Pharmacodynamics DSA

Question 1

What does it mean when a drug has a high affinity? low affinity?

Answer 1

a. strong interaction with receptor; you need less of it

b. weak interaction with receptor; you need more of it

Question 2

What are the types of bonds by which a drug binds to a receptor?

Answer 2

a. Covalent - non reversible; must make more receptors and enzymatically remove the drug
b. Non covalent - reversible
1. Ionic - strongest
2. Hydrogen - middle
3. Hydrophobic - least

Question 3

What is Kd?

Answer 3

• the measure of how strong the affinity is
• it represents when 50% of receptors have been filled, so the lower Kd the higher the affinity

Kd = [ligand] [receptor] / [LR]

Question 4

What is selectivity?

Answer 4

• determined by its affinity to various binding sites

- the more selective, the less affinity it has for multiple sites

Question 5

What is intrinsic activity?

Answer 5

• ability of a drug to change a receptor’s activity and produce a physiological response
• agonist have an intrinsic activity; antagonist do NOT

Question 6

What are the three types of agonists?

Answer 6

a. Full - fully activate Rs; produce a max effect/intrinsic activity
b. Partial - partially activate the R; sub-max effect/intrinsic activity
c. Inverse - decrease R signaling; intrinsic activity is present and is related to the inhibition of R function (complete opposite of full agonist)

Question 7

What are the three types of antagonists?

Answer 7

a. Pharmacologic - acts at same R as endogenous Ls and agonist drugs
b. Chemical - chemical antagonist makes the other drug unavailable
c. Physiological - b/t endogenous pathways regulated by different Rs

Question 8

What type of pharmacological antagonist is surmountable?

Answer 8

competitive - if you add more agonist, you’ll see that effect

Question 9

What is Emax? ED50?

Answer 9

• the maximal effect that can be produced by a drug

- the dose of drug that produces 50% of its maximal effect

Question 10

Do you want a high TI or a low TI?

Answer 10

high because it means that it is less toxic

Question 11

What is signal transduction?

Answer 11

• process by which cells transmit, receive, and respond to information from their environment and from each other

Question 12

What is a response element?

Answer 12

the sequence on an enhancer or promoter that the TF binds to

Question 13

What are the four types of G proteins?

Answer 13

a. Gs - adenylyl cyclase activation
b. Gi - adenylyl cyclase inactivation
c. Gq - PLC activation
d. Gt - cytoskeletal rearrangements

Question 14

Gs

Answer 14

• activates all isoforms of adenylyl cyclase and Src tyrosine kinase

Question 15

Gi

Answer 15

• inhibits adenylyl cyclase 5, 6, and 13

- activates tyrosine kinase Src

Question 16

Gq

Answer 16

• activates phospholipase Cbeta

Question 17

G12/13 (Gt)

Answer 17

• activates Rho GTPases

Question 18

Receptor Tyrosine Kinases (RTKs) transmit the action of what growth factors?

Answer 18

• IGF-1
• Insulin
• VEGF
• EGF
• NGF
• PDGF

Question 19

Janus Kinases (JAKs) transmit the action of what growth factors?

Answer 19

• GH (somatotropin)
• EPO
• Leptin
• Interferons
• ILs 2 to 10, 15

Question 20

What are the ligands for nuclear receptors?

Answer 20

lipophilic molecules that can cross the membrane

• steroid hormones
• thyroid hormones
• Vit D and A
• Lipid mediators (ex. FFAs and their products)