Brainscape's Knowledge GenomeTM

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


See full index

Bs 3054 - molecular and cellular Pharmacology > Topic 8: Drug Discovery > Flashcards

Topic 8: Drug Discovery Flashcards

1
Q

Why do ion channels make attractive drug targets?

A

many types, some are tissue selective allows for manipulation of electrochemical gradients

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

what drug binds to the SUR subunits of the K-ATP channels and causes closing?

A

Sulfonylureas and meglitinides

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

what is an inward rectifer

A

allows for the infux of ions more than its efflux

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

why are poly aminies more attracted to the pore when the membrane depolarises?

A

positivly charged so more attceted to pore ass depolarisation of the memebrane

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

What does ATP concentration and ADP concentration do to the open probability of Kir6

A

high atp closes low atp opens
ADP binding casues channel openig

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

What does ATP concentration and ADP concentration do to the open probability of Kir6

A

high atp closes low atp opens
ADP binding casues channel openig

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

what happens to membrane potenitail when k-ATP channels open

A

hyperpolarasation

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

what is the mechanism of stimulus secretion coupling in B cells

A

low glucose leads to less ATP and more ADP
ADP binds to K-ATP channels- opens
deplariation causes the cloisng og CA2+ channels
less ca2+ less secreation.

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

how does high glucose lead to insulin secretion

A

high glucose extrecellular
diffuseses - more metablism more ATP less
ADP
closingof K - ATP channels
depolation of the cell
opening of Ca2+ l type channels
simulation of secreation if insulin (vescicle binding)

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

What happens to insulin secretion when k ATP channels are inhibited?

A

no hyperpolariastion so more ca2+ opening and entry and hence moere insulin secreation.

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

what is permenat neonatal diabeties casuesed by ?

A

Kir6.2 Activating mutations
two forms mild and severe
mild is caused by a mutation to the ATP binding site - favours the open state
severe is caused by a gating mutation, increased open probbality - hyperpolarisation in many tissues.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what form of permanant neonatal diabeties will respond to sulfonylourea therapy?

A

mild

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

what causes congenital hyperinsulinism? what is it treated by?

A

mutaion in the SUR1 binding domain, causes the cahnnelto remain closed even in high ADP concentraion trated by channel openers such as diazoxide.

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

what are two 5-HT antagonists?

A

Alosetron and ondansetron

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

what part of the brain controls the vomit reflex?

A

the vomiting centre

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what ligand is the nicotinic receptor superfamily sensitive to?

A

5-HT - cation selective excitatory receptors

17
Q

what is the 5-HT 3 receptor coupled to?

A

Nothing it is an ion channel (ligand gated) the other 5-HT receptors are GPCRs

18
Q

what is a Cys-loop receptor?

A

has a signature extracellular loop of 13 amino acids flanked by cysteines, which form covalent bonds
this loop forms a closed loop between the ligand binding domains and the channel domains.

19
Q

what are the two ways the vomiting reflex can be activated?

A

chemoreceptor trigger zone and the GI tract

20
Q

Where are the highest levels of 5-HT 3 receptors found?

A

in the vomiting centre and chemoreceptor trigger zone

21
Q

why can the chemoreceptor zone detect chemicals in the blood?

A

it is not within the BBB

22
Q

what can the chemoreceptor trigger zone be stimulated by?

A

toxins in the blood
higher brain centres

23
Q

how does the chemorecepror trigger zone set off the vomiting reflex?

A

release of 5-HT, stimulates pathways to VC
vomiting

24
Q

how does the GI tract stimulate vomiting?

A

enetrochromaffin cells are stimulated by luminal stimuli
release of 5-HT which stimulates peripheral 5-HT 3 receptors on vagal afferents, AP to brain stem
relase of 5-HT in brain stem - stimulation of VC

25
Q

What subunit is required to form functional 5-ht 3 channels

A

5-HT 3A

26
Q

why is no current observed through 5-HT 3B-E channels?

A

they do not form funtional channels

27
Q

What is Memantine used for?

A

Alzheimers - prevents neurotoxicity form excessive stimulation of glutamate receptors - slows progression

28
Q

What can protein kinases do?

A

alter enzymic activity
alter interaction with other cellular components
alter localisation
alter stability
alter interactor specificity

29
Q

what do protein phospatases do?

A

dephosphorylate preoteins

30
Q

what is MAPK signalling

A

Mitogen-activated protein kinase signalling
uses a cascade of multiple kinases

31
Q

how does stimulation of EGFR lead to stimulation of ERK
check in text book

A

agonist binding
dimerastion
activation of Grb2 and sos
Sos is a GEF for Ras
GTP for GDP exchange
phosraption of Raf
then MEK
then ERK

32
Q

What do many of the current PK inhibitors bind to ?

A

the ATP binding site this has significant problems as high ATP in the cell - problem for competitive inhibition
most PK have similar ATP binding site this makes specificity a problem

33
Q

how is pharma trying to manipulate MAPK signalling?

A

by interfering with lipidation- Farnesyl / geranyl traferase inhibitors- clinical efficacy but can effect other proteins

34
Q

what is a novel pharmaceutical approach for pain reduction

A

u opioid receptor antagonism but biased to hetromer bias
may reduce tolerance build up and enhance anti noicoceptor

35
Q

why might B-blockers work in CHF

A

reduce sympatic activation and cardiac output but aslo recued myocardial O2 demand and stress (reduced perifiral vasoconstriction

36
Q

what happens to the relationship between b1 and b2 receptors in the heart as we age or in CHF

A

normally B1 to B2 is 4:1 but this changes to 1:1

37
Q

What does the inverse agonism theory of why B blockers treat heart failure?

A

increase sympatetic drive leads to downregulation of B receptors
B-blockers increase receptor counts by acting as inverse agonits

38
Q

What is the ligand basised theory of CHF treatment with B blockers

A

bindig diffrent B arrestins
diffrent signalling cascades

Bs 3054 - molecular and cellular Pharmacology (7 decks)

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