2020B Question 11
Using opioids as examples describe and illustrate with graphs what you understand by the terms potency, efficacy, partial agonist, competitive antagonist, therapeutic index.
Examiner Report
It was expected that candidates would provide basic definitions, provide examples to support the definitions, and draw labelled graphs to demonstrating key points.
For the most part this basic pharmacology question was answered well, perhaps because it has been asked before. The examiner’s comments at that time are still relevant. Most candidates were able to give passable definitions, draw correct log dose - response curves demonstrate key points, and correctly use opioids as examples.
Definitions were sometimes worded awkwardly or omitted. Some candidates linked efficacy with intrinsic activity, then neglected to explain either term. An opioid example of therapeutic index was rarely mentioned.
Model Answer
Structure:
- Definitions
- Graphs
Definitions
| Term | Detail |
|---|---|
| Potency | - Measure of dose (or concentration) of drug required to produce a given effect - Ratio of ED50’s gives relative potency (also ratio of TD50’s or LD50’s) - It’s the main determinant of dose |
| Efficacy | - The max receptor response achievable by a drug; comprises - Affinity: How likely it is to bind - Intrinsic activity (IA): Propensity to activate the receptor once bound |
| Full agonist | - IA = 1 - High affinity for active conformation |
| Partial agonist | - 0 < IA ≤1 - Usually comparable affinity for both active and inactive conformation |
| Competitive antagonist | - IA = 0 - Affinity for active/inactive at same ratio as natural state of flux - Prevents access of endogenous ligand to active site - No change to maximal response. |
| Inverse agonist | - -1 < IA ≤0 - High affinity for inactive conformation, reduces constitutive receptor activity |
| Therapeutic index | - LD50:ED50 (animals) or TD50:ED50 (humans), where - ED50 = median effective dose - TD50 = median toxic dose - LD50 = median lethal dose - Indicator of drug safety for clinical use. |
Graphs
| Term | Detail |
|---|---|
| Potency |
(Population quantal log dose-response curve) |
| Partial agonist / Efficacy |
(Individual graded log dose-response curve) |
| Competitive reversible antagonist |
(Population quantal log dose-response curve) |
| Therapeutic Index |
(Population quantal log dose-response curve) |
