Pharodynamics II Flashcards

1
Q

Stereospecificity

A

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

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2
Q

Saturability

A

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

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3
Q

What is the response to a drug dependent upon?

A
  • Amount of drug reaching the site
  • Drug-receptor interaction
  • Status of the receptor (super or desensitized
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4
Q

Intracellular Receptors

A

Unbound to the membrane and only responds to lipid soluble drugs

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5
Q

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

A

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.

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6
Q

Tyrosine Kinase Receptor

A

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.

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7
Q

Cytokine Receptor

A

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.

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8
Q

Ligand Gated Receptors

A

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

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9
Q

G-Protein Linked Receptors

A

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

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10
Q

What is the ternary sequence of G-Protein action?

A

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

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11
Q

How does the GPCR signal via adenylyl cyclase?

A
  • GPCR activates AC will lead to the conversion of ATP to cAMP
  • cAMP activates PKA
  • PKA Pi proteins
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12
Q

How does the GPCR signal via phospholipase C?

A
  • GPCR activates PLC leads to PIP2 lysis into DAG and IP3
  • -DAG activates PKC -> PKC Pi proteins
  • -IP3 releases Ca2+ -> activates calmodulin dep. kinases
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13
Q

Tachyphylaxis

A

Rapid development of diminished responsiveness after administration of a drug

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14
Q

Pharmacodynamic Tolerance (Desensitization)

A

Decreased responsiveness to a drug that occurs slowly over time

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15
Q

Homologous Desensitization

A

Receptors Pi by kinases on agonist-bound receptor lose responsiveness

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16
Q

What happens to the DR curve with homologous desensitization?

A

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

17
Q

Heterologous Desensitization

A

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.

18
Q

What happens to the DR curve with heterologous desensitization?

A

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

19
Q

Supersensitivity

A

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

20
Q

What happens to the DR curve in super sensitivity?

A

DR curve shifts left and EC50 decreases

21
Q

What are some mechanisms for desensitization?

A
  • Pi of the receptor and binding with B-arrestin
  • Receptor down regulation
  • Receptors may become “uncoupled”
22
Q

What is an example of desensitization?

A

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