What is an adverse drug reaction? Classify (with drug examples) the different types.

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College Answer

This question was very poorly answered. Textbooks give different classifications so some largesse was allowed, but both immunologic and physicochemical (kinetic and dynamic)  were expected. Marks were allocated for both type and an example - some candidates failed to provide examples or listed a drug side effect without explanation. Some candidates were ‘creative’ with classification systems but where appropriate examples were given marks were awarded. No marks were gained for detailed descriptions of LD50 and therapeutic ratios.

Discussion

It is pleasing to see the examiners being generous with their marking ina question about a definition which nobody can agree upon. Truly, each author on this topic gives a different definition. Here's a couple by the WHO:

  • An adverse drug event is “any untoward medical occurrence that may present during treatment with a pharmaceutical product but which does not necessarily have a causal relationship with this treatment” (WHO definition, 2005)
  • An adverse drug reaction is “a response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for the modification of physiologic function.” (WHO definition, 2005)

A common classification system which is not "creative" is the alphabetic A-B-C-D-E-F system originally proposed by  Edwards et al (2000).

A: Dose-related reactions
  • This can include adverse effects at either normal dose or overdose.
  • These may include expected extensions of the therapeutic effect of the drug, eg. bleeding in heparin.
  • Toxic effects eg. serotonin syndrome
  • Side effects are included, eg. anticholinergic effects of tricyclics 
B: Non-dose-related reactions
  • This refers to drug effects which are totally unrelated to the dose (i.e. any exposure is enough to trigger such a reaction).
  • Allergic reactions
  • Anaphylaxis
  • Idiosyncratic reactions, eg. purpura or drug-induced SLE
C: Dose and time-related reactions
  • This refers to drug effects which occur due to dose accumulation, or with prolonged use
  • Adrenal suppression with corticosteroids is one example.
D: Time related reactions
  • This refers to drug effects which occur due to prolonged use in a drug which doesn't tend to accumulate.
  • An example might be tardive dyskinesia after decades of using typical antipsychotics
E: Withdrawal reactions
  • This refers to the undesired effects of ceasing the drug
  • Classical examples might include opiate withdrawal and rebound hypertension after stopping clonidine.
F: Unexpected failure of therapy
  • This category has been added to describe an undesirable reduction in the drug's efficacy (or, the undesirable increase thereof)
  • Examples may include increased clearance by dialysis and plasmapheresis, drug interactions altering metabolism, and the effects of critical illness on protein binding and elimination.

References

Edwards, I. Ralph, and Jeffrey K. Aronson. "Adverse drug reactions: definitions, diagnosis, and management.The Lancet 356.9237 (2000): 1255-1259.

Schatz, S., and R. Weber. "Adverse drug reactions." Pharmacy Practice 1 (2015): 1.

Kaufman, Gerri. "Adverse drug reactions: classification, susceptibility and reporting." Nursing Standard (2014+) 30.50 (2016): 53.

Rawlins MD, Thompson JW. "Pathogenesis of adverse drug reactions." In; Davies DM, ed. Textbook of adverse drug reactions. Oxford: Oxford University Press, 1977: 10

Rawlins, Michael D. "Clinical pharmacology. Adverse reactions to drugs." British medical journal (Clinical research ed.)282.6268 (1981): 974.

Vervloet, Daniel, and Stephen Durham. "Adverse reactions to drugs." BMJ 316.7143 (1998): 1511-1514.