2010/06/07

NEOFILIN

Pharmacological properties: theophylline (1,3-theobromine) - a natural compound, an alkaloid. Its mechanism of action is mainly due to the blocking of adenosine receptors, inhibition of phosphodiesterases, increases the content of intracellular cAMP and decrease intracellular calcium ion concentration. Consequently, the relaxation of bronchial smooth muscle, gastrointestinal tract, biliary tract cancer, coronary, cerebral and pulmonary blood vessels, dilates coronary arteries, decreases peripheral vascular resistance. The drug increases the tone of respiratory muscles (intercostal muscles and diaphragm) reduces pulmonary vascular resistance and improves oxygenation of the blood, activates the respiratory center of the medulla oblongata, increases its sensitivity to carbon dioxide, improves alveolar ventilation, which reduces the severity and reduce the frequency of episodes of apnea. Theophylline eliminates angiospasm, increases collateral blood flow and blood oxygen saturation, and a general decrease perifocal edema, cerebrospinal fluid and thus reduces intracranial pressure. It improves the rheological properties of blood, reduces blood clots, inhibits platelet aggregation (factor inhibiting platelet activation and prostaglandin F2-α), normalizes microcirculation. Has antiallergic effect by inhibiting degranulation of mast cells and reducing the level of allergy mediators (serotonin, histamine, leukotrienes). Promotes renal blood flow, has a diuretic effect due to a decrease in the reabsorption of tubular, increases the excretion of water, chloride ions, sodium, etc. The effect of drug is fully developed after 3-4 days of starting treatment.

When administered theophylline completely absorbed in the gastrointestinal tract, bioavailability is about 90%. When receiving theophylline in the form of tablets with prolonged action the maximum concentration achieved after 6 h. The binding to plasma proteins is in healthy adults - about 60% of patients with liver cirrhosis - 35%. Penetrates histohematogenous barriers, dividing in the tissues. About 90% of theophylline is metabolized in the liver with involvement of several isozymes of cytochrome P450 to inactive metabolites - 1,3-dimetilmochevoy acid, 1-metilmochevoy acid and 3-methylxanthine. Excreted mainly by the kidneys as metabolites; unchanged output in adults up to 13% in children - up to 50% of the drug. Partially allocated to breast milk. The half-life of theophylline depends on the age and the presence of concomitant diseases and of adult patients with asthma - 6-12 h in children older than 6 months - 3-4 hours, with tobacco smoking - 4-5 h, y the elderly and in heart failure, abnormal liver function, pulmonary edema, COPD and bronchitis - more than 24 h, which requires appropriate correction of the interval between doses of the drug. Therapeutic concentrations of theophylline in blood in order to achieve a bronchodilator effect - 10-20 mg / ml for the stimulative effect on the respiratory center - 5-10 ug / ml. Toxic concentration - above 20 ug / ml.

Indications: asthma, including asthma status, chronic obstructive bronchitis and pulmonary disease with symptoms of bronchial obstruction, pulmonary hypertension, sleep apnea syndrome.

APPLICATION: dose is selected individually depending on the severity of disease, body weight, age, metabolism in smokers.

In adults the initial dose is usually 0.3 1 g once a day. After 3 days in the absence of serious side effects, the dose can be increased to maintenance - 0,6 g (0,3 g, 2 times a day), in the case of predominantly nocturnal and early morning attacks - 0.6 g once in the evening. In smoking patients the initial dose is 0.3 g 1 per day, which with good endurance gradually increase every 2 days at 0,3 g to maintenance - 0,9-1,2 g (0,6 g in the evening, 0,3 -0.6 g in the morning).

For persons weighing less than 60 kg daily dose is 0.3 grams (1 time per day or 0.2 g in the evening and the morning of 0,1 g) birth weight less than 40 kg initial dose is 0.2 g 1 times day, keeping - 0,4 g (0,2 g, 2 times a day).

For children aged 12-16 years with body weight 40-60 kg initial dose is 0.3 g 1 per day. After 3 days, with good tolerance dose can be increased to maintenance - 0,6 g (0,3 g, 2 times a day).

For children aged 6-12 years weighing 20-40 kg initial dose is 0.2 g 1 per day. After 3 days, with good tolerability the dose can be increased to maintenance - 0,4 g (0,2 g, 2 times a day). The initial dose for children aged 3-6 years weighing up to 20 kg of 0.1 1 g once a day. 3 days later with good tolerability the dose can be increased to maintenance - 0,2 g (0,1 g, 2 times a day).

CONTRAINDICATIONS: Hypersensitivity to the drug's components, and xanthine derivatives (caffeine, pentoxifylline), epilepsy, peptic ulcer or duodenal ulcer, glaucoma, simultaneous reception Oleandomycin or erythromycin, hemorrhagic stroke, bleeding in the retina of the eye, acute myocardial infarction, marked coronary atherosclerosis, forerunner of internal bleeding, pregnancy and lactation, age 3 years, severe hypertension, tachyarrhythmia, hypertrophic obstructive cardiomyopathy, hyperthyroidism.

SIDE EFFECTS: headache, dizziness, agitation, tremor, anxiety, insomnia, convulsions, tachycardia, arrhythmia, lower blood pressure, discomfort and pain in the epigastric region, vomiting, heartburn, aggravation of cholecystitis, cholestatic hepatitis, increased activity of ALT, AST in serum ; allergic reactions - skin rash, itching, flu-like syndrome, difficulty in nasal breathing.

Cautions: severe disease of the cardiovascular system, liver, virus infections, the elderly, drug dose should be reduced and applied with caution. Smokers of efficacy may be reduced.

Engagement: when used with drugs theophylline and sympathomimetics with diuretic drugs is mutual reinforcement of their actions, with-adrenoceptor blockers in the therapy of lithium and their effects are mutually reduced. Pharmacological effects of theophylline may be reduced (due to increase its clearance through the induction of microsomal liver enzymes), while the use of xanthine, carbamazepine, phenytoin, rifampicin, isoniazid, terbutaline. Allopurinol, cimetidine, isoprenaline, cyclosporine A, macrolide antibiotics (erythromycin, Oleandomycin), lincomycin, oral contraceptives (estrogens) and antiserum to increase the risk of side effects of theophylline (due to the reduction of its clearance), which necessitates the correction of the dose. The risk for side effects of GCS mineralokortikoidov, means for anesthesia (increased risk of ventricular arrhythmias), xanthine and means that excite the central nervous system (increased neurotoxicity), ephedrine and efedrinsoderzhaschih drugs, in-sympathomimetics.

OVERDOSE:

Symptoms in adults: convulsions, increased body temperature, cardiac abnormalities (tachycardia, ventricular arrhythmias, hypotension).

Symptoms in children: irritability, mental disturbances, fever, nausea, cramps, tachycardia, hypotension, dyspnea.

Treatment: the cessation of drug administration, gastric lavage, irrigation, bowel combination of polyethylene glycol and salt, activated charcoal method, stimulation of excretion of theophylline from the body (forced diuresis, hemosorbtion, plasmasorption, hemodialysis, peritoneal dialysis) and of symptomatic means: when expressed nausea and vomiting - metoclopramide or ondansetron, in convulsions - diazepam.

Storage: Store in original container at 25 ° C.