Adverse effects

Classify and describe adverse drug effects.

An adverse effect is:

  • A noxious or unintended effect associated with administration of a drug at the normal dose
    • i.e., not an overdose
    • Occur:
      • Mainly in young and middle-aged individuals
      • Twice as common in women
      • May be exacerbated by asthma and pregnancy.
  • Distinct from an adverse event, which is an untoward occurrence during treatment that does not necessarily have a causal relationship to drug administration

Adverse effects can be classified by mechanism as follows:

Type A Adverse Reactions

These are related to the pharmacological action of the drug. They are:

  • Common
  • Related to dose (dose-response relationship)
  • Temporally associated with drug administration
  • Reproducible
  • Pharmacologically predictable based on understanding of the drug in question
    • e.g hypokalaemia secondary to diuretic use

They typically result in:

  • Organ-selective injury
  • More pronounced with long-term use and in risk groups:
    • Extremes of age
    • Pregnancy
    • Renal failure
  • High morbidity but low mortality
    Treatment is to decrease dose.

Type B Adverse Reactions

These are patient-specific or idiosyncratic reactions. They are:

  • Rare
    Potentially genetic, but poorly understood.
  • Independent of dose
    • Occur with low doses
    • Do not have a dose-response relationship
  • Not pharmacologically predictable
    Important causes include:
    • Acetylator status
    • CYP450 variants
    • Receptor abnormalities
    • Enzyme alterations/deficiencies
      • e.g. Suxamethonium apnoea
  • Not necessarily reproducible

They typically result in:

  • Immuno-allergic reactions
  • Pseudo-allergy
  • Idiosyncratic reaction
  • Low morbidity but high mortality
    • e.g. Stevens-Johnson Syndrome or anaphylaxis following penicillin administration

Treatment is to cease the medication.

Type C Adverse Reactions

These are 'statistical effects' associated with monitoring. They are:

  • Typically an increased frequency of background disease that is detected due to increased screening
  • Atypical for a drug reaction and not pharmacological predictable
  • No identifiable temporal relationship
  • Not reproducible

References

  1. RHB Meyboom, M Lindquist, ACG Egberts. An ABC of Drug-Related Problems. Drug Safety 2000;22:415-23.
  2. Pirmohamed M, Breckenridge AM, Kitteringham NR, Park BK. Adverse drug reactions. BMJ. 1998 Apr 25;316(7140):1295-8. Open Access Review.
  3. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients—a meta-analysis of prospective studies. JAMA 1998;279: 1200-5.
Last updated 2019-07-18

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