Pharmacology and Therapeutics
Core Principles
Candidates must understand pharmacokinetics (absorption, distribution, metabolism, elimination) and pharmacodynamics (receptor agonism and antagonism, dose-response, therapeutic index). Know first-pass metabolism, bioavailability, half-life and steady state (roughly four to five half-lives), volume of distribution, and the meaning of loading versus maintenance doses. Understand hepatic phase I and phase II metabolism, cytochrome P450 interactions, and how inhibitors and inducers change drug levels. Recognize renal clearance and how kidney function alters dosing. Know pregnancy and lactation categories conceptually, and the major mechanisms of adverse drug reactions, including hypersensitivity and idiosyncratic reactions.
Therapeutic Reasoning
Questions test drug selection by indication, contraindication, and interaction, not memorized brand names. Understand narrow therapeutic index drugs, monitoring (drug levels, INR, renal function), and the concept of polypharmacy and deprescribing in older adults. Know that antagonists without intrinsic activity block effects but do not lower baseline below zero, while partial agonists produce a ceiling effect.
Traps
Common traps: confusing half-life with duration of action, assuming an inducer acts immediately (enzyme induction takes days to weeks), forgetting that prodrugs require activation, and missing that a drug cleared renally needs dose reduction even if it is hepatically metabolized. Another trap is choosing an interacting drug when a safer alternative exists.
Worked Example
Rule of thumb: when a new drug is added to a stable regimen, ask which enzyme handles each drug and whether the combination is an inhibitor or inducer pair. For a patient stable on warfarin who starts an antibiotic that inhibits CYP2C9, expect the INR to rise and plan earlier monitoring and possible dose reduction rather than waiting for bleeding.