Pathophysiology and Drug Action Exam 2 (Set 2) Flashcards
What are some differences between agonist and antagonist binding?
-binding results in induced fit; different induced fit to activate it than to deactivate it
-antagonists have no effect on receptor activity
What different responses are represented in the “ligand spectrum”?
Super agonist = over 100% effect/response
Full agonist = 100%
Partial agonist = 0%<x<100%
Silent Antagonist= 0%
Partial Inverse Agonist= -100%<x<0%
Full Inverse Agonist= -100%
What is Potency?
-dose of the drug required to produce a particular effect of given intensity (DC50, IC50,EC50)
-ED50
-higher potency does not necessarily mean greater effectiveness or more side effects
-most potent=left side of graph
What is efficacy?
-biological response resulting from the drug-receptor interaction
-strong agonist has high affinity AND high efficacy
-efficacy is MORE important than potency as a drug property
describe the concept of a partial agonist
-produces reduced response even at full receptor occupancy
-can competitively inhibit the response to a full agonist
explain Partial agonist theory and how it can be used to manage drug therapy
-can be useful in anxiety medications, opioids
-reduces potential for side effects in some cases due to maximal effect not being achieved (less toxicity)
-partial agonists will displace full agonists and lower total response
describe the features of an inverse agonist
-produces opposite response of an agonist
-response can be altered by agonist, partial agonist, and antagonist (share binding site)
-reversal of constitutive activity (ligand independent)
What are the three types of receptor antagonists?
-competitive (reversible)
-non-competitive (reversible)
-irreversible (non-competitive inhibition)
describe competitive antagonism
-reversible
-antagonist combines with the same site on the receptor as the agonist
-increasing dose of agonist will reverse action
-AT VERY HIGH ANTAGONIST CONCENTRATIONS, RAISING THE AGONIST CONCENTRATION WILL PRODUCE A RESPONSE STILL
What is a Schild plot used for?
-orphan receptors with no known ligand
-used to determine affinity of an agonist for a receptor
-in presence of competitive antagonist
describe noncompetitive antagonism
-antagonist produces its effect at a site other than the site used by the agonist
-no competition for a single binding site
-increases the KD and decreases Emax of the agonist
-AT VERY HIGH CONCENTRATIONS OF ANTAGONIST, NO AMOUNT OF AGONIST CAN PRODUCE A RESPONSE
describe irreversible antagonism
-all receptors (including spare ones) are being binded and this causes the maximal response to progressively decrease
compare reversible and irreversible antagonists
-irreversible binds to same site as agonist but does not displace easily
-irreversible involves covalent reaction between the antagonist and receptor
–inhibition continues even after an irreversible antagonist is removed
-competitive inhibition changes the EC50 while noncompetitive inhibition does not change EC50 but decreases max response
explain the concept of spare receptors to explain drug action
-maximal response is achieved before all receptors are occupied
-important in the action of irreversible antagonists
Which of the following is NOT true regarding spare receptors?
A. It is tissue/system dependent
B. Allow a noncompetitive antagonist to look like a competitive agonist
C. Spare receptors are independent of effector numbers (e.g. adenylyl cyclase)
D. may differ between signaling pathways with the same receptor
C. Spare receptors are independent of effector numbers (e.g. adenylyl cyclase)
Which of the following is NOT true regarding antagonists?
A. Irreversible and allosteric antagonists have similar effects on the dose response curves of agonists
B. In the absence of spare receptors, a noncompetitive antagonist increases the Emax
C. Irreversible antagonists typically bind the orthosteric site
D. Antagonist affinity can be estimated using a Schild plot
B. In the absence of spare receptors, a noncompetitive antagonist increases the Emax
describe functional antagonism
-two drugs can influence a physiological system but in opposite directions
ex. histamine effect on blood pressure (decreases it) can be offset by epinephrine (increases it)
describe chemical antagonism
-chemical reaction that occurs between an agonist and an antagonist to form an inactive product
-agonist is inactivated due to chemical reaction with the antagonist
ex. calcium containing antacids and tetracycline antibiotics
describe the mechanisms of allosteric modulators and their potential benefit in drug therapy
-allosteric modulators bind at a site that is not where the agonist or antagonist binds
-can modulate affinity and efficacy
-PAMs and NAMs
benefits are increased specificity for receptors; increased safety due to ceiling effect; more physiological/temporal signaling
