Mechanisms of Adverse Drug Effects

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  • Adverse drug reactions can be classified as:
  • Type A (augmented) reactions
  • Dose related
  • Predictable from drug pharmacology
  • Common
  • Can normally be managed with dose adjustment
  • Examples - bleeding with warfarin, headache with GTN
  • Mechanisms - too much of the desired effect, desired effect at wrong site (GTN headache), or additional unwanted pharmacological action
  • Type B (bizarre) reactions
  • Not dose related
  • Unpredictable
  • Irreversible
  • Uncommon
  • Drug needs to be stopped
  • Examples - anaphylaxis to penicillins, hepatotoxicity with halothane
  • Mechanism - poorly understood, often genetic/immunological basis
  • Type C - chronic reactions
  • Type D - delayed reactions
  • Type E - end of treatment effects
  • Factors increasing risk of ADRs:
  • Age, race, gender, specific illness, delayed metabolism/clearance, polypharmacy, history of drug reaction
  • Drug interactions can occur as a result of:
  • Pharmacodynamics - medications with same effects potentiating each other
  • Absorption - medications can affect each other's absorption
  • Distribution - protein bound drugs can displace each other, increasing unbound fractions
  • Metabolism - drugs can induce or inhibit metabolism of other drugs
  • Excretion - amiodarone can reduce excretion of digoxin
  • Cytochrome P-450s can be induced (by st john's wort) or inhibited (by grapefruit juice)