Pharmacology: Theophylline (3,7-dihydro-1,3-dimethyl-1-H-purine-2,6-dione) is a xanthine bronchodilator.
Theophylline directly relaxes the smooth muscle of the bronchial airway and pulmonary blood vessels; increases diaphragmatic contractility. Theophylline is also a central respiratory stimulant.
Mechanism of Action: Main mechanism of action of xanthines is inhibition of phosphodiesterase, which results in an increase in cyclic adenosine monophosphate (cAMP).
Other Effects: Inhibition of extracellular adenosine (which causes bronchoconstriction), stimulation of endogenous catecholamines, antagonism of prostaglandins, PGE2 and PGF2, direct effect on mobilization of intracellular calcium resulting in smooth muscle relaxation and β-adrenergic agonist activity on the airways.
Salbutamol [1-(4-(RS)-hydroxy-3 hydromethylphenyl)2-(t-butylamino) ethanol] is a selective β2-adrenoceptor agonist with effects on smooth and skeletal muscle. These include bronchodilation, relaxation of uterine muscle and antiallergic effect. Smooth muscle relaxation is thought to occur via the adenyl cyclase-cyclic adenosine monophosphate (cAMP) system.
Pharmacokinetics: Absorption: Theophylline is completely absorbed after oral administration.
Metabolism and Excretion: Xanthines are biotransformed in the liver (85-90%) to 1,3-dimethyluric acid, 3 methylxanthine and 1-methyluric acid. Excretion is by the kidneys: <15% of the drug is excreted unchanged.
Salbutamol is well absorbed from the GIT. The proportion of circulating drug that is protein bound is approximately 10%. Transfer of the drug across the placenta has been demonstrated both in vitro and in vivo.