Pharmacokinetics Lecture Notes

Overview

• Pharmacokinetics: Study of how the body processes drugs.
  • Processes include: absorption, distribution, metabolism, and excretion (ADME).

ADME Components

1. Absorption

   • Entry of drugs into the body via various routes:
     • Oral, Intravenous (direct to bloodstream), Intramuscular, Inhalation, Transdermal, Sublingual, Eye/Ear/Nasal for localized delivery.
   • Influencing factors:
     • Food in stomach, stomach acidity, blood flow to GI tract.
     • Cell membrane crossing via:
       • Passive Transport: No energy required.
         • Passive diffusion (small, lipid-soluble, non-polar molecules).
         • Facilitated diffusion (larger, water-soluble, polar molecules).
       • Active Transport: Energy required (ATP needed, carrier proteins involved).
       • Endocytosis: For large molecules.
   • Bioavailability:
     • Fraction of administered drug dose that reaches systemic circulation unchanged.
     • First Pass Effect: Oral drugs metabolized in gut/liver before reaching circulation, reducing bioavailability.

2. Distribution

   • Movement of drugs to various body tissues.
   • Factors affecting distribution:
     • Membrane Permeability: Lipophilic drugs cross membranes easily.
     • Molecular Size
     • Plasma Protein Binding: Reduces distribution.
   • Volume of Distribution: Theoretical distribution of drug in body tissues vs. blood.

3. Metabolism

   • Conversion of drugs into active/inactive forms (metabolites).
   • Occurs primarily in the liver.
   • Phase 1: Modification via cytochrome P450 enzymes (oxidation, reduction).
   • Phase 2: Conjugation with polar compounds for easier elimination.

4. Excretion

   • Removal of drugs from the body mainly through urine.
   • Can also occur via bile, feces, lungs, and skin.
   • Clearance: Rate of drug elimination from blood.

Key Pharmacokinetic Concepts

• Half-life: Time for plasma concentration of drug to reduce by half.
  • Determines duration of drug action and dosing frequency.
• Elimination Kinetics:
  • Zero Order Kinetics: Constant rate, independent of concentration (e.g., aspirin).
  • First Order Kinetics: Rate proportional to concentration; most drugs follow this.
• Steady State Concentration:
  • Achieved after 4-5 half-lives.
  • Balance between drug administration and elimination.
  • Importance: Effective and safe drug concentration.
  • Loading Dose: Used to rapidly achieve therapeutic concentration for drugs with long half-lives.

Remember: Subtract complexity, understand the fundamentals of pharmacokinetics to effectively manage drug therapy.