Pharmacodynamics Overview

Pharmacodynamics

• Pharmacodynamics is the study of the mechanism of action of a drug and the drug-receptor interaction to cause a pharmacological effect in the body.

Mechanisms of Drug Action

• Molecular Pharmacology is the study of the relationship between drug concentration and effect.
• Drug actions broadly encompass changes a substance produces on the body's functions.
• 5 Main Drug Actions:
  • Stimulation: Increased activity of specialized cells.
  • Depression: Decreased functional activity of specialized cells.
  • Irritation: Intense stimulation leading to injury.
  • Replacement: Providing missing substances.
  • Cell Destruction (Cytotoxicity): Killing cells.

Targets of Pharmacological Action

• Most drugs exert their effect by selectively interacting with a specific biomolecule, usually a protein.
• Target Proteins:
  • Ion Channels: Pore-forming proteins that allow selective flow of ions.
  • Carrier Proteins: Transport molecules or ions across biological membranes.
  • Enzymes: Catalysts that increase the rate of chemical reactions.
  • Receptors: Proteins that bind ligands and trigger a cellular response.

Ion Channels

• Ion channels are regulated by transmitting substances or membrane potentials.
• Drugs can act on ion channels by binding to specific receptors or blocking the channel pore.

Carrier Proteins

• Carrier proteins transport substances across membranes.
• Transport can be passive (not energy-dependent) or active (requires energy).

Enzymes

• Enzymes are potential drug targets.
• Drugs can influence enzyme synthesis or activity.
• Enzyme Inhibition can be:
  • Unspecific: Inhibits multiple enzymes.
  • Specific: Inhibits a specific enzyme.
    • Competitive: Drug competes with the substrate for the active site.
    • Non-competitive: Drug binds to an allosteric site, altering enzyme activity.

Receptors

• Receptors are molecules that specifically bind to ligands, such as drugs.
• Ligands that bind to receptors can be:
  • Endogenous ligands: Natural substances like neurotransmitters or hormones.
  • Pharmaceutical drugs: Therapeutic agents.
  • Toxins: Harmful substances.

Types of Receptors

• Ligand-gated Ion Channels (Ionotropic Receptors): Rapid synaptic transmission (e.g., nicotinic acetylcholine receptors).
• G-Protein-Coupled Receptors (GPCRs): Metabotropic receptors, seven transmembrane helices, slower signal transduction (e.g., muscarinic acetylcholine receptors).
• Kinase-linked Receptors: Have catalytic activity, involved in growth regulation and cell differentiation (e.g., insulin receptors).
• Nuclear Receptors: Regulate DNA transcription, can be in the cytoplasm or nucleus (e.g., steroid hormone receptors).

Drug-Receptor Interaction

• Agonists: Activate receptors, producing a similar effect to the endogenous ligand.
  • Full Agonist: High efficacy, maximum response with low receptor occupancy.
  • Partial Agonist: Low efficacy, cannot achieve maximum response even with full receptor occupancy.
• Inverse Agonists: Bind to the same receptor as an agonist but induce the opposite response.
• Antagonists: Bind to the receptor, preventing agonist binding or receptor activation.
  • Competitive Antagonists: Reversibly bind, decreasing available binding sites for agonists.
  • Non-competitive Antagonists: Bind irreversibly, reducing available receptors or altering agonist binding.

Dose-Response Relationship

• Dose: The amount of drug administered to produce a specific response.
• Dose-Response Curve: Relates the dose of a drug to the intensity of the response.

Mechanisms of Regulation of Receptors

• Hyper-sensitization: Increased receptor sensitivity due to prolonged lack of agonist.
• Under-sensitization: Decreased receptor sensitivity due to chronic stimulation.

Explore the principles of pharmacodynamics, focusing on drug mechanisms, actions, and interactions with target proteins. This quiz covers key concepts such as stimulation, depression, and the role of ion channels in drug efficacy.