Inflammatory Bowel Disease Flashcards
(80 cards)
1
Q
2 MAJOR FORMS OF IBD:
A
Ulcerative colitis (UC) Crohn’s disease (CD)
2
Q
risk factors for IBD? (11)
A
- SMOKING
- DIET
- MICROBIOME
- Medication
- Sleep
- Stress
- Physical activity
- Air pollution
- UV exposure/vitamin D
- Appendectomy
- Heavy metal
3
Q
How does IBD begin?
A
with an infection
4
Q
Summarise IBD into 4 stages:
A
1) complex interplay between host and microbes
2) disrupted innate immunity and impaired tolerance
3) pro inflammatory compensatory mechanisms
4) physical damage and chronic inflammation
5
Q
Gut layer affected by CD
A
all
6
Q
Gut layer affected by UC
A
mucosa/submucosa
7
Q
Regions affected by UC
A
Rectum, spreads proximally
8
Q
Regions affected by CD
A
any part of GI
9
Q
Cure success of surgery CD?
A
Not always curative
10
Q
Cure success of surgery UC?
A
Curative
11
Q
Pattern of inflammation, UC?
A
Continuous
12
Q
Pattern of inflammation, CD?
A
Patchy
13
Q
CD rarity of abscesses/fissures/fistulae?
A
Common
14
Q
UC rarity of abscesses/fissures/fistulae?
A
Not common
15
Q
Which IBD has IFN’s involved?
A
CD, gamma and alpha
16
Q
Which IBD is TH1 mediated
A
CD
17
Q
Which IBD is TH2 mediated
A
UC
18
Q
IL in CD?
A
17 and 23
19
Q
IL in UC?
A
5 and 13
20
Q
T cell expansion and apoptosis in CD?
A
Florid expansion, defective apoptosis
21
Q
T cell expansion and apoptosis in UC?
A
Limited clonal expansion, normal T cell apoptosis
22
Q
Systemic clinical features of IBD?
A
Anaemia, fevers, sweats, jaundice Abdominal pain Arthritis Weight loss Skin rash Diarrhoea
23
Q
Supportive therapies for IBD?
A
Fluids, blood, nutritional support
24
Q
Symptom therapies for IBD: active disease?
A
Glucocorticoids, aminosalicylates and immunosuppressives
25
Symptom therapies for IBD: preventing remission?
Glucocorticoids, aminosalicylates and immunosuppressives
26
Curative therapies IBD? (2)
Microbiome manipulation, biologic therapies (anti TNFalpha antibodies)
27
Aminosalicylate examples?
Mesalazine or olsalazine
28
MoA of aminosalicylates? (3)
1. Regulation of NF-B/MAPK- downregulates pro-inflammatory cytokines
2. Regulation of COX-2- downregulates prostaglandin production
3. (smaller way) they can scavenge oxidants
29
Relationship between Mesalazine and olsalazine
Olsalazine has to be activated by gut flora in the colon and split into the two mesalazine molecules
30
How can aminosalcylates be targeted at the colon
Olsalazine has to be activated by gut flora in the colon
31
What are aminosalicylates such as mesalazine AKA?
5-aminosalicylic acid
32
First line treatment for UC?
Aminosalicylates
33
Effectiveness of Aminosalicylates in UC?
- First line in inducing and maintaining remission
| - Good evidence base
34
Effectiveness of Aminosalicylates in CD?
- Ineffective in inducing remission
35
First line treatment for CD?
Glucocorticoids
36
Examples of glucocorticoids?
Prednisolone, Fluticasone, budesonide
37
Effect of glucocorticoids?
- Powerful anti-inflammatory and immunosuppressive drugs
38
what are glucocorticoids Derived from
cortisol
39
Main culprit in IBD? (the cell)
dendritic cells
40
Difference in treatment for CD and UC?
First line is aminosalicylates in UC and glucocorticoids in CD
41
Prednisolone vs budesonide?
Prednisolone for CD causes more side effects than budesonide but prednisolone is better at inducing remission in active CD
42
First treatment for mild CD?
- Budesonide
43
What is budesonide used for?
Mild CD
44
STRATEGIES FOR MINIMISING UNWANTED EFFECTS OF GCs: (3)
- Administer topically - fluid or foam enemas or suppositories
- Use a low dose in combination with another drug
- Use an oral or topically administered drug with high hepatic first pass metabolism e.g. Budesonide so little escapes into the systemic circulation
45
What does azathioprine do?
An immunosuppressive
Purine antagonist
Interferes with DNA synthesis and cell replication
46
What type of nuceleotide does azathioprine interfere with
Purines
47
What is the active form of azathioprine
6-mercaptopurine
48
What is the prodrug of 6-mercaptopurine
Azathioprine
49
2 ways 6-mercaptopurine interferes with DNA synthesis?
One active form of the drug inhibits de novo purine synthesis and the other gets incorporated into DNA
50
Where/how is 6-mercaptopurine cleaved from Azathioprine
By gut flora in the gut
51
Where does 6-mercaptopurine impair immune responses? (4)
- cell- and antibody-mediated immune responses
- lymphocyte proliferation
- mononuclear cell infiltration
- synthesis of antibodies
52
What does 6-mercaptopurine enhance re. immune responses? (4)
- T-cell apoptosis
53
Azathioprine success in UC and CD?
- Some success in inducing remission in Ulcerative Colitis
- No benefit in CD active disease
- Mainly used to maintain remission in CD
54
Time for azathioprine to become useful in Crohns disease?
3 to 4 months treatment for clinical benefit
55
What is azathioprine useful for re. CD?
It is effective in maintaining remission of CD
56
Unwanted side effects of azathioprine? (5)
- Nearly 10% patients have to stop treatment because of the serious side effects
- Pancreatitis
- Bone marrow suppression
- Hepatotoxicity
- Increased risk (~ 4 fold) of lymphoma and skin cancer
57
How to deliver drugs more efficiently for IBD? (4)
1) Enteric coating ensures degradation in the colon as it resists degradation in acidic pH of stomach
2) Time dependent, self destructive polymer packaging
3) Pressure/osmotic controlled packaging that relies on the more aqueous environment of the colon, which allows water in and pushes drug out
4) Even more complex polymers combine time and pH factors as time can mean premature drug release if the digestion is slow, and pH factors can mean the drug is released prematurely in the small intestine rather than the colon
58
Anti-TNFalpha drug?
Infliximab
59
How can you manipulate the microbiome? (3)
1. Nutrition-based therapies
2. Faecal microbiota replacement (FMT) therapies
3. Antibiotic Treatment - Rifaximin
60
Success of probiotics in CD?
No evidence
61
Success of probiotics in UC?
Is evidence for it
62
Probiotics vs 5-ASA in UC
both equally effective
63
Success rate of faecal microbiota therapies?
Not enough evidence
64
how does rifaximin work?
Interferes with bacterial transcription by binding to RNA polymerase
65
Successfulness of rifaximin in CD?
Induces and sustains remission
66
Topical steroids vs 5-ASA in inducing UC remission?
topical 5-asa is more successful
67
Successfulness of rifaximin in UC?
May be beneficial in UC
68
What are biologic therapies in IBD?
Anti-TNFalpha antibodies
69
Example of anti-TNFalpha antibody/biologic therapy?
Infliximab
70
MoA of anti-TNFalpha Ab? (5)
- Anti-TNF reduces activation of TNF receptors in the gut
- Reduces downstream inflammatory events
- Also binds to membrane associated TNF
- Induces cytolysis of cells expressing TNF
- Promotes apoptosis of activated T cells
71
Route of admin of infliximab?
IV
72
Half life of infliximab?
9.5 days
73
Repeat infusion frequency?
Every 8 weeks
74
Which IBD is ANTI-TNF therapy useful for
CD
75
Success of ANTI-TNFalpha in CD?
Success
76
Success of ANTI-TNFalpha in UC?
unsuccessful
77
Why isANTI-TNFalpha much more useful in CD than UC?
Crohns is TH1 driven, UC is TH2, TH2 has TNF α much less involved
78
Adverse effects of anti-TNFalpha therapy (7)
- 4x - 5x increase in incidence of tuberculosis
- Also risk of reactivating dormant TB
- Increased risk of septicaemia
- Worsening of heart failure
- Increased risk of demyelinating disease
- Increased risk of malignancy
- Can be immunogenic – azothiaprine reduces risk, but raises TB/maligancy risk
79
Combining infliximab with what improves its effectiveness?
Azathioprine
80
New targets for IBD? (4)
- Integrin (needed for cells to migrate)
- Interleukins (IL12; IL17; IL23)
- Interleukin receptors
- Janus kinase (JAK) cytoplasmic cell signalling
