PHC 222 Part(I) Dr. Huda Al Salem Lecture (7). Factors that affect the efficacy 2-...
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Transcript of PHC 222 Part(I) Dr. Huda Al Salem Lecture (7). Factors that affect the efficacy 2-...
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PHC 222Part(I)
Dr. Huda Al Salem
Lecture (7)
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Factors that affect the efficacy
2 -Concentration-Response Curves:Agonist
AntagonistPartial agonistDesensetization
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Concentration-Response CurveTo 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
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Concentration-Response CurveAGONIST 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 theDose of the drug?
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Concentration-Response Curve
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Concentration-Response CurveEC50
Is the concentration of a compound where 50%of its maximal effect isObserved.
EC50 value of a drug will depend on
the biological effect being studied.
Example:
EC50 of Aspirin as analgesic is significantly different from it when used as anticoagulant
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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
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Concentration-Response Curve
AGONIST CRC:1 -Agonists with similar structures acting on the same
receptor will exhibit similar plots
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Concentration-Response CurveAGONIST CRC:
2 -The slopes of these plots are not always similar
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Concentration-Response CurveANTAGONIST CRC:
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Concentration-Response CurveANTAGONIST CRC:Antagonists inhibit the action of an agonist.
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Concentration-Response Curve
Two Types of antagonists present1 -Competitive 2- Non-competitive
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Concentration-Response Curve
Competitive antagonist Non-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
E d' K E /̂ dZ ͗
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Concentration-Response CurvePARTIAL AGONIST:
They are compounds that act as both agonists & antagonistsHow?
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
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Concentration-Response Curve
DESENSETIZATIONIs 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