Euphylline, ampoules 2.4%, 5ml, 10pcs – Novosibkhimpharm

Composition

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1 ml of solution for intravenous use contains: Active ingredient:

aminophylline 24 mg

Pharmacological action

Euphylline is a bronchodilator, PDE inhibitor. It is an ethylenediamine salt of theophylline (which facilitates solubility and increases absorption). It has a bronchodilating effect, apparently due to a direct relaxing effect on the smooth muscles of the respiratory tract and blood vessels of the lungs. It is believed that this effect is caused by selective suppression of the activity of specific PDEs, which leads to an increase in the intracellular concentration of cAMP. The results of in vitro experimental studies show that the main role seems to be played by isoenzymes of types III and IV. Inhibition of the activity of these isoenzymes may also cause some side effects of aminophylline (theophylline), including vomiting, hypotension, and tachycardia. Blocks adenosine (purine) receptors, which may be one of the factors of action on the bronchi.

Reduces airway hyperreactivity associated with the late-phase reaction caused by allergen inhalation, through an unknown mechanism that does not relate to PDE inhibition or blockage of adenosine action. There are reports that aminophylline increases the number and activity of T-suppressors in the peripheral blood. Increases mucociliary clearance, stimulates diaphragm contraction, improves respiratory and intercostal muscle function, stimulates the respiratory center, increases its sensitivity to carbon dioxide, and improves alveolar ventilation, ultimately leading to a reduction in the severity and frequency of apnea episodes. By normalizing the respiratory function, it helps to saturate the blood with oxygen and reduce the concentration of carbon dioxide. Increases lung ventilation in conditions of hypokalemia.

It has a stimulating effect on the activity of the heart, increases strength and heart rate, increases coronary blood flow and increases the need for oxygen in the myocardium. Reduces the tone of blood vessels (mainly blood vessels of the brain, skin and kidneys). It has a peripheral venodilating effect, reduces pulmonary vascular resistance, lowers pressure in the small circle of blood circulation. Increases renal blood flow, has a moderate diuretic effect. Dilates extrahepatic bile ducts. Stabilizes mast cell membranes, inhibits the release of mediators of allergic reactions. Inhibits platelet aggregation (suppresses platelet activation factor and PgE2a), increases the resistance of red blood cells to deformation (improves the rheological properties of blood), reduces thrombosis and normalizes microcirculation. It has a tocolytic effect, increases the acidity of gastric juice. In high doses, it has an epileptogenic effect.

Pharmacokinetics In the body, aminophylline is metabolized at physiological pH values to release free theophylline. Bronchodilating properties are manifested at concentrations of theophylline in blood plasma of 10-20 mcg / ml. Concentrations above 20 mg / ml are toxic. The stimulating effect on the respiratory center is realized at a lower concentration-5-10 mcg / ml. Binding of theophylline to plasma proteins is approximately 40%; in newborns, as well as in adults with diseases, binding decreases. Binding to plasma proteins in adults is about 60%, in newborns-36%, in patients with cirrhosis of the liver – 36%. Penetrates through the placental barrier (the concentration in the fetal blood serum is slightly higher than in the maternal serum). It is excreted in breast milk.

Theophylline is metabolized in the liver with the participation of several cytochrome P450 isoenzymes, the most important of which is CYP1A2. In the process of metabolism,1,3-dimethyl uric acid,1-methyluric acid and 3-methylxanthine are formed. These metabolites are excreted in the urine. In unchanged form,10% is excreted in adults. In newborns, a significant part is excreted in the form of caffeine (due to the immaturity of the pathways of its further metabolism), in unchanged form – 50%. Significant individual differences in the rate of hepatic metabolism of theophylline are the cause of pronounced variability in the values of clearance, plasma concentration, and half-life. Hepatic metabolism is affected by factors such as age, tobacco addiction, diet, diseases, and concurrent drug therapy.

T1 / 2 of theophylline in non-smoking patients with bronchial asthma with almost no pathological changes from other organs and systems is 6-12 hours, in smokers-4-5 hours, in children-1-5 hours, in newborns and premature infants-10-45 hours. T1 / 2 of theophylline increases in the elderly and in patients with heart failure or liver disease. Clearance decreases in patients with heart failure, liver dysfunction, chronic alcoholism, pulmonary edema, and chronic obstructive pulmonary disease. Ethylenediamine does not affect the pharmacokinetics of theophylline.

Indications

• asthmatic status (additional therapy),
• neonatal apnea,
• ischemic cerebral circulation disorder (as part of combination therapy),
• left ventricular failure with bronchospasm and respiratory disorders of the Cheyne-Stokes type,
• edematous syndrome of renal origin (as part of complex therapy);
• acute and chronic heart failure (as part of combination therapy).

Contraindications

• hypersensitivity to aminophylline and theophylline.
• severe arterial hyper-or hypotension,
• tachyarrhythmias,
• stomach and duodenal ulcer in the acute phase,
• hyperacid gastritis,
• severe liver and/or kidney function disorders,
• epilepsy,
• hemorrhagic stroke,
• retinal hemorrhage,
• simultaneous use with ephedrine in children,
• children’s age (up to 12 years).

Side effects

From the central nervous system:  dizziness, sleep disturbances, anxiety, tremors, seizures.

From the cardiovascular system:  palpitations, heart rhythm disturbances; with rapid intravenous use-the appearance of pain in the heart, a decrease in blood pressure, tachycardia (including in the fetus when taken in the third trimester of pregnancy), arrhythmias, a decrease in blood pressure, cardialgia, an increase in the frequency of angina attacks.

From the digestive system:  nausea, vomiting, gastroesophageal reflux, heartburn, exacerbation of peptic ulcer disease, diarrhea; with prolonged ingestion – anorexia.

From the urinary system:  albuminuria, hematuria.

Allergic reactions:  skin rash, itching, fever.

From the side of metabolism:  rarely-hypoglycemia.

Local reactions:  compaction, hyperemia, soreness at the injection site; rectal application of irritation of the rectal mucosa, proctitis.

Other services:  chest pain, tachypnea, flushing of the face, albuminuria, hematuria, hypoglycemia, increased diuresis, increased sweating.

Interaction

When used concomitantly with sympathomimetics, the effect is mutually enhanced; with beta-blockers and lithium preparations, the effect is mutually reduced. The intensity of action of aminophylline may decrease (due to an increase in its clearance) when used simultaneously with phenobarbital, rifampicin, isoniazid, carbamazepine, sulfinpyrazone, phenytoin, as well as in smokers. The intensity of action of aminophylline may increase (due to a decrease in its clearance) when used simultaneously with macrolide antibiotics, lincomycin, quinolones, allopurinol, beta-blockers, cimetidine, disulfiram, fluvoxamine, hormonal contraceptives for oral use, isoprenaline, viloxazine and when vaccinated against influenza. Xanthine derivatives may potentiate hypokalemia due to the action of beta-2-adrenergic stimulants, corticosteroids, and diuretics. Antidiarrheal drugs and enterosorbents reduce the absorption of aminophylline Pharmacologically incompatible with acid solutions.

How to take, course of use and dosage

The dose of the drug is set individually. If necessary, the dose of the drug can be increased at intervals of 2-3 days until the optimal therapeutic effect is achieved. The duration of the course of treatment is from several days to several months.

Intravenous use of the drug should be carried out carefully and slowly, at least for 5 minutes. The dose of the drug is selected individually, taking into account the possibility of different rates of excretion in different patients.

Overdose

Overdose causes hyperemia of the facial skin, insomnia, motor agitation, anxiety, photophobia, anorexia, diarrhea, nausea, vomiting, epigastric pain, gastrointestinal bleeding, tachycardia, ventricular arrhythmias, tremor, generalized convulsions, hyperventilation, and a sharp drop in blood pressure. With severe poisoning, epileptoid seizures (especially in children without any precursors), hypoxia, metabolic acidosis, hyperglycemia, hypokalemia, skeletal muscle necrosis, confusion, and renal failure with myoglobinuria can develop.

Treatment of overdose depends on the clinical picture, including drug withdrawal, stimulation of its elimination from the body (forced diuresis, hemosorption, plasma sorption, hemodialysis, peritoneal dialysis) and the appointment of symptomatic agents. To stop seizures, diazepam is used (in injections). Do not use barbiturates. In case of severe intoxication (Euphylline content is more than 50 g/l), hemodialysis is recommended.

Special instructions

Use with caution in patients with severe coronary insufficiency (acute phase of myocardial infarction, angina pectoris), advanced atherosclerosis, hypertrophic obstructive cardiomyopathy, frequent ventricular extrasystole, increased convulsive readiness, hepatic and/or renal insufficiency, peptic ulcer of the stomach and duodenum (in the anamnesis), with recent bleeding from the gastrointestinal tract, uncontrolled hypothyroidism (the possibility of accumulation) or thyrotoxicosis, with prolonged hyperthermia, gastroesophageal reflux, prostatic hypertrophy, in elderly patients, in children (especially inside). Correction of the dosage regimen of aminophylline may be required for heart failure, liver function disorders, chronic alcoholism, fever, acute respiratory infections. Elderly patients may need to reduce the dose. When replacing the used dosage form of aminophylline with another, clinical monitoring and monitoring of theophylline concentration in blood plasma is necessary. Aminophylline is not used simultaneously with other xanthine derivatives. During the treatment period, you should avoid eating foods containing xanthine derivatives (strong coffee, tea).

Cautiously used simultaneously with anticoagulants, with other derivatives of theophylline or purine. Concomitant use with beta-blockers should be avoided. Aminophylline should not be used simultaneously with glucose solution.

Form of production

Solution for intravenous use.

Storage conditions

In a place protected from light at a temperature of 10 to 25 C. Freezing is unacceptable.

Shelf

life is 3 years. Do not use after the expiration date indicated on the package.

Active ingredient

Aminophylline

Conditions of release from pharmacies

By prescription

Dosage form

infusion solution