Pharmacology - PHARMACOKINETICS (MADE EASY)

Overview of Pharmacokinetics

  • Pharmacokinetics: What the body does to a drug

Steps in Pharmacokinetics

  • Absorption: Drug enters bloodstream

  • Distribution: Drug disperses in fluids in and out of cells

  • Metabolism: Drug modified for easier excretion (mainly by the liver)

  • Elimination: Drug and metabolites excreted via bile, urine, and feces

Detailed Breakdown of Steps

Administration Routes

  • Parenteral, topical, nasal, rectal, etc.

  • All routes except IV must cross a membrane to enter circulation

Absorption Mechanisms

  • Passive Diffusion: Movement from high to low concentration; lipid-soluble drugs pass easily through membranes

  • Facilitated Diffusion: Larger molecules require carrier proteins to assist movement from high to low concentration

  • Active Transport: Energy-dependent transport using ATP to move drugs against concentration gradient

  • Endocytosis: Engulfment of very large molecules by cell membrane

  • Factors Affecting Absorption: pH, surface area, blood flow

Bioavailability

  • Definition: Measure of drug absorption into systemic circulation

  • AUC: Area under the curve comparing oral drug exposure to IV drug exposure

Distribution Factors

  • Lipophilicity: How drugs pass through membranes

  • Blood Flow: Organs vary in blood supply (e.g., brain vs. skin)

  • Capillary Permeability: Varies by organ (e.g., brain has tight junctions)

  • Binding to Plasma Proteins: Affect speed of distribution; albumin is a major binding protein

  • Volume of Distribution (Vd): Theoretical volume occupied by the drug to achieve plasma concentration; helps in dosing estimation

Elimination Process

  • Total Body Clearance: Sum of individual clearance processes

  • First-Order Kinetics: Amount eliminated proportionate to drug concentration

  • Zero-Order Kinetics: Constant amount eliminated irrespective of concentration

  • Half-Life: Time to reduce the plasma concentration by half; important for dosing and steady state

Steady State Concentration

  • Achieved when administration rate equals elimination rate, typically in 4-5 half-lives

  • Important in maintaining therapeutic effect without toxicity

  • May require loading doses in urgent situations

Role of the Liver in Metabolism

  • Phase 1 Reactions: Make drugs more hydrophilic via oxidation, hydrolysis, reduction (catalyzed by cytochrome P450 enzymes)

  • Phase 2 Reactions: Conjugation to produce polar conjugates for easier elimination

  • Important cytochrome P450 enzymes: CYP 3A4/5, CYP 2D6, CYP 2C8/9, CYP 1A2

Drug Interactions

  • Inducers: Phenytoin, carbamazepine, rifampin, alcohol, barbiturates, St. John's Wort (mnemonic: PCRABS)

  • Inhibitors: Grapefruit, protease inhibitors, azole antifungals, cimetidine, macrolides (except azithromycin), amiodarone, nondihydropyridine calcium channel blockers (mnemonic: GPACMAN)