Paper I
2025 March (Supplementary (SAY)) (2019 Scheme) · 100 marks · 180 min

Question

Define Pharmacodynamics. Explain the various factors modifying drug action with examples. (2+8)

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Answer

Pharmacodynamics The study of the biochemical and physiological effects of drugs on the body and their mechanisms of action — in short, “what the drug does to the body,” in contrast to pharmacokinetics (“what the body does to the drug”).

Factors modifying drug action

  • Age — neonates have immature renal/hepatic elimination, prolonging half-life of many drugs (e.g. chloramphenicol → grey baby syndrome) and a more permeable blood-brain barrier; the elderly show declining renal function, reduced hepatic blood flow, and altered receptor responsiveness, producing higher rates of adverse drug reactions.
  • Body size — dose is calculated on body weight (or occasionally BSA, chiefly for anticancer drugs), since the same absolute dose reaches a different effective concentration depending on distribution volume.
  • Sex and pregnancy — women generally need doses toward the lower end of the standard range; pregnancy alters absorption, distribution volume, protein binding, and elimination simultaneously, making the net effect on any individual drug hard to predict from first principles.
  • Genetics (pharmacogenetics) — dose needed for the same effect can vary several-fold on a purely genetic basis, e.g. slow/fast acetylator status for isoniazid, low-activity CYP2C9 variants slowing warfarin metabolism, and G6PD deficiency precipitating hemolysis with oxidant drugs.
  • Route of administration — e.g. propranolol given IV bypasses the extensive first-pass hepatic metabolism it undergoes orally.
  • Concurrent disease — hepatic/renal impairment alters drug metabolism/excretion; hypoalbuminemia raises the free fraction of highly protein-bound drugs.
  • Drug interactions — pharmacokinetic (enzyme induction/inhibition, protein-binding displacement) or pharmacodynamic (synergism/antagonism) interactions with co-administered drugs.
  • Tolerance and cumulation — repeated dosing can progressively reduce response (tolerance) or, for slowly eliminated drugs, cause toxic accumulation even without a dosing error.

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