Teofillin

Theophylline has a bronchodilator effect.

Indications Theophylline

It is used in bronchial obstruction syndrome caused by various factors:

• BA (as a drug of choice in the case of asthma, provoked by physical exertion, and in addition in the form of an additional means for other forms of the disease);
• flowing chronic bronchitis obstructive character;
• pulmonary emphysema, hypertension or heart;
• edema syndrome, developing due to renal pathology (combination therapy);
• sleep apnea.

[1], [2], [3]

Release form

The release of the drug is sold in tablets, having a prolonged form. The volume of tablets is 0.1, 0.2 or 0.3 g of the substance. Inside the box contains 20, 30 or 50 tablets.

[4], [5], [6], [7], [8],

Pharmacodynamics

Theophylline is a purine derivative and bronchodilator drug. The drug inhibits the activity of PDE, resulting in increased accumulation of cAMP within the tissues, helps block purine endings, and at the same time reduces the amount of calcium ions transported through the cell wall channels and lowers the contractile activity of smooth muscles.

Contributing to the relaxation of the muscles of the blood vessels (especially vessels in the epidermis and kidneys with the brain) and bronchi, the drug leads to a peripheral vasodilator effect, and in addition it potentiates the renal circulation and has a moderate diuretic effect. The drug stabilizes the cells of labrocytes, and also inhibits the release of the conductors of allergic signs.

The drug potentiates the MCC, improves respiratory processes in the diaphragm, increases the functional ability of the respiratory and intercostal muscles, and also stimulates the work of the respiratory center. Inside the blood, it reduces carbon dioxide and stabilizes the flow of oxygen. When hypokalemia potentiates pulmonary ventilation.

Also, the drug increases the coronary circulation, stimulates the activity of the heart muscle, increases the strength of its contractions and frequency, and in addition reduces the need for oxygen. Weakens the resistance of the pulmonary vessels and the pressure inside the small circle of blood flow. The drug expands the bile ducts (extrahepatic) and prevents platelet aggregation, inhibiting the activation of platelets and PG E2-α. In addition, it increases the stability of red blood cells relative to the deformation, positively affecting the rheological characteristics of the blood. Slows down blood clots and stabilizes microcirculation.

Prolonged release of the active ingredient leads to the achievement of its therapeutic parameters inside the plasma after 3-5 hours and allows you to maintain this level in the period of 10-12 hours. As a result, taking the drug 2 times a day, you can provide a permanent medicinal effect.

[9], [10], [11], [12], [13], [14], [15],

Pharmacokinetics

The drug has good absorption from the gastrointestinal tract, as well as bioavailability indicators, which are approximately 88-100%. Synthesis with protein is about 60%. Tmax values fluctuate around the 6 o'clock position. The substance passes through the placenta and is excreted in breast milk.

The drug is 90% exposed to metabolic processes inside the liver, in which hemoprotein P450 enzymes are involved (the most important is CYP1A2). At the same time, the main metabolic products are released - 3-methylxanthine, as well as 1,3-dimethyl uric acid.

Metabolic products of drugs, and with them another 7-13% of the unchanged element (in children, this indicator reaches 50%) are excreted through the kidneys. Due to incomplete metabolic processes in newborns, most of the drug is excreted in the form of caffeine.

For people who do not smoke, the half-life of the drug is 6-12 hours, and for smokers it decreases to 4-5 hours. In persons with renal or hepatic diseases, as well as alcoholism, the T1 / 2 indicator is prolonged.

With insufficient liver or respiratory function, CHF, fever in severe form, viruses and in age groups up to 12 months or above 55 years of age, the total clearance is reduced.

[16], [17], [18], [19], [20]

Dosing and administration

It is recommended to select the dosage of the drug individually for each patient.

The average size of the initial portion per day is 0.4 g. If the medicine in this dose is tolerated without complications, its 1-fold increase by approximately 25% is allowed. It is necessary to increase portions with 2-3-day intervals until the optimum therapeutic result is reached.

The maximum allowable daily dosages that can be taken without monitoring theophylline blood parameters are: 18 mg / kg (adolescents 12-16 years old) and 13 mg / kg (age group 16 years old).

In the absence of the effect of taking the above dosages (the need to increase the portion) or with the development of toxic manifestations, subsequent treatment should be performed against the background of regular monitoring of blood values of drugs. The most optimal portions are considered within 10-20 μg / ml. Lower doses do not have the required efficacy, and higher doses do not lead to a significant potentiation of exposure, but dramatically increase the likelihood of developing negative symptoms.

[31], [32], [33]

Use Theophylline during pregnancy

Prescribe medication for breastfeeding or pregnancy is allowed only occasionally and with extreme caution.

Contraindications

Main contraindications:

• hyperacid gastritis;
• ulcers inside the gastrointestinal tract during the acute stage, as well as bleeding in the same area;
• epileptic seizures;
• reduced or elevated blood pressure values with severe severity;
• hemorrhagic stroke;
• severe tachyarrhythmias;
• hemorrhage in the eye retina;
• the presence of strong sensitivity in relation to theophylline, and in addition to other xanthine derivatives (pentoxifylline with theobromine and caffeine).

Caution is required when used in such cases:

• severe coronary insufficiency (this includes the acute stage of myocardial infarction and angina);
• hypertrophic cardiomyopathy having an obstructive form;
• vascular atherosclerosis;
• CHF;
• failure of the liver or kidneys;
• often developing extrasystole of the ventricles;
• enhanced convulsive readiness;
• BPH;
• previously diagnosed ulcer inside the gastrointestinal tract or recent bleeding in the same area;
• prolonged hyperthermia;
• hypothyroidism or hyperthyroidism;
• GERD;
• use of the elderly.

[21], [22], [23]

Side effects Theophylline

Taking the medication can lead to the following symptoms:

• disorders of the central nervous system: dizziness, tremor, feeling of irritability, agitation or anxiety, and in addition, insomnia and headaches;
• malfunctions of the cardiovascular system: palpitations, cardialgia, tachycardia (also noted in the fetus in the case of using drugs in the 3rd trimester), arrhythmias, a decrease in blood pressure and an increase in angina pectoris attacks;
• lesions affecting the digestive organs: diarrhea, exacerbation of ulcers, heartburn, gastralgia, nausea, and GERD, vomiting and appetite deterioration (with prolonged use);
• allergy symptoms: itching and rash on the epidermis, and in addition to this feverish state;
• other: pain in the sternum, hematuria, tachypnea, hyperhidrosis, flushing of the skin on the face, hypoglycemia, potentiation of diuresis and albuminuria.

Often, with a decrease in the portion of the drug, the severity of negative symptoms also decreases.

[24], [25], [26], [27], [28], [29], [30]

Overdose

Intoxication with the drug leads to such disorders: diarrhea, bleeding inside the gastrointestinal tract, weakening of appetite, nausea, up to vomiting (sometimes bloody) and gastralgia. In addition, facial hyperemia, ventricular arrhythmias, tachycardia and tachypnea. There is also a feeling of anxiety, tremor, insomnia, motor agitation, convulsions and photophobia.

In severe poisoning, epileptoid seizures can occur (especially in children), a feeling of confusion, hypoxia, metabolic acidosis, hyperglycemia, and besides skeletal muscle necrosis, hypokalemia, decreased blood pressure and renal failure with myoglobinuria.

To eliminate the disorders, you need to cancel the medication, conduct gastric lavage, prescribe activated charcoal and laxatives, and in addition perform intestinal lavage (using polyethylene glycol and electrolytes). In addition, the procedures of plasma sorption, forced diuresis and hemosorption are performed; hemodialysis can also be performed, but it is ineffective. Symptomatic measures are also prescribed.

With severe nausea with vomiting, intravenous metoclopramide or ondansetron must be injected.

With the appearance of seizures, it is required to ensure and control the patency of the respiratory ducts, and with this, perform oxygen therapy. It is possible to stop the attack with diazepam (0.1-0.3 mg / kg (maximum 10 mg) intravenously).

[34], [35], [36], [37], [38], [39], [40]

Interactions with other drugs

Theophylline clearance level decreases with the combination of drugs with allopurinol, lincomycin and macrolides, and in addition with cimetidine, propranolol, oral contraception and isoprenaline.

The use together with β-adrenergic blockers (especially non-selective) can cause bronchoconstriction, because of which the bronchodilatory effect of theophylline is weakened, and in addition, the activity of β-adrenergic blockers is possible.

The therapeutic effect of Theophylline is potentiated when it is used together with caffeine, substances that stimulate the activity of β2-adrenergic receptors, as well as with furosemide.

Aminoglutetimid increases theophylline excretion, due to which its medication effect may be weakened.

The combination with disulfiram or acyclovir increases blood levels of drugs, which also potentiates the likelihood of side effects.

Simultaneous use with diltiazem, nifedipine, and also with felodipine or verapamil often has little or moderate effect on the blood values of the drug, but does not change the severity of its bronchodilator effects (there are reports of potentiation of negative manifestations when combined with verapamil or nifedipine).

Using the medication together with lithium salts may weaken their medicinal properties.

The combination of the drug with phenytoin leads to a mutual weakening of therapeutic efficacy and a decrease in the performance of their active elements.

Drug effect of the drug is weakened when combined with isoniazid, carbamazepine, and also sulfinpyrazone, phenobarbital or rifampicin.

A significant increase in blood values of drugs develops when it is used together with enoxacin or other fluoroquinolones.

[41], [42], [43], [44], [45]

Storage conditions

Theophylline is required to be maintained at temperature indicators not exceeding 25 ° C.

[46], [47], [48], [49], [50]

Shelf life

Theophylline can be used within 36 months of the manufacture of the therapeutic agent.

[51], [52],

Application for children

Theophylline in a standard oral form should not be used in children under 3 years of age; tablets of the prolonged type are prohibited for use in children under 12 years of age.

[53], [54], [55], [56], [57], [58], [59],

Analogs

Analogues of drugs are medicines Euphyllinum, Theobromin, Theofedrin-H with Diprofillin, and also Neo-Theofedrin.

[60], [61], [62], [63], [64], [65], [66], [67]

Reviews

Theophylline receives fairly good reviews from physicians, although it is not 100% positive, because the drug still has some negative manifestations. This is due to the fact that only an experienced doctor who has all the necessary knowledge for this purpose can be engaged in prescribing the drug. For example, he should know that the medicine is ineffective at removing acute attacks, while demonstrating an excellent result with long-term treatment. At the same time, it is necessary to take into account the patient’s history, his individual sensitivity, the presence of concomitant pathologies, the use of other drugs and the rest of what an ordinary person who does not have an appropriate medical practice cannot do. That is why it is necessary to use Theophylline exclusively with the appointment of a doctor - in this case, the result of therapy will be positive.