Definitions and classification of ADRs
An adverse drug reaction (ADR) can be defined as ‘an appreciably harmful or unpleasant reaction resulting from an intervention related to the use of a medicinal product; adverse effects usually predict hazard from future administration and warrant prevention, or specific treatment, or alteration of the dosage regimen, or withdrawal of the product
Since 2012, the definition has included reactions occurring as a result of error, misuse or abuse, and to suspected reactions to medicines that are unlicensed or being used off-label in addition to the authorised use of a medicinal product in normal doses
Medicines that have been particularly implicated in ADR-related hospital admissions include antiplatelets, anticoagulants, cytotoxics, immunosuppressants, diuretics, antidiabetics and antibiotics. Fatal ADRs, when they occur, are often attributable to haemorrhage, the most common suspected cause being an antithrombotic/anticoagulant co-administered with a non-steroidal anti-inflammatory drug (NSAID)
There are several terms commonly used to describe adverse effects of drug therapy:
- An adverse drug reaction (ADR) is an unwanted or harmful reaction experienced following the administration of a drug or combination of drugs under normal conditions of use and is suspected to be related to the drug. An ADR will usually require the drug to be discontinued or the dose reduced.
- An adverse event is harm that occurs while a patient is taking a drug, irrespective of whether the drug is suspected to be the cause.
- A side-effect is any effect caused by a drug other than the intended therapeutic effect, whether beneficial, neutral or harmful. The term ‘side-effect’ is often used interchangeably with ‘ADR’ although the former usually implies an effect that is less harmful, predictable and may not even require discontinuation of therapy (e.g. ankle oedema with vasodilators).
- Drug toxicity describes adverse effects of a drug that occur because the dose or plasma concentration has risen above the therapeutic range, either unintentionally or intentionally (drug overdose).
- Drug abuse is the misuse of recreational or therapeutic drugs that may lead to addiction or dependence, serious physiological injury (such as damage to kidneys, liver, heart), psychological harm (abnormal behaviour patterns, hallucinations, memory loss), or death.
Classification of adverse drug reactions
- ABCDE Classification
- DoTS Classification
Traditionally, ADRs have been classified into two types:
- Type A reactions – sometimes referred to as augmented reactions – which are ‘dose-dependent’ and predictable on the basis of the pharmacology of the drug
- Type B reactions – bizarre reactions – which are idiosyncratic and not predictable on the basis of the pharmacology
- The further categories C (‘chronic’ treatment effects), D (‘delayed’ effects), and E (‘end of treatment’ effects) have been proposed (the ‘ABCDE’ classification).
Type A ADRs relate to the mechanism of action (i.e. the known pharmacology) of the medication, and are associated with high morbidity and low mortality.
Clinical examples of Type A ADRs are common and physicians often need to reduce the dosages of the medicine so that the patients can tolerate the treatment. Patients can be empowered to be aware of the ADRs and reduce the incidence of unnecessary Type A ADRs.
In contrast, Type B ADRs are idiosyncratic and cannot be predicted from the known pharmacology of a drug. These reactions are associated with low morbidity and high mortality. Formal recording of the incidence of Type B reactions can be life-saving.
An alternative and perhaps more comprehensive classification scheme is ‘DoTS’, which classifies reactions dependent on the Dose of the drug, the Time course of the reaction and relevant Susceptibility factors (such as genetic, pathological and other biological differences)
Riedl MA, Casillas AM. Adverse drug reactions: types and treatment options. Am Fam Physician. 2003 Nov 1;68(9):1781-90. PMID: 14620598.
Coleman JJ, Pontefract SK. Adverse drug reactions. Clin Med (Lond). 2016;16(5):481-485. doi:10.7861/clinmedicine.16-5-481