Theophylline

Theophylline has a bronchodilatory effect.

Indications Theophylline

It is used for broncho-obstruction syndrome caused by various factors:

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

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Release form

The drug is released in tablets, which have a prolonged form. The volume of tablets is 0.1, 0.2 or 0.3 g of the substance. Inside the box there are 20, 30 or 50 tablets.

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Pharmacodynamics

Theophylline is a purine derivative and a bronchodilator. The drug inhibits PDE activity, thereby increasing the accumulation of cAMP inside tissues, helps block purine endings, and at the same time reduces the amount of calcium ions transferred through cell wall channels and reduces the contractile activity of smooth muscles.

By promoting relaxation of the muscles of 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 renal blood circulation and has a moderate diuretic effect. The drug stabilizes labrocyte cells, and also inhibits the processes of releasing conductors of allergic symptoms.

The medicine potentiates the MCC, improves respiratory processes in the diaphragm, increases the functional capacity of the respiratory and intercostal muscles, and stimulates the work of the respiratory center. In the blood, it reduces carbon dioxide levels and stabilizes oxygen supply. In hypokalemia, it potentiates pulmonary ventilation.

The drug also enhances coronary circulation, stimulates cardiac muscle activity, increases the force of its contractions and frequency, and in addition reduces the need for oxygen. Reduces pulmonary vascular resistance and pressure within the pulmonary circulation. The drug dilates bile ducts (extrahepatic) and prevents platelet aggregation, inhibiting the process of platelet activation and PG E2-α. In addition, it increases the resistance of red blood cells to deformation, positively affecting the rheological characteristics of the blood. Slows down thrombus formation and stabilizes microcirculation.

The prolonged release of the active ingredient leads to the achievement of its therapeutic indicators in the plasma after 3-5 hours and allows maintaining this level for 10-12 hours. As a result, taking the medicine 2 times a day can provide a constant medicinal effect.

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Pharmacokinetics

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

The drug undergoes 90% metabolic processes inside the liver, in which enzymes of the hemoprotein P450 (the most important is CYP1A2) participate. In this case, the main metabolic products are released - 3-methylxanthine, as well as 1,3-dimethyluric acid.

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

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

In case of liver or respiratory failure, CHF, severe fever, viruses and in age groups up to 12 months or over 55 years of age, the values of total clearance are reduced.

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Dosing and administration

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

The average size of the initial daily dose is 0.4 g. If the drug is tolerated at this dose without complications, it is allowed to increase it 1-fold by approximately 25%. The doses should be increased at 2-3-day intervals until the optimal therapeutic result is achieved.

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

If there is no effect from taking the above dosages (there is a need to increase the portion) or if toxic manifestations develop, subsequent treatment should be carried out against the background of regular monitoring of blood values of the drug. The most optimal portions are considered to be within 10-20 mcg/ml. Lower doses do not have the required effectiveness, and higher doses do not lead to a significant potentiation of the effect, but sharply increase the likelihood of developing negative symptoms.

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Use Theophylline during pregnancy

Prescribing the medication during 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;
• decreased or increased blood pressure values with severe manifestation;
• hemorrhagic form of stroke;
• severe tachyarrhythmia;
• hemorrhage in the area of the retina;
• the presence of strong sensitivity to theophylline, as well as other xanthine derivatives (pentoxifylline with theobromine and caffeine).

Caution is required when using in the following cases:

• severe coronary insufficiency (this includes the acute stage of myocardial infarction and angina pectoris);
• hypertrophic cardiomyopathy with obstructive form;
• vascular atherosclerosis;
• CHF;
• liver or kidney failure;
• frequently developing ventricular extrasystole;
• increased convulsive readiness;
• prostate adenoma;
• previously diagnosed ulcer inside the gastrointestinal tract or recent bleeding in the same area;
• prolonged hyperthermia;
• hypothyroidism or hyperthyroidism;
• GERD;
• use in elderly people.

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Side effects Theophylline

Taking the medication may cause the following side effects:

• CNS dysfunction: dizziness, tremor, feeling of irritability, agitation or anxiety, as well as insomnia and headaches;
• disturbances in the functioning of the cardiovascular system: palpitations, cardialgia, tachycardia (also observed in the fetus in the case of drug use in the 3rd trimester), arrhythmia, decreased blood pressure and increased frequency of angina attacks;
• lesions affecting the digestive organs: diarrhea, exacerbation of ulcers, heartburn, gastralgia, nausea, as well as GERD, vomiting and loss of appetite (with prolonged use);
• allergy symptoms: itching and rashes on the epidermis, and in addition to this, a feverish condition;
• Others: chest pain, hematuria, tachypnea, hyperhidrosis, facial flushing, hypoglycemia, increased diuresis and albuminuria.

Often, when the dose of the drug is reduced, the severity of negative symptoms also decreases.

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Overdose

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

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

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

In case of severe nausea with vomiting, metoclopramide or ondansetron should be administered intravenously.

If convulsions occur, it is necessary to ensure and control the patency of the respiratory ducts, and at the same time perform oxygen therapy. The attack can be stopped with diazepam (0.1-0.3 mg/kg (maximum 10 mg) intravenously).

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Interactions with other drugs

The clearance rate of theophylline decreases when the drug is combined with allopurinol, lincomycin and macrolides, as well as with cimetidine, propranolol, oral contraception and isoprenaline.

Use together with β-blockers (especially non-selective ones) can cause bronchoconstriction, which weakens the bronchodilatory effect of theophylline, and in addition, a decrease in the activity of the β-blockers themselves is possible.

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

Aminoglutethimide increases the excretion of theophylline, which may weaken its medicinal effect.

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

Concomitant use with diltiazem, nifedipine, and also with felodipine or verapamil often has a weak or moderate effect on the blood levels of the drug, but does not change the severity of its bronchodilatory effect (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 the therapeutic effectiveness and a decrease in the indicators of their active elements.

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

A significant increase in blood levels of the drug develops when it is used together with enoxacin or other fluoroquinolones.

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Storage conditions

Theophylline must be kept at temperatures not exceeding 25°C.

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Shelf life

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

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Application for children

Theophylline in standard oral form should not be used in children under 3 years of age; extended-release tablets are prohibited for use in children under 12 years of age.

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Analogues

Analogues of the drug are the medications Euphyllin, Theobromine, Theofedrine-N with Diprophylline, and also Neo-Theofedrine.

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Reviews

Theophylline receives quite good reviews from doctors, although not 100% positive, because the drug still has some negative effects. This is due to the fact that only an experienced doctor with all the necessary knowledge can prescribe the drug. For example, he should know that the drug is ineffective in relieving acute attacks, while it demonstrates excellent results with long-term treatment. At the same time, it is necessary to take into account the patient's medical history, his individual sensitivity, the presence of concomitant pathologies, the use of other drugs and other things that an ordinary person who does not have the appropriate medical practice cannot do. That is why Theophylline should be used exclusively with a doctor's prescription - in this case, the result of therapy will be positive.