Dose Response Relationship Flashcards
Good fit
Good fit is necessary between drug and receptor.
Only compounds with similar structures will react with same receptors, generally.
Stereospecificity is important.
Graded Dose-Response Curve
Dose is related to Magnitude of Effect
Quantal Dose-Response Curve
Dose is related to % of Subjects showing a specified response
Spare Receptors
To produce maximal response, it is not required to have all of the Receptors occupied.
Spare receptors are not necessary to produce max response.
Factors Affecting Response
Response:
–Effect seen or measured as a result of drug-receptor interaction.
Magnitude of effect is a function of Dose administered.
Other Factors:
Affinity:
–Sum of forces of attraction between drug and receptor
(mutual affinity between drug and receptor)
–Determines the Concentration of Drug in Biophase necessary for interaction to occur.
Intrinsic Activity:
–Ability of a drug to initiate a Response
Responsiveness of Tissue (varies by person and by age)
Effectiveness of Reflexes in resisting change (varies by person)
Potency
*Dose of a drug required to produce a certain response Compared to a Standard of Reference.
Potency is Comparative, not absolute.
Potency is related to Affinity.
Efficacy
Refers to the Maximum Response..
Efficacy is related to Intrinsic Activity.
- The Greater the Efficacy, the Greater the Intrinsic Activity.
- Therapeutic Efficacy is more important than potency.
Full Agonist vs Partial Agonist
Agonists have both Potency (Affinity) and Efficacy (Intrinsic Activity).
Full Agonists: Have Maximum Efficacy.
Partial Agonists: Have only Partial Efficacy.
Note: Partial Agonist will act as a Competitive Antagonist when given with a High dose of Full Agonist; results in a downward shift to the level of max effect of the partial agonist.
Competitive Antagonist
Have Affinity
No Intrinsic Activity
Competes with Agonist for the Same Specific Receptors.
–Takes Longer to work.
- -Gives a *Parallel, *Right Shift on the Dose-response curve.
- -The greater the concentration of the competitive antagonist, the greater the shift.
= Means that larger dose of the Agonist is required to achieve effect in the presence of the Competitive Antagonist.
Parallel = the Maximal effect can still be achieved, just need higher dose.
–Competitive Antagonist receptor interactions are usually Reversible.
–In rare cases when it is Irreversible, you get a Right Shift along with a Downward shift (Reduced Effect) because not all of the competitive antagonist will come off.
Physiological Antagonist
Physiological Antagonists are *AGONISTS.
They act at Their Own Specific Receptors, producing effects that are Opposite to the Effects of the Agonist.
Example: Epinephrine to treat Anaphylactic Shock.
Non-Competitive Antagonist
Non-Competitive Antagonist has its own receptor located near the Agonist’s receptor.
Binding of the Non-Competitive Antagonist to its own receptor induces a conformational change in the area, impact the conformation of the nearby Agonist receptor.
Resulting in Less Affinity, Less Intrinsic activity, or Both for Binding of the Agonist to the Agonist Receptor.
Gives a *Downward Shift on curve.
Chemical Antagonist
No Receptor involvement.
The Chemical Antagonist directly interacts with the Agonist.
Therapeutic Index
= LD50 / ED 50
Greater the index, the safer the drug.
Graphed on a Quantal Dose-Response curve.
ED50 = Effective dose in Half the population being tested.
LD50 = Lethal dose in Half the population being tested.
