FRCA Notes

Adverse Drug Reactions

  • An adverse drug reaction is the occurrence of any drug effect that is not of therapeutic, diagnostic or prophylactic benefit to the patient
  • Occurs when the drug has been given at the standard dose, via the appropriate route in order to manage a condition
  • Can generally be divided into:
    1. Reactions that happen to anyone: overdose, side-effects, interactions
    2. Reactions that happen to susceptible individuals: intolerance, idiosyncrasies (genetic polymorphisms)
    3. Reactions that happen due to allergy e.g. anaphylaxis and anaphylactoid reactions

  • Can be classified according to various systems:
    • Type A/B
    • Extended type A/B
    • DoTS
    • Coombs

Anaphylaxis

  • An anaphylactic reaction is classically described as one whereby a patient undergoes:
    • An IgE antibody-mediated response
    • To a substance to which they have previously been sensitised
    • Characterised by release of vasoactive mediators and systemic symptoms.

Anaphylactoid reactions

  • An anaphylactoid reaction a response to a substance that is
    • Not IgE-antibody mediated
    • To a substance to which they do not need to have been previously sensitised
    • But is characterised by the same release of vasoactive mediators and systemic symptoms as an anaphylactic reaction

Type A/B

  • Type A reactions are common, dose-dependent reactions
  • They are an extension of the known pharmacological effect of the drug

  • Type B reactions are uncommon, dose-independent reactions
  • The patient will exhibit signs and symptoms of a drug reaction
  • Encompasses anaphylactic and anaphylactoid reactions

Extended Type A/B

  • A simple method from A - F, although falls down because drug reactions can be part of more than one class
Mnemonic Example Type
Augmented Propofol and hypotension Dose-related
Bizzarre Anaphylaxis Dose-unrelated
Chronic Propofol Infusion Syndrome Dose & time related
Delayed Fluoride Nephrotoxicity Time-related
End-of-use On cessation i.e. rebound HTN with clonidine Withdrawal
Failure Oral contraceptive pill Unexpected failure


Dose-related

  • Adverse drug reactions which can occur at:
    • Supratherapeutic doses e.g. toxic effects
    • Therapeutic doses e.g. side-effects
    • Subtherapeutic doses e.g. in susceptible individuals

Time-related

  • Rapid reaction: drug administered too quickly
  • First-dose reaction: e.g. hypotension with ACE-I
  • Early reaction: abates due to tolerance e.g. headache with nitrates
  • Intermediate reaction: e.g. Coombs type II-IV reactions
  • Late reaction: risk increases with repeated uses, including withdrawal symptoms
  • Delayed reaction: e.g. carcinogenesis

Susceptibility

  • Includes genetic variation, age, gender, physiological variation, exogenous factors, presence of disease state
  • Includes anaphylaxis

Type I (immediate)

  • IgE-mediated to exogenous antigen, rapid (minutes), e.g. allergy

Type II (cytotoxic)

  • IgG/IgM-mediated to cell-surface antigen, minutes-hours, organ-specific e.g. Goodpasture's syndrome

Type III (immune complex)

  • IgG/IgM-mediated to soluble antigens deposited in tissues, hours, e.g. SLE

Type IV (delayed)

  • T-cell and TNF-ɑ mediated, takes many days, e.g. TB