Pharmacodynamics - Part 4

Question 1

What is an agonist?

Answer 1

Drugs which alter the physiology of a cell by binding to the target and causing similar effects as the natural NTs or inducer of the receptors

Question 2

What is a partial agonist?

Answer 2

A drug which does not produce maximal effect even when all the receptors are occupied.

Question 3

An agonist has high _______ while a partial agonist has a lower ______.

Answer 3

efficacy (bis)

Question 4

How should an H-bond be labelled?
How should a hydrophobic interaction be indicated?
How should an ionic bond be indicated?

Answer 4

H-bond - dashed line
Vdw - zig zag
Ionic - normal bond

Question 5

Once a NT or ligand binds to the receptor, this causes a ______ in the receptor and makes a ________ interaction.
i.e. _______ fit allows for ________ interaction

Answer 5

change
tighter
induced
stronger

Question 6

All drug actions occur due to ________ ________ between the ligand and receptor.

Answer 6

intermolecular interactions

Question 7

An ______ will have similar intermolecular interactions as the natural compound.

Answer 7

agonist

Question 8

Partial agonists and antagonists are sometimes useful for the study of ________ of the receptors.

Answer 8

subtypes

Question 9

Why can a partial agonist also be called a partial antagonist?

Answer 9

Since the partial agonist essentially blocks the normal, maximum strength reaction from taking place - instead a weaker reaction occurs

Question 10

What two compounds mimic the physiological effect of Ach?

Answer 10

Nicotine

Muscarine

Question 11

Nicotinic acid binds to what, more strongly?

Muscarinic acid?

Answer 11

Ion channel - Nicotinic

GPCR - Muscarinic

Question 12

Ligands that elicit a _______ biological action tend to share a similar ____-________ bonding pattern.

Answer 12

similar

inter-molecular

Question 13

What are common characteristics of Acetylcholine and Nicotine and Muscarine?
What are these functional groups called?
(You may want to refer to slide 33 - pharmacodynamics 3)

Answer 13

Cationic center
Hydrogen bond acceptor

Pharmacophores

Question 14

What are some possible medical uses of nicotinic Ach receptor agonists?

Answer 14

1 - Memory improvement in Alzheimer’s patients

2 - Controlling symptoms of Tourette’s Syndrome

Question 15

________ effect is elicited by the _______ interaction.

Answer 15

biological

ligand

Question 16

The observed leves of biological effect from drug action depend on what?

Answer 16

1 - The number of sites the ligand occupies (occupational theory)
2 - The rate the ligand associates and dissociates (rate theory)
3 - The ability of the ligand to induce the conformational change to the ligand-target complex

Question 17

Agonists generate _______ conformational changes that produce a _________ response.

Answer 17

specific

biological

Question 18

Antagonists produce __________ conformational changes and ___ biological response.

Answer 18

non-specific

no

Question 19

What are antagonists?

Answer 19

Drugs which inhibit or block responses caused by agonists.

Question 20

What is a competitive antagonist?

Answer 20

• Drug which competes with an agonist for the same site on a receptor/target.

Question 21

Competitive agonist:

______ doses of an ________ can generally overcome _________

Answer 21

high
agonist
antagonist

Question 22

Antagonist action:

• Antagonist binds to the ______ site but ____ to produce the correct _______ fit
• receptor is ___ _______
• _________ messenger is ______ from binding

Answer 22

binding, fails, induced
not activated
normal, blocked

Question 23

An antagonist tends to have _______ intermolcular interactions as an agonist, and is ______ than the agonist

Answer 23

similar

longer

Question 24

What is a non-competitive antagonist?

Answer 24

Drug that binds to a site other than the agonist-binding domain, and inhibits action

Question 25

Non-competitive antagonist:

- Induces a ________ ______ in the receptor such that the _______ no longer _________ the ______ binding site

Answer 25

conformational change, agonist, recognizes, agonist

Question 26

Non-competitive antagonist:

- ______ doses of an agonist ______ overcome the antagonist in this situation

Answer 26

high

doesn’t

Question 27

What is an irreversible antagonist?

Answer 27

Drug that permanently binds to the receptor binding site, therefore they can not be overcome with agonist

Question 28

An irrerversible antagonist would have what kind of bonds?

Answer 28

Non-hydrolyzable covalent bonds

Question 29

_________ ________ are useful for the study of the receptor.

Answer 29

irreversible antagonists

Question 30

An irrerversible antagonist will have a ____ Kd.

Answer 30

low

Question 31

An irreversible antagonist will bind where?

Answer 31

Agonist binding site and elsewhere (Antagonist binding site)

Question 32

What is an alkaloid?

Answer 32

Naturally extracted compound that contains a nitrogen

Question 33

Describe a typical Ach antagonist.

Answer 33

H-bond acceptor,
N-center
Bulky structure to occupy additional sites

Question 34

Reversible allosteric antagonists:

• Antagonist binds _______ to an ________ site
• ________ bonds formed between antagonist and binding site
• Induced fit ______ the shape of the receptor
• ______ _____ is distorted and is ____ recognized by the messenger
• __________ messenger concentration _______ reverse antagonism

Answer 34

reversible, allosteric
intermolecular
changes/alters
binding site, not
increasing, doesn't

Question 35

Antagonist by umbrella effect:

• Antagonist binds ______ to a _________ binding site
• ________ bonds formed between antagonist and binding site
• Antagonist ______ with the messenger binding site
• _______ is blocked from the binding site

Answer 35

reversibly, neighbouring
intermolecular
overlaps
messenger

Question 36

How does the antagonist block messenger binding by the umbrella effect?

Answer 36

Large structure blocks messenger binding through steric hindrance