Lecture #108: Pharmacology: Pharmacodynamics Part 2: Quantifying Agonism and Antagonism and Pharmacodynamic Variability in Individuals and Populations

what is the Two-state receptor model?

Receptors exist in active (Ra) and inactive (Ri) states without ligand; agonists shift equilibrium toward Ra

What is a Classical receptor model?

Receptors are inactive without ligand; agonist binding activates receptor, antagonist blocks activation

What is a Full agonist?

High affinity for active state; produces maximal effect

What is a Partial agonist?

Moderate preference for active state; produces submaximal effect even at high doses

What is a Neutral antagonist?

Equal affinity for active and inactive states; no effect but blocks agonist binding

What is an Inverse agonist?

High affinity for inactive state; reduces basal receptor activity

What is a Competitive antagonist?

Binds same receptor site as agonist; reversible; shifts dose-response curve right; no change in Emax

What is an Irreversible antagonist?

Covalent or very high affinity binding; reduces Emax; cannot be overcome by more agonist

What is a Noncompetitive antagonist?

Reduces agonist Emax without affecting binding; effect cannot be overcome by more agonist

What is a Positive allosteric modulator?

Increases agonist affinity or efficacy at receptor

What is a Negative allosteric modulator?

Decreases agonist affinity or efficacy at receptor

What is a Physiologic antagonist?

Acts at a different receptor to produce opposite physiological effect

What is a Chemical antagonist?

Interacts directly with drug to inactivate or sequester it

What is Receptor desensitization?

Reduced receptor signaling efficiency; receptor-G protein uncoupling

What is Receptor downregulation?

Internalization and degradation of receptors; decreases cell responsiveness

Define Tachyphylaxis

Rapid decrease in response after repeated doses

What is Resensitization?

Receptors return to membrane after agonist removal; responsiveness restored

What is Supersensitivity?

Upregulation of receptors after chronic antagonist exposure; exaggerated response after withdrawal

What is the Effect of continuous agonist exposure?

Decreased response due to desensitization/downregulation

What it the Effect of continuous antagonist exposure?

Increased receptor density and sensitivity

Describe Population pharmacodynamic variability

When Individuals vary in response to same drug dose

What is the Quantal dose-response curve?

It Plots % of population showing a specified effect vs log dose

What is ED50?

Dose producing effect in 50% of population

What is LD50?

Dose lethal in 50% of population

What is TD50?

Dose producing toxicity in 50% of population

What is the Therapeutic index formula?

LD50 / ED50 or TD50 / ED50

What is the Therapeutic index meaning?

Measure of drug safety margin

What is the Therapeutic window?

Range of doses with high efficacy and low toxicity; does not guarantee safety in all patients