DOSE RESPONSE CURVES (slides 1-23) - MARCH 11TH
Definitions and Concepts
Graded Response: A type of response that can take on a range of values.
Example: Measuring blood pressure can yield various values like 120, 110, or 118.
Applies to various physiological measurements like heart rate and body temperature.
Quantile Response: An all-or-nothing (binary) response.
Example: Conditions such as either being pregnant or not, or being alive or dead. There are no degrees of these responses.
Characteristics of Dose-Response Curves
Graded response vs. Quantile response: Both respond to values similarly, but they differ fundamentally.
Types of Dose-Response Curves:
Comparison of linear dose-response curves vs. logarithmic dose-response curves.
Plateau: A key characteristic of some response curves representing maximum effect.
Efficacy and Potency
Efficacy: A measure of how effectively a drug produces a desired response.
Potency: Refers to the amount of drug needed to produce an effect; inversely related to dose. Lower doses indicate higher potency.
Efficacy vs. Potency:
Sometimes different drugs within the same class will show varied efficacy and potency.
Graph Axes Definitions
X-axis: Typically represents the log of the concentration or dose administered.
Y-axis: Represents the response of measured outcomes (e.g., heart rate, blood pressure, cell death).
Maximum response is often defined in studies based on the data collected.
Sigmoidal Curve Representation
When plotting the log of the concentration, the resulting curve is typically sigmoidal.
Linear Portion of the Curve: Most linear between 16% to 84% of the maximum response. This area is crucial for accurate determination of important values such as ED50 (Effective Dose 50) and LD50 (Lethal Dose 50).
Key Values for Dose-Response Relationships
ED50: The effective dose at which 50% of the maximum response is observed.
LD50: The lethal dose at which 50% of subjects would experience death.
Therapeutic Index: A calculation that compares ED50 and LD50 helping to gauge drug safety.
Drug Responses and Curves
Various drugs can be plotted on a dose-response graph to compare efficacy and potency:
Red Curve: Represents Drug A, serves as a baseline for efficacy.
Blue Curve: Drug B, shifted to the left indicating higher potency than Drug A with a lower ED50.
Green Curve: Drug C is less potent and shows lower efficacy (not reaching max response).
Examples of Drug Comparisons
Analgesics Example:
Fentanyl: Highly potent with typical dosing in micrograms.
Morphine: Less potent than fentanyl, dosed in milligrams.
Codeine: Least potent, dosed at higher milligram levels, also less efficacious.
Calculation of ED50 and Therapeutic Considerations
Determining potent drugs:
Shifts to left indicate increased potency (lower ED50), while shifts right indicate decreased potency.
Understanding EC50 and toxic responses using dose-response graphs can guide drug development.
Agonists, Antagonists and Modulators
Full Agonist: Offers 100% activity at the target receptor.
Partial Agonist: Provides less than 100% activity, can act as competitive antagonists.
Neutral Antagonist: Exhibits no activity on its own but blocks other interventions.
Inverse Agonist: Acts to reduce activity at a receptor, opposite to that of an agonist.
Selectivity vs. Specificity of Drugs
Selectivity: Drug preferentially binds to one receptor type over others with some off-target interactions likely observed.
Example: Cardioselective beta-blockers primarily target beta-1 receptors but can interact with beta-2 receptors.
Specificity: A drug exclusively targets one receptor or process without off-target effects, often rare in practice.
Summary Remarks
Illustrations of dose-response curves play a critical role in pharmacological studies.
Understanding the relationship between drug parameters is essential for predicting therapeutic outcomes.
The role of dose-response curves and linear vs. log representations influences pharmacological and therapeutic investigations significantly.