02: Dose Response Relationship 2

Question 1

What does a kinase do?

Answer 1

It phosphorylates something

Question 2

What does IP3 do once it is activated

Answer 2

Helps release Calcium Ion from the lumen of the ER

Question 3

What is the membranous enzyme that is activated under the Gq transduction mechanism

Answer 3

PIP2

Question 4

What two messengers does PIP2 activate in the transduction pathway?

Answer 4

DAG and IP3

Question 5

Tyrosine Kinase Receptor are individual transmembranous proteins, but what happens when ligands bind to their extracellular receptors?

Answer 5

Two individual receptors dimerize and activate Tyrosine Kinase activity

Question 6

What is the structure that spans the membrane in a tyrosine kinase receptor?

Answer 6

Single alpha helix

Question 7

What makes up the intracellular tail of the tyrosine kinase receptor?

Answer 7

Several tyrosine molecules

Question 8

What is a common ligand for tyrosine kinase receptors

Answer 8

Insulin

Question 9

What is the structure of intracellular receptors?

Answer 9

They have a DNA binding domain attached to a ligand binding and transcriptional control domains

Question 10

What is an Agonist

Answer 10

Molecules that activate receptors. A drug with affinity and efficacy

Question 11

What is an Antagonist

Answer 11

Molecules that bind to receptor sites bind prevents any response. They have affinity and no efficacy

Question 12

What is the formula for a drug-receptor interaction

Answer 12

Drug (D) + Receptor (R) = DR —> Effect

Question 13

What is the drug affinity formula (Kd)

Answer 13

Kd = k2/k1

Question 14

What is a spare receptor?

Answer 14

Spare receptor are drug receptors that will bind the drug ligand but they will not transduce a response.

Question 15

What ion channels are typically being affected when the beta/gamma complex of a GPCR is the effector molecule instead of the alpha unit?

Answer 15

Potassium (K+)

Question 16

After DAG is activated, what molecule does it effect?

Answer 16

PK-C

Question 17

What types of cellular receptors are most relevant to diabetes?

Answer 17

Tyrosine Kinase Receptors

Question 18

What are Intracellular Receptors typically mediated by?

Answer 18

Hormones

Question 19

What are the two basic domains of the Intracellular Receptors?

Answer 19

A DNA binding domain attached to a ligand-binding and transcription controlling domain

Question 20

Are the effects of an intracellular receptor experienced quickly or slowly?

Answer 20

Slowly, the effect takes a long time because the effector proteins have to be synthesized after the DNA has been stimulated by the transduction pathway.

Question 21

What does Kd mean?

Answer 21

It is the concentration of a drug we 50% of the binding sites are bound

Question 22

What is Emax

Answer 22

The enzyme is maximally bound by the ligand

Question 23

What is affinity?

Answer 23

How “tightly” the drug binds to the receptor

Question 24

What is an example of a common drug whose break down product binds irreversibly to liver cells increasing the chances for overdose

Answer 24

Acetominophen/Tylenol

Question 25

Is irreversible binding a problem that many drugs have (like Tylenol does)?

Answer 25

No, its actually rare. Some drugs have slow dissociation rates however.

Question 26

Using Simple Occupancy Theory: If a receptor has 4 binding sites for drug molecules and 3 of the 4 are successfully bound by the drug, what would its efficacy be? What if only 1 binding site were bound?

Answer 26

3 bound sites = 75%

1 bound site = 25%

Question 27

What does the existence of spare receptors allow for in terms of a drug’s response vs. a cell’s receptor capacity?

Answer 27

It means that a maximal response is possible without total receptor occupancy

Question 28

How does the presence of spare receptors increase the sensitivity of the system?

Answer 28

Because of the spare receptors you can up the dose of the drug (ie Morphine) to increase the effect after a tolerance has built up.

Question 29

Tolerance represents a shift in which direction on the Dose Response/Occupancy Curve?

Answer 29

A Shift to the Right

Question 30

What does the term Pharmacokinetics describe?

Answer 30

The study of the concentration of a drug needed to reach the receptor and elicit a response

Question 31

What does the term Pharmacodynamics describe?

Answer 31

It is the study of how a drug transduces a response once it has succesfully docked with its target receptor

Question 32

What are we trying to describe with a Dose-Response curve?

Answer 32

the EC50 which describes the dose at which a response is observed in 50% of the experimental population

Question 33

When reviewing Dose-Response curves, what is the difference between EC50 and ED50?

Answer 33

EC50 implies that the test was done on cells in a dish; and that a concentration was tested, not a dosage

Question 34

What do you need on the Dose-Response curve in order to determine the ED50??

Answer 34

You need a plateau

Question 35

Why do you need a plateau on the D-R curve to calculate ED50?

Answer 35

Because the Plateae represents the Emax, and the ED50 is 50% of the Emax