18th March 2024

Classification of adverse drug reactions

ADRs can be classified into six subtypes with the mnemonic:

• Augmented – dose-related: these result from an increased effect of the drug’s pharmacology when given at the usual dose
• Bizarre – non-dose-related: these cannot be predicted from the drug’s pharmacology
• Chronic – time-related and dose-related: the effect may persist for an extended period of time despite withdrawal of the drug
• Delayed – time-related: the observed effect presents a period of time after the administration of the drug (therefore, these reactions can be particularly difficult to relate to the initial drug)
• End of Use – withdrawal: these include withdrawal effect of the drug after discontinuation
• Failure – failure of therapy

Of the ADRs described above, the most common type is an augmented/dose-related; these constitute 80% of ADRs.

In this way, type A may be considered pharmacological and type B immunological:

Type A reactions: These may arise from pharmacokinetic or pharmacodynamic variations. At this point, we can review what is meant by these terms:

Examples of pharmacokinetic causes of ADRs include pharmacogenetic variations. Application of pharmacogenetics within clinical practice is rapidly increasing as genetic variations are identified which affect a particular drug’s pharmacokinetics within an individual: this allows individual assessment of a drug’s safety and efficacy and can advise dosing. A clinical example is checking a patient’s thiopurine S-methyltransferase (TPMT) prior to initiation of azathioprine therapy. Specific genetic variations within the TPMT gene affect the metabolism of azathioprine; patients with genetic mutations that confer a low TPMT activity may be unable to effectively metabolise azathioprine causing build-up and risk of myelosuppression. Conversely, patients with higher TMPT levels may metabolise azathioprine more effectively than others, necessitating a higher dose.

Pharmacodynamic-mediated ADRs may occur when multiple drugs taken in combination have similar, potentiating or competing, antagonistic effects on their specific target site, often at a receptor level. A different example is that of a cutaneous folliculitis associated with endothelial growth factor receptor (EGFR) antagonists. EGFR is a common target in a variety of cancer therapeutics, but its blockade is associated with a rash that is dose-dependent and can limit its use.

Type B reactions: These are non-dose dependent and considered to have an immunological basis. Here, we can consider Gell and Coombs’ classification of hypersensitivity reactions: