Pharmacodynamics II

Question 1

Spare receptors exist when

Answer 1

It is possible to elicit a maximum

biological response without occupying all of the available receptors.

Question 2

When spare receptors exist, what happens to the concentration-response curve (EC50)?

Answer 2

EC50 is shifted to smaller concentrations (left)

Question 3

When spare receptors exists, how is Kd effected?

Answer 3

Kd remains the same

Question 4

If EC50 is lower than Kd then there are

Answer 4

Spare receptors

Question 5

In the case of spare receptors, is the maximal response still produced?

Answer 5

Yes, the maximal response is still produced due to amplification of the cell signaling mechanism

Question 6

What is the clinical implication of spare receptors?

Answer 6

Use a lower dose

Question 7

How do competitive antagonists effect ED50 and Emax?

Answer 7

ED50 of agonist increases Emax does not change

Question 8

How do non-competitive antagonists effect ED50 and Emax?

Answer 8

ED50 may/maynot change

Emax decreases

Question 9

Do competitive antagonists bind to the same or different receptor site as agonist?

Answer 9

Bind to same receptor site as agonist

Question 10

How do competitive antagonist effect affinity of an agonist for its receptor?

Answer 10

Decrease affinity (increase Kd) of an agonist for its receptor

Question 11

What is the relationship between competitive antagonist and potency of agonist?

Answer 11

As antagonist concentration increases, potency of agonist decreases (increase EC50)

Question 12

With the addition of a competitive antagonists would the curve for agonist shift to the left or right?

Answer 12

Right

Question 13

Do competitive antagonists have an effect on maximal response?

Answer 13

No

Question 14

Can the effects of a competitive antagonist be overcome?

Answer 14

Yes, effects can be overcome by increasing dose of agonist

Question 15

What are the two mechanisms for non-competitive antagonists

Answer 15

1. Inhibit agonist binding at active site by binding to a secondary site on the receptor (allosteric)
2. Irreversibly (covalent) bind to the same site as an agonist

Question 16

How do non-competitive antagonist effect affinity and potency of an agonist for its receptor?

Answer 16

Affinity (Kd) and potency (EC50) may or may not change

Question 17

How do non-competitive antagonist effect Emax and Bmax?

Answer 17

Decreases Emax and Bmax

Question 18

Can the effects of a non-competitive antagonist be overcome?

Answer 18

No

Question 19

Explain physiologcial/functional antagonism and give an example

Answer 19

Two drugs that act on different receptors or by different mechanisms, to counteract effects of agonist

Ex: Reversing a fall in blood pressure produced by histamine with epinephrine

Question 20

Explain chemical antagonism

Answer 20

Directly interacts with agonist and inactivates it

Question 21

Partial agonists have higher/lower efficacy than full agonist?

Answer 21

Lower efficacy (α); cannot produce the same maximal response as full agonists

Question 22

The dose response curve for a partial agonist will have higher/lower Emax and Bmax?

Answer 22

Lower Emax and Bmax

Question 23

What are the effects of a single concentration of full agonist and increasing concentrations of partial agonist?

Answer 23

Response caused by full agonist decreases
Response caused by partial agonist
increases
Total response gradually decreases

Question 24

Partial agonists can act as competitive antagonists in the presence of ____?

Answer 24

Full agonist

The particular agonist binds to the receptor, displacing the agonist, and the overall effect is lower.

Question 25

What is an example of molecule that binds to intracellular receptors and how do they work?

Answer 25

Lipid soluble ligands (hormones, steroids) | Modify gene transcription

Question 26

Are the effects of intracellular receptors a) immediate or slow b) short-term or long-lasting

Answer 26

a) Effects are not immediate | b) Effects are long lasting

Question 27

What is a common transmembrane receptor?

Answer 27

Tyrosine kinase receptors

Question 28

How do transmembrane receptors work?

Answer 28

Self phosphorylation

Question 29

Tyrosine kinase receptors activate what pathway? | What are examples?

Answer 29

Activate the Ras/Raf signaling pathway 1. Insulin 2. Epidermal and nerve growth factor 3. Platelet-derived growth factor

Question 30

Cytokine receptors activate what pathway? | What are examples?

Answer 30

Activate JAK/STAT 1. Growth hormone 2. Erythropoietin 3. Interferons and interleukins

Question 31

What are 2 examples of ligand ion channels?

Answer 31

Acetylcholine binding to nicotinic receptors | GABA (benzodiazepines, barbiturates, ethanol)

Question 32

Do ion channels have a slow or rapid response?

Answer 32

Very rapid response

Question 33

How do G-protein coupled receptors work?

Answer 33

``` Signal amplification Gs (stimulatory) increases cAMP Gi (inhibitory) decreases cAMP Gq activates PLC Ca2+ release DAG activates PKC ```

Question 34

Are βeta receptors activated by Gs, Gi, or Gq?

Answer 34

Gs

Question 35

Are α2 receptors activated by Gs, Gi, or Gq?

Answer 35

Gi

Question 36

Is desensitization reversible or irreversible?

Answer 36

Reversible, a second exposure to agonist will produce the response again

Question 37

Stimulation of G-protein receptors either stimulate or inhibit the formation of

Answer 37

cAMP

Question 38

Polyphosphoinositide signaling uses ___ proteins to activate ___

Answer 38

Gq | PLC

Question 39

Polyphosphoinositide signaling and Gq proteins have what effect on Ca and kinases?

Answer 39

Increase Ca | DAG activates protein kinase C (PKC)

Question 40

Are α1 receptors activated by Gs, Gi, or Gq?

Answer 40

Gq

Question 41

Cyclic GMP uses nitric oxide (NO) because

Answer 41

it is diffusible and can be synthesized in one cell and exert its effect in another cell

Question 42

If a system has spare receptors then 1. The dose response curve shifts to the right 2. The dose response curve does not change 3. The dose/response curve shifts to the left 4. The maximal binding (Emax) decreases 5. The EC50 and Kd are the same

Answer 42

The dose/response curve shifts to the left

Question 43

An agonist has: 1. High efficacy but low affinity 2. Intrinsic activity of zero 3. Both efficacy and affinity 4. High affinity but no efficacy

Answer 43

3. Both efficacy and affinity

Question 44

A drug is a competitive antagonist. Therefore: 1. It has low affinity for the receptor 2. It binds irreversibly to the receptor 3. It has higher efficacy than a partial agonist 4. It can be displaced by a large enough concentration of agonist

Answer 44

4. It can be displaced by a large enough concentration of agonist

Question 45

In the presence of a partial agonist, why doesn’t the dose response curve start at zero?

Answer 45

Because the partial agonist itself causes some stimulation of the receptor

Question 46

Desensitization is generally mediated by what?

Answer 46

Phosphorylation

Question 47

What does it mean if a biological effect is amplified?

Answer 47

The biological response is greater than the degree of receptor occupancy (g proteins)

Question 48

What does cGMP cause?

Answer 48

Relaxation of smooth muscle