Brainscape's Knowledge GenomeTM

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


See full index

342 > gastrointestinal pharmacology - advances > Flashcards

gastrointestinal pharmacology - advances Flashcards

1
Q

PPI long term limitations for hyperacidity - 7

A

risk of infractures

risk of pneumonia

c. difficile diarrhoea

vitamin b12 deficiency

chronic kidney disease

dementia

difficulties in drug delivery - enteric coated capsules used to avoid protonation when entering stomach so can reach small intestine e.g with omeprazole

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

attempts to overcome ppi issues - 8

A

major advance - potassium ion competitive acid blockers (P-CABs)

development of potent H2 receptor agonist

gastrin agonists

non-benzimidazole PPI

extended and delayed release PPIs

PPI combination

new agents with longer half lives

new generation of PPIs

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

potassium ion competitive acid blockers (P-CABs) mechanism of action

A

acid pump antagonists

block K+ H+ -ATPase K+ channel of proton pump

causes competitive reversible food independent inhibition of gastric acid secretion

works on parietal cells

rapid, more sustained

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

potassium ion competitive acid blockers (P-CABs) vs PPIs - which are better

A

potassium ion competitive acid blockers (P-CABs) sllow for longer lasting, rapid, consistent increase in intra gastric pH

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

PPIs require transformation to the active ____ form while P-CABs

A

sulfonamide

act directly on K+ H+ ATPase proton pump

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

PPIs have a lower concentration in the ____ while P-CABs

A

parietal cell acid space/ cannuliculi

have a higher concentration in parietal cell acid space

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

PPIs bind ___ while P-CABs bind ___ to K+H+ ATPase

A

covalently and irreversibly

competitively and reversibly (competes with K+ ions)

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

in PPIs, the duration of affect is related to the half life of the ____ while in P-CABs it is related to the half life of the ____

A

sulphonamide-enzyme complex

drug in plasma

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

PPIs have a ___ onset of action while P-CABs have

A

delayed as unstable in cannuliculi, rapidly degraded so few doses/days needed for effect, need to be activated to active form in stomach acid first

full effect from first dose as not prodrug, no need for activation and binds stable

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

PPIs have ____ inhibition of gastric acid while P-CABs have ____

A

food dependent

food independent acid inhibition

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

PPIs result in ____ acid suppression while P-CABs result in ___ acid suppression

A

incomplete

complete, prolonged

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

P-CAB example

A

vonoprazan fumarate - first in class

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

vonoprazan fumarate is effective for

A

endoscopic erosive oesophagitis - linked to GORD

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

vonoprazan fumarate is effective at __mg compared to ___ at ___mg

A

20mg

lansoprazole (PPI)

30mg

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

vonoprazan fumarate vs lansoprazole

A

faster healing - 8 weeks

more effective for GORD than PPIs

inc treatment efficacy

more effective long term treatment for severe Barrett’s oesophagus

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

vonoprazan fumarate has antisecretory effects. what does this mean in terms of advances in future

A

antisecretory effects - could be used as treatment for H. pylori treatment which is otherwise difficult to treat via antibiotics due to acquired resistance

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

P-CABs

A

still in trial phase, need to test and compare to PPIs

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

new developments in constipation pharma - 4

A

selective 5-HT4 receptor agonists

intestinal chloride channel activators

modifiers of bile acid recycling and synthesis

sodium/ hydrogen exchanger inhibitors

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

selective 5-HT4 receptor agonists examples - 2

A

prucalopride

velusetrag

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

intestinal chloride channel activators examples - 3

A

lubiprostone

linaclotide

plecanatide

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

modifiers of bile acid recycling and synthesis examples - 2

A

elobixibat

NGM282

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

sodium/ hydrogen exchanger inhibitor example for treating constipation

A

tenapanor

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

compare new constipation drugs to older ones

A

new - higher efficacy, but less comparitive studies, more expensive, conflicting studies

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

2 studies comparing old and new laxatives

A

study tegaserod (newer) vs polyethylene glycol (old) - old was better for symptoms, and better tolerated

study bisacodyl vs new laxatives meta analysis, old was superior in inc bowel movement per week

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

advances in constipation treatment

A

individualised therapy

pelvic floor biofeedback therapy preffered over laxatives. if no worky, tailored therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

pelvic floor biofeedback therapy preffered over laxatives. if no worky, tailored therapy for constipation. what are some examples - 2

A

5-HT4 receptor agonist (prucalopride) for pt with slow intestinal transit

ileal bile acid transport inhibitors if deficiency of bile acids reaching colon

27
Q

chronic bowel disorder ibs advances - 2

A

difficult as multifactorial

partial agonists instead of full agonists/ antagonists to reduce side effects and cardiotoxicity

nover receptor targets

28
Q

nover receptor targets for treating ibs examples - 3

A

TLR - inhibits ibs symptoms

HR - inhibits hypersensitivity

TRPV1 - inhibits hypersensitivity

29
Q

current therapy in ibd

A

currently incurable, but can relieve symptoms, and remission

30
Q

advances in ibd chron’s disease treatment research

A

mycobacterium avium paratuberculosis (MAP) infection shown to link to chron’s disease - potential for vaccine? in cows intestines

CD patients more likely to have MAP in intestine, but some have MAP without CD so we dk yet

31
Q

treatments in ibd chron’s disease - targeting MAP

A

RHB-104 antibiotic cocktail

32
Q

RHB-104 antibiotic cocktail consists of - 3

A

clarithromycin

rifabutin

clofazimine

33
Q

RHB-104 antibiotic cocktail studies

A

1st clinical trial found link between its use and remission

after a year, 25% symptom dec vs 12% placebo

styll more research needed bc who had MAP?? also abx r old school theres resistance now so is there even a point

34
Q

targeted therapy advancements for IBD - 4

A

TNF-alpha inhibitors

recognition of anti inflammatory cytokines that doenregulate T lymphocute proliferation

synthesis of selective adhesion molecule inhibitors that suppress T lymphocyte transport into gut epithelium

sustained drug release platforms

35
Q

TNF-alpha inhibitors

A

most promising targeted therapy advancement for IBD

fabrication of inhibitors of inflammatory cytokines including TNF-alpha that results in T lymphocyte apoptosis

36
Q

natural products can be useful for treating inflammatory effects of ibd, examples - 7

A

curcumin

silymarin

ginger-derived NPs

quercetin

grape exosome-like NPs

embelin

natural polysaccharides

(but, all low oral bioavaliability)

37
Q

natural product drug delivery is aided with nanoparticles. stimuli responsive NP approaches - 3

A

pH-sensitive approaches

enzyme - sensitive approaches e.g. proteases

redox-sensitive NPs e.g. azo-prodrugs sulfasalazine

38
Q

advantages of using NPs - 3

A

less toxicity

can deliver to specific site - in this context, colon (although this is a challenge for now)

degraded in colon

39
Q

vedonlizumab

A

new therapy for IBD

biologic

works specifically on GI tract, less risk of systemic circulation side effects

40
Q

GI cancer therapy study - oxaliplatin and ibudilast

A

oxaliplatin - improves survival in colorectal and upper GI cancer BUT can cause moderate to severe neurotoxicity in most patients

causing cold sensitivity in extremities, numbness

ibudilast - pilot study shows can prevent oxilaplatin neurotoxicity

41
Q

ibudilast mechanism of action

A

selective phosphodiesterase inhibitor with anti inflammatory properties

well tolerated

does not impact oxaliplatin pharmacokinetics or of other chemotherapeutic agents

42
Q

GI cancer therapy study - oxaliplatin and MRP2

A

oxaliplatin transporter candidate gene expression in tumours linked to patient response to med

MRP2 found to be a oxaliplatin transporter that limits oxaliplatin accumulation and response in human GI cancer

thus, MRP2 screening can help determine if patient needs MRP2 inhibitor AS WELL AS oxaliplatin

43
Q

GI cancer therapy study - pembrolizumab and MMR deficiency

A

first immunotherapy

mismatch repair MMR deficiencies can predict response to immune checkpoint blockade targeting in CD274 and PDCD1 pathway in multiple cancer types (including metastatic GI cancers)

pembrolizumab is anti PDCD1 antibody to treat mismatch repair-deficient tumours

approved by FDA

44
Q

precision GI oncology study - aspirin in colorectal cancer

A

colorectal cancer with PIK3CA mutations - basis of clinical trials

HPGD expression levels in normal colon combined with WNT signalling pathway polymorphism can help preduct efficacy of aspirin for chemoprevention

all these treatments btw consider diet, llifestyle, encironmental factors as a combined treatment alongside

45
Q

precision GI oncology study 3 startegies for implementation

A

1 - implement clinical biomarkers and monitor them

2 - conduct comparative effectiveness research to assess clinical management schemes

3 - develop systems to optimize clinical practice based on new evidence

46
Q

drug delivery - peptides, proteins, antibodies, oligonucleotides ___ be delivered orally

A

cannot despite research efforts

47
Q

novel drug delivery - what is used now and why

A

sublingual and buccal routes

highly vascularised
local and systemic drug delivery
allow for direct absorption via venous drainage to superior vena cava
fast onset
good for patients who suffer swallowing and also bypasses first pass hepatic metabolism
good for highly suitable drugs
few enzymes needed - only salivary amylase, less likely interactions and modifications
mouth is neutral so facilitates admin of srugs stable in neutral ph
easy to self admin

48
Q

sublingual admin

A

under tongue

49
Q

buccal admin

A

between gums and teeth

50
Q

disadvantages of sublingual and buccal admin - 6

A

risk of patient swallowing

not suitable for all drugs

usually small doses best work

bitter taste

may irritate mucosa

not for sustained admin

51
Q

example of sublingual drug admin - 3

A

liquid (sprays, drops)

solid (tablets, patches)

semi solid (gels)

52
Q

oral vaccinations advantages

A

pain free, self admin
rapid mass vaccination during pandemics

oral cavity, stomach, small intestines can be targeted by oral vaccinations

53
Q

disadvantages of oral vaccinations

A

current limited to live-attenuated and inactivated vaccines against enteric diseases

degradative process digest biologics and mucosal barriers in GI tract limit absorption - research needed to understand how to overcome

54
Q

wirelessly contolled ingestible capsule

A

ingested
electronic pill
release pill in response to smartphone commands

allow long term drug release over several days using polymers

can stay in stomach for a month and help monitor gastric environment

can help monitor heart and breathing rate

battery can eventually if research works be replaced with antenna or STOMACH ACID WTF

55
Q

sublingual tissue and buccal tissue have a pH of

A

approx 7

56
Q

which has the bigger surface area - buccal or sublingual tissue

A

buccal - twice as much

57
Q

both buccal and sublingual tissue have __ enzyme activity

A

low - less pre metabolism of meds

58
Q

tenapanor mechanism of action

A

inhibits sodium/hydrogen exchanger 3 (NHE3) in GI tract

inc intestinal fluid by dec sodium absorption from intestinal lumen, inc osmosis, inc water retential in intestine lumen

softer stool

clinical trials shown useful in relieving constipation in IBD

minimal systemic absorption, no dependence unlike stimulant laxatives

59
Q

tenapanor side effects - 2

A

diarrhea - 16% of pts in clinical trials
due to excess water retention

abdominal distension (swollen)

60
Q

intestinal chloride channel activator mechanism of action

A

gulanylate cyclase c agonists

guanylate cyclase c receptors in intestine activation

inc intracellular cGMP - cyclic guanosine monophosphate

activates CFTR which promotes secretion of Cl- and bicarbonate ions into intestine lumen

osmosis, inc water into lumen

softens stool

also can cause diarrhoea

61
Q

tlr inhibitors in ibs treatment/ case study

A

toll like receptor inhibitors

still investigating

e.g. tranilast, anti allergy drug, shown effect in alleviating visceral hypersensitivity in ibs rat models by suppressing TLR4 signalling

62
Q

TRPV1 antagonists in treating ibs

A

trpv1 channels involved in pain perceptionm associated with ibs hypersensitivity

ginotonin derived from ginseng can inhibit this potentially

63
Q

jst a summary list of advances tbh

A

overcoming PPI issues: potassium ion competitive acid blockers (P-CABs)

constipation pharma - selective 5-HT4 receptor agonists, intestinal chloride channel activators

pelvic floor biofeedback therapy preffered over laxatives e.g. selective 5-HT4 receptor agonists

ibs new novel drug targets

ibd symptom relief - RHB-104 antibiotic cocktail targets MAP, naturals like ginger-derived NPs , biologics like vedonlizumab
ibd therapy research - TNF-alpha inhibitors
nanoparticles

64
Q

examples of advances

A

p cab example - vonoprazan fumarate for oesophagitis

selective 5-HT4 receptor agonists - prucalopride

intestinal chloride channel activators - plecatanide

new laxative tegaserod

ibs new targets e.g. HR - inhibits hypersensitivity, sublingual and buccal routes delivery

RHB-104 antibiotic cocktail - clarithromycin, rifabutin, clofazimine

342 (21 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions