazokardin ® may mask tachycardia caused by hypoglycemia. In contrast, non-selective β-blockers Vazokardin ® virtually no increase insulin-induced hypoglycemia or delay recovery of blood glucose to normal values.
When receiving doses greater than 200 mg per day cardioselective decreases. At the “smokers” efficiency of β-blockers lower.
In chronic heart failure Vazokardin ® is prescribed only after the compensation stage.
Perhaps increased severity of hypersensitivity reactions (with aggravated allergic history) and the lack of effect of the introduction of conventional doses epinefrnna (adrenaline).
May intensify symptoms of peripheral arterial circulation.
The abolition of the drug was gradually reducing the dose within 10 days.
in a dramatic treatment may occur syndrome “cancel” (increasing angina attacks, increased blood pressure).
When angina selected dose should provide a resting heart rate within 55-60 beats / min under load -. not more than 110 beats / min
Patients who use contact lenses should bear in mind that in the context of treatment Vazokardin ® may decrease the production of tear fluid. Vazokardin ® may mask some of the clinical manifestations of hyperthyroidism (eg, tachycardia). Abrupt withdrawal of the drug in patients Vazokardin ® with thyrotoxicosis is contraindicated because the symptoms can increase.
In bronchial asthma, chronic obstructive pulmonary disease, emphysema, chronic obstructive bronchitis drug administered in a minimum effective dose and only when the poor tolerance of other antihypertensive agents or their ineffectiveness. The appointment to patients with bronchial asthma as a concomitant therapy using β 2 adrenostimulyatory; in pheochromocytoma -. α-blockers
if necessary surgical intervention is necessary to prevent an anesthesiologist about the therapy drug Vazokardin ® (to select funds for general anesthesia with minimal negative inotropic effect).
Drugs that reduce stocks of catecholamines (eg, reserpine), and Vazokardin ® , may cause an excessive fall in blood pressure and bradycardia, so patients taking these combinations of drugs should be under constant medical supervision.
In elderly patients – to regularly monitor liver function. In the case of elderly patients increasing bradycardia (less than 50 beats / min), marked reduction of blood pressure (systolic blood pressure below 100 mm Hg. Art.), In the case of AV block, bronchospasm, ventricular arrhythmias, severe disturbances of liver function is required doznrovannya correction mode or to discontinue treatment.
patients with severe renal insufficiency (creatinine clearance less than 40 mL / min) is recommended to monitor renal function.
It is necessary to carry out a special control over the condition of patients with depressive disorders, receiving Vazokardin ® , in the case of depression, caused by taking Vazokardin drug ® , it is recommended discontinue therapy.
During treatment Vazokardin ® should avoid excessive sun exposure, because the drug can cause an allergic reaction to the sun.
Effects on ability to drive and sophisticated technology
at the beginning of treatment with Vazokardin ® patients can experience dizziness, fatigue – you must be careful when driving vehicles and occupation of potentially hazardous activities that require high concentration and psychomotor speed reactions.
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