Pharmacokinetics Lecture Notes

Introduction

• Pharmacokinetics vs Pharmacodynamics: Understanding the difference.
• Pharmacokinetics: What the body does to a drug.

Key Processes in Pharmacokinetics

1. Absorption

   • Drug must be absorbed to enter the bloodstream.
   • Routes of administration: Parenteral, topical, nasal, rectal, etc.
   • Membrane crossing: Necessary unless drug is given intravenously.
   • Methods of Absorption:
     • Passive Diffusion: Movement from high to low concentration, water-soluble pass through channels, lipid-soluble pass through membranes.
     • Facilitated Diffusion: Large molecules need carrier proteins, still from high to low concentration.
     • Active Transport: Energy-dependent, using ATP.
     • Endocytosis: Large drugs engulfed by cell membrane.
   • Factors Affecting Absorption: pH, surface area, blood flow.
   • Bioavailability: Amount of drug reaching systemic circulation.
   • AUC (Area Under Curve): Used for comparing routes of administration.

2. Distribution

   • Movement from circulation to tissues.
   • Factors Influencing Distribution:
     • Lipophilicity: Lipid-soluble drugs pass membranes easily.
     • Blood Flow: High in certain organs like the brain.
     • Capillary Permeability: Varies by organ (e.g., liver vs. brain).
     • Binding to Proteins and Tissues: Albumin binding slows distribution.
     • Volume of Distribution (Vd): Theoretical volume needed to contain the drug.

3. Metabolism

   • Primarily occurs in the liver.
   • Phase 1 Reactions: Oxidation, hydrolysis, reduction using cytochrome P450 enzymes.
   • Phase 2 Reactions: Conjugation to make drugs more water-soluble.

4. Elimination

   • Main routes: Hepatic, renal, biliary.
   • Kinetics:
     • First Order: Proportional elimination to drug concentration.
     • Zero Order: Constant elimination irrespective of concentration.
   • Half-life: Time to reduce plasma concentration by half, important for dosing.
   • Steady State: Reached when administration rate equals elimination rate.
   • Loading Dose: Used to quickly reach therapeutic level.

Drug Metabolism Enzymes

• Cytochrome P450 Enzymes: Key in drug metabolism.
• Notable ones:
  • CYP 3A4 and 5
  • CYP 2D6
  • CYP 2C8 and 9
  • CYP 1A2
• Inducers: "PCRABS" mnemonic (Phenytoin, Carbamazepine, etc.)
• Inhibitors: "GPACMAN" mnemonic (Grapefruit, Protease inhibitors, etc.)

Conclusion

• Importance of understanding pharmacokinetics to predict drug behavior in the body.
• Application in drug dosing and therapeutic management.