Xanthines

Original article by Tom Leach | Last updated on 7/6/2014
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Introduction

These are naturally occurring chemicals found in tea, coffee, chocolate and other related foods. They are chemically similar to caffeine. They have vasodilating, bronchodilating, anti-inflammatory and immunomodulating actions, but the mechanisms of these are uncertain.
These drugs have greater side effects, and fewer beneficial effects than β2 agonists.
 

Mechanism

  • this is not well understood, but it is known that they inhibit phosphodiesterase enzymes, and this results in the accumulation of cAMP within a cell, thus reducing intracellular Ca2+ in a similar way to β2 agonists.
  • They have a very narrow therapeutic window – so you have to constantly monitor – can be a pain!
 

Drugs

There are only two compounds in use clinically:
  • Theophylline – given orally – metabolised by the P450 system (thus drug interactions are likely – particularly with drugs that inhibit enzymes in the P450 system, such as erythromycin, clarithromycin, ciprofloxacin – so you have to be VERY careful if you put an asthmatic on anti-biotics!), and half-life is about 8 hours, but this varies widely.
  • Aminophylline – given IV
 

Unwanted effects

  • Tachycardia
  • Agitation – the drugs have a stimulatory effect on the CNS which can lead to agitation, tremor, nervousness, sleep problems. This effect can also cause increased respiration and thus may be useful in those with COPD who have a tendency to retain CO2 (‘blue bloaters’).
  • Seizures
  • There is a very narrow therapeutic window – this is range in which the drug is effective, without this effectiveness being outweighed by adverse effects. Careful titration is necessary, as the drug can become highly toxic at doses >200μl/mol (and the normal therapeutic dose is about 100μl/mol), and causes noticeable adverse effects at 110μl/mol.
 

Clinical use

  • Theophylline is given to patients already taking steroids and β2-agonists, where these drugs are not effectively controlling the condition
  • IV aminophylline is given in severe attacks of asthma