Pharmacokinetics (ADME), pharmacodynamics, dose-response, ED50/LD50, therapeutic index, drug resistance.
Pharmacology
Pharmacokinetics (ADME)
What the body does to a drug: Absorption, Distribution, Metabolism, Excretion. Key parameters: C_max, T_max, AUC, t½, Vd, CL. Compartment…
Pharmacodynamics
What a drug does to the body: receptor binding → downstream effect. Dose-response curves, efficacy, potency, agonist/antagonist classes.…
Dose-response curve
Sigmoidal relation between drug concentration + biological effect, parameterised by ED50 (median effective dose) + Hill coefficient.…
ED50, LD50, therapeutic index
ED50: dose producing half-maximal effect in half the population. LD50: dose killing half. Therapeutic index TI = LD50/ED50 — higher is…
Drug metabolism (cytochrome P450)
Hepatic enzymatic transformation of drugs. Phase I (oxidation by CYP450) + phase II (conjugation by UGT, SULT). CYP3A4 metabolises ~50% of…
Receptor theory
Clark 1926: drug effect proportional to receptor occupancy. Agonist (activates), partial agonist (submax), antagonist (blocks), inverse…
Drug resistance
Reduced drug efficacy from target mutation, efflux-pump upregulation, metabolic bypass, or sanctuary sites. Antimicrobial (MRSA, XDR-TB),…
Bioavailability & first-pass metabolism
Fraction of oral dose reaching systemic circulation unchanged. First-pass CYP/UGT in gut + liver can be >90% (e.g., lidocaine). Dictates…
Therapeutic drug monitoring
Plasma-level measurement to individualise dosing of narrow-TI drugs (digoxin, lithium, vancomycin, tacrolimus). Targets…
Clinical trial phases
Phase I (safety, n~20-80), Phase II (efficacy + dose, n~100-300), Phase III (confirmatory, n~1000+), Phase IV (post-market surveillance).…