2.Graded response curve
-In the first cage, each human is given a dosage of the drug.
-In each subsequent cage, the humans in that cage will receive a higher and higher dosage.
-After waiting amount of time for drug to work, % of humans affected is plotted as a fxn of the administered dose.
-Dose-response curve for THERAPEUTTIC EFFECT is generated.
-When you LOSE this, you are asleep.
-Means that the TD50 is much higher than the ED50, so you can take extra and it shouldn’t matter.
Desired = 10X
-Once the drug effects have subsided, the subject is then tested with a higher dose, etc.
-Mean ED50, TD50 generated
-If drug A had an ED50 with a log dose of 1, and drug B had an ED50 with a log dose of 100, drug A is 100x more potent as drug B
-The RPS is the “fingerprint” for the RECEPTOR and its SUBTYPES
-A way for pharmaceutical companies to determine which drugs target specific receptor subtypes
-Ex. A is morphine and B is aspirin
-Adding an agent can increase maximum response (shift up), lower ED50 (shift left) or BOTH
-Signal transduction becomes uncoupled
-Cardiac glycosides with Na/K-ATPase
2. Binding to receptor initiates biological response (receptor is transducer, once activated – cellular transduction occurs)
Antagonists DO NOT
2. Intrinsic activity (how big of a response is generated by receptor once drug binds)
B – middle
C – Lowest efficacy
-B – reaches maximum response, but uses all receptors; therefore, efficacy lower than A
-C – reaches lower response than A and B; lowest efficacy
Spare receptor effect = maximal dose achieved without all receptors being bound