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Pharmacology: This agent is effective on blood vessel system exclusive of heart. It enhances heart contraction through the coronary artery and renal vessel dilatation, and relieve bronchiole maintain normal breath function. Aminophylline has the same actions and uses of theophylline and used similarly as a bronchodilator in the management of asthma and chronic obstructive pulmonary disease. Aminophylline is a xanthine and relaxes bronchial smooth muscle, relieves bronchospasm, and has a stimulant effect on respiration. It stimulates the myocardium and CNS, decreases peripheral resistance and venous pressure and causes diuresis. It is still not clear how aminophylline exerts these effects. Inhibition of phosphodiesterase with resulting increase in intracellular cyclic adenosine monophosphate (cyclic AMP) occurs, and may play role. Other proposed mechanisms of action include adenosine receptor antagonism, prostaglandin antagonism, and effects on intracellular calcium.
Pharmacokinetics: Aminophylline, a complex of theophylline with ethylene diamine, readily liberates theophylline in the body. Theophylline is rapidly and completely absorbed from liquid preparations, capsules, and uncoated tablets; the rate, but not the extent of absorption are decreased by food and may also affect theophylline clearance. Modified-release preparations of theophylline can usually provide adequate plasma concentrations were given every 12 hours. However, there is a considerable variability in their absorption characteristics and in effect of food. It is generally recommended that if a patient is transferred from one preparation to another then this should be reiterated. Peak of serum-theophylline concentrations occur 1 to 2 hours after ingestion of modified-release preparations. Rectal absorption is rapid from enemas, but may be following intramuscular injection is slow and incomplete. Theophylline is approximately 40% bound to plasma proteins, but in neonates, or adults with liver disease, binding is reduced. Optimum therapeutic serum concentrations are generally considered to range from 10 to 20 μg per mL (55 to 110 μmol per litre) although some consider a lower range appropriate. Theophylline is metabolised in the liver to 1,3-dimethyluric acid (via the intermediate demethylation to 3-methylxanthine. Demethylation to 3-methylxanthine is catalysed by the cytochrome P450 isoenzyme CYP1A2; hydroxylation to 1-methyluric acid is catalysed by CYP2E1 and CYP3A3. The metabolites are excreted in the urine. In adults about 10% of a dose of theophylline is excreted unchanged in the urine, but in neonates around 50% is excreted unchanged, and a large portion is excreted as caffeine. Considerable inter-individual differences in the rate of hepatic metabolism of theophylline result in a large variation in clearance, serum concentrations, and half-lives. Hepatic metabolism is further affected by factors such as age, smoking, disease, diet and drug interactions. The serum half-life of theophylline in an otherwise healthy, non-smoking, asthmatic adult is 6 to 12 hours, in children 1 to 5 hours, in cigarette smokers 4 to 5 hours and in neonates and premature infants 10 to 45 hours. The serum half-life of theophylline may be increased in the elderly and in patients with heart failure or liver disease. Theophylline crosses the placenta; it also enters breast milk.
