lecture recording on 12 February 2025 at 19.27.25 PM

Pharmacodynamics Overview

• Pharmacodynamics: The study of what drugs do to the body and how they do it.

• Focus on drug absorption, distribution, action at target sites, and interactions at molecular and chemical levels.

Drug-Receptor Interactions

• Receptor Binding Types: Understanding how drugs bind to receptors is critical. This includes knowledge from chemistry.

• Receptor Confirmations: Receptors can exist in various shapes (confirmations). These include:

  • Active Confirmations: Transduce signals and lead to physiological effects.

  • Inactive Confirmations: Predominantly present when no ligand is bound.

• Equilibrium Shifts: Drugs can shift the balance between active and inactive receptor states.

  • Agonists: Bind preferentially to active confirmations, enhancing receptor activity and effect.

    • Full Agonists: Maximize the signaling response by binding to the active form and pulling inactive forms into the active conformation.

Types of Agonists

• Partial Agonists: Bind to both active and inactive confirmations, but with less efficacy than full agonists.

  • Examples:

    • Varenicline (Chantix): Reduces nicotine craving without full agonistic effects.

    • Buprenorphine: Used for opioid addiction; helps mitigate cravings without fully activating receptors.

• Biased Agonists: Investigational drugs that selectively activate certain signaling pathways, minimizing adverse effects connected with other pathways.

Inverse Agonists

• Bind exclusively to the inactive confirmation of constitutively active receptors.

• Possess negative efficacy, effectively reducing baseline signaling.

Antagonists Overview

• Antagonists: Block active receptor sites from being activated by ligands or other drugs.

Competitive Antagonists

• Bind to both active and inactive confirmations, preventing receptor activation.

  • Mechanism: Reversible binding, meaning higher concentrations of agonists can outcompete the antagonists.

  • Effect on Graph: Causes a rightward shift in the dose-response curve, increasing EC50 (decreasing potency).

Non-competitive Antagonists

• Cannot be outcompeted by increased agonist doses; they alter receptor availability irreversibly.

  • Mechanisms:

    • Covalent Binding: Permanently alters the active site.

    • Allosteric Binding: Changes receptor shape, making the active site unavailable for agonist binding.

  • Effect on Graph: Results in a depression of Emax, not recoverable by increased agonist doses.

Dose-Response Curves

• EC50: Effect concentration required to reach half the maximum effect; relates to drug potency.

• Analyzing Shifts:

  • Right Shift: Indication of reduced agonist potency due to competitive antagonists.

  • Left Shift: Indication of enhanced potency due to allosteric activators.

Study Strategies

• Understand and apply concepts using graphs and dose-response relationships.

• Compare agonists and antagonists, focusing on their mechanisms of action, affinities, and impacts on receptor confirmations.

• Continuous discussion and practice with peers to reinforce understanding of pharmacodynamic principles.