Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Pharmacology > Inflammatory bowel disease > Flashcards

Inflammatory bowel disease Flashcards

(36 cards)

Start Studying
1
Q

What are the 2 main forms of IBD?

A
  • Ulcerative colitis

- Crohn’s disease

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

How does the incidence of CD and UC differ in Western Europe compared to the rest of the world and why?

A

The incidence of both UC and CD are twice as high in the Western Europe compared to the Eastern

This may be to do with diet and other lifestyle factors

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

Who does IBD affect?

A

IBD can affect people of any age: children, adolescents and adults

It most commonly occurs and presents first in late adolescents and young adults

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

What are the genetic risk factors for IBD?

A
  • The causes are incompletely understood
  • There is genetic predisposition to Crohn’s: 201 loci have been identified and people of White European origin are most susceptible
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the 3 most important environmental risk factors for IBD?

A

smoking, diet and microbiome

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

What kind of conditions are IBD?

A

autoimmune

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

Compare Crohn’s and Ulcerative Colitis on the following points:

  • what mediates the disease?
  • which gut layers are affected?
  • which regions of the gut are affected?
  • inflamed areas are?
  • are abscesses/fissures/fistulae common?
  • can surgery cure?
A

Crohn’s

  • Th1-mediated e.g. IFN-gamma, TNF-alpha, IL-17, IL-23, florid T cell expansion, defective T cell apoptosis
  • All layers
  • Any part of GI tract
  • Patchy
  • Common
  • Not always curative

UC:

  • Th2- mediated .g. IL-5, IL-13, limited clonal expansion, normal T cell apoptosis
  • Mucosa and submuscoa
  • Rectum
  • Continuous
  • Not common
  • Curative
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Layers of gut revise

A

…

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

What are the symptoms of UC and CD?

A
  • ulcers
  • diarrhoea
  • abdominal pain
  • fevers
  • sweating
  • anaemia
  • arthritis
  • weight loss
  • skin rashes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the supportive treatments available?

A
  • Fluid/electrolyte replacement
  • Blood transfusion/oral iron if necessary
  • Nutritional support (malnutrition common in IBD patients)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are some symptomatic treatments (for active disease and preventing relapse)?

A

Aminosalicylates e.g. mesalazine, olsalazine

Glucocorticoids e.g. Prednisolone

Immunosuppressive agents e.g. Azathioprine

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

Aminosalicylclates - what is the active component?

A

Mesalazine or 5-aminosalicylic acid (5-ASA, olsalazine (2 of the 5-ASAs joined)

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

Pharmacokinetics of aminosalicyclates - mesalazine and olsalazine

A

Mesalazine –does not need to be metabolised and is absorbed by small bowel and colon. Good at maintaining remission in UC. Topical 5-ASA is better than topical steroids at inducing UC remission. Combined topical 5-ASA and oral steroids better at inducing remission than oral 5-ASA alone

Olsalazine –metabolised by gut flora and absorbed by the colon. So olsalazine only works in the colon

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

Which 2 pathways regulated inflammation?

A

NF-KB/MAPK: down-regulate pro-inflammatory cytokines – TNF-alpha, IL-1B and IL-6

COX-2: down-regulates prostaglandins – PGE2 and PGF2

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

Aminosalicyclates for UC and CD

A

Ulcerative Colitis

  • First line for both inducing and maintaining remission
  • Good evidence base for this

Crohn’s Disease

  • Literature is unclear
  • It is ineffective in inducing remission in Crohn’s
  • Less clear cut than utility in UC
  • Glucocorticoids are probably better in Crohn’s
  • It may be effective in a subgroup of patients
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Glucocorticoids: examples and what do they do

Study These Flashcards
A
  • Examples: Prednisolone, Fluticasone, Budesonide
  • These are powerful anti-inflammatory and immunosuppressive drugs
  • They are derived from the hormone cortisol – so they have lots of side effects
  • They activate intracellular Glucocorticoid Receptors which can then act as positive or negative TFs
17
Q

How do glucorticoids work in IBD?

Study These Flashcards
A
  • Glucocorticoids act at multiple points in the inflammation seen in bowel disease
  • They can inhibit the production of IL-1 and TNF-alpha by dendritic cells
  • Dendritic cells are thought to have an important role in IBD
  • They have very potent anti-inflammatory and immunosuppressive actions of GCs
  • When given systemically, chronic glucocorticoid administration causes many unwanted effects
18
Q

How do aminosalicyclates work?

Study These Flashcards
A
  • Inhibitionof IL-1, TNF-a and PAF(Platelet Activating Factor)
  • Decrease antibody secretion
  • Non-specific cytokine inhibition
  • Reduce cell migration –macrophages
  • Localised inhibition of immune responses
19
Q

How can glucocorticoids be used whilst minimising SE?

Study These Flashcards
A

-Glucocorticoids have many long-term use side effects -> methods for reducing SEs:

  • Administer topically
  • Use a low-dose in combination with another drug (steroid-sparing agent)
  • Use an oral/topical drug with high first-pass metabolism (e.g. Budesonide), so little escapes systemically
20
Q

Pros and cons of budenoside

Study These Flashcards
A
  • Has fewer SE than prednisolone
  • Glucocorticoids have many long-term use side effects -
  • Oral GCs are better than Budesonide at inducing remission in active Crohn’s disease
  • Budesonide is a better than placebo at preventing CD relapse
21
Q

Glucocorticoids in UC and CD

Study These Flashcards
A

Ulcerative colitis

  • Use of glucocorticoids is in decline, due to evidence that aminosalicylates are superior
  • Glucocorticoids are best avoided due to their side effects

Crohn’s Disease

  • Glucocorticoids remain the drugs of choice for inducing remission in Crohn’s
  • Budesonide is preferred if the disease is mild
  • Patients are likely to get side effects if GCs are used to maintain remission (long-term use)
22
Q

What is azathioprine?

Study These Flashcards
A
  • immunosupressive agent
  • pro-drug that is activated by gut flora to form 6-mercaptopurine
  • purine antagonist
23
Q

How does azathioprine work?

Study These Flashcards
A
  • Interferes with cell replication and DNA synthesis
24
Q

Azathioprine activation, roles of different products formed

Study These Flashcards
A
  • Azathioprine can be activated to become 6-mercaptopurine
  • This can be metabolised by multiple routes
  • When it is metabolised to 6-TMP, it is further metabolised to produce the active drug gents
  • 6-MeMPN inhibits de novo purine synthesis
  • 6-TGN acts like a false purine molecule and gets incorporated into DNA
25
What are the effects of azathioprine on the immune system - what does it impair and enhance?
Azathioprine impairs: - Cell-mediated and antibody-mediated immune responses - Lymphocyte proliferation - Mononuclear cell infiltration - Synthesis of antibodies Azathioprine enhances: - T cell apoptosis
26
Azathioprine and UC and CD
Ulcerative Colitis - Some success in Ulcerative Colitis - But there is no real reason to use it if the response is good with 5-ASA Crohn’s Disease - Azathioprine has no benefit at all in active disease - It is mainly used to maintain remission - Recent Cochrane review shows it be glucocorticoid-sparing - Azathioprine has a slow onset – 3 to 4 months treatment for clinical benefit to be observed Azathioprine is effective in maintaining remission over long-term use.
27
What are the unwanted effects of azathioprine?
Nearly 10% patients have to stop treatment because of the side effects – these are not trivial - Pancreatitis - Bone marrow suppression - Hepatotoxicity - Increased risk (around 4 fold) of lymphoma and skin cancers 6-MeMPN is hepatotoxic, despite being an inactive by-product of metabolism (in terms of protection). 6-TU is also inactive, but becomes toxic if taken with allopurinol (a drug taken for gout), because allopurinol inhibits xanthine oxidase. Gout is not uncommon. 6-TGN is beneficial in terms of immunosuppression, but also causes the myelosuppression associated with azathioprine
28
What are some potentially curative therapies?
Curative options include manipulation of the microbiome and biologic therapies - Anti-TNF alpha e.g. Infliximab (monoclonal antibody to TNF-alpha)
29
How can the microbiome be manipulated?
1. Nutrition-based therapies - There is no evidence for probiotics in food stuffs have any impact at all in Crohn’s disease - There is some evidence for probiotics for maintenance of remission in Ulcerative Colitis 2. Faecal microbiota replacement (FMT) therapies - Re-populating a patient’s bowel with healthy gut flora may solve the problem - There is insufficient evidence for FMT. More studies are needed 3. Antibiotic Treatment with RIFAXIMIN - This interferes with bacterial transcription by binding to RNA polymerase - It induces and sustains remission in moderate Crohn’s disease - This may be beneficial in ulcerative colitis too - Microbiome modulator – rifaximin reduces inflammatory mediator mRNA in experimental colitis
30
Anti-TNFa alpha antibodies - how does it work?
- Infliximab - Antibodies will mop up any soluble TNF-alpha before it can bind and activate receptors. TNF-alpha is an upstream, pro-inflammatory mediator. - Anti-TNF alpha reduces activation of TNF a receptors in the gut - Reduces downstream inflammatory events - Also binds to membrane associated TNF alpha -> induces cytolysis of cells expressing TNF alpha - Promotes apoptosis of activated T cells
31
How is infliximab administered, how often is it administered?
Intravenously and has a very long half-life (9.5 days) Most patients relapse after 8–12 weeks, therefore the infusion needs to be repeated every 8 weeks
32
Results from anti-TNF alpha antibodies
- It has been used successfully in the treatment of Crohn’s disease - Only 60% of patients respond within 6 weeks – we haven’t understood the underlying pathology - Potentially curative, but many patients relapse with this treatment - Successful in some patients with refractory disease and fistulae (great for maintaining fistula closure)
33
What are the problems with anti-TNF alpha antibodies?
- Emerging evidence that up to 50% responders lose response within 3 years time - This is due to production of anti-drug antibodies and increased drug clearance
34
What are some adverse effects associated with anti-TNF alpha antibodies?
- 4x to 5x increase in incidence of tuberculosis - Also a risk of reactivating dormant TB - Increased risk of septicaemia - Worsening of heart failure - Increased risk of demyelinating disease (e.g. multiple sclerosis) - Increased risk of malignancy
35
Infliximab..
- Early use is better than using it as a last resort | - Combined infliximab and azathioprine therapy may be more effective than the antibody alone
36
What are some new targets for IBD?
Integrins (needed for cells to migrate) Interleukins (IL12; IL17;IL23) Interleukin receptors Janus kinase (JAK) cytoplasmic cell signalling

Pharmacology (26 decks)

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