Overview
This lecture covers the foundational concepts of pharmacokinetics (drug movement through the body) and pharmacodynamics (drug effects on the body), focusing on dosing, drug elimination, and response curves.
Pharmacokinetics Basics
- Pharmacokinetics refers to the movement of a drug throughout the body.
- Main components: Absorption, Distribution, Metabolism, and Elimination (ADME).
- Drug concentration over time has phases: absorption (drug enters blood), Cmax (peak), elimination, and Cmin (trough).
- Steady state is achieved when drug administration equals elimination, usually after 4-5 half-lives.
- Dosage formulations (e.g., extended-release) and dosing frequency affect fluctuations in drug levels.
- Loading dose is used to achieve steady-state concentration rapidly.
Drug Elimination Kinetics
- First order kinetics: constant fraction (50%) of drug eliminated per half-life; dependent on concentration.
- Zero order kinetics: constant amount eliminated per unit time; independent of concentration (e.g., high-dose aspirin, phenytoin).
- Most drugs are first order; zero order drugs are more likely to cause toxicity.
Pharmacodynamics Principles
- Pharmacodynamics describes the drug's effect on physiological or biochemical processes.
- Dose-response curve: S-shaped; measures dose required for 50% effect (EC50 or ED50) and maximum efficacy.
- Potency: drug requiring less dose to achieve the same effect has lower ED50/EC50; does not mean more effective.
- Efficacy: maximum effect a drug can produce, regardless of dose.
Therapeutic Index and Drug Safety
- Therapeutic index (TI) = LD50 / ED50; higher TI means a safer drug.
- Narrow TI drugs (e.g., digoxin, lithium) require monitoring.
- New drugs generally have wider TIs to improve safety and convenience.
Dose-Response Relationships and Tolerance
- Competitive antagonists shift the dose-response curve right (higher doses needed for same effect).
- Tolerance develops when increasing doses are needed over time for the same effect (curve shifts right).
- Irreversible antagonists decrease maximum efficacy (curve shifts downward).
Key Terms & Definitions
- Cmax — Maximum (peak) plasma concentration of a drug after dosing.
- Cmin — Minimum (trough) plasma concentration before next dose.
- Steady State — Drug intake equals elimination; stable concentration.
- First Order Kinetics — Constant percentage of drug cleared per time.
- Zero Order Kinetics — Constant amount of drug cleared per time.
- EC50/ED50 — Concentration or dose for 50% of maximal effect.
- LD50 — Dose causing death in 50% of subjects.
- Therapeutic Index (TI) — Ratio of lethal to effective dose; indicates safety margin.
- Potency — Amount of drug needed for a given effect.
- Efficacy — Maximal effect a drug can produce.
- Loading Dose — Initial larger dose to rapidly achieve therapeutic concentration.
Action Items / Next Steps
- Review formulas for maintenance dose, steady-state concentration, and loading dose.
- Prepare for detailed ADME lecture (absorption, distribution, metabolism, elimination).
- Know which drugs require therapeutic drug monitoring and why.