Theophylline

Theophylline is a methylxanthine derivative with a narrow therapeutic index.

Has phosphodiesterase inhibiting activity in the body.

It is well absorbed orally and distributed in all tissues.

Mechanisms of action.

• Inhibition of phosphodiesterase activity hence relaxation of bronchial smooth muscles.
• Inhibits synthesis and secretion of inflammatory mediators from mast cells and basophils.
• A competitive antagonist of adenosine thus binds to adenosine receptors and blocks adenosine-mediated bronchodilation.

Clinical uses.

• Bronchial asthma and COPD by causing bronchodilation.
• Apnoea in premature infants.
• Chronic bronchitis and emphysema.

Adverse effects.

• Theophylline has a narrow margin of safety and hence has dose-dependent toxicity.
• CNS: Headache, insomnia, restlessness, and seizure.
• CVS: palpitations,hypotension,ventricular tachycardia,cardiac arrest.
• GIT: GI disturbance and protenuria.
• Alopecia,metallic taste and diuresis.

Contraindication.

• Hypersensitivity reaction to any xanthine.
• Peptic ulcers
• Epilepsy.

Drug Interactions

• Agents which enhance theophylline metabolism primarily by inducing CYP1A2 to lower its plasma level; hence the dose has to be increased, i.e., Smoking, phenytoin, rifampicin, phenobarbitone.
• Drugs that increase its plasma levels include; thiabendazole, erythromycin, and isoniazid.