Pharodynamics II

Question 1

Stereospecificity

Answer 1

All activity of a drug is usually found in one isomer or will be more potent in one that the other

Question 2

Saturability

Answer 2

High does will increase the response to the drug but only UP TO A POINT

Question 3

What is the response to a drug dependent upon?

Answer 3

• Amount of drug reaching the site
• Drug-receptor interaction
• Status of the receptor (super or desensitized

Question 4

Intracellular Receptors

Answer 4

Unbound to the membrane and only responds to lipid soluble drugs

Question 5

How long does the effect of intracellular receptors take to activate and how long can it last?

Answer 5

There is a lag to its activation because more will active gene expression, taking 30+ min to kick in.

The effects will persist for hours/days long after the drug is gone due to the presence of the proteins.

Question 6

Tyrosine Kinase Receptor

Answer 6

Transmembrane protein that once activated, these receptors can phosphorylate tyrosines or serines on various downstream proteins.

Autophosphorylation of tyrosines on the receptor’s cytoplasmic side can intensify or prolong the duration of receptor activation although it is subject to down regulation.

Question 7

Cytokine Receptor

Answer 7

Similar to the TKR but it uses a separate tyrosine kinase that is non-intrinsic - JAKs Pi STATs.

STATs will dimerize and travel to the nucleus to elicit their effect on the cell.

Question 8

Ligand Gated Receptors

Answer 8

Pentamer of a channel where transmitters such as ACh can bind to the alpha subunit that will lead to the opening of the channel within MILLISECONDS, making this one of the fastest receptors to elicit a response

Question 9

G-Protein Linked Receptors

Answer 9

Crosses the membrane 7 times with the N-teminus extracellular and the C-terminus intracellular where binding will lead the GPCRs to relay secondary messengers for activation

Question 10

What is the ternary sequence of G-Protein action?

Answer 10

B-A-GDP -> B-A-GTP -> A-GTP -> Protein action on Adenylyl Cyclase -> B + A-GDP -> Cycle repeats

Question 11

How does the GPCR signal via adenylyl cyclase?

Answer 11

• GPCR activates AC will lead to the conversion of ATP to cAMP
• cAMP activates PKA
• PKA Pi proteins

Question 12

How does the GPCR signal via phospholipase C?

Answer 12

• GPCR activates PLC leads to PIP2 lysis into DAG and IP3
• -DAG activates PKC -> PKC Pi proteins
• -IP3 releases Ca2+ -> activates calmodulin dep. kinases

Question 13

Tachyphylaxis

Answer 13

Rapid development of diminished responsiveness after administration of a drug

Question 14

Pharmacodynamic Tolerance (Desensitization)

Answer 14

Decreased responsiveness to a drug that occurs slowly over time

Question 15

Homologous Desensitization

Answer 15

Receptors Pi by kinases on agonist-bound receptor lose responsiveness

Question 16

What happens to the DR curve with homologous desensitization?

Answer 16

DR curve shifts right and Emax is only affected if receptor loss is high.

Question 17

Heterologous Desensitization

Answer 17

Activation of one receptor leads to the decrease in responsiveness to one or more subtypes and it is not limited to the population bound by the agonist so it has a more widespread effect.

Question 18

What happens to the DR curve with heterologous desensitization?

Answer 18

DR curve shifts right and Emax is only affected if receptor loss is high.

Question 19

Supersensitivity

Answer 19

Loss of activity on receptors leads to increased receptor density and enhanced coupling which will increase its responsiveness

Question 20

What happens to the DR curve in super sensitivity?

Answer 20

DR curve shifts left and EC50 decreases

Question 21

What are some mechanisms for desensitization?

Answer 21

• Pi of the receptor and binding with B-arrestin
• Receptor down regulation
• Receptors may become “uncoupled”

Question 22

What is an example of desensitization?

Answer 22

Loss of bronchodilation in response to B-adrenergic agonists in asthmatics