Euphyllinum

General characteristics. Structure:

Active ingredient: 150 mg of Aminophyllinum.

Pharmacological properties:

Pharmacodynamics. Broncholitic means, FDE inhibitor. Represents etilendiaminovy salt of theophylline (that facilitates solubility and increases absorption). Has the bronchodilatory effect caused, apparently, by the direct weakening impact on smooth muscles of respiratory tracts and blood vessels of lungs. Believe that this action is caused by selective suppression of activity of specific FDE that leads to increase in intracellular concentration of tsAMF. Results of pilot studies of in vitro show that a main role is played, apparently, by isoenzymes III and IV types. Suppression of activity of these isoenzymes can also cause some side effects of Aminophyllinum (theophylline), including vomiting, arterial hypotension and tachycardia. Blocks adenosine (purine) receptors that can be one of action factors on bronchial tubes.

Reduces the hyperreactivity of respiratory tracts connected with a late phase of the reaction caused by inhalation of allergens by means of the unknown mechanism which does not belong to inhibition of FDE or to blockade of action of adenosine. There are messages that Aminophyllinum increases number and activity of T-suppressors in peripheral blood.

Increases mukotsiliarny clearance, stimulates reduction of a diaphragm, improves function of respiratory and intercostal muscles, stimulates a respiratory center, increases its sensitivity to carbon dioxide and improves alveolar ventilation that finally leads to decrease in weight and frequency of episodes of an apnoea. Normalizing respiratory function, promotes blood saturation by oxygen and to decrease in concentration of carbonic acid. Strengthens ventilation of the lungs in the conditions of a hypopotassemia.

Exerts the stimulating impact on action of the heart, increases force and ChSS, increases a coronary blood stream and increases the need of a myocardium for oxygen. Reduces a tone of blood vessels (mainly vessels of a brain, skin and kidneys). Has peripheral venodilatiruyushchy effect, reduces pulmonary vascular resistance, lowers pressure in a small circle of blood circulation. Increases a renal blood stream, renders moderate diuretic effect. Expands extrahepatic bilious ways. Stabilizes membranes of mast cells, slows down release of mediators of allergic reactions. Slows down aggregation of thrombocytes (suppresses a factor of activation of thrombocytes and PgE2α), increases resistance of erythrocytes to deformation (improves rheological properties of blood), reduces a thrombogenesis and normalizes microcirculation. Possesses tokolitichesky action, increases acidity of a gastric juice. In high doses possesses epileptogenic action.

Pharmacokinetics. In an organism Aminophyllinum is metabolized at physiological PH values with release of free theophylline. Bronkhodilatiruyushchy properties are shown at concentration of theophylline in a blood plasma of 10-20 mkg/ml. Concentration over 20 mg/ml is toxic. The exciting effect on a respiratory center is implemented at lower concentration - 5-10 mkg/ml.

Linkng of theophylline with proteins of plasma makes about 40%; at newborns, and also at adults with diseases binding decreases. Linkng with proteins of plasma at adults makes about 60%, newborns have 36%, at patients with cirrhosis - 36%. Gets through a placental barrier (concentration in blood serum of a fruit slightly higher, than in mother's serum). It is allocated with breast milk.

Theophylline is metabolized in a liver with the participation of several isoenzymes of P450 cytochrome, the most important of which is CYP1A2. In the course of metabolism 1,3-dimethyl uric acid, 1-methyl-uric acid and 3 methylxanthine are formed. These metabolites are removed with urine. In not changed look at adults 10% are removed. At newborns a considerable part is removed in the form of caffeine (because of immaturity of ways of his further metabolism), in not changed look - 50%.

Significant individual differences of speed of hepatic metabolism of theophylline are the reason of the expressed variability of values of clearance, concentration in plasma, an elimination half-life. Hepatic metabolism is influenced by such factors as age, addiction to tobacco smoking, a diet, diseases, at the same time carried out medicinal therapy.

Theophylline T1/2 at non-smoking patients with bronchial asthma practically without pathological changes from other bodies and systems makes 6-12 h, smokers have 4-5 h, children have 1-5 h, newborn and premature children have 10-45 h.

T1/2 of theophylline increases at elderly people and at patients with heart failure or diseases of a liver.

The clearance decreases at heart failure, abnormal liver functions, an alcoholism, a fluid lungs, a chronic obstructive pulmonary disease.

Ethylene diamine does not influence theophylline pharmacokinetics.

Indications to use:

For parenteral use: the asthmatic status (additional therapy), an apnoea of newborns, disturbance of cerebral circulation on ischemic type (as a part of a combination therapy), a left ventricular failure with a bronchospasm and disturbance of breath as Cheyn-Stokes, an edematous syndrome of renal genesis (as a part of complex therapy); acute and chronic heart failure (as a part of a combination therapy).

For intake: a bronkhoobstruktivny syndrome of various genesis (including bronchial asthma, HOBL, including emphysema of lungs, chronic obstructive bronchitis), hypertensia in a small circle of blood circulation, a pulmonary heart, night an apnoea; acute and chronic heart failure (as a part of a combination therapy).

Route of administration and doses:

The dose of drug is established individually.

Inside adults should apply 0,15 g on reception 1-3 times a day after food, to children at the rate of 7-10 mg/kg a day in 4 receptions.

If necessary the dose of drug can be increased at an interval of 2-3 days before achievement of optimum therapeutic effect.

Duration of a course of treatment from several days to several months.

Features of use:

Theophylline gets through a placental barrier. Use of Aminophyllinum at pregnancy can lead to creation of potentially dangerous concentration of theophylline and caffeine in a blood plasma of the newborn. Newborns whose mothers at pregnancy received Aminophyllinum (especially in the III trimester) need medical observation for control of possible symptoms of intoxication of theophylline.

Theophylline is emitted with breast milk. At use of Aminophyllinum for the nursing mother in the period of a lactation emergence of irritability in the child is possible.

Thus, use of Aminophyllinum at pregnancy and in the period of a lactation (breastfeeding) is possible in cases when the estimated advantage of therapy for mother exceeds potential risk for a fruit or the child.

With care to apply at heavy coronary insufficiency (an acute phase of a myocardial infarction, stenocardia), widespread atherosclerosis, a hypertrophic subaortic stenosis, frequent ventricular premature ventricular contraction, the increased convulsive readiness, at a liver and/or renal failure, a peptic ulcer of a stomach and duodenum (in the anamnesis), at recently postponed bleeding from a GIT, an uncontrollable hypothyroidism (a possibility of cumulation) or a thyrotoxicosis, at a long hyperthermia, a gastroesophageal reflux, a prostatauxe, at patients in advanced age, at children (especially inside).

Correction of the mode of dosing of Aminophyllinum can be required at heart failure, abnormal liver functions, an alcoholism, fever, ORZ.

At patients of advanced age reduction of a dose can be required.

When replacing of the applied dosage form of Aminophyllinum by another clinical observation and control of concentration of theophylline in a blood plasma is necessary.

Aminophyllinum is not applied along with other derivatives of xanthine. During treatment it is necessary to avoid the use of the foodstuff containing xanthine derivatives (strong coffee, tea).

With care apply along with anticoagulants, with other derivatives of theophylline or purine.

It is necessary to avoid simultaneous use with beta adrenoblockers.

Aminophyllinum should not be applied along with glucose solution.

Not to apply rektalno at children.

Side effects:

From TsNS: dizziness, sleep disorders, concern, tremor, spasms.

From cardiovascular system: feeling heartbeat, disturbances of a cordial rhythm; at bystry in introduction - emergence of pains in heart, decrease in the ABP, tachycardia (including at a fruit at reception in the III trimester of pregnancy), arrhythmias, decrease in the ABP, a cardialgia, increase in frequency of attacks of stenocardia.

From the alimentary system: nausea, vomiting, gastroesophageal reflux, heartburn, aggravation of a peptic ulcer, diarrhea; at long intake - anorexia.

From an urinary system: albuminuria, hamaturia.

Allergic reactions: skin rash, itch, fever.

From a metabolism: seldom - a hypoglycemia.

Local reactions: consolidation, a hyperemia, morbidity in the place of an injection; at rectal use irritation of a mucous membrane of a rectum, a proctitis.

Others: a stethalgia, a tachypnea, feeling of inflows to the person, an albuminuria, a hamaturia, a hypoglycemia, strengthening of a diuresis, the increased sweating.

Interaction with other medicines:

At simultaneous use to sympathomimetics there is mutual strengthening of action; with beta adrenoblockers and drugs of lithium - action mutually decreases. Intensity of action of Aminophyllinum can decrease (owing to increase in its clearance) at simultaneous use with phenobarbital, rifampicin, an isoniazid, carbamazepine, Sulfinpyrazonum, Phenytoinum, and also at smokers.

Intensity of action of Aminophyllinum can increase (owing to reduction of its clearance) at simultaneous use with antibiotics from group of macroleads, lincomycin, with hinolona, Allopyrinolum, beta adrenoblockers, Cimetidinum, Disulfiramum, fluvoksaminy, hormonal contraceptives for intake, izoprenaliny, viloksaziny and at vaccination against flu.

Derivatives of xanthine can exponentiate the hypopotassemia caused by action of stimulators β2-адренорецепторов, corticosteroids and diuretics.

Antidiarrheal drugs and enterosorbents reduce absorption of Aminophyllinum.

Pharmaceutical it is incompatible with solutions of acids.

Contraindications:

Heavy arterial hyper - or hypotension, tachyarrhythmias, a peptic ulcer of a stomach and duodenum in an aggravation phase, hyperacid gastritis, heavy abnormal liver functions and/or kidneys, epilepsy, a hemorrhagic stroke, an eye retinal apoplexy, simultaneous use with ephedrine for children, children's age (up to 3 years, for the prolonged peroral forms - up to 12 years), hypersensitivity to Aminophyllinum and theophylline.

Overdose:

It is shown by diarrhea, a gastralgia, a loss of appetite, a tachypnea, motive excitement, spasms, a photophobia, uneasiness, a tremor of extremities, tachycardia, a hyperemia of integuments of the person, gastrointestinal bleeding, vomiting, nausea, ventricular arrhythmias, sleeplessness. At a serious poisoning epileptoidny attacks, falling of blood pressure, a hypopotassemia, a hyperglycemia, confusion of consciousness, a necrosis of muscular tissue, a hypoxia, a renal failure with a myoglobinuria, a metabolic acidosis are registered.

The gastric lavage, and intestines by a combination of electrolytes and polyethyleneglycol, purpose of enterosorbents, performing symptomatic therapy, a hemodialysis, plazmosorbtion, hemosorption, artificial diuresis is required. At development of a convulsive syndrome carry out an oxygenotherapy, provide passability of respiratory tracts. For stopping of an attack intravenously enter 0,1-0,3 mg/kg of diazepam. At severe vomiting and nausea appoint Ondansetron and Metoclopramidum.

Storage conditions:

List B. To store in dry, protected from light and the place, unavailable to children, at a temperature not above 30 °C.

Issue conditions:

According to the recipe

Packaging:

10 pieces - planimetric strip packagings (3) - packs cardboard.