Lecture 6 Part 1

Question 1

Once a drug is bound to its receptor, what can happen?

Answer 1

it can elicit 2 types of responses:

-agonist action (stimulant effect)
-antagonist action (block the activity)

Question 2

true or false

if a drug has a stimulating effect, it has agonist action

Answer 2

true

Question 3

true or false

if a drug blocks activity, it has agonist action

Answer 3

FALSE – antagonist action

Question 4

what was one of the 1st proposed theories of drug-receptor interaction and subsequent events?

who proposed it?

Answer 4

the occupancy theory - tissue response is proportional to the number of receptors occupied

proposed by Clark and Gaddum

Question 5

according to the occupancy theory proposed by Clark and Gaddum, more receptors occupied =………

Answer 5

greater activity

Question 6

according to the dose response curve for acetylcholine, as the concentration of Ach increases, what happens?

Answer 6

the % response (% contraction of rat jejunum) increases until its flattened out

Question 7

as mentioned, in the dose response curve for acetylcholine, as the concentration of acetylcholine increases, the % response increases until its FLATTENED OUT.

according to the occupancy theory, what is going on at this point where the curve is flattened out?

Answer 7

all the receptors are occupied at this point

HOWEVER, it is now known that only a small fraction of receptors (not all) need to be occupied to obtain this maximal, flattened out response

Question 8

true or false

the muscarinic effects of acetylcholine cause the contraction of smooth muscle

Answer 8

true

Question 9

scenario: analogues of acetylcholine are able to contract smooth muscle to the same degree as acetylcholine, but HIGHER DOSES are required to produce the SAME EFFECT.

these analogues are said to possess……..

Answer 9

the same INTRINSIC ACTIVITY as acetylcholine (because they all can reach the same maximum) but LOWER AFFINITY for the receptor (because higher doses are required to produce the same effect)

Question 10

how can affinity of acetylcholine analogues to their receptor be estimated?

Answer 10

by comparing the concentration of drug required to produce the pharmacological response equivalent to the conc required by a STANDARD DRUG (typically, the dose required to produce a 50% response is compared)

Question 11

why is the %response of 50% used to estimate the affinity of a drug to its receptor?

Answer 11

at a % response of 50%, the sigmoidal curve is usually linear and thus easier to identify

Question 12

what does EC 50 mean

Answer 12

half maximal effective concentration

halfway between the baseline and maximal effect

Question 13

the occupancy theory was modified how and by whom

Answer 13

Ariens and Stephenson modified the occupancy theory to include the antagonists.
they divided the drug-receptor interaction into 2 steps:

1. Combination of drug and receptor (initial affinity)
2. Production of effect (intrinsic activity)

Question 14

true or false

only agonists may have structural features that contribute to drug-receptor affinity, but ANY DRUG possesses the intrinsic activity

Answer 14

FALSE

any drug may have structural features that contribute to drug-receptor affinity, but ONLY AGONISTS possess the intrinsic activity

Question 15

identify the type of drug

Shows decreased response. This is attributed to a decrease in intrinsic activity. The affinity for the receptor may increase, decrease, or remain equivalent

Answer 15

PARTIAL AGONIST

Question 16

explain what partial agonists are

Answer 16

they’re able to have the same, increased, or decreased affinity to the receptor, but it shows a decreased response – only partial efficacy. (decrease in intrinsic activity)

Question 17

name the type of drug

No response. the drug is either inactive or it is an antagonist

Answer 17

type of drug cannot be identified with a dose response curve.

need different methods to identify if binding or not – add something that’s known to bind, see if you get displacement. isotope labeling is another technique

Question 18

identify the type of drug

as the concentration of drug increases, the response increases until it flattens out and there is no further response

Answer 18

agonist

Question 19

identify the type of drug

Gives same maximal response, but higher dose is required to get the maximal response

Answer 19

it is an agonist (bc it can produce same maximal response) with LOWER AFFINITY

Question 20

true or false

an agonist with lower affinity as different intrinsic activity than the original agonist

Answer 20

FALSE – same intrinsic activity, but lower affinity for the receptor

Question 21

true or false

if a drug is found to be inactive/an antagonist from a dose response curve, more information is needed to confidently determine if the drug is inactive or an antagonist

Answer 21

true

Question 22

who introduced the rate theory for drug-receptor interactions?

Answer 22

peyton

Question 23

according to the rate theory, if a drug has a fast forward reaction with the receptor (binding) and a slow reverse reaction (unbinding), the drug is a __________

Answer 23

antagonist

Question 24

according to the rate theory, if a drug has a fast forward reaction with the receptor (fast binding) and a fast reverse reaction (fast unbinding) the drug is a __________

Answer 24

agonist

Question 25

who proposed the macromolecule Perturbation theory?

Answer 25

belleau

Question 26

the Macromolecule Perturbation Theory is meant to explain what?

Answer 26

the agonist, partial agonist, and antagonist nature of drugs

Question 27

explain the macromolecule perturbation theory

Answer 27

the interaction of drugs with receptors (macromolecules) can produce:

-SCP (specific conformational changes)
-NSCP (nonspecific conformational changes)
-SCP + NSCP

if a drug binds to its receptor and causes SCP, it causes activity is an agonist

if it causes NSCP, it has no activity and is an antagonist

if both, it is a partial agonist

Question 28

true or false

NSCP (non specific conformational changes) are not productive

Answer 28

true

Question 29

the rate theory was used to explain what that the occupancy theory could not explain?

Answer 29

an initial “spike” in drug response that then settles down and levels off

initial spike occurs before equilibrium is reached

Question 30

the drug-receptor interaction is complicated and often times involves…..

Answer 30

a second messenger

Question 31

who modified the occupancy theory?

Answer 31

ariens and stephenson – included the antagonists.
drug-receptor interaction in 2 steps:
1. combination of drug and receptor (initial affinity)
2. production of effect (intrinsic activity)

Question 32

true or false

antagonists can have the same affinity as agonists

Answer 32

TRUE – antagonists just do not have intrinsic activity (production of effects), but they can bind to the receptor with the same affinity

Question 33

if size of the drug fits between agonist and antagonist, what can happen?

Answer 33

SCP and NSCP can flip back and forth — partial agonist