Preparatory Mindset
Pharmacology is the study of how drugs interact with the body. Split your thinking into two halves: Pharmacokinetics (what the BODY does to the drug — absorption, distribution, metabolism, excretion) and Pharmacodynamics (what the DRUG does to the body — receptors, dose-response, efficacy vs potency). Most exam mistakes come from confusing PK and PD concepts.
Core Concepts
Ch01: General Principle (PK & PD)
Purpose: Quick-reference key drug concepts
Key Concepts Summary
Pharmacokinetics (PK) — "What the body does to the drug"
| Concept | Definition | Clinical Implication |
|---------|-----------|---------------------|
| Absorption | Movement from admin site → bloodstream | Oral → first-pass effect; IV bypasses |
| First-pass effect | Liver metabolizes drug before systemic circulation | Oral drugs require higher doses than IV |
| Bioavailability (F) | F = AUC_oral/AUC_IV | % of oral drug reaching systemic circulation |
| Distribution | Drug moves from blood → tissues | Vd small = stays in plasma (protein-bound); Vd large = wide tissue distribution |
| Volume of Distribution (Vd) | Vd = D/C | Small Vd = extensive protein binding, concentrated in plasma |
| Protein Binding | Reversible binding to albumin | Only free drug is active; displacement interactions cause toxicity |
| Metabolism | Liver (CYP450), Phase I + Phase II | Liver disease → dose reduction needed |
| Excretion | Kidneys (main), bile, lungs, sweat | Alkalinizing urine → ↑ excretion of weak acids (aspirin poisoning) |
| Half-life (t½) | Time for plasma conc to drop 50% | 5 half-lives → steady state |
| Steady State (Css) | Rate in = Rate out | Achieved after ~5 half-lives |
| Clearance (Cl) | Volume of plasma cleared/unit time | Depends on liver + kidney function |
| Loading Dose | Single large initial dose | Rapidly reach Css without waiting 5 t½ |
| Ion Trapping | Non-ionized ↔ ionized equilibrium | Weak acids trapped in alkaline compartments |
Pharmacodynamics (PD) — "What the drug does to the body"
| Concept | Definition | Key Point |
|---------|-----------|-----------|
| EC₅₀ | Conc for 50% max effect | Measure of potency |
| Efficacy (Emax) | Max effect achievable | Measure of effectiveness |
| Therapeutic Index (TI) | LD50/ED50 or LD5/ED95 | Safety margin; larger TI = safer |
| LD₅₀ | Dose lethal to 50% | Acute toxicity measure |
| ED₅₀ | Dose effective in 50% | Potency in population |
| Intrinsic Activity (α) | Ability to activate receptor | Full agonist α=1; Partial 0<α<1; Antagonist α=0 |
| Affinity | Ability to bind receptor | Measured by Kd |
| Competitive Antagonist | Binds reversibly, shifts curve right | Emax unchanged, EC50 ↑ |
| Partial Agonist | α<1; agonistic alone, antagonistic with full agonist | Ceiling effect + competitive antagonism |
| Inverse Agonist | Produces opposite effect of agonist | Constitutive receptor activity |
| Graded Response | Continuous effect in one individual | e.g., BP change in mmHg |
| Quantal Response | All-or-none in population | e.g., % of patients with headache relief |
| Side Effect | Unintended at therapeutic dose | Due to low selectivity |
| Toxic Effect | Excessive dose or prolonged use | Dose-dependent |
| Withdrawal/Rebound | Sudden stop → symptom exacerbation | e.g., Clonidine withdrawal |
Exam-Frequency Core Points (from exam notes)
High-Yield Points
- First-pass metabolism: oral drugs → liver → reduced bioavailability
- Half-life: 5 half-lives to reach steady state
- Ion trapping: weak acids trapped in basic compartments
- Therapeutic index = LD50/ED50 — narrow TI drugs require monitoring
- Volume of distribution: large Vd = extensive tissue distribution
- CYP450 inducers (rifampin, phenobarbital): ↓ drug levels
- CYP450 inhibitors (ketoconazole, cimetidine): ↑ drug levels
- Protein binding: only FREE drug is active; displacement interactions cause toxicity
Topic Summary
Pharmacokinetics describes drug movement (ADME), while pharmacodynamics describes drug action at receptors. Key concepts: half-life determines dosing interval, first-pass metabolism reduces oral bioavailability, and the therapeutic index separates effective from toxic doses.