0501. Renewed interest in methyl xanthines

From a paediatric perspective the methyl xanthines have been relegated to the back burner for treatment of asthma and largely been replaced by drugs that are regarded as being more-effective bronchodilators. However some methyl xanthines are still accepted for management of neonatal apnoea. Initally the effects of xanthines on the lungs and other organs were accepted as largely being due to their inhibitory effects on phosphodiesterase, and the resultant increases in levels of cyclic-AMP. Recently, however, much attention has been focused on the additional actions of theophylline as an adenosine receptor blocker, and in the same way as more-specific ß2-stimulants were developed for treatment of asthma, efforts are under way to develop specific A1 and A2 adenosine receptor blockers. Respiratory stimulation, as seen in the neonatal situation, is now recognized as probably being due to adenosine blockade rather than to cyclic-AMP elevation, and interesting effects are also noted in other situations. Renal effects are also interesting and the role of theophylline in preventing and treating contrast nephropathy has been the focus of attention for some time. Here the consensus is that this is due to blockade of the vasoconstrictive effects of adenosine in the kidney. The drug has now also been used with some success in preventing cisplatin-induced renal dysfunction and to preserve renal function in asphyxiated newborns, with response in both situations again being accredited to the drug's adenosine-blocking capabilities.

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