Paper I — 2024 June (Supplementary) (2019 Scheme) — Q3
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Paper I
2024 June (Supplementary) (2019 Scheme) · 100 marks · 180 min
Question
Discuss the factors modifying drug action. Describe the clinical importance of plasma
protein binding of drugs. (4+4)
Q38 marksShort Essays
Answer
a) Factors modifying drug action
Body size — dose calculated on body weight/BSA.
Age — neonates have immature renal/hepatic elimination; the elderly have declining renal function and altered receptor responsiveness.
Sex and pregnancy — smaller average body size in women; pregnancy alters absorption, distribution, and elimination simultaneously.
Genetics (pharmacogenetics) — dose needed for the same effect can vary several-fold on a purely genetic basis (e.g. acetylator status, G6PD deficiency).
Concurrent disease and drug interactions — renal/hepatic impairment alters pharmacokinetics; co-administered drugs produce pharmacodynamic synergism/antagonism.
Route of administration and cumulation — different routes alter onset/bioavailability; slowly eliminated drugs accumulate with chronic dosing.
Tolerance/tachyphylaxis — reduced response with repeated use.
b) Clinical importance of plasma protein binding
Acidic drugs bind mainly to albumin, basic drugs to alpha-1-acid glycoprotein. Only the free (unbound) fraction is pharmacologically active; the bound fraction acts as a temporary reservoir.
Duration of action: highly bound drugs tend to have longer duration, since bound drug is unavailable for metabolism/filtration.
Hypoalbuminemia (renal failure, cirrhosis, malnutrition) raises the free fraction and risks toxicity at “normal” total plasma concentrations — particularly relevant for phenytoin and furosemide.
Displacement interactions: two drugs competing for the same binding site — the higher-affinity drug displaces the lower-affinity one, transiently raising its free concentration; usually self-correcting unless the displaced drug’s metabolism/excretion is also impaired.
Volume of distribution: highly bound drugs have a smaller Vd (largely confined to plasma).
Dialysis: highly protein-bound drugs are poorly removed by hemodialysis.
