Pharmacology: Kinetics, Dynamics and the Numbers Questions Love
What the body does to the drug
Pharmacokinetics covers absorption, distribution (volume of distribution, Vd), metabolism (phase I oxidation/reduction/hydrolysis via CYP450; phase II conjugation) and excretion. Link them with three equations you should be able to use instantly: t½ = 0.693 × Vd / CL, loading dose = (Vd × target concentration) / F, and maintenance rate = CL × target concentration / F.
The classic trap: order of kinetics
First-order elimination removes a constant fraction per unit time. Zero-order removes a constant amount; this is saturable and applies to phenytoin, ethanol and high-dose salicylates, so a small dose increase produces a disproportionate, sometimes toxic, rise in concentration. Steady state is reached after roughly 4–5 half-lives - not one or two.
What the drug does to the body
Know agonist, partial agonist, inverse agonist and antagonist. Competitive antagonism is surmountable (curve shifts right, same maximal effect); noncompetitive antagonism lowers maximal effect. Potency sits on the x-axis (ED50), efficacy on the y-axis (Emax); therapeutic index = TD50/ED50.
Traps that recur
Confusing half-life with duration of action; assuming a long half-life means a safer drug (it means slower titration and accumulation); forgetting enzyme induction takes days to weeks (rifampicin, carbamazepine, phenytoin, St John's wort) while inhibition is fast (ketoconazole, macrolides, ritonavir, grapefruit); missing active metabolites (codeine to morphine via CYP2D6).
Worked example
70 kg adult, Vd 0.5 L/kg = 35 L, target 2 mg/L, F = 1. Loading dose = 35 × 2 / 1 = 70 mg. Rule of thumb: after any dose change, wait ~5 half-lives before interpreting a serum level.