Paper I — 2023 January (Supplementary) (2019 Scheme) — Q4
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Paper I
2023 January (Supplementary) (2019 Scheme) · 100 marks · 180 min
Question
Briefly describe kinetics of elimination. Add a note on factors modifying drug action.
(4+4)
Q48 marksShort Essays
Answer
a) Kinetics of elimination
First-order kinetics — the rate of elimination is directly proportional to plasma concentration; a constant fraction of the drug present is eliminated per unit time, so clearance stays constant regardless of dose. Applies to most drugs at therapeutic concentrations, since the eliminating enzymes/transporters are present in excess and unsaturated. Plasma half-life is meaningfully constant for a first-order drug: ~50% eliminated after 1 half-life, ~93% after 4-5 half-lives.
Zero-order (capacity-limited) kinetics — the eliminating mechanism is saturated, so a constant amount is eliminated per unit time regardless of concentration; clearance falls as concentration rises. Ethanol follows zero-order kinetics throughout its clinical range. Phenytoin, aspirin (in overdose), and theophylline follow first-order kinetics at low doses but shift to zero-order once the eliminating enzyme saturates — beyond that point, small dose increases cause disproportionately large rises in plasma concentration, the reason phenytoin requires therapeutic drug monitoring rather than simple linear dose titration.
b) 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, via pharmacokinetic or pharmacodynamic mechanisms.
