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The total peripheral resistance at the beginning of the use of β-blockers (in the first 24 hours after oral administration) – increases (as a result of increasing activity retsiproktnogo α-adrenoceptor stimulation and removal of .beta. 2 adrenoceptor) which after 1-3 days back to the original, but with long-term appointment – is reduced.
Acute antihypertensive dianabol pills action is due to a decrease in cardiac output, stable antihypertensive effect develops within 2-3 weeks due to a decrease in the synthesis of renin, and the accumulation of plasma renin activity, inhibition of renin activity angiotensin system (of great importance in patients with baseline renin hypersecretion) and central nervous system, reduction of the aortic arch baroreceptor sensitivity (not enhance their activity occurs in response to a decrease in blood pressure) and, ultimately, decreased peripheral sympathetic effects. Reduces high blood pressure at rest, exertion and stress.
Antiangialny effect is determined by a decrease in myocardial oxygen demand by reducing heart rate (diastole lengthening and improving myocardial perfusion) and contractility, as well as a decrease in the sensitivity of the myocardium to the effects of the sympathetic innervation. Reduces the number and severity of angina attacks and increases exercise tolerance.
Blood pressure decreased after 15 minutes, the maximum – in 2 hours or reduction continued for 6 hours and diastolic blood pressure changes slower: a steady decline is observed after several weeks of continuous administration.
Antiarrhythmic effect due the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP levels, hypertension), decrease in the rate of spontaneous excitation of the sinus and ectopic pacemakers and slowing of atrioventricular conduction (primarily 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 the heart rate, and may even lead to the restoration of sinus rhythm.
It prevents the development of migraine.
when used in medium-therapeutic doses, unlike nonselective beta-blockers, has a less pronounced effect on the organs that contain β 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 β-adrenoceptor subtypes.

Pharmacokinetics
Metoprolol is rapidly and almost completely (95%) absorbed in the gastrointestinal tract. The maximum plasma concentration is reached 1-2 hours after ingestion. The half-life averages 3.5 hours (ranging from 1 hour up to 9 hours).
The bioavailability was 50% when the first reception and increases to 70% when applied repeatedly. Eating increases bioavailability by 20 – 40%. The bioavailability of metoprolol increased by cirrhosis of the liver.
The connection to plasma proteins averaged 10%.
The drug penetrates the blood-brain and placental barriers. Provided in the breast milk in small amounts.
It is metabolized in the liver. Metabolites not possess pharmacological activity. 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 down the metabolism of the drug, and in the cases of liver function failure, the dose should be reduced.
Do not removed by hemodialysis.

Indications

– Arterial hypertension (as monotherapy or in combination with other antihypertensive drugs), including hyperkinetic type of tachycardia
– ischemic heart disease: myocardial infarction (secondary prevention, complex therapy), prevention of angina attacks;
– cardiac arrhythmias (supraventricular tachycardia , ventricular premature beats)
– gepertireoz (complex therapy);
– the prevention of migraine attacks.

Contraindications

– Hypersensitivity to metoprolol or other ingredients, other beta-blockers;
– cardiogenic shock;
– antrioventrikulyarnaya (AV) block II – III degree;
– sinoatrial (SA) block;
– sick sinus syndrome;
– bradycardia;
– heart failure decompensated;
– 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.
– lactation (see section “Pregnancy and lactation. ‘);
– simultaneous reception of MAO inhibitors or simultaneous intravenous administration of verapamil (see “Interaction with other medicinal products”).
– the age of 18 years (effectiveness and safety have been established).

Precautions (see also “Special instructions.) – Diabetes, metabolic acidosis, bronchial asthma, chronic obstructive pulmonary disease (emphysema, chronic obstructive bronchitis), obliterating peripheral vascular disease (” intermittent “claudication, Raynaud’s syndrome), chronic liver and / or renal failure, myasthenia gravis, pheochromocytoma, AV block I degree, thyrotoxicosis, depression (including history), psoriasis, pregnancy, old age.

Pregnancy and lactation.

During pregnancy, taking into account the prescribed ratio of benefit / risk (in connection with the development of fetal bradycardia, hypotension, hypoglycemia). This careful monitoring, especially in the development of the fetus. Strict monitoring of the newborn for 48-72 hours after the delivery.
The effect of metoprolol on the newborn, breastfeeding is not known, so women taking METOKARD should stop breastfeeding.

Dosing and Administration

The tablets are taken orally simultaneously with the adoption of food or immediately after a meal, the tablets 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 dianabol pills therapeutic effect daily dose can be gradually increased up to 100 – 200 mg, and / or additional administration of other antihypertensive agents.
The maximum daily dose of 200 mg.

Angina pectoris, arrhythmia, migraine prophylaxis
100 – 200 mg per day in two divided doses (morning and evening).

Secondary prevention of myocardial infarction
200 mg per day in two divided doses (morning and evening).

Functional disorders of cardiac activity, accompanied by palpitations
100 mg per day in two divided doses (morning and evening).

In elderly patients with impaired renal function, as well as the need for dialysis dose is not changed.

If abnormal liver function the dose should be reduced depending on the clinical condition.

Side effect

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 responses. Rare: paresthesia of the extremities (in patients with “intermittent claudication” and Raynaud’s syndrome), depression, anxiety, decreased alertness, drowsiness, insomnia, “nightmares”, confusion, or short-term memory impairment, muscle weakness. From the sensory organs: rarely – decreased vision, decreased secretion of tear fluid, dryness and soreness of the eyes, conjunctivitis, tinnitus. cardio-vascular system: sinus bradycardia, heart rate, lowering blood pressure, orthostatic hypotension, dizziness, and sometimes loss of consciousness). Rarely – reduction of myocardial contractility, a temporary aggravation of symptoms of chronic heart failure (edema, 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), conduction disturbances infarction. With the digestive system: nausea, vomiting, abdominal pain, dry mouth, diarrhea, constipation, change in taste, abnormal liver function. For the skin: urticaria, pruritus, rash, exacerbation of psoriasis, psoriasiform skin reactions, flushing of the skin, rash , photodermatosis, increased sweating, reversible alopecia. respiratory system: nasal congestion, difficulty exhaling (bronchospasm when administered at high doses – a loss of selectivity and / or in predisposed patients), dyspnea. On the part of the endocrine system: hyperglycemia in patients with non-insulin dependent diabetes mellitus hypothyroidism. Laboratory findings: rarely – thrombocytopenia (unusual bleeding and hemorrhage), agranulocytosis, leukopenia, increased activity of “liver enzymes”, is extremely rare – hyperbilirubinemia. Effect on the fetus: possible intrauterine growth retardation, hypoglycemia, bradycardia.Other: pain in the back or joints, like all beta-blockers, and in rare cases may cause a slight increase in body mass, decreased libido and / or potency.

 

Overdose

Symptoms: expressed severe sinus bradycardia, dizziness, nausea, vomiting, cyanosis, marked reduction in blood pressure, arrhythmia, ventricular ekstasistoliya, bronchospasm, fainting, in acute overdose – cardiogenic shock, loss of consciousness, coma, antrioventrikulyarnaya blockade (until the development of a complete transverse blockade . and cardiac arrest), cardialgia
The first signs of overdose appear within 20 minutes – 2 hours 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 event of excessive reduction in blood pressure, bradycardia and heart failure – in / at intervals of 2-5 minutes adrenostimulyatorov beta – to achieve the desired effect or / 0.5 – 2 mg atropine sulfate. With no positive effect – dopamine, dobutamine or norepinephrine (noradrenaline). as a follow up, perhaps the appointment of 1 – 10 mg of glucagon production transvenous intracardial electrical stimulator .. If bronchospasm should be entered in / stimulants beta-2 adrenergic receptors dianabol pills metoprolol poorly displayed by hemodialysis.

 

Interaction with other drugs

Not recommended simultaneous application with MAO inhibitors due to the significant increase in the hypotensive action. Break in treatment between receiving MAO and metoprolol inhibitors should not be less than 14 days.
Simultaneous in / with the introduction of verapamil can cause heart failure.
Co-administration of nifedipine results in significant reduction in blood pressure.
Means for inhalation general anesthesia (derivatives of hydrocarbons) increase the risk of depression function . infarction and of arterial hypotension
Beta adrenostimulyatorov, theophylline, cocaine, etrog (sodium retention), indomethacin and other nonsteroidal anti-inflammatory drugs (sodium retention and blockage of prostaglandin synthesis by the kidneys) weaken hypotensive effect.
increased inhibitory action is noted in the central nervous system – with the standard ; cardiodepressive summation effect – with the means for general anesthesia; increased risk of peripheral circulatory disorders – with ergot alkaloids.
In a joint reception with hypoglycemic agents for oral administration may reduce the effect; insulin -. increasing the risk of hypoglycemia, increased its severity and extension, masking some symptoms of hypoglycemia (tachycardia, sweating, increased blood pressure)
When combined with antihypertensives, diuretics, nitroglycerin or blockers of slow calcium channels may develop sharp decline in blood pressure (special caution is needed in combination with prazosin); an increase in the severity of deceleration in heart rate and suppression of atrioventricular conduction -. when using metoprolol and verapamil, diltiazem, antiarrhythmics (amiodarone), reserpine, alpha-methyldopa, clonidine, guanfacine, funds for general anesthesia and cardiac glycosides
If metoprolol and clonidine are taking at the same time, then the cancellation of metoprolol, clonidine overturned in a few days (due to “cancel” the risk of the syndrome).
Inductors of microsomal liver enzymes (rifampicin, barbiturates) lead to increased metabolism of metoprolol, a decrease of metoprolol plasma concentrations and a decrease in effect. Inhibitors (cimetidine, oral contraceptives, phenothiazines) – increase the concentration in plasma.
The allergens used for immunotherapy, or allergen extracts for skin tests when combined with metoprolol, increase the risk of systemic allergic reactions or anaphylaxis; iodine-containing contrast media for the on / in the increase 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; Extend the anticoagulant effect of coumarin.
When combined with ethanol increases the risk of significant decrease in blood pressure.
Tri- and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), hypnotics, sedatives and drugs increase CNS depression.

special instructions

Monitoring of patients taking beta-blockers, including regular monitoring of heart rate (HR) and blood pressure, the content of blood glucose in diabetic patients. If necessary, for patients with diabetes, the dose of insulin or hypoglycemic agents appointed inside, be selected individually.
It should teach the patient’s heart rate calculation method and instruct on the need of medical advice in heart rate less than 50 beats / min. When you receive a dose greater than 200 mg per day decreases cardioselective.
In heart failure dianabol pills treated with metoprolol begin only after the compensation stage.
Increased severity of hypersensitivity reactions are possible (with aggravated allergic history) and the lack of effect of the introduction of the usual doses of epinephrine (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 “cancel” syndrome (increased angina attacks, high blood pressure).
Particular attention is to remove the drug should be given to patients with angina.
angina voltage selected dose should ensure that the heart rate at rest within 55-60 beats / min, a load – no more than 110 beats / min.
Patients who use contact lenses should bear in mind that during treatment with beta-blockers may reduce the production of the tear liquid.
metoprolol may mask some of the clinical manifestations 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.
If necessary, the appointment of patients with asthma, as concomitant therapy using beta-2 adrenostimulyatorov; with pheochromocytoma -. alpha-blockers
if necessary surgical intervention must notify the anesthesiologist of the therapy (means choice for general anesthesia with minimal negative inotropic effects), removal of the drug is not recommended.
Drugs that reduce stocks of catecholamines (eg, reserpine), may enhance the action beta-blockers, so patients taking these combinations of drugs should be under constant supervision of a physician to identify excessive reduction in blood pressure and bradycardia.
In elderly patients – to regularly monitor liver function. Correction of dosage regimen is required only 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.), Atrioventricular block, bronchospasm, ventricular arrhythmias, severe liver dysfunction sometimes you need to stop treatment.
Patients with severe renal impairment is recommended to monitor renal function. There should be a special control over the condition of patients with depressive disorders, receiving metoprolol; in the case of depression, caused by the intake of beta-blockers, it is recommended to discontinue therapy.
Due to the lack of sufficient clinical data product is not recommended for use in children.

Effects on ability to drive and sophisticated technology

At the beginning of treatment with metoprolol patients can experience dizziness, fatigue. In this case, they should refrain from driving motor vehicles and activities potentially hazardous activities that require high concentration and psychomotor speed reactions. Subsequently, dose definition of security is carried out individually. steroiden kaufen

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