L17 - receptor antagonists and modulators

Question 1

ligand

Answer 1

something that binds to a receptor

Question 2

agonist

Answer 2

ligand that binds to a receptor and activates it to cause a response

Question 3

antagonist

Answer 3

ligand that binds but does not activate the receptor

Question 4

competitive antagonists

Answer 4

compete with agonist for the same receptor binding site

Question 5

reversible competitive antagonist

Answer 5

increasing the agonist concentration cause lead to agonist outcompeting the antagonist and binding to the receptor

Question 6

irreversible receptor antagonist

Answer 6

permanently binds to receptor, no amount of agonist will change this

Question 7

concentration response curve when there in a reversible antagonist

Answer 7

• higher conc of agonist is needed to elicit same response
• look at notes to see pictures

Question 8

when you increase conc of reversible antagonist what happens to Emax and E50 of agonist?

Answer 8

• Emax stays same
• EC50 increases/ gets larger

Question 9

concentration response curve when there in an irreversible antagonist

Answer 9

• higher concentrations of agonist will not have an effect on
• reduced response
• so emax decreases

Question 10

when you increase conc of irreversible antagonist what happens to Emax and E50 of agonist?

Answer 10

• emax of agonist reduces
• ec50 gets bigger

Question 11

how to measure antagonism?

Answer 11

schild plot and pA2

Question 12

what is a schild plot?

Answer 12

finds nature and potency of antagonist

Question 13

y axis of schild plot

Answer 13

log (dose ratio - 1)

Question 14

x axis of schild plot

Answer 14

log (concentration of antagonist)

Question 15

how to calculate dose ratio?

Answer 15

EC50 agonist with antagonist/ EC50 agonist withOUT antagonist

Question 16

what is the pA2 value determined from?

Answer 16

• where the line intersects the x-axis
• negative log value of concentration

Question 17

pA2 equation for measuring antagonism?

Answer 17

pA2 = log (dose ratio -1) - log (conc of antagonist)

Question 18

what does pA2 measure?

Answer 18

antagonist potency

Question 19

higher PA2 =

Answer 19

more potent antagonist

Question 20

if 2 antagonists have same pA2 value, what does this suggest?

Answer 20

they both act through same receptor

Question 21

if the shape of the schild plot is linear what does this indicate about the nature of antagonism?

Answer 21

competitive antagonism

Question 22

if the shape of the schild plot is curved what does this indicate about the nature of antagonism?

Answer 22

non competitive antagonism

Question 23

where do agonists + competitive antagonists bind on?

Answer 23

orthosteric site of receptor

Question 24

where do other drugs/ molecules (allosteric modulators) bind to on a receptor to modify affects of agonists?

Answer 24

allosteric site

Question 25

affinity modulation

Answer 25

affects how agonist binds to orthosteric site of receptor (alter how well the agonist binds to the receptor)

Question 26

efficacy modulation

Answer 26

affects how agonist activates the receptor

Question 27

allosteric agonism

Answer 27

allosteric modulators that push the receptor into an active conformation

Question 28

what do affinity allosteric modulators cause?

Answer 28

• alter how well agonist binds to receptor
• so more or less of the agonist is needed for the same response
• shifts concentration response curve to the left if it is positive affinity modualtion
• right if it negative

Question 29

what do efficacy allosteric modulators cause?

Answer 29

• alter how well agonist activates the receptor
• full response of agonist is increased or decreased
• positive modulation = curve goes up
• negative modulation = curve goes down (non-comp antagonism)