Pharmacology Chapter on Drug-Receptor Interactions

Learning Objectives

• Describe receptor physiology and different receptor types.
• Explain key steps in signal transduction, including second messenger involvement.
• Understand how ligands or drugs regulate each receptor type.
• Establish the relationship between drug concentration and biological response.
• Analyze drug-response curves, including hyperbolic and log-transformed representations.
• Define key terms: agonist, antagonist, partial agonist, right-shift, left-shift, antagonism.
• Differentiate concepts such as potency, maximal efficacy, tolerance, tachyphylaxis, and selectivity.

Drug Receptors

• Pharmacodynamics investigates how drugs interact with the body and affect pharmacologic responses.
• Receptors determine the specificity and quantitative relationship between the dose of a drug and its effects.
• Molecular characteristics (size, shape, charge) of drugs influence their binding affinity to receptors.

Dose-Response Relationship

• Drug efficacy is illustrated in dose-response curves, which plot drug concentration against biological response.
• Affinity between receptors and drugs determines the concentration required for a response.
• Spare receptors are those exceeding the amount necessary for a full effect, influencing therapeutic outcomes.

Agonists and Antagonists

• Agonists activate receptors, mimicking physiological signals.
• Antagonists prevent receptor activation by not inducing a signal; they block agonist action by occupying binding sites.
• Partial agonists activate receptors but produce a lesser effect compared to full agonists.

Signal Transduction

• Drug-receptor binding triggers signal transduction, producing cellular responses through secondary messengers.
• Receptors can exist in inactive (R) and active (R*) states; agonists shift the equilibrium to the R* state, generating biological effects.
• Partial agonists shift the equilibrium but to a lesser extent than full agonists.

Inverse Agonists

• Inverse agonists produce effects opposite to agonists upon binding to the receptor, while antagonists have no intrinsic activity.
• Antagonists can diminish the effect of agonists without acting independently.

Competitive Antagonism

• Competitive antagonists bind reversibly to the same site as the agonist, inhibiting receptor activation.
• Their effect can be overcome by increasing agonist concentration, shifting the agonist's dose-response curve to the right.

Receptor Types

• Transmembrane receptors, including enzyme-linked and tyrosine kinase receptors, facilitate signaling in response to ligands like insulin.
• Ligand-gated ion channels open in response to ligand binding, while voltage-gated channels respond to changes in membrane potential.
• G-protein coupled receptors (GPCRs) activate intracellular G-proteins upon ligand binding, leading to further signaling cascades.

G-Protein Coupled Receptors (GPCRs)

• GPCRs interact through trimeric G-proteins composed of three subunits (α, β, γ).
• Upon activation, the α subunit exchanges GDP for GTP, dissociating from the βγ complex to activate downstream signaling pathways.
• Common effectors activated by GPCRs include adenylyl cyclase and phospholipase C, generating secondary messengers like cAMP.

Desensitization and Tachyphylaxis

• Repeated agonist exposure can lead to receptor desensitization, resulting in reduced drug effectiveness over time.
• Understanding tachyphylaxis is crucial for managing treatment regimens to avoid diminished responses.

Explore the intricate dynamics of drug-receptor interactions in this quiz. Learn about the roles of agonists and antagonists and how they influence receptor activity. The quiz will test your understanding of pharmacodynamics and the factors affecting these interactions.