Antagonists

Question 1

What is the definition of an antagonist?

Answer 1

Any drug which reduces the response to another drug

Question 2

What types of antagonists exist?

Answer 2

Competitive
Non-competitive
Physiological
Pharmacokinetic
Chemical

Question 3

Describe how competitive antagonists work

Answer 3

They compete with naturally occurring chemicals mediators and agonist drugs to bind to the same receptors, but will not evoke a cellular response

Question 4

What is the intrinsic efficacy of competitive antagonists?

Answer 4

They are neutral so 0
But they may still have a high affinity

Question 5

What are the two types of competitive antagonists?

Answer 5

Reversible
Irreversible

Question 6

How do reversible antagonists work?

Answer 6

The can associate and dissociate again, the effects are overcome by adding more agonist as higher chances of agonist binding
Ionic bonds can be broken

Question 7

How is a log concentration response curve altered by a reversible competitive antagonist?

Answer 7

The curve is shifted further to the right
As more antagonist is added, more receptors will be occupied by antagonists, higher numbers of agonist are needed to overcome this

Question 8

How is agonist affinity affected by the presence of antagonists?

Answer 8

Agonist affinity appears to reduce

Question 9

Is the max response changed by reversible antagonists?

Answer 9

No, the max response can still be achieved but will require much greater numbers of agonist

Question 10

What is the equation for dose ratio (DR)?

Answer 10

DR = apparent EC50 / EC50

Question 11

How is the EC50 changed when in the presence of reversible antagonists?

Answer 11

It appears to be greater due to the right ward shift

Question 12

Can reversible antagonist affect inverse agonists as well?

Answer 12

Yes, they will also move inverse agonist graphs to the right

Question 13

What is the definition of pA2?

Answer 13

It is a measure of how potent a competitive reversible antagonist is
Defined as -log10 molar concentration of antagonist at which the agonist concentration needs to be doubled to elicit the same level of response as in the absence of the antagonist
Or when DR =2

Question 14

What does the pA2 say about the antagonist?

Answer 14

Typically between 4 and 12
pA2 of 8 means a very potent antagonist, strong bonds and effective competitor

pA2 of 4 means a very weak antagonist, weak bonds and ineffective competitor

Question 15

How do calculate pA2?

Answer 15

Plot results generated from log10 concentration response curves of agonist with various antagonist concentration
(Schild plot)

Question 16

What is the schild equation?

Answer 16

Log10 (DR-1) = Log10 [A] + pA2

Question 17

What point of a schild plot is used to determine pA2?

Answer 17

-pA2 is where y=0
Therefore this value must be minused to get pA2

Question 18

How do irreversible competitive antagonists work?

Answer 18

They associate and remain associated with the receptor indefinitely - they receptor is now permanently blocked
Increasing the agonist concentration will have no impact on the response
Usually dependent on covalent bonds

Question 19

What effect do irreversible competitive antagonists have on log concentration response curves?

Answer 19

There is a progressive reduction in maximum response to agonist without any rightward parallel shift in agonist log concentration response curve

Question 20

How do non- competitive antagonists work?

Answer 20

Affects the action of agonists at some point in the chain leading to the response
Do not compete with the agonist for the same receptor site
Can be reversible or irreversible
Normally reduce the max response

Question 21

What is an allosteric site?

Answer 21

A receptor site for a non-competitive antagonist on an unoccupied receptor.
When bound will cause a conformational shape change that alters agonist binding and or signal transduction

Question 22

How do local anaesthetics work as non competitive antagonists?

Answer 22

They interfere with signal transduction downstream of nicotinic receptors for acetylcholine in nerve fibres

Question 23

How do physiological (functional) antagonists work?

Answer 23

Acts on separate cells or tissues or on a different population of receptors on the same cell
Two systems are involved
Are really agonists acting on receptors coupled to opposing actions

Question 24

What is the intrinsic efficacy of physiological antagonists?

Answer 24

Since they’re actually agonists of different cells they have an efficacy value of +1

Question 25

How do pharmacokinetic antagonists work?

Answer 25

By decreasing the concentration of the agonist by interfering with its absorption, distribution, metabolism, or excretion
Reduces the concentration of it in the vicinity of its molecular target