Drug Receptor Interactions

Question 1

What are the four types of receptor

Answer 1

enzymes
carrier molecules
ion channels
neurtransmiters

Question 2

Law of Mass Action

Answer 2

The rate of a chemical reaction is proportional to the product of the concentration of the reactants

Question 3

Equilibrium when rate of associations =

Answer 3

rate of dissociations

Question 4

The equilibrium dissociation constant (KD) represents what

Answer 4

the concentration of drug required to occupy 50% of the receptors at equilibrium.

Question 5

what is Kd

Answer 5

a measure of affinity of any one drug for a receptor

Question 6

Hill Langmuir equation

Answer 6

Fractional occupancy =

[D] / [D] + KD

Question 7

what is the equilibrium dissociation constant for agonists

Answer 7

pD2 = -log10(KD)

Question 8

what is efficacy

Answer 8

the amount of receptors that need to be occupied to elicit the maximum response (this does not need to be 100% of receptors|)
effectiveness of the drug
the ability of the drug to eilcicate a response once bound to its receptor

Question 9

how is the response calculated via occupancy theory

Answer 9

[DR] / [RT]
DR = the number of occupied receptors
RT = total number of receptors
therefore its the percentage of receptors occupied
it Is also equal to the function of the stimulus

Question 10

how do you calculate occupancy

Answer 10

k2/k1

rate constant of dissociations over the rate constant of associations

Question 11

what are the left over receptors called if 100% occupancy of receptors is not required

Answer 11

spare receptor(s) (theory)

Question 12

What kind of relationship do the graphs associated with affinity and efficacy have

Answer 12

sigmoidal relationship

Question 13

Partial Agonists

Answer 13

these have low efficacy as they never reach the max poetical response, however it does increase the percentage of the response

Question 14

full agonist

Answer 14

this enhances the reaction causing the response to reach its % max as the concentration of the agonist increases.

Question 15

occupancy/binding when you add both partial and full agonists

Answer 15

may bind to all the receptors so at full occupancy but some are bound by partial and some full so it will not reach its max % response due to the low efficacy of the partial agonist

Question 16

competitive antagonism

Answer 16

a drug which interacts/binds reversibly with receptors to form a complex but does NOT ENVOKE RESPONSE
Competes for the active sites so occupies them but does not activate them
MAX RESPONSE OF AGONIST REMAINS THE SAME

Question 17

what is Ka

Answer 17

equilibrium dissociation constant for an antagonist
- the concentration of antagonist that makes it necessary to add twice as much agonist to produce a response as would be needed in the absence of the antagonist

Question 18

what happens to a log dose-response curve when a competitive antagonist is added

Answer 18

It is displaced to the right as increasing the concentration of an agonist overcomes the antagonist inhibiting qualities
The linear sections are parallel

Question 19

what is the schild equation

Answer 19

r = ([A]/KA) + 1
r = the ratio by which [D] must be increased to overcome competition by [A]

Question 20

what is pA2

Answer 20

pA2 = -log10(KA)

a way of comparing the affinity of an antagonist

Question 21

irreversible competitive antagonism

Answer 21

binds to the receptor but dissociates slowly, if at all
all others are loosely bound. Therefore these cannot be out competed even after an increase in concentration of the agonist

Question 22

what effect does irreversible competitive antagonism have on the log dose-receptor curve

Answer 22

the curve is decreased
the maximum response to the agonist Is decreased.
overtime the agonists bind and unbind as they are loosely attached, when they unbind the irreversible competitive antagonist can bind and therefore it continues to go down over time as more and more agonists are replaced with the antagonists which never unbind

Question 23

allosteric modulators

Answer 23

bind to sites on the receptor other than the agonist binding site and can modify agonist activity
- these are regulatory
- can modify affinity or efficacy
- potentiate (increase the power) or inhibit
conformational change on the active site to just changes function
- a form of uncompetitive antagonist as it blocks by steric hinderance and not direct competition for the active site

Question 24

inverse agonists

Answer 24

they act to dampen the response - they bind and elicit a RESPONSE and this is the key difference between them being an agonist and an antagonist.
- these can be overcome by increasing the conc of the agonist

Question 25

what is affinity a measure of

Answer 25

the concentration range over which a drug binds to its receptor (KD OR KA)

Question 26

examples of drug receptor interactions

Answer 26

direct control of the ion channel - hyperpolarisation

direct control of effector enzyme - protein phosphorylation