Metoprolol organic chemistry

General characteristics. Structure:

Active ingredient: 25 mg or 50 mg of a metoprolol of tartrate.

Excipients: hydrophosphate calcium dihydrate, sodium carboxymethylstarch (примогель), cellulose microcrystallic, K90 povidone (пласдон K90).

The heart drug possessing anti-anginal, anti-hypertensive and antiarrhytmic action.

Pharmacological properties:

Pharmacodynamics. Metoprolol Organika treats cardioselective blockers β1-адренорецепторов, not having internal sympathomimetic activity and membrane stabilizing properties. Possesses anti-hypertensive, anti-anginal and antiarrhytmic action. OPSS at the beginning of use of beta adrenoblockers (in the first 24 h after intake) – increases (as a result of reciprocal increase of activity of alpha adrenoceptors and elimination of stimulation β2-адренорецепторов) which in 1-3 days is returned to initial, and at long appointment – decreases.

Anti-hypertensive action is caused by reduction of cordial emission and synthesis of a renin in kidneys, activity oppression system renin-angiotensin-aldosteronovoy (has bigger value at patients with initial hypersecretion of a renin) iTsNS, recovery of sensitivity of baroreceptors of an aortic arch (there is no strengthening of their activity in response to decrease in the ABP) and, as a result, reduction of peripheral sympathetic influences. Reduces raised by the ABP at rest, at a physical tension and a stress.

The anti-anginal effect is defined by decrease in need of a myocardium for oxygen as a result of ChSS urezheniye (lengthening of a diastole and improvement of perfusion of a myocardium) and contractility, and also decrease in sensitivity of a myocardium to influence of a sympathetic innervation. Reduces number and weight of attacks of stenocardia and increases tolerance to an exercise stress. At supraventricular tachycardia, atrial fibrillation, sinus tachycardia at functional heart diseases and a hyperthyroidism urezhat ChSS or can even lead to recovery of a sinoatrial rate. Prevents development of migraine. At use in average therapeutic doses, in difference from non-selective beta adrenoblockers, exerts less expressed impact on the bodies containing β2-адренорецепторы (a pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchial tubes and a uterus) and on carbohydrate metabolism. At use in high doses (more than 100 mg/days) renders the blocking effect on both subtypes of β-adrenoceptors..........

Pharmacokinetics. After administration of drug inside almost completely (about 95%) it is absorbed from a GIT. Cmax in a blood plasma is reached in 1.5-2 h. Bioavailability increases at meal by 20-40% and increases in the course of course treatment. Linkng with proteins of plasma - 10%. Gets through GEB and a placental barrier, it is allocated with breast milk. It biotransformirutsya intensively in a liver with formation of metabolites, two metabolites of Metoprolol Organik have beta and adrenoceptor blocking activity. CYP2D6 isoenzyme participates in Metoprolol Organik's metabolism. T1/2 makes about 3.5 h of plasma. The general speed of removal from plasma (clearance) makes about 1 l/min. About 3% - in not changed look, the rest - in the form of metabolites are removed generally by kidneys (95%). At a renal failure removal of metabolites decreases and practically removal of not changed Metoprolol Organik does not change.

At cirrhosis Metoprolol Organik's bioavailability increases.

At patients of advanced age considerable change in Metoprolol Organik's pharmacokinetics in comparison with patients of young age is not observed.

The renal failure does not demand a drug dose decline, and at abnormal liver functions the dose of drug has to be lowered.

Indications to use:

— arterial hypertension (in monotherapy or in a combination with other antihypertensives);

— the functional disturbances of cordial activity which are followed by tachycardia;

— Ischemic heart disease: a myocardial infarction (secondary prevention — complex therapy), prevention of attacks of stenocardia;

— disturbances of a heart rhythm (supraventricular tachycardia; ventricular premature ventricular contraction);

— hyperthyroidism (complex therapy);

— prevention of attacks of migraine.

Route of administration and doses:

Tablets pripimat inside along with meal or right after food, tablets can be halved, but not to chew and wash down with liquid.

Arterial hypertension. The initial daily dose makes 50-100 mg in 1-2 receptions (in the morning and in the evening). At insufficient therapeutic effect the daily dose can be gradually increased to 100-200 mg and/or other anti-hypertensive means are in addition appointed. The maximum daily dose - 200 mg.

Secondary prevention of a myocardial infarction. 200 mg/days in two steps (in the morning and in the evening).

Stenocardia, arrhythmias, prevention of attacks of migraine. 100-200 mg/days in 2 receptions (in the morning and in the evening).

The functional disturbances of cordial activity which are followed by tachycardia. 100 mg/days in 2 receptions (in the morning and in the evening)

At a hyperthyroidism. 150-200 mg/days in 3-4 receptions.

At elderly patients, at renal failures (KK less than 40 ml/min.), and also in need of carrying out a hemodialysis, the dose is not changed.

At the expressed abnormal liver functions the dose of drug should be lowered depending on a clinical state.

Features of use:

With care: сахарньй diabetes, a metabolic acidosis, bronchial asthma, a chronic obstructive pulmonary disease, emphysema, chronic obstructive bronchitis, abnormal liver functions, kidneys (clearance of creatinine less than 40 ml/min.), a myasthenia, a pheochromocytoma (at simultaneous use of alpha adrenoblockers), a thyrotoxicosis, a depression (including the anamnesis), psoriasis, disturbances of peripheric circulation (the alternating lameness, Reynaud's syndrome), pregnancy, children's age (efficiency safety are not defined), advanced age, the burdened allergological anamnesis, AV blockade of the I degree.

Control of the patients accepting beta adrenoblockers includes observation of ChSS and. The ABP (at the beginning of reception - daily, then - 1 time in 3-4 months), concentration of glucose in blood at patients with a diabetes mellitus (1 time in 4-5 months). It is necessary to train the patient in a technique of calculation of ChSS and to instruct about need of medical consultation at ChSS less than 50/min.

Strengthening of expressiveness of allergic reactions (against the background of the burdened allergological anamnesis) and lack of effect of introduction of usual doses of Epinephrinum is possible.

At elderly patients it is recommended to exercise control of function of kidneys (1 times in 4-5 months).

Can strengthen symptoms of disturbance of peripheric arterial circulation.

At an angina of exertion the picked-up dose of drug has to provide ChSS at rest within 55-60 уд. / mines, at loading - no more than 110 уд. / min.

At smokers efficiency of beta adrenoblockers is lower.

Metoprolol Organika can mask some clinical displays of a thyrotoxicosis (for example, tachycardia). Sharp cancellation at patients with a thyrotoxicosis is contraindicated as it is capable to strengthen symptomatology.

At a diabetes mellitus can mask the tachycardia caused by a hypoglycemia. Unlike non-selective beta adrenoblockers practically does not strengthen the hypoglycemia caused by insulin and recovery of concentration of glucose in blood to normal value does not detain.

In need of use for patients with the accompanying bronchial asthma it is necessary to apply beta2-adrenomimetik in addition; at a pheochromocytoma - alpha adrenoblockers.

In need of carrying out surgical intervention it is necessary to warn the anesthesiologist about Metoprolol Organik's reception (the choice of drug for the general anesthesia with the minimum negative inotropic effect), drug withdrawal is not recommended.

In case of the accruing bradycardia (less than 50/mines), arterial hypotension (systolic the ABP is lower than 100 mm hg), AV blockade, a bronchospasm, ventricular arrhythmias, heavy disturbances of functions of a liver and kidneys it is necessary to reduce a dose or to stop treatment.

It is recommended to stop therapy at emergence of skin rashes and development of the depression caused by reception of beta adrenoblockers.

Drug withdrawal is carried out gradually, reducing a dose within 10 days. At the sharp termination of treatment there can be a syndrome of "cancellation" (strengthening of attacks of stenocardia, increase, the ABP). Special attention at drug withdrawal needs to be paid to patients with stenocardia.

The patients using contact lenses have to consider that against the background of treatment by beta adrenoblockers reduction of products of the lacrimal liquid is possible.

Influence on ability to driving of motor transport and to control of mechanisms. During treatment it is necessary to be careful when driving motor transport and occupations other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

During pregnancy appoint taking into account careful weighing of a ratio advantage/risk, especially, in early durations of gestation (in connection with possible development in the newborn of bradycardia, hypotension, a hypoglycemia and paralysis of breath). Treatment needs to be interrupted for 48-72 h before childbirth. When it is impossible, it is necessary to provide strict observation of the newborn during 48-72 h after delivery. If administration of drug Metoprolol Organika is necessary in the period of a lactation, breastfeeding needs to be stopped.

At the expressed abnormal liver functions the dose of drug should be lowered depending on a clinical state.

At renal failures (KK less than 40 ml/min.), and also in need of carrying out a hemodialysis, the dose is not changed.

At elderly patients, at renal failures (KK less than 40 ml/min.), and also in need of carrying out a hemodialysis, the dose is not changed.

Side effects:

Below the listed side effects classified as follows: often (≥1%, but <10%), infrequently (≥0.1%, but <1%), it is rare (≥0.01%, but <0.1%), is very rare (<0.01%).

From a nervous system: often - weakness, dizziness and a headache; infrequently - decrease in concentration of attention, drowsiness/sleeplessness, nightmares, a depression, muscular spasms, paresthesias in extremities (at patients with the alternating lameness and Reynaud's syndrome); seldom - nervousness, alarm, a tremor, spasms, a depression, decrease in attention; very seldom - slackness, increased fatigue, concern, confusion of consciousness or short-term loss of memory, a hallucination, an adynamy, a myasthenia.

From sense bodys: seldom - decrease in sight, a xerophthalmia, decrease in secretion of the lacrimal liquid, dryness and morbidity of eyes, conjunctivitis, a sonitus, decrease in hearing.

From cardiovascular system: often - a sinus bradycardia, heartbeat, decrease in the ABP, orthostatic hypotension (dizziness, sometimes a loss of consciousness), a cold snap of the lower extremities; infrequently - heart failure, AV blockade, an edematous syndrome, a stethalgia; seldom - decrease in contractility of a myocardium, arrhythmia, manifestation of a vasomotor spasm (strengthening of disturbance of peripheric circulation), disturbance of conductivity of a myocardium, a cardialgia; very seldom - aggravation of earlier existing AV conductivity disturbances.

From the alimentary system: often - nausea, an abdominal pain, a lock or diarrhea; infrequently - vomiting; seldom - dryness of a mucous membrane of an oral cavity, in some cases - an abnormal liver function (dark urine, yellowness of scleras or skin, a cholestasia), disturbance of flavoring feelings.

From integuments: infrequently - rash, dystrophic changes of skin; seldom - a reversible alopecia; very seldom - a photosensitization, an exacerbation of psoriasis, an itch, an erythema, a small tortoiseshell, a hyperhidrosis.

From respiratory system: often - an asthma; infrequently - a bronchospasm; seldom - vasculomotor rhinitis, диспноэ.

From endocrine system: seldom - a hyperglycemia (at patients with a diabetes mellitus 2 types), a hypoglycemia (a diabetes mellitus of 1 type), a hypothyroidism.

Allergic reactions: very seldom - urticaria, a skin itch, rash.

Laboratory indicators: seldom - thrombocytopenia (unusual bleedings and hemorrhages), an agranulocytosis, a leukopenia, increase in activity of liver enzymes; very seldom - a hyperbilirubinemia.

Influence on a fruit: very seldom - a pre-natal growth inhibition, a hypoglycemia, bradycardia.

Others: infrequently - a dorsodynia or joints, increase or a degrowth of a body, decrease in a libido and/or potentiality, at the sharp termination of treatment - a withdrawal (strengthening of attacks of stenocardia, increase in the ABP), rhinitis, arthritis, Peyroni's disease.

Interaction with other medicines:

At simultaneous use:

- antiarrhytmic drugs (hininopodobny means and Amiodaronum) strengthening of inotropic and dromotropic effects is possible;

- blockers of calcium channels (verapamil, diltiazem, nifedipine) or other antiaritmika there is a decrease in a mshgutny and stroke output of heart, ChSS, and at in administration of verapamil there is a threat of a stop
hearts;

- barbiturates Metoprolol Organik's metabolism accelerates that leads to reduction of its efficiency;

- inductors or inhibitors of microsomal enzymes change of concentration of Metoprolol Organik in plasma - decrease at rifampicin reception, - increase at reception of Cimetidinum, ethanol, a gidralazin, inhibitors of the return serotonin reuptake (a paroksetin, fluoxetine, sertraline), peroral contraceptives is possible;

- indometacin and other NPVP, TsOG inhibitors decrease in an antigipertenzivnogodeystviye is possible;

- blockers of calcium channels, cardiac glycosides, Reserpinum, nitrates the risk of development of arterial hypotension, bradycardia, AV blockade, negative inotropic effect increases;

- insulin and peroral antidiabetic means increase in risk of development of a hypoglycemia;

- drugs, inhalation anesthetics and some other drugs influencing TsNS, in particular somnolent drugs (to bromazepa, lorazepam), tranquilizers (chlordiazepoxide, trimetozine, Tofizopamum), three - and tetracyclic antidepressants mutual potentiation of cardiodepressive effect;

- the allergens used for an immunotherapy, or extracts of allergens for skin tests the risk of development of heavy system reactions and an anaphylaxis increases;

- iodinated X-ray contrast medicines for in/in introductions increase risk of development of anaphylactic reactions;

- Norepinephrinum, Epinephrinum and other sympathomimetics the risk of development of arterial hypertension increases;

- a fenilpropanolamina in high doses - paradoxical increase in the ABP (up to hypertensive crisis);

- a clonidine - risk of the expressed increase in the ABP at sharp cancellation of a clonidine against the background of a concomitant use Metoprolol Organik therefore in case of cancellation of a clonidine, the gradual termination of reception of Metoprolol Organik needs to be begun some days before his cancellation;

- sympathomimetic means, ganglioblokator, other blockers of β-adrenoceptors ((((((((((for example, eye drops), MAO inhibitors of V type careful monitoring of a condition of the patient is necessary;

- diazepam decrease in clearance and increase in AUC diazepam is possible that can lead to strengthening of its effects and reduction of speed of psychomotor reactions;

- lidocaine lidocaine removal disturbance is possible;

- fluoxetine leads to oppression of metabolism of Metoprolol Organik and his cumulation that can strengthen cardiodepressive action and cause bradycardia, the probability of medicinal interaction remains even in several days after cancellation;

- fluoxetine. The case of development of a lethargy is described;

- ciprofloxacin - reduction of clearance of Metoprolol Organik from an organism;

- ergotamine strengthening of disturbances of peripheric circulation is possible;

- estrogen anti-hypertensive action of Metoprolol Organik decreases;

- a mibefradila at patients with low activity of an isoenzyme of CYP2D6 increase in concentration of Metoprolol Organik in a blood plasma and increase in risk of development of toxic effects is possible.

Contraindications:

— cardiogenic shock;

— AV blockade of the II-III degree (without artificial pacemaker);

— sinuatrial blockade;

— sick sinus syndrome;

— heavy bradycardia (ChSS less than 50 уд. / mines);

— chronic heart failure in a decompensation stage;

— Printsmetal's stenocardia;

— acute myocardial infarction (ChSS less than 45 уд. / mines, PQ interval more than 0.25 sec., systolic ABP less than 100 mm hg);

— lactation period;

— concomitant use of MAO inhibitors;

— simultaneous in/in introduction of blockers of slow calcium channels like verapamil, diltiazem;

— age of 18 years (efficiency and safety are not established);

— a pheochromocytoma (without simultaneous use of alpha adrenoblockers);

— heavy disturbances of peripheric circulation;

— severe forms of bronchial asthma and chronic obstructive pulmonary disease;

— hypersensitivity to Metoprolola Organik or to other components of drug, other beta adrenoblockers.

Overdose:

Symptoms: the expressed sinus bradycardia, dizziness, AV blockade (up to development of total cross block and a cardiac standstill), the expressed decrease in the ABP, a faint, arrhythmia / ventricular premature ventricular contraction, an acute heart failure; cardiogenic shock, cardiac standstill, bronchospasm, loss of consciousness, coma, nausea, vomiting, cyanosis, hypoglycemia, spasms. The first signs of overdose are shown in 20 min. - 2 h after administration of drug.

Treatment: a gastric lavage and purpose of the adsorbing medicines, symptomatic therapy: at the expressed decrease in the ABP — the patient has to be in the provision of Trendelenburga; in case of excessive decrease in the ABP, bradycardia and heart failure - in/in introduction with an interval of 2-5 min. beta адреностимуляторов - before achievement of desirable effect or in/in introduction of 0.5-2 mg of Atropini sulfas. In the absence of positive effect — a dopamine, Dobutaminum or Norepinephrinum. As the subsequent measures statement of a transvenoznogointrakardialny electrostimulator is possible. At a bronchospasm it is necessary to enter into beta-adrenergic agonists. At spasms - slow in/in administration of diazepam. The hemodialysis is inefficient.

Storage conditions:

To store in the place protected from light at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

20 pieces - banks (1) of light-protective glass - a pack cardboard.
30 pieces - banks (1) of light-protective glass - a pack cardboard.
50 pieces - banks (1) of light-protective glass - a pack cardboard.
60 pieces - banks (1) of light-protective glass - a pack cardboard.
10 pieces - packagings planimetric cell (2) - packs cardboard.
10 pieces - packagings planimetric cell (3) - packs cardboard.
10 pieces - packagings planimetric cell (5) - packs cardboard.
10 pieces - packagings planimetric cell (6) - packs cardboard.
20 pieces - banks polymeric (1) - packs cardboard.
30 pieces - banks polymeric (1) - packs cardboard.
50 pieces - banks polymeric (1) - packs cardboard.
60 pieces - banks polymeric (1) - packs cardboard.