Lecture 18 - Pharmacodynamics Q and A

Question 1

what is a ligand ?

Answer 1

A ligand is a substance that can interact with a target protein -or receptor
• Ligands usually bind to a specific site(s) on the signalling protein
• Ligands can be endogenous signalling molecules e.g. hormones neurotransmitters or ions such as Ca2+
• Ligands can be exogenous molecules – drugs

Question 2

What is an agonist ?

Answer 2

An agonist is a substance that binds to a receptor and
activates the receptor to then produce a measurable
biological response

Question 3

What is an antagonist ?

Answer 3

Antagonists are ligands that have affinity for a receptor
or target protein but do not produce a biological
response.
• Antagonists block the effects of agonists.

Question 4

What is affinity ?

Answer 4

Affinity is a measure of the strength (or avidity) with

which a ligand or drug binds to a receptor.

Question 5

What is the measurement used to define affinity ?

Answer 5

Affinity is measured by Kd (dissociation constant) Affinity

• Kd is defined as the concentration of ligand at which
50% of all available receptors are bound

• The lower the value of Kdthe greater the affinity

Question 6

Which of the following drugs has the
highest affinity?
            Kd
Drug A -1 x 10-3 M
Drug B- 9 x 10-3 M
Drug C - 3 x 106 M 
Drug D - 3 x 109 M
Drug E - 3 x 10-9 M

Answer 6

Drug E - lowest conc needed for Kd

Question 7

What is intrinsic efficacy ?

Answer 7

the ability of a ligand to activate the receptor - which can lead to generation of a cellular response

Question 8

What is ligand efficacy ?

Answer 8

the ability to cause a measurable biological response

Question 9

What is agonist potency ?

Answer 9

Potency is defined as the concentration of a drug that
evokes 50% of its maximal response (Emax). The term
EC50 is used to represent this concentration.

• The lower the value for EC50 , the more potent is the
drug or ligand (because a lower concentration of drug
is required to generate 50% of the maximal response).

Question 10

What is a partial agonist ?

Answer 10

Partial agonists are ligands that evoke responses that
are lower than the maximal response of a full agonist
(ie. they have lower Emax values).

Question 11

Compared to a full agonist, a partial
agonist has:

Higher affinity
Lower affinity
Higher intrinsic efficacy
Lower intrinsic efficacy
Lower potency
Higher potency

Answer 11

Lower intrinsic effeicacy

Question 12

graph - 
A - 60% response - 1 drug conc
B - 100% response -  2 drug conc
C - 40% response - 3 drug conc
D - 90% response - 4 drug conc

which has highest intrinsic activity?
Which has highest potency ?

Answer 12

highest intrinsic activity - B - highest response

highest potency - A - lowest dug conc needed for 50 % response - EC50

Question 13

look at and do Q 15 of the lecture

Answer 13

have ya done it ?

Question 14

what is antagonsim vs functional antagonsim

Answer 14

1. Antagonism of the action of an agonist AT ITS RECEPTOR
   using a ligand (ANTAGONIST).
2. Antagonism of a cellular/tissue event being mediated by one
   mechanism by another mechanism (FUNCTIONAL ANTAGONISM). - this could be another agonist

Question 15

Name the three main types of drug antagonism. For
each type, indicate both the location of the antagonist binding
site and the possible type(s) of binding at the site

Answer 15

2. Irreversible competitive antagonism
   Takes place at the same binding site as the endogenous ligand
   irreversible interaction reflects high affinity with very slowdissociation – may be covalent binding.
3. Reversible competitive antagonism
   Takes place at the same binding site as the endogenous ligand(s)

Interaction is by relatively weak (non-covalent) bonding.

3. Binding occurs at separate allosteric site - no competition for site access.

Question 16

Experiments show that only 10% of muscarinic (M3) receptors in airways smooth muscle need to bind acetylcholine (ACh) to achieve maximal contraction. The EC50 for ACh is  10-7 M compared to a Kd 10-6 M.
What pharmacodynamic principle explains the difference between the EC50 and Kd for ACh at the M3 receptor?

Answer 16

Spare muscarinic receptors

Question 17

A new drug Painex developed to reduce chronic pain acts on a subset of glutamate receptors in the CNS. With increasing concentration, Painex increases the Kd for glutamate. At higher concentrations it reduces the Emax of glutamate by 50%. What best describes the likely pharmacodynamic action of this drug?

Answer 17

Non competitive antagonsit