Antagonists & dose response curves (L4)

Question 1

what is an antagonist?

Answer 1

a drug which blocks the response to an agonist

pure antagonists do not by themselves cause any action by binding to the receptor

Question 2

what are the 3 general classes of antagonists?

Answer 2

chemical
physiological
pharmacological

Question 3

what are chemical antagonists?

Answer 3

binding of 2 agents trendier active drug, inactive

commonly called chelating agents (binding agents)

Question 4

what are physiological antagonists?

Answer 4

2 agents with opposite effects cancel each other out

Question 5

what are pharmacological antagonists?

Answer 5

bind to receptor and block the normal action of an agonist on receptors

Question 6

what are non-receptor antagonists?

Answer 6

either chemical or physiological antagonists

Question 7

what are receptor antagonists?

Answer 7

can have different sites for binding
• orthosteric
• allosteric

can act in a reversible or irreversible way

Question 8

what are reversible antagonists?

Answer 8

competitive

Question 9

what are competitive antagonists?

Answer 9

reversible

share a structural similarity to the agonist

Question 10

what are non-competitive active site antagonists?

Answer 10

stronger chemical interaction with the binding site - covalent bond

cannot dissociate the antagonist from the binding site

Question 11

what is a non-competitive antagonist?

Answer 11

allosteric binding - has a different structure and doesn’t bind to the active site

binding to the allosteric site stops the agonist binding

either reversible or irreversible

Question 12

do antagonists have efficacy?

Answer 12

no

AR* doesn’t exist

Question 13

what are the 3 types of pharmacological antagonism?

Answer 13

competitive
irreversible
non-competitive

Question 14

what is competitive antagonism?

Answer 14

binds and prevents agonist action but can be overcome with increased agonist concentration

causes parallel shift to the right of the agonist-repose curve

Question 15

what is irreversible antagonism?

Answer 15

binds and forms irreversible covalent bonds with receptor

causes parallel shift to right of agonist-repose curve and reduced maximal asymptote

Question 16

what is non-competitive antagonism?

Answer 16

signal transduction rather than receptor effects

downstream responses are blocked

reduced slope and maximum of agonist-response curve

Question 17

what is the dose ratio?

Answer 17

agonist plus increasing concentration of competitive antagonist

measures the shift to the right

dose ratio = agonist + (antagonist EC50 (x) / agonist EC50 (y))

Question 18

what is the Schild plot?

Answer 18

for competitive antagonists

mathmatical model for identifying and comparing the strength of antagonists

only works if we know the drug is working competitively and at the active site

Question 19

what is the Schild equation?

Answer 19

r - 1 = [B] / Kb

r = dose ratio
[B] = antagonist conc 
Kb = antagonist dislocation constant

Question 20

what are pA2 values?

Answer 20

describe the activity of a receptor antagonist in simple numbers

pA2 = -logKb

only works if relationship is linear and slope of Schild plot = 1

Question 21

what is the irreversible competitive antagonist?

Answer 21

non-competitive active site antagonist

reduced maximal response

binds irreversible with the receptor
antagonism cannot be overcome by increased agonist concentration

Question 22

what happens in irreversible antagonism?

Answer 22

increased EC50
parallel shift to the right

looks similar to a partial agonist

Question 23

how can you tell if a drug is a partial agonist or an irreversible antagonist?

Answer 23

you know what you put in the system

Question 24

what is non-competitive antagonism?

Answer 24

blocks signal transduction events
allosteric binding site
reduces slope and maximal effect

looks same as irreversible antagonists

Question 25

what is the therapeutic index (TI) ?

Answer 25

risk to benefit ration
= TD50/ED50 or LD50/ED50

helps to distinguish whether we could give the drug the title of being relatively safe or relatively dangerous

uses quantal dose curves

Question 26

what does TD and LD stand for?

Answer 26

toxic dose or lethal dose

Question 27

what does a large therapeutic window indicate?

Answer 27

a safer drug

bigger concentration range between desired and toxic effect

unlikely for patient to be near the toxic range

Question 28

what does a small therapeutic window indicate?

Answer 28

a more dangerous drug

higher risk to benefit decision

more likely to get adverse side effects