Inflammatory Bowel Disease Flashcards
What are the two major forms of inflammatory bowel disease
Ulcerative Colitis (UC) Crohn’s Disease (CD)
What are the risk factors for IBD
Genetics
Environmental Factors:
Smoking (more prevalent in CD)
Diet/obesity
Gut microbiome
Describe the pathogenesis of IBD
Potentially due to a defective interaction between the mucosal immune system and the gut flora
- Disrupted innate immunity
- Uncontrolled inflammation
- Physical damage to epithelium and leakiness of tight junctions
Describe ulcerative colitis (mediators, affected tissues, distribution, continuity)
Th2 mediated, dependent on cytokines IL-5 and IL-13
Affects mucosa and submucosa
Always starts in the rectum and spreads proximally
Continuous
Describe Crohn’s disease (medators, affected tissues, distribution, continuity )
Th1 mediated, dependent on cytokine TNF-alpha
Penetrates all the way through the gut
Affects any point in the GI tract – from mouth to anus
Skips lesions
Describe how IBD presents clinically
Abdominal pain and crampitng Diarrhoea, bloody faeces Bloating Rectal abscess Fever Weight loss
What is the first line treatment for IBD patients who present with bloody diarrhoea
Fluid/electrolyte replacement
Blood transfusion/iron replacement
What is the first line treatment for IBD patients who appear malnourished
Nutritional support
What are the three classes of drugs used in symptomatic treatment for IBD
Glucocorticoids
Aminosalicylates
Immunosuppressives
What are glucocorticoid drugs and give examples of glucocorticoids used in IBD treatment
Anti-inflammatory immunosuppressants
Prednisolone, fluticasone, budesonide
Describe the pharmacokinetics of glucocorticoids in IBD treatment
High hepatic first pass metabolism means that little active glucocorticoid escapes into the systemic circulation
Describe the use of glucocorticoids in ulcerative colitis
Aminosalicylates have been proven to be better
Used topically normally and IV if severe
Describe the use of glucocorticoids in Crohn’s disease
Drug of choice in inducing remission
High chance of side effects
How are the side effects of glucocorticoids minimised
Topical admin
Low dose combinations
Topical/oral admin with first pass metab
Compare budenoside to prednisolone
Budesonide has fewer side effects than prednisolone but prednisolone is better than inducing remission so decisions are made case by case
Give examples of aminosalicylates used in IBD treatment and where are they absorbed
Mesalazine or 5-aminosalicylic acid (5-ASA)
Absorbed in the small bowel and colon
What gives aminosalicylates their anti-inflammatory effect
Inhibition of IL-1, TNF-alpha and Platelet Activating Factor Decreased antibody secretion Non-specific cytokine inhibition Reduced cell migration (macrophages) Inhibition of localised immune response
Describe the use of aminosalicylate in ulcerative colitis
First line in inducing and maintaining remission
Describe the use of aminosalicylate in Crohn’s disease
Effectiveness is questioned in active disease
Thought to help maintain surgically induced remission
Give examples of immunosuppressives used in IBD
Azathioprine
Methotrexate
Cyclosporin
Describe the use of azathioprine in IBD
Maintains remission in CD and some UC patients
Describe how azathioprine is activated
activated in vivo by gut flora to 6-mercaptopurine (purine antagonist) - interferes with DNA synthesis and cell replication
What does azathioprine impair
cell- and antibody-mediated responses, lymphocyte proliferation, mononuclear cell infiltration
What does azathioprine enhance
T cell apoptosis
What proportion of patients stop treatment using azathioprine due to side effects and what might these be
Pancreatitis
Bone marrow suppression
Hepatotoxicity
Increased risk of lymphoma and skin cancer
Which drugs is contraindicated for use with azathioprine
Allopurinol (used to treat gout) interacts with Azathioprine
What type of drug is methotrexate and what does it do
Folate antagonist
Reduces synthesis of purines, interfering with DNA synthesis and replication
Give examples of potential curative therapies of IBD
Manipulation of the gut microbiome
Biological therapies
Anti-TNF alpha e.g. infliximab
Anti-alpha4-inteferin e.g. natalizumab
Describe the manipulation of the gut microbiome in IBD
Nutrition Based Therapies (exclusive enteral nutrition EEN)
Probiotic therapy
Faecal Microbiota Replacement Therapies
What is rifamixin and how does it work
Antibiotic treatment for IBD
Binds to RNA polymerase and interferes with transcription
Induces and sustains remission in moderate CD
Describe biological therapies for IBD
Anti-TNF-alpha antibodies: Infliximab and Adalimumab
Successful in the treatment of CD - Responds within 6 weeks
Potentially curative
Some evidence of effectiveness in UC
What is the mechanism of action of biological therapies for IBD
Causes downregulation of many cytokines - reduced leukocyte activation
Induces cytolysis of TNF-alpha cells and apoptosis of activated T cells
What are the side effects of using biological therapies for IBD
Increased risk of septicaemia
Worsening heart failure
Increased risk of demyelinating disease
Increased risk of malignancy
