Xanthines

Question 1

Give examples of Xanthines ?

Answer 1

• Theophylline
• Aminophylline (this is a combination of theophylline and ethylenediamine which can be given by injection, as it is more soluble than theophylline alone

Question 2

What are the indications of Xanthines?

Answer 2

Asthma

• Third /Fourth line drug in severe chronic asthma. May be of benefit to children who cannot use inhalers and adults with nocturnal symptoms.
• Acute severe asthma which is not responding to nebulised short acting β2 agonists.

COPD

• May be used as IV therapy in severe acute exacerbation of COPD (no longer used as standard treatment for stable COPD management).

Question 3

What the contraindication of Xanthines ?

Answer 3

Caution

• Cardiac disease (xanthines stimulate the heart, having positive chronotropic and ionotropic actions therefore there is a risk these patients may develop tachy-arrhythmias).
• Epilepsy (xanthines have a stimulant effect on the CNS, increasing the risk of convulsions in epileptic patients).
• Elderly
• Liver failure
• Pregnancy and Breastfeeding

Question 4

How Xanthines work (Mechanism of Xanthines) ?

Answer 4

Administration of xanthines results in dilatation of the airways and is a useful drug in the treatment of airway obstruction (especially asthma). However, the way in which xanthines produce effects in respiratory disease is still not fully understood.

The smooth muscle relaxation which occurs with xanthines is attributed to the inhibition of the phosphodiesterase isoenzyme, with resultant rise in cellular cAMP levels. However, when the enzyme is isolated, the concentrations of xanthines that are required to achieve inhibition exceed the therapeutic range. Therefore there must be another mechanism of action in which xanthines lead to broncho-dilatation. Several such mechanisms have been proposed.

There is also evidence to suggest that xanthines have anti-inflammatory / immunomodulatory and broncho-protective effects that are mediated by other molecular mechanisms.

See Obstructive Airway Disease, Prof K Kerr.

Question 5

Administration of Xanthines?

Answer 5

• Theophylline is given orally.
• Aminophylline is given by slow IV infusion. A loading dose should be administered followed by an infusion. If a patient is normally prescribed theophylline and they require an aminophylline infusion, a loading dose should not be given. Cardiac monitoring is required. In prolonged use and during acute therapy in a patient who takes theophyllines regularly, it is important to measure the plasma theophylline concentration because serious adverse reactions (convulsions and arrhythmias) can precede the signs of toxicity.

Question 6

What are the adverse reactions of Xanthines?

Answer 6

• Theophyllines cause tachy-arrhythmias including ventricular tachycardia.
• Theophyllines reduce the seizure threshold and may cause seizures.
• Other common side effects include nausea and vomiting and headache.
• Aminophylline can cause allergy and urticaria due to the ethylenediamine component.