Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Neuropharmacology > Pharmacodynamics > Flashcards

Pharmacodynamics Flashcards

1
Q

Definition of pharmacodynamics

A

how binding relationships between drugs (ligands) and their receptors and how dosing affects those relationships (dose-response relationships).
aka: the study of drug actions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Ligand definition

A

Is a drug/neurotransmitter that binds to a receptor. Discussed as both exogenous drugs and endogenous neurotransmitters when binding to a receptor.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Difference between pharmacokinetics and pharmacodynamics

A

Pharmacokinetics: study of what body does to the drugs
Pharmacodynamics: study of what the drug does to the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Four types of receptors

A
  1. LGIC
  2. GPCR
  3. Nuclear Receptors
  4. Receptor tyrosine kinases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q
  1. LGIC mechanism
A

(aka ionotropic receptors)
sit within phospholipid bilayer of membrane and when activated allows charged particles (ions) to pass through fatty membrane via facilitated diffusion.
When ligand binds to the receptor, it causes a conformational change in structure of receptor that opens a central pore/channel to allow select ions across membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

LGIC importance in body and example (1st discovered)

A

all neurons contain LGIC’s and are well-known neurotransmitter receptors (most)

Nicotinic receptor first discovered

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

All LGIC’s have:

A

5 subunits in receptor oriented around central core where the ions would normally go thru (pentamers)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Every nicotinic receptor has at least

A

2 alpha subunits among others. alpha subunit has the Ach (ligand) binding domain. You need 2 Ach ligands to bind to the 2 alpha subunits to result in conformational change for nicotinic receptor to open.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Each subunit composed of

A

4 transmembrane domains (TMI 4). 5 put together makes a pentamer channel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

For nicotinic receptor…

A

K+ ions are allows to flow thru central core when Ach binds to it. This results in a very rapid response to Ach binding to it.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Takehome messages (two) of LGIC’s

A

Single action (ligand to bind) to open the receptor channel, are thus rapid (main advantage).

LCIC receptor can be both inhibitory or excitatory neuronal firing (depending on which ions can flow across channel).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q
  1. GPCR’s
A

Metabotropic receptors
Sit across membrane (7 transmembrane domains)
Primary ligand binding site at end tail
Inner portion binds to a G-protein.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

When a ligand binds to a GPCR

A

causes conformational change in receptor structure allowing receptor’s GDP inside membrane to interact with a G protein.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

G-protein

A

guanine nucleotide-binding protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Steps of GPCR’s mechanism

A
  1. ligand binds to active site
  2. interacts with g-protein
  3. releases GDP
  4. Takes on GTP
  5. alpha subunit cleaves from beta-gamma subunit
  6. cleaved two are now active sites that have ability to phosphorylate other subunits inside the cell
  7. GTP eventually loses phosphate group and alpha subunit rebinds with beta-gamma subunit and they again become inactive until next time g-protein interacts with them.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Purpose of a GPCR?

A

To activate second messengers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

second messengers

A

small molecules or ions that relay signals received by cell-surface receptors to effector proteins inside cell.

Broadcast the first message relayed by GPCR’s

Typically at low concentrations in resting cells and can be rapidly produced or released when cells are stimulated.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Once G-protein has been cleaved, that active 2nd messenger can

A

phosphorylate multiple other proteins in the cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Difference b/w GPCR and LGIC

A

when ligand binds to LGIC, only effects that one receptor and making membrane leaky for that one ion. gpcr opens cascades of proteins, etc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Kinase

A

adds phosphate group to a protein, inducing conformational change in the protein and activates it. Uses ATP as energy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Phosphatase

A

removes a phosphate group from protein, inducing conformational change in the protein and resets it to its inactivated state.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

2nd messengers and downstream effects of drugs from GPCR’s in cells all involve

A

phosphorylation/dephosphorylation of proteins.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

The primary mode of intracellular signaling is

A

the tug of war between kinases and phosphatases and if/if not phosphorylated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Three types of second messengers

A
  1. Adenylyl cyclase and cAMP
  2. PIP3 activation of PLC to generate the two second messengers called DAG and IP3
  3. Ca2+ ions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q
  1. Adenylyl cyclase and cAMP (second messenger)
A

critical pathway for intracellular enzyme signaling and drug interactions. Drug acts on Gi, Gs or G0

26
Q

If receptor is (once ligand binds)
Gs
Gi
G0

A 
Gs= it increases adenylyl cyclase activity and increases cAMP levels in cell (stimulates)
Gi= it decreases adenylyl cyclase activity and decreases cAMP levels in cell (inhibits)
G0= No effect on cAMP (probably acting on another system like PKA... adds a pi group).
27
Q

Steps of Andenylyl cyclase and cAMP secondary messenger

A
  1. activated by ligand
  2. G protein alpha subunit travels inside membrane and binds to active site of adenylyl cyclase.
  3. adenylyl cyclase uses ATP as energy and activates second messenger cAMP
  4. activates PKA which results in phosphorylation of dephosphorylation in protein and response in cell.
28
Q
  1. PIP3 and PLC pathways (Gq)
A
  1. Ligand binds
  2. G-protein alpha subunit cleaves and activates PLC in cell membrane
  3. cleaves PIP3 into
    a) DAG (fat soluble, stays in membrane, which activates PKC then can phosphorylate other proteins or cell response could be LGIC, too
    b) IP3 which goes to cell’s EF, activates CA2+, binds to Ca2+ channels and increases concentration of Ca2+ in intracellular space.
29
Q
  1. Ca2+ pathway
A

once Ca2+ released from ER via IP3 gated Ca2+ channel, binds to calmodulin and activates other proteins in the cytoplasm.

linked to memory (calcium calmodulate 2)

30
Q

Main advantage of GPCR’s

A

Their ability to activate second messenger cascades producing signal amplification, resulting in prolonged effect by phosphatase (slower than LGIC’s)

31
Q
  1. Nuclear receptors
A

aka: intracellular receptors

typically sit within cytosol (inside cell, outside nucleus)

receptors that respond to steroid hormones

When ligands bind to the receptor, the receptors dimerize (pair up) and translocate to the nucleus.

32
Q

What happens to Nu-R when dimerization and translocation occurs?

A

effects transcription and thereby production of new proteins in the cell. They bind to a response element on DNA

33
Q

How are Nu-R’s able to sit in cytosol and not embedded in the membrane?

A

Because these ligands binding to it are fat soluble (steroid hormone receptors), thus uncharged and can pass thru easily.

34
Q

Why are nuclear receptors the slowest?

A

You have to wait for receptors to translocate to the nucleus and production (transcription and translation) of new proteins takes approx 1hour

35
Q

Example of nuclear receptor:

A

Estrogen receptor. Estrogen and Estrogen receptors dimerize, then pair up and translocate to the nucleus. Causes changes in transcription and protein production as a result and depending on the gene ERE is on and what other cofactors are also bound at the same time, can either increase or decrease protein production.

36
Q

Nuclear receptor speed

A

is slow in effect, but could with K+ channel proteins change the rate of firing via upregulation or downregulation of protein production effecting firing rate of neuron.

37
Q

Interesting caveat of estrogen receptors

A

Past thought there were two estrogen receptors (ERa and ERb). Yet, if you give estrogen to female rat, behav is impacted rapidly. This implies that it is impossible that there are only two estrogen receptors (nuclear, thus slow) and therefore couldn’t possible have a behavioural effect before an hour and are acting another way.

Current thoughts:
GPER1
+
mERa and mERb

38
Q

GPER1

A

is a GPCR estrogen receptor, via g-protein can have second messengers and effects cascading in addition to ERa and ERb

39
Q

mERa and mERb

A

Are estrogen receptors linked/anchored to the membrane. When estrogen binds to them, they don’t have the machinery or g-protein to interact with since the receptors by nature were made to bind to DNA, so they don’t have an area that can interact w/ g-proteins

40
Q

How do mER’s have effects on secondary messengers?

A

mER’s interact with some GCPR’s

41
Q

Main difference and advantage of nuclear receptors

A

to activate long-term changes in the cell.

42
Q

Note about GCPR’s and Nu-R’s

A

Nuclear receptors are most known to have slow onset and long term changes in the cell but GCPR’s also capable of the same.

Also NU-R’s can be anchored to membrane for more rapid changes (~15min)

43
Q
  1. Receptor Tyrosine Kinases
A

sit in membrane and dimerize with ligand binding. The intracellular side can interact with residues and cause a response.

44
Q

Receptor tyrosine kinases tend to bind with

A

Growth factors, cytokines and hormones

45
Q

Endogenous (definition)

A

(NT’s) compounds that originate from within the body

46
Q

Exogenous (definition)

A

(drugs) compounds that originate from outside the body

47
Q

Affinity (defintion)

A

is the degree to which a ligand will associate and dissociate with it’s receptor (calculated at Kd or Ki)

48
Q

Ligand’s affinity for receptor bonds depends on

A

ligands and receptor

can have strong or weak bonds

49
Q

For most drugs (wrt bonding)

A

they have weak bonding, where ligand can pop off at some sort of constant rate

50
Q

Three types of weak ligand bonds and one type of strong bond

A
  1. Ionic
  2. H-bonds
  3. Vanderwaals

Covalent (permanent). Once bound, it is on until receptor is recycled by the cell

51
Q

Kd

A

depends on specific ligand and receptor (relationship is important)

52
Q

Law of mass action

A

concentration of (dose of drug) ligand and concentration of (amount of) receptor is in that area of brain, neuron or pathway it is expressing results in a reversible reaction with ligand and receptors in equilibrium with the ligand bound to the receptor (response).

53
Q

Increase dose of a drug results in a ______. But, if someone has more receptors, must have _____.

A

greater response, less of drug for same response

54
Q

Greater affinity means more…

A

rapid binding and slower dissociation

55
Q

Magnitude of response from drug dependent on (two things)

A
  1. Dose of drug
  2. Receptors present. But receptors are not constant in brain and CNS and certain types of receptors respond very rapidly to any drug exposed.
56
Q

Reduction of receptor signaling (two ways):

A
  1. Desensitization
  2. Downregulation
    a) sequestration
    b) reduced transcription
57
Q
  1. Desensitization
A

once a receptor is activated repeatedly it will have lesser response in the future due to phosphorylation (makes it less sensitive). It is quite rapid.

58
Q
  1. Downregulation and the two main types:
A

there will be fewer receptors after repeated stimulation.

a) sequestration occurs when neuron internalizes receptor into cytosol and it is hidden and no longer available to be activated
b) reduced transcription occurs when neuron reduces the amount of receptor it makes.

59
Q

3 ways that downregulation occurs

A
  1. desensitization
  2. receptor sequestration
  3. reduced transcription
60
Q

pharmacodynamic tolerance

A

is when receptors desensitize or downregulate and you need more drug to have the same effect

61
Q

Pharmacodynamic tolerance (at level of cell where drug is having its effect) does NOT equal: ______

A

Pharmacokinetic tolerance (in liver)

Neuropharmacology (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions