Anaprilin

General characteristics. Structure:

Active agent: propranolol of 40 mg.

Pharmacological properties:

Non-selective beta adrenoblocker. Has anti-hypertensive, anti-anginal and antiarrhytmic effect. Owing to blockade of β-adrenoceptors reduces stimulated catecholamines formation of tsAMF from ATP, as a result of it reduces intracellular receipt of calcium ions, renders negative hrono-, dromo-, batmo-and inotropic action (reduces ChSS, conductivity and excitability oppresses, reduces contractility of a myocardium). At the beginning of use of OPSSOPSSOPSS β-adrenoblockers in the first 24 h increases (as a result of reciprocal increase of activity of α-adrenoceptors and elimination of stimulation β2-адренорецепторов vessels of skeletal muscles), but in 1-3 days is returned to initial, and at prolonged use decreases.
The hypotensive effect is connected with reduction of minute volume of blood, sympathetic stimulation of peripheral vessels, decrease of the activity a system renin-angiotenzinovoy (matters at patients with initial hypersecretion of a renin), sensitivity of baroreceptors of an aortic arch (there is no strengthening of their activity in response to decrease in the ABP) and influence on TsNS. The hypotensive effect is stabilized by the end of the 2nd week of course appointment.
Anti-anginal action is caused by decrease in need of a myocardium for oxygen (at the expense of a negative chronotropic and inotropic effect). Reduction of ChSS leads to lengthening of a diastole and improvement of perfusion of a myocardium. Due to increase in end diastolic pressure in a left ventricle and increases in stretching of muscle fibers of ventricles can increase oxygen requirement, especially at patients with chronic heart failure.
The antiarrhytmic effect is caused by elimination of aritmogenny factors (tachycardia, a superactivity of a sympathetic nervous system, the increased maintenance of tsAMF, arterial hypertension), reduction of speed of spontaneous excitement of sinus and ectopic pacemakers and delay of AV carrying out. Oppression of carrying out impulses is noted preferential in antegrade and to a lesser extent in retrograde the directions through an AV node and on additional ways. Belongs to the II class of antiarrhytmic means. Reduction of expressiveness of ischemia of a myocardium - due to decrease in need of a myocardium for oxygen, a postinfarction lethality can also decrease thanks to antiarrhytmic action.
Ability to prevent development of a headache of vascular genesis is caused by reduction of expressiveness of expansion of cerebral arteries owing to a beta adrenoblokady of vascular receptors, inhibition of the thrombocytes caused by catecholamines of aggregation and a lipolysis, decrease in a platelet stickness, prevention of activation of blood-coagulation factors during adrenaline release, stimulation of intake of oxygen in fabric and reduction of secretion of a renin.
Reduction of a tremor against the background of use of propranolol is caused preferential by blockade peripheral β2-адренорецепторов.
Increases atherogenous properties of blood. Strengthens reductions of a uterus (spontaneous and caused by the means stimulating a myometrium). Raises a tone of bronchial tubes. In high doses causes sedation.

Pharmacokinetics. After intake about 90% of the accepted dose, but bioavailability low owing to metabolism at "the first passing" are absorbed through a liver. Cmax in a blood plasma is reached in 1-1.5 h. Linkng with proteins of 93%. T1/2 makes 3-5 h. It is removed by kidneys preferential in the form of metabolites, in not changed look - less than 1%.

Indications to use:

Arterial hypertension; angina of exertion, unstable stenocardia; sinus tachycardia (including at a hyperthyroidism), supraventricular tachycardia, a takhisistolichesky form of atrial fibrillation, supraventricular and ventricular premature ventricular contraction, an essential tremor, prevention of migraine, alcoholic abstinence (agitation and trembling), uneasiness, a pheochromocytoma (auxiliary treatment), a diffusion and toxic craw and thyrocardiac crisis (as supportive application, including at intolerance of thyreostatic drugs), sympathoadrenal crises against the background of a diencephalic syndrome.

Route of administration and doses:

Individual. At intake the initial dose makes 20 mg, a single dose - 40-80 mg, reception frequency - 2-3
Maximum doses: at intake - 320 mg/days.

Features of use:

With care to apply at patients with bronchial asthma, HOBL, at bronchitis, dekompensirovanny heart failure, a diabetes mellitus, at a renal and/or liver failure, a hyperthyroidism, a depression, a myasthenia, psoriasis, occlusal diseases of peripheral vessels, at pregnancy, in the period of a lactation, at patients of advanced age, at children (efficiency and safety are not defined).
During treatment the exacerbation of psoriasis is possible.
At a pheochromocytoma propranolol can be applied only after alpha adrenoblocker reception.
After a long course of treatment propranolol should be cancelled gradually, under observation of the doctor.
Against the background of treatment by propranolol it is necessary to avoid in/in administrations of verapamil, diltiazem. For several days before carrying out an anesthesia it is necessary to stop reception of propranolol or to pick up anesthetic with the minimum negative inotropic effect.

Influence on ability to driving of motor transport and to control of mechanisms
At patients whose activity requires special attention the issue of propranolol use on an outpatient basis should be resolved only after assessment of individual reaction of the patient.

Side effects:

- From TsNS and a peripheral nervous system: increased fatigue, weakness, dizziness, headache, drowsiness or sleeplessness, bright dreams, depression, concern, confusion of consciousness, hallucination, tremor, nervousness, concern.
- From sense bodys: reduction of secretion of the lacrimal liquid (dryness and morbidity of eyes).
- From cardiovascular system: a sinus bradycardia, AV blockade (up to development of total cross block and a cardiac standstill), arrhythmias, development (aggravation) of chronic heart failure, decrease in the ABP, orthostatic hypotension, manifestation of a vasomotor spasm (strengthening of disturbance of peripheric circulation, a cold snap of the lower extremities, Reynaud's syndrome), a stethalgia.
- From the alimentary system: nausea, vomiting, discomfort in epigastric area, a lock or diarrhea, abnormal liver functions (dark urine, yellowness of scleras or skin, a cholestasia), taste changes, increase in activity of hepatic transaminases, LDG.
- From respiratory system: nose congestion, bronchospasm.
- From endocrine system: change of concentration of glucose of blood (hypo - or a hyperglycemia).
- From system of a hemopoiesis: thrombocytopenia (unusual bleedings and hemorrhages), leukopenia.
- Dermatological reactions: sweating strengthening, psoriazopodobny skin reactions, aggravation of symptoms of psoriasis.
- Allergic reactions: itch, skin rash, small tortoiseshell.
- Other: dorsodynia, arthralgia, decrease in a potentiality, withdrawal (strengthening of attacks of stenocardia, myocardial infarction, increase in the ABP).

Interaction with other medicines:

At simultaneous use with hypoglycemic means there is a risk of development of a hypoglycemia due to strengthening of action of hypoglycemic means.

At simultaneous use with MAO inhibitors there is a probability of development of undesirable manifestations of medicinal interaction.

Cases of development of the expressed bradycardia at use of propranolol concerning the arrhythmia caused by digitalis drugs are described.

At simultaneous use with means for an inhalation anesthesia the risk of oppression of function of a myocardium and development of arterial hypotension increases.

At simultaneous use with Amiodaronum arterial hypotension, bradycardia, fibrillation of ventricles, an asystolia are possible.

At simultaneous use with verapamil arterial hypotension, bradycardia, диспноэ are possible. Cmax in a blood plasma raises, AUC increases, the clearance of propranolol owing to oppression of his metabolism in a liver under the influence of verapamil decreases.

Propranolol does not influence verapamil pharmacokinetics.

The case of development of heavy arterial hypotension and cardiac standstill at simultaneous use with a haloperidol is described.

At simultaneous use with gidralaziny Cmax in a blood plasma and AUC propranolol raises. Believe what гидралазин can reduce a hepatic blood stream or inhibit activity of liver enzymes that leads to propranolol metabolism delay.

At simultaneous use propranolol can inhibit effects of Glibenclamidum, Glyburidum, Chlorproramidum, Tolbutamidum since non-selective beta2-adrenoblockers are capable to block β2-адренорецепторы a pancreas, connected with insulin secretion.

The emission of insulin caused by action of derivatives of sulphonylurea from a pancreas is inhibited by beta adrenoblockers that somewhat interferes with development of hypoglycemic effect.

At simultaneous use with diltiazem concentration of propranolol in a blood plasma owing to inhibition of his metabolism under the influence of diltiazem increases. The additive oppressing influence on action of the heart in connection with delay of carrying out the impulse through an AV node caused by diltiazem is observed. There is a risk of development of the expressed bradycardia, stroke and minute output considerably decreases.

At simultaneous use cases of increase in concentration of warfarin and Fenindionum in a blood plasma are described.

At simultaneous use with doxorubicine in pilot studies cardiotoxicity strengthening is shown.

At simultaneous use propranolol interferes with development of bronkhodilatiruyushchy effect of an izoprenalin, salbutamol, a terbutalin.

At simultaneous use cases of increase in concentration of Imipraminum in a blood plasma are described.

At simultaneous use with indometacin, Naproxenum, piroxicam, acetylsalicylic acid reduction of anti-hypertensive effect of propranolol is possible.

At simultaneous use with ketanseriny development of the additive hypotensive effect is possible.

At simultaneous use with a clonidine anti-hypertensive action amplifies.

At the patients receiving propranolol in case of sharp cancellation of a clonidine development of heavy arterial hypertension is possible. Believe that it is connected with increase in maintenance of catecholamines in the circulating blood and strengthening of their vasopressor action.

At simultaneous use with caffeine reduction of efficiency of propranolol is possible.

At simultaneous use strengthening of effects of lidocaine and bupivacaine (including toxic), apparently, owing to delay of metabolism of local anesthetics in a liver is possible.

At simultaneous use from lithium the carbonate described a case of development of bradycardia.

At simultaneous use the case of strengthening of side effect of Maprotilinum is described that is caused, apparently, by delay of his metabolism in a liver and cumulation in an organism.

At simultaneous use with meflokhiny QT interval increases, the cardiac standstill case is described; with morphine - the oppressing action on TsNS caused by morphine amplifies; from sodium amidotrizoaty - cases of heavy arterial hypotension are described.

At simultaneous use with nizoldipiny are possible increase in Cmax and AUC propranolol and a nizoldipin in a blood plasma that leads to heavy arterial hypotension. There is a message on strengthening of the beta blocking action.

Cases of increase in Cmax and AUC propranolol, arterial hypotension and reduction of ChSS at simultaneous use with nikardipiny are described.

At simultaneous use with nifedipine for patients with an ischemic heart disease development of the expressed arterial hypotension, increase in risk of development of heart failure and myocardial infarction is possible that can be caused by strengthening of negative inotropic effect of nifedipine.

The patients receiving propranolol have a risk of development of the expressed arterial hypotension after reception of the first dose of Prazozinum.

At simultaneous use with Prenylaminum QT interval increases.

At simultaneous use with propafenony concentration of propranolol in a blood plasma increases and toxic action develops. Believe what пропафенон inhibits metabolism of propranolol in a liver, reducing its clearance and increasing serumal concentration.

At simultaneous use of Reserpinum, other anti-hypertensive means the risk of development of arterial hypotension and bradycardia increases.

At simultaneous use Cmax and AUC of a rizatriptan raises; with rifampicin - concentration of propranolol in a blood plasma decreases; from succinylcholine chloride, Tubocurarini chloridum - change of action of muscle relaxants is possible.

At simultaneous use the clearance of theophylline owing to delay of his metabolism in a liver decreases. There is a risk of development of a bronchospasm in patients with bronchial asthma or with HOBL. Beta adrenoblockers can block an inotropic effect of theophylline.

At simultaneous use with Fenindionum cases of some increase in bleeding without changes of indicators of coagulability of blood are described.

At simultaneous use with flekainidy the perhaps additive cardiodepressive action.

Fluoxetine inhibits CYP2D6 isoenzyme that leads to oppression of metabolism of propranolol and its cumulation and can strengthen cardiodepressive action (including bradycardia). Fluoxetine and, mainly, its metabolites are characterized by long T1/2 therefore the probability of medicinal interaction remains even in several days after fluoxetine cancellation.

Quinidine inhibits CYP2D6 isoenzyme that leads to propranolol metabolism oppression, at the same time its clearance decreases. Strengthening of beta and adrenoceptor blocking action, orthostatic hypotension are possible.

At simultaneous use in a blood plasma concentration of propranolol, Chlorpromazinum, thioridazine increase. Perhaps sharp reduction of the ABP.

Cimetidinum inhibits activity of microsomal enzymes of a liver (including CYP2D6 isoenzyme), it leads to oppression of metabolism of propranolol and its cumulation: strengthening of negative inotropic effect and development of cardiodepressive action is observed.

At simultaneous use hypertensive action of Epinephrinum amplifies, there is a risk of development of heavy life-threatening hypertensive reactions and bradycardia. Bronchodilatory action of sympathomimetics (Epinephrinum, ephedrine) decreases.

At simultaneous use cases of reduction of efficiency of ergotamine are described.

There are messages on change of hemodynamic effects of propranolol at simultaneous use with ethanol.

Contraindications:

AV blockade of II and III degrees, sinuatrial blockade, bradycardia (ChSS less than 55 уд. / mines), SSSU, arterial hypotension (systolic the ABP less than 90 mm hg, especially at a myocardial infarction), chronic heart failure of IIB-III of a stage, an acute heart failure, cardiogenic shock, hypersensitivity to propranolol.

Use at pregnancy and feeding by a breast
Use of propranolol at pregnancy is possible only in that case when the estimated advantage for mother exceeds potential risk for a fruit. In need of use during this period careful observation of a condition of a fruit is necessary, for 48-72 h before childbirth propranolol should be cancelled.
It must be kept in mind that perhaps negative impact on a fruit: pre-natal growth inhibition, hypoglycemia, bradycardia.
Propranolol is emitted with breast milk. In need of use in the period of a lactation it is necessary to establish medical observation of the child or to stop breastfeeding.

Use at abnormal liver functions
With care to apply at patients at a liver failure.

Use at renal failures
With care to apply at patients at a renal failure.

Use for elderly patients
With care to apply at patients of advanced age.

Use for children
With care to apply at children (efficiency and safety are not defined).

Overdose:

There are no data.

Storage conditions:

In the dry, protected from light place.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets of 40 mg; 10 mg: 50 pieces.