Disease processes may increase the risk and severity of adverse drug reactions in three ways.
1 Disease may lead to changes in the pharmacokinetics of a drug. A reduction in protein binding or reduced renal or hepatic clearance will potentiate the effects of certain drugs.
2 Changes in receptor density and function may occur.
For example, there is evidence that the enhanced bronchoconstrictor effects of J3-adrenoceptor antagonists in asthmatic patients may be due to a reduction (‘downregulation’) in J3-receptor number produced by longterm treatment with J3-agonists such as salbutamol.
The sensitivity of patients with myasthenia gravis to the neuromuscular blocking effects of streptomycin, neomycin or kanamycin may be due to drug-induced changes in cholinergic receptors.
3 Some inherited diseases are associated with enhanced drug toxicity.
There are also several examples of disease-related enhanced drug toxicity the nature of which is not yet understood