A clinician's spec sheet to drugs — pharmacokinetics, pharmacodynamics, and the major classes by mechanism, with named molecules.
Pharmacology is the science of how chemicals interact with living systems. Two halves: pharmacokinetics (what the body does to the drug) and pharmacodynamics (what the drug does to the body).
Toxicology studies harm. Therapeutics studies use. Clinical pharmacology bridges molecule and patient. Pharmacogenomics personalizes choice and dose by genotype (e.g., CYP2D6, HLA-B*57:01).
Pharmacokinetics is captured in four letters:
| Step | Meaning | Key concepts |
|---|---|---|
| A — Absorption | Drug → bloodstream | Bioavailability (F), first-pass effect |
| D — Distribution | Blood → tissue | Volume of distribution (Vd), protein binding |
| M — Metabolism | Biotransformation (mostly liver) | CYP450 enzymes (CYP3A4, CYP2D6) |
| E — Excretion | Drug → out | Renal (urine), biliary (feces) |
The half-life (t½) is the time for plasma concentration to fall by half. Steady state takes ~4–5 half-lives. Dosing frequency follows from t½.
The relationship between dose and effect is typically sigmoid on a log-dose scale. Two key parameters:
The therapeutic index = LD₅₀ / ED₅₀: the ratio of toxic to therapeutic dose. Drugs with narrow indices (warfarin, lithium, digoxin) require monitoring.
| Family | Speed | Examples |
|---|---|---|
| Ion channels | milliseconds | Nicotinic ACh, GABA-A, NMDA |
| GPCRs | seconds | β-adrenergic, opioid μ, muscarinic |
| Kinase-linked | minutes | Insulin, growth-factor receptors |
| Nuclear (NHR) | hours | Estrogen, glucocorticoid, thyroid |
Drugs may be agonists (activate), partial agonists (activate sub-maximally — e.g., buprenorphine), antagonists (block), or inverse agonists (suppress constitutive activity).
Inhibit cyclooxygenase (COX-1, COX-2), reducing prostaglandin synthesis. Anti-inflammatory, anti-pyretic, analgesic. Examples: ibuprofen, naproxen, aspirin, celecoxib. GI bleeding and renal effects are dose-dependent.
Centrally acting analgesic and antipyretic. Mechanism still debated (likely COX-3 / endocannabinoid). Hepatotoxic above ~4 g/day in adults; the leading cause of acute liver failure in the US.
Agonists at μ-opioid receptors. From weakest to strongest: codeine, tramadol, hydrocodone, oxycodone, morphine, fentanyl (~100× morphine). Constipation, respiratory depression, dependence.
For neuropathic pain: gabapentin, pregabalin, tricyclics (amitriptyline), SNRIs (duloxetine).
| Class | Mechanism | Example |
|---|---|---|
| Statins | HMG-CoA reductase inhibitors | atorvastatin, rosuvastatin |
| ACE inhibitors | ↓ angiotensin II | lisinopril, ramipril |
| ARBs | AT1 receptor block | losartan, valsartan |
| β-blockers | β-adrenergic antagonist | metoprolol, carvedilol |
| Ca²⁺ blockers | L-type Ca channel | amlodipine, diltiazem |
| Diuretics | ↑ Na/water excretion | hydrochlorothiazide, furosemide |
| Anticoagulants | ↓ clotting factors | warfarin, apixaban, heparin |
| Antiplatelets | Block platelet activation | aspirin, clopidogrel |
β-lactams: penicillin, amoxicillin, cephalexin, ceftriaxone, meropenem. Glycopeptides: vancomycin.
30S inhibitors: tetracyclines, aminoglycosides (gentamicin). 50S: macrolides (azithromycin), clindamycin, linezolid.
Fluoroquinolones (ciprofloxacin) inhibit DNA gyrase. Sulfonamides + trimethoprim (Bactrim) block folate synthesis.
Selection pressure favors resistant strains. WHO lists antibiotic resistance as a top global threat — MRSA, ESBL E. coli, CRE, MDR-TB.
Cytochrome P450 enzymes in the liver (and gut) metabolize ~75% of clinically used drugs. The dominant isoforms:
| Isoform | % of drugs | Notable substrates |
|---|---|---|
| CYP3A4 | ~50% | statins, midazolam, many oncology drugs |
| CYP2D6 | ~25% | codeine → morphine, many antidepressants |
| CYP2C9 | ~10% | warfarin, NSAIDs |
| CYP1A2 | ~5% | caffeine, theophylline |
Inducers (rifampin, St. John's Wort) accelerate metabolism and lower drug levels. Inhibitors (clarithromycin, grapefruit juice for CYP3A4) raise them. Drug-drug interactions are frequently mediated through CYP enzymes.
ADRs are classified by Rawlins-Thompson:
| Phase | Subjects | Question |
|---|---|---|
| Pre-clinical | Cells, animals | Safe enough? |
| Phase I | 20–80 healthy | Safety, PK |
| Phase II | 100–300 patients | Efficacy signal, dose-finding |
| Phase III | 1,000–5,000 | Efficacy vs. comparator, safety at scale |
| Phase IV | Post-marketing | Rare ADRs, real-world effectiveness |
Most candidates fail. From IND to FDA approval, ~10% of drugs entering Phase I succeed. Average development cost: $1–2 billion.
A modern pharmacy stocks ~3,000 drug products. Worldwide, the WHO Model List of Essential Medicines names roughly 480 — the medicines a basic functioning health system requires.
Roger Seheult, MD walks through clinical pharmacology in concise lectures suitable for first-year medical students and the curious public.
Approved drugs are among the most rigorously tested chemicals in human history. Yet effect sizes vary widely between individuals (pharmacogenomics) and between populations (under-representation in trials). Real-world effectiveness is often smaller than RCT efficacy. The WHO Model List, FDA Orange Book, and BNF (British National Formulary) are authoritative starting references.
Drug names appear here for educational reference. Do not start, stop, or adjust prescriptions without a clinician. Counterfeit medications are a global threat — buy only from licensed pharmacies.