Lecture+1_Mechanisms_of_Drug_Action

Mechanisms of Drug Action

  • Understanding drug-receptor interactions is crucial in anesthesia as it influences therapeutic outcomes and side effects.

Course Overview

  • Course Title: Pharmacology and Physiology for Anesthesia

  • Lecturer: Dr. Abbas AlZubaidi

  • Institution: College of Healthcare Technologies, AUIB

Introduction to Drug-Receptor Interactions

  • Importance: Key for understanding anesthesia efficacy and safety.

  • Objectives:

    • Historical background of the receptor concept.

    • Basic principles of drug-receptor interactions.

    • Introduction to pharmacodynamics and pharmacogenetics.

Historical Background

  • Early Concepts: Use of plant-derived compounds in therapy.

  • 17th Century: Specificity of drugs was noted (e.g., Peruvian bark for malaria).

  • De Jong’s analogy: Receptors compared to a 'remote lady' emphasizing selective interaction.

Development of Receptor Theory

  • Paul Ehrlich: Introduced the term 'receptor', laying the foundation for receptor theory.

  • John Langley: Experimented with 'receptive substances' demonstrating drug action specificity.

  • A.J. Clark: Hyperbolic relationship in dose-response, highlighting drug-receptor interaction principles.

Modern View of Receptors

  • Definition: Receptors are specific cellular macromolecules for drug binding.

  • Key Concepts:

    • Affinity: Strength of ligand binding.

    • Efficacy: Ability to produce a response.

    • Specificity: Selectivity of receptors for ligands.

    • Agonism and Antagonism: Activation vs. inhibition of receptor functions.

    • Dose-Response Curve: Relationship between drug dose and effect.

Drug-Receptor Interactions

  • Binding Mechanisms: Involves hydrogen bonds, ionic bonds, and hydrophobic interactions.

  • Dose-Response Curve: Mathematical representation of relationship between drug concentration and effects.

Historical Beginnings of the Receptor Concept

  • 17th Century: Establishment of drug specificity for diseases.

  • Peruvian bark as an early example for treatment of malaria.

  • Sobernheim’s Selective Affinity: Proposed that drugs bind selectively to body sites.

Modern Development of Receptor Concept

  • Langley’s Experiment: Demonstrated competitive antagonism using nicotine and curare.

  • Clark’s Contributions: Explored dose-response relationship and receptor complexes.

  • Ariens and Stephenson: Distinguished affinity and efficacy as crucial concepts in drug development.

Pharmacodynamics

  • Definition: Examination of drug effects on body physiology.

  • Drug Binding: Engages with active and inactive receptor conformations.

  • Mathematical Models: Describe receptor states and drug interactions.

Efficacy and Agonism

  • Full Agonists: Stabilize active receptor conformation, maximizing response.

  • Partial Agonists: Similar affinity for both receptor states, leading to partial response.

  • Inverse Agonists: Prefer inactive conformation, diminishing basal activity.

Antagonism

  • Competitive Antagonists: Bind at the same site as agonists, can be overcome by increased agonist.

  • Non-Competitive Antagonists: Bind irreversibly, reducing effectiveness of any concentration of agonist.

Allosteric Drug Interactions

  • Defined by binding at non-active sites, modulating receptor response.

  • Example: Benzodiazepines enhance GABA_A receptor activity.

Pharmacogenetics

  • Definition: Refers to genetic variability impacting drug response.

  • Importance: Facilitates personalized medicine.

  • Examples: Polymorphisms affecting GABA receptor efficacy.

Drug Discovery and Development

  • Historical Methods: Relied on natural products and trial-and-error.

  • Modern Techniques: Utilize molecular biology for rapid screening of compounds.

  • Pharmacophore Modeling: Identifies essential features for drug-target interactions.

Structure-Activity Relationship (SAR)

  • Analyzes how chemical structure changes affect pharmacological activity.

  • Example: Beta-blockers' interaction with adrenergic receptors.

Identification of Drug Targets

  • Utilizes molecular cloning and high-throughput screening for compound evaluation.

  • Key in developing new anesthetic agents.

From Drug Binding to Physiological Effect

  • Initiates with drug binding, leading to physiological changes.

  • Dose-response relationships highlight drug potency and efficacy.

Pharmacogenomics and Personalized Medicine

  • Variability in genetic profiles crucially influences drug metabolism.

  • Allows for tailored anesthesia practices based on genetic backgrounds.

Examples of Genetic Variability in Anesthesia

  • Case studies show variability due to receptor polymorphisms.

  • Clinically relevant for anesthesia practitioners for optimal drug administration.

Emerging Developments in Molecular Pharmacology

  • Incorporates advanced techniques for improved drug therapies.

  • Promises future directions in personalized anesthesia.

Mathematical Representations

  • Describes dose-response relationships and graphical visualization of drug effects.

  • Focuses on quantitative understanding of pharmacodynamics.

Case Study Summaries

  • Scenario analysis applying pharmacodynamic principles to anesthesia situations.

  • Highlights the significance of personalized approaches in patient care.

Review of Key Concepts

  • Historical and modern perspectives of receptor theory and pharmacodynamics.

  • Importance of pharmacogenetics in tailoring drug therapies.

Summary and Future Directions

  • Receptor theory as fundamental in pharmacology, emphasizing drug interactions and genetic impacts for future personalized medicine.

Additional Resources

  • Provides reading lists and online databases for further study.

Assignments

  • Case study analysis task to reinforce lecture content.

Closing Remarks

  • Recaps key lecture takeaways and previews upcoming topics.