Lecture 73 Flashcards
Antagonists elicit _____ response (Emax = 0) when binding to receptor. Partial agonists elicit _____ response relative to Full Agonists (Full Agonists have _____ Emax value.) Note that partial Agonists can act as _____ of Full Agonists.
How does Tamoxifen affect the activity of the E2 receptor in breast vs endometrial tissue?
Agonists elicit LOWER response relative to Full Agonists (Full Agonists have HIGHEST Emax value.) Partial Agonists can act as ANTAGONISTS of Full Agonists.
Tamoxifen binding the E2 receptors prevents binding of the coregulator proteins, and thus blocks the transacetylase activity. In endometrial tissue, it only LESSENS the transacetylase activity, but allows the coregulators to bind.
Histamine receptors are examples of the _____ selected Model of action (as opposed to the Induced Fit Model), where there is some constitutive activity as a result of some receptors spontaneously entering their active state. In this model, Full agonists bind only the ____ state (R’) of the receptor, stabilizing it so that when 100% of receptors are occupied, they are all R’.
Partial agonists bind both the ____ (R’)and ____ (R) states in a ratio where more are in the R’ than is seen in basal activity.
Neutral Antagonists bind R’ and R in a ratio that is ____ to the basal ratio (so it doesn’t alter constitutive activity).
Partial Inverse Agonists mostly bind to the R state, with few binding and stabilizing the R’ state, such that there are _____ in the R state than in the basal ratio.
Full Inverse Agonists bind only R, such that 100% binding = 100% in the R state (completely eliminating constitutive activity).
CONFORMATION Selected
ACTIVE
ACTIVE and INACTIVE, where more are ACTIVE than observed in basal activity.
EQUAL to the basal ratio.
MORE in the R state than in the basal ratio.
Orthoseric binding = binding at ___ site (competitive antagonists bind in this way.) _____ is an example that competes with ACh for binding at Muscarinic receptors.
ACTIVE
ATROPINE is an example
Emax values will ____ and EC50 values will ____ in response to a Competitive inhibitor, while Emax values will _____ and EC50 values will ____ in response to Non-competitive inhibitors (negative allosteric modulators).
Emax values will REMAIN THE SAME and EC50 values will INCREASE in response to Competitive inhibitors, while Emax will DECREASE and EC50 will REMAIN THE SAME in response to Non-competitive inhibitors.
Benzodiazipines are considered _____ allosteric modulators. Which direction would this shift a dose response curve?
POSITIVE
Left
A RIGHT shift in a response curve with respect to tolerance indicates _____ tolerance (increased ____ of the drug,) where as a decrease in Emax with respect to tolerance indicates ______ tolerance (____-regulation of the receptor.)
A RIGHT shift in Response curve with respect to tolerance indicates PHARMACOKINETIC tolerance (increased CLEARANCE of the drug,) while a decrease in the Emax indicates PHARMACODYNAMIC tolerance (DOWN-regulation of the receptor.)
_____ is an example of a drug that exhibits both Pharmacodynamic and Pharmacokinetic tolerance.
METHADONE
Super-sensitivity follows cessation of an antagonist and results from ____-regulation (Emax ______) of receptors in response to use of antagonist.
Results from UP-regulation (Emax INCREASES.)
The term Spare Receptors refers to the fact that some drugs can elicit a _____ response when not all of the receptors are occupied (the rate-limiting step is not activation of the receptor from ligand binding). The biggest example of this is ____ receptors.
Spare Receptors refers to the fact that some drugs elicit a MAXIMUM response when not all of the receptors are occupied. The biggest example of this is INSULIN receptors.
