BASIC PRINCIPAL PART I & II

Page 1: Introduction

  • Basic Principal Part I for Physician Assistant Pharm 507.

Page 2: Drug Development and Testing

  • Food and Drug Administration (FDA)

    • Regulates efficacy and safety of drugs.

    • Exception: FDA does not regulate foods, nutritional supplements, or herbal remedies.

Page 3: Preclinical Animal Studies

  • New drug studies must begin with preclinical animal studies.

  • Must test on at least two different animal species.

  • Key data includes:

    • Organ system toxicity after acute, subacute, chronic exposure.

    • Mutagenicity testing (e.g., Ames test).

    • Carcinogenic potential assessments.

Page 4: Clinical Testing Phases

  • Phase 1: Preliminary safety and pharmacokinetics in 20-100 healthy volunteers.

    • Question: "Is it safe?"

  • Phase 2: Drug efficacy in 100+ patients with target disease.

    • Question: "Does it work?"

  • Phase 3: Larger efficacy study in 1,000+ patients vs. placebo and controls.

    • Question: "How well does it work, and what are the side effects?"

  • Phases 1-4 lead to marketing approval (NDA) and post-marketing surveillance.

Page 5: Testing Overview

  • In vitro, Animal, Clinical studies: Testing proceeds through these stages before marketing.

  • Time-frame: Average duration of 20 years.

  • Key Terms:

    • IND (Investigational New Drug Application).

    • NDA (New Drug Application).

Page 6: Requirements for Prescribing Scheduled Drugs

  • DEA number is essential.

  • Schedule II-IV drugs need prescriptions:

    • Schedule II cannot be telephoned; must be written.

    • Refill requirements: Triplicate for II; III-IV can only be refilled max 5 times in 6 months.

Page 7: Schedules of Controlled Substances

  • Schedule I: Heroin, LSD, marijuana, hallucinogens.

  • Schedule II: Codeine, Oxycodone, morphine, amphetamine.

  • Schedule III: Acetaminophen/codeine mixtures, Ketamine.

  • Schedule IV: Tramadol, Diazepam (Valium).

  • Schedule V: Codeine-containing cough syrups.

Page 8: Package Inserts (PIs)

  • Contains essential information about drug:

    • Chemical makeup, indications, contraindications, warnings, adverse reactions, interactions, dosing, and supply form.

Page 9: Drug Warnings and Recalls

  • Importance of Black Box Warning for drug safety.

  • Differentiation between labeled and off-label uses.

  • Overview of Orphan Drugs and Drug Recall procedures.

Page 10: Conclusion of Part I

  • Summary of Basic Principles discussed.

Page 11: Additional Notes

  • Continuation of Basic Principal content for Physician Assistant program.

Page 12: Case Study Overview

  • Case: 48-year-old man with acute difficulty breathing; treated with epinephrine.

    • Diagnosis: Bronchial asthma.

    • Treatment changes: Discontinue propranolol due to contraindication; switch to verapamil.

    • Considerations: Discuss alternative treatments.

Page 13: Drug Receptors

  • Explanation of drug receptors:

    • Determine drug response and selectivity.

    • Mediate actions of drug agonists and antagonists.

Page 14: Macromolecular Nature of Drug Receptors

  • Drug receptors are primarily proteins:

    • Best characterized as regulatory proteins, enzymes, transport and structural proteins.

Page 15: Aspects of Drug Receptor Function

  • Three important aspects:

    • Quantitative relation of drug concentration to response.

    • Role of receptors in chemical signaling.

    • Influence on therapeutic/toxic effects.

Page 16: Receptor Types

  • Intracellular Receptors: For steroids; modifies gene expression.

  • Membrane Receptors:

    • Directly coupled to ion channels.

    • Coupled via G-proteins to intracellular effectors.

Page 17: G Protein Coupling

  • Gs Proteins: Increase cAMP production with agonist binding; includes receptors for catecholamines.

  • Gi Proteins: Decrease cAMP with agonist binding; includes alpha adrenoreceptors.

  • Gq Proteins: Activate phospholipase C & release second messengers (IP3, DAG).

Page 18: Pharmacokinetics Overview

  • Key processes include Absorption, Distribution, Metabolism, Excretion.

  • Biodisposition involves drug permeation across membranes.

Page 19: Factors Influencing Drug Permeation

  • Key factors:

    • Lipid and water solubility.

    • Concentration gradient.

    • Surface area and vascularity affect systemic circulation absorption.

Page 20: Drug Transport Mechanisms

  • Understanding of diffusion and transport mechanics across membranes crucial for pharmacology.

Page 21-22: Drug Ionization

  • Many drugs are weak acids or bases; ionization affects permeation.

  • Nonionized forms can cross biomembranes; Henderson-Hasselbalch equation determines ionization percentage.

Page 23-25: Ionization and Renal Clearance

  • Ionization impacts renal clearance; only nonionized forms undergo active secretion.

  • Strategies to enhance renal elimination via urine pH manipulation.

Page 26: Visualization of Ionization Impact

  • Overview of how pH level affects drug ionization in nephrons.

Page 27: Drug Transport Modes

  • Three basic modes of transport across membranes:

    • Passive diffusion (no energy, down gradient).

    • Facilitated diffusion (no energy, carrier required).

    • Active transport (requires energy, against gradient).

Page 28: Conclusion of Part II

  • Summary of Basic Principal content in pharmacology.