Question 16

Classify and describe adverse drug reactions with examples of each.

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College Answer

Candidates should have provided a definition of adverse drug reactions and then a
classification. There are at least two widely accepted systems for classification, either was
acceptable; though candidates often switched between both which led to a less structured
answer. The WHO classification is comprehensive and logical, though both Rang and Dale and
Goodman and Gilman also have sections on this topic.
Common errors were the citing of examples with the incorrect mechanism, describing only drug
interactions rather than all adverse reactions and focussing the answer on the 4 hypersensitivity
reactions which could only score a low mark. Some candidates confused drug errors with
adverse reactions.

Discussion

There are in fact several possible systems, and none of them are viewed as canonical. One specific system, in a form originally described by Edwards et al (2000), has a reasonable level of brevity and memorability which makes it suitable for exam preparation. It originated from a book chapter by Rawlin & Thompson (1977) which is obviously not easily available to the casual Googler. The authors classified ADRs into "dose-related" and "not dose-related", which were arbitrarily designated "Type A" and "Type B". Four years later (1981) the same authors decided to rename these as “Augmented” and “Bizarre”, for what other authors describe as "mnemonic purposes". The other below-listed classification categories were added over the subsequent years by other authors.

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.

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