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).…
PBPK physiological pharmacokinetics
Physiologically-based PK: organism partitioned into compartments (liver, kidney, fat, muscle, ...) with blood-flow-limited or…
Emax / Clark occupancy pharmacodynamics
Clark 1933 / Hill-Langmuir: drug effect E = E_max [D]^n / (EC_50^n + [D]^n) follows from receptor occupancy at equilibrium. Operational…
Receptor occupancy (Clark 1937)
A Clark 1937 receptor-occupancy theory; modern dose-response + Hill-coefficient + functional-selectivity biased-agonism.
Hill-Langmuir saturation
Hill 1910 + Langmuir 1916 receptor-saturation; modern allosteric-modulator + bitopic-ligand + GPCR-bias paradigms.
Pharmacodynamics (Rang)
H Rang 1986 'Pharmacology'; modern Bonn-Miller 2017 cannabinoid PD; basis of clinical pharmacology textbook.
PK (Dost 1953)
F H Dost 1953 'Der Blutspiegel'; modern compartmental + non-compartmental + population-PK NONMEM + Phoenix.
Drug discovery (Paul 2010)
S Paul 2010 'How to improve R&D productivity' Nature Rev Drug Discov; modern average $2.6B / drug-launch.
Pharmacogenomics (Relling 2015)
M Relling 2015 + CPIC-guidelines; modern CYP2C19-clopidogrel + TPMT-thiopurine + DPYD-fluoropyrimidine clinical-actionable.
Magic bullet (Ehrlich 1907)
P Ehrlich 1907 (Nobel 1908) magic-bullet + 1909 salvarsan; modern modern foundational text + targeted-therapy + immune-conjugate ADC 2024.
Receptor theory (Clark 1933)
A J Clark 1933 + Hill 1909 receptor-occupancy; modern modern foundational text + Stephenson 1956 efficacy + Furchgott 1966 partial-agonist.
Schild (1947)
H Schild 1947 + Arunlakshana 1959 Schild-plot pA2; modern modern foundational text + functional-antagonism + 2024 GPCR allosteric Schild.
Opioid receptor (Pert-Snyder 1973)
C Pert-S Snyder 1973 opioid-receptor-binding; modern modern foundational text + μ/κ/δ + 2024 G-protein-biased agonist oliceridine pain.
EDRF/NO (Furchgott 1980)
R Furchgott 1980 (Nobel 1998) endothelium-derived-relaxing factor; modern modern foundational text + NO-cGMP + Viagra + 2024 NO-cGMP…
Operational model (Black-Leff 1983)
J Black-P Leff 1983 (Black Nobel 1988) operational-model τ; modern modern foundational text + functional-selectivity + ligand-bias 2024.