1. PHC 222 Part(I) Dr. Huda Al Salem Lecture (7)

2. Factors that affect the efficacy 2- Concentration-Response Curves: Agonist Antagonist Partial agonist Desensetization

3. Concentration-Response Curve To get a quantitative information concerning the dose- response relationship of any drug.. they study the effect of the drug on an isolated tissue (in vitro). Examples: guinea big ileum or atria, rabbit jejunum, rat atria, canine coronary artery….etc

6. Concentration-Response Curve AGONIST CRC: The response due to an agonist increases with increasing concentration of the agonist until it reaches a maximum. At this point, further increase in dose have no further effect on the response. How to calculate the Dose of the drug?

7. Concentration-Response Curve

8. EC 50 Is the concentration of a compound where 50% of its maximal effect is Observed. EC 50 value of a drug will depend on the biological effect being studied. Example:

9. Concentration-Response Curve Agonist CRC is used during preclinical drug development to compare the potency of the different analogues of a lead compound. Potency is a measure of drug activity It is proportional to affinity & efficacy

10. Concentration-Response Curve AGONIST CRC: 1- Agonists with similar structures acting on the same receptor will exhibit similar plots

11. Concentration-Response Curve AGONIST CRC: 2- The slopes of these plots are not always similar

12. Concentration-Response Curve ANTAGONIST CRC:

13. Concentration-Response Curve ANTAGONIST CRC: Antagonists inhibit the action of an agonist.

14. Concentration-Response Curve Two Types of antagonists present 1- Competitive 2- Non-competitive

15. Concentration-Response Curve Competitive antagonistNon-competitive antagonist Non-covalent bonds, reversible Covalent bonds, irreversible Its effect can be reversed by increasing the concentration of the agonist The action is not dependent on the concentration of the agonist

16. Concentration-Response Curve PARTIAL AGONIST : They are compounds that act as both agonists & antagonists How? They act as antagonists by preventing endogenous ligands from binding to their receptors. But their binding to the receptor results in a weak activation of the receptor. Why? 1- There is no perfect fit to the receptor site so does not cause enough change in receptor conformation.. 2- It has a structure that can bind to receptor in two different ways

17. Concentration-Response Curve DESENSETIZATION Is the loss of biological response after continuing or increasing dose of a drug. Other names.. Tachyphylaxis or drug tolerance It appears that the drug starts by acting as a full agonist but its repeated use results in partial agonistic action. Rate theory is the only explanation of this phenomenon