Pharmacology and Therapeutics
What this domain tests
Questions probe whether you can predict drug behavior in a specific patient: absorption and clearance, half-life and steady state, interactions, dose adjustment in organ failure, and recognition of adverse effects. Mechanism questions usually reduce to a clinical consequence.
Core rules
- Pharmacokinetics is absorption, distribution, metabolism, and elimination. Volume of distribution determines loading dose (Vd × target concentration / bioavailability); clearance determines maintenance dose; half-life links the two.
- Steady state is reached after about four to five half-lives; a loading dose achieves therapeutic levels immediately without shortening the time to steady state.
- Most drugs follow first-order kinetics (constant fraction eliminated per unit time). Zero-order drugs eliminate a constant amount, so small dose increases cause disproportionate rises: phenytoin, ethanol, and high-dose salicylates are classic examples.
- Cytochrome P450 interactions matter: inhibitors (azoles, macrolides, protease inhibitors, grapefruit) raise substrate levels; inducers (rifampin, carbamazepine, phenytoin, St John's wort) lower them.
- Adjust for renal function using estimated clearance for renally eliminated drugs; adjust hepatically cleared drugs by clinical monitoring because no single formula is reliable.
- Adverse drug reactions: type A are dose-dependent and predictable from mechanism; type B are idiosyncratic and not. Therapeutic index describes the safety margin.
- Prescribe with stewardship in mind: right indication, right dose, right duration, and deprescribing where benefit no longer exists.
Worked example
A patient on warfarin is started on trimethoprim-sulfamethoxazole for a urinary infection and presents with bruising and an INR of 6. Reasoning: the antibiotic inhibits CYP2C9, reducing warfarin metabolism, and also displaces protein binding and alters gut flora. The interaction is predictable and rapid. Management is to stop or replace the antibiotic, withhold warfarin, give vitamin K if bleeding risk warrants, and monitor INR closely; the lesson is to anticipate the interaction at the time of prescribing rather than after the bruise.
Traps that cost marks
- Expecting steady state after a single dose or after two half-lives.
- Applying first-order assumptions to phenytoin.
- Forgetting active metabolites and prodrugs.
- Labeling any adverse effect as an allergy.
- Missing that a new drug, not a new disease, explains the symptom.