Nuelin SR Mechanism of Action

Pharmacology: Pharmacodynamics: Theophylline has a direct relaxant effect on the smooth muscle of bronchial airways and pulmonary blood vessels, serving as a bronchodilator and pulmonary vasodilator. It also exhibits activities typical of xanthines such as CNS stimulation including the respiratory centre, cardiac stimulation, coronary vasodilatation, diuresis and increased gastric secretion. The mechanism of action of theophylline in vivo has not been fully elucidated. One mechanism of smooth muscle relaxation may be inhibition of phosphodiesterase that reduces intracellular hydrolysis of cyclic AMP. Increased intracellular concentrations of cyclic AMP have been associated with relaxation of bronchial smooth muscle. There is no evidence that tolerance develops with continued use of theophylline. Theophylline is closely related to the other xanthines, caffeine and theobromine. Generally, the xanthines relax smooth muscle, act on the kidney to produce diuresis, stimulate the central nervous system and stimulate cardiac muscle.
Pharmacokinetics: Nuelin-SR Tablets are a sustained release formulation appropriate for long term use. Steady-state conditions are usually achieved after 4 days therapy. It is now generally believed that plasma concentrations of 10-20 µg/mL constitute a therapeutic range, although some patients may benefit from levels below this. Theophylline is well absorbed throughout the gastrointestinal tract. The bioavailability of theophylline from Nuelin-SR Tablets is approximately 100%. Peak levels after administration of Nuelin-SR Tablets usually occur at 4 to 6 hours post-dose. Total bioavailability is not altered by food intake. Single dose studies with Nuelin-SR Tablets show that food delays the rate of absorption slightly, especially in children. In multiple dosing situations, a slower rate of theophylline absorption leads to lower peak-trough fluctuation. The plasma half-life of theophylline in adults varies considerably. In healthy adults it ranges from 3 to 12 hours. The half-life is shortened by smoking. The half-life of theophylline is prolonged by reduced hepatic function, congestive heart failure, pulmonary disease, severe hypoxia, reduced thyroid function, acute febrile states, viral infections and administration of some drugs. Patients with a prolonged half-life of theophylline, from whatever cause, require a reduced dosage. In children aged 1-9 years, the half-life is usually significantly shorter than in adults, averaging about 3.5 hours. In newborns and neonates, clearance is extremely slow. Approximately 50-70% of circulating theophylline is bound to the plasma proteins of adults, but binding is decreased to about 40% in newborn infants and in adults with hepatic cirrhosis. Theophylline partitions into saliva and breast milk and crosses the placental barrier. Theophylline is metabolised in the liver, principally to 1,3-dimethyluric acid with other metabolites being 3-methylxanthine and 1-methyluric acid. 3-Methylxanthine has some pharmacological activity, but less than theophylline. Theophylline and its metabolites are excreted by the kidney. About 10% of the administered dose is excreted unchanged in the urine