Drug-Receptor Theory XL Fall 2024 Fundamentals of Pdynamics

Introduction

  • Review session for Exam 2 led by Doctor Castellon.

  • Discussion format: Open for questions regarding pharmacology concepts.

  • Doctor Castellon will present from 1 PM to 2 PM, followed by Doctor Gacy.

Cyclic AMP and Intracellular Signaling

  • Cyclic AMP (cAMP)

    • Acts as a second messenger in intracellular signaling.

    • Levels can increase or decrease based on receptor interactions with agonists.

    • Key role in triggering protein phosphorylation.

  • Receptor Activation

    • When a ligand binds, it activates a receptor, leading to a cascade of intracellular signals.

    • Activation reference through measurement of cAMP levels to indirectly assess receptor activation.

Potency vs Efficacy

  • Efficacy

    • Defined as the maximum effect an agonist can produce.

    • Example: Drug A (full agonist) achieves higher efficacy compared to Drug B (partial agonist).

  • Potency

    • Refers to the amount of drug needed to produce 50% of its maximum effect (ED50).

    • Drug B may have higher potency as it requires a lower concentration to reach 50% effect even though it has lesser efficacy.

Drug Receptor Interaction

  • Activation and Desensitization

    • Continuous exposure to an agonist may lead to desensitization, whereby the receptor becomes less responsive.

    • Phosphorylation of receptors by beta arrestin leads to internalization and reduced membrane receptors.

  • Regulation

    • Upregulation occurs when receptor activation is lacking, leading to increased receptor numbers to enhance responsiveness.

Competitive vs Non-competitive Antagonism

  • Competitive Antagonism

    • Agonists and antagonists compete for the same binding site, requiring higher agonist concentrations without altering maximum efficacy.

  • Non-competitive Antagonism

    • Antagonists bind persistently to the receptor, decreasing both efficacy and requiring increased concentrations of agonists to achieve effects.

Enzyme-Catalyzed Reactions in Pharmacology

  • Oxidation and Reduction Reactions

    • Cytochrome P450's Role: Major for most oxidations.

    • Key cofactors include NADPH for reductions and oxygen for oxidations.

    • Alcohol dehydrogenase is central for converting alcohols to aldehydes; generates NADH.

  • Phase II Reactions

    • Involves conjugation reactions, such as glucuronidation, sulfate conjugation, and amino acid conjugation.

    • Glucuronidation most commonly involves OH, NH, and SH groups.

Chemical Structures for Pharmacological Reactions

  • Must recognize basic chemical structures:

    • Phenol, Alcohol, Aldehyde, Carboxylic Acid, Ester, Amide, etc.

  • Understand cofactors and enzymes associated with reactions:

    • Alcohol to aldehyde via alcohol dehydrogenase requires NAD+.

    • Aldehyde to carboxylic acid requires aldehyde dehydrogenase, also needing NAD+.

    • Hydrolysis reactions involve water and specific enzymes (e.g., esterase).

Conclusion

  • Exam preparation includes understanding mechanisms of drug action, receptor interactions, and metabolic pathways.

  • Students encouraged to ask questions for clarification on complicated topics.