Inflammatory Bowel Disease Flashcards
What are the major forms of IBD?
- ulcerative colitis
- crohn’s disease
What are the risk factors of IBD?
- Genetic predisposition – in 163 loci.
- Environmental factors – smoking (CD especially), diet/obesity, gut microbiome.
- Obesity – ONLY for CD and not for UC
Describe the pathogenesis of IBD
defective interactions between the mucosal immune system and the gut flora -> leads to disrupted innate immunity -> uncontrolled inflammation -> physical damage
What are the features of ulcerative colitis?
- Th2-mediated
- Dependant on IL-5 & IL-13 cytokines
- Affects mucosa and submucosa
- Starts in rectum, spreads proximally
- Always continuous
- Surgery can be curative
What are the features of Crohn’s disease?
- Th1-mediated -> worst inflammatory response
- Dependant on TNF-a cytokine
- Penetrates all through gut wall
- Affects any point of the GI tract
- Causes patchy (not continuous) inflammation - Hard to cure with surgery and often reoccurs
- Abscesses, fissures and fistula more common
What are the clinical features of IBD?
- Right iliac fossa pain
- Skin rash
- Diarrhoea, blood, mucus
- Weight loss
- Arthritis, arthralgia
- Abdominal pain
- Anaemia
What are the supportive therapies for IBD?
- Fluid/electrolyte replacement
- Blood transfusion or oral iron
- Nutritional support – as malnutrition is common
What are the symptomatic treatments?
- glucocorticoids e.g prednisolone
- aminosalicylats e.g mesalazone
- immunosuppressives e.g azathioprine
What are some potentially curative treatments/
- manipulation of microbiome
- drugs :
> anti-TNF e.g infliximab
> anti-a-4-integrins e.g natalizumab
How are aminosalcylates used in IBD?
- Ulcerative colitis – first line in inducing and maintaining remission with a good evidence base
- Crohn’s disease – non-effective in active disease but may help maintain surgically-induced remission
- anti-inflammatory drugs
What are the mechanisms of action of aminosalcyates?
- Inhibition of 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
Describe the pharmakokinetics of 5-ASA (mesalazine) and derivatoves (olsalazine)
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
How are glucocorticoids used in IBD?
Ulcerative colitis – use is in decline, can be used topically or via IV. 5-ASA seems to be superior
Crohn’s disease – drug of choice for inducing remission, SEs likely if used to maintain remission
Describe the pharmacokinetics of glucocorticoids
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 -> Budesonide has fewer SEs than Prednisolone
> Oral GCs are better than Budesonide at inducing remission in ACTIVE Crohn’s disease
> Budesonide is a better than placebo at preventing CD relapse
What are examples of immunosuppressives used in IBD?
Azathioprine – Both UC and CD
- CD - used to maintain remission – superior to placebo & Budesonide in CD
- UC - useful for maintaining remission in SOME patients
- Considered a “Steroid-sparing agent”
- Slow onset of action – 3-4 months’ treatment is required before clinical benefits are seen
Methotrexate – efficacy in SOME IBD patients
- A folate antagonist
- Reduces the synthesis of thymidine and other purines
- Not widely used due to significant side effects (in over 40% of patients)
Cyclosporine – UC
