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.