GIT Lec 5 Pt 1 - Inflammatory Bowel Disease Flashcards
What is ulcerative colitis?
Ulcerative colitis is a chronic relapsing inflammatory disease which characteristically involves the rectum, but can also extend to involve the colon and even the small intestine.
What are the characterizing symptoms of UC?
- Diarrhea; either bloody or pus-containing.
- Dehydration
- Abdominal pain and cramping
- Rectal bleeding
- Fever
- Painful, urgent bowel movement
- Associated symptoms include: weight loss, skin disorders and joint pain.
What is Crohn’s disease?
It’s a disease that characteristically involves segments of the large and small intestines causing transmural involvement leading to strictures and bowel obstruction.
What is Crohn’s disease characterized by?
- Severe persistent diarrhea; either bloody or pus containing
- Abdominal pain and cramps
- Rectal bleeding
- Fatigue
- Unintended weight loss
What are the classes of drugs used in the treatment of IBD?
- Glucocorticoids:
A. Topical
B. Systemic: prednisolone and corticotropin - Aminosalicylates (ASA):
A. Prodrugs: sulphasalizine, olsalazine and balsazide - Immunomodulators:
I. Azathioprine
II. Methotrexate
III. Cyclosporine
IV. Tacrolimus - Biological therapy:
A. Anti-TNF alpha antibody: infliximab, CDP571 & Etanercept
B. Anti-adhesion therapies: anti-alpha4 integrin antibody (natalizumab) - Antibiotics: metronidazole & ciproflaxacin
- Probiotics
- Miscellaneous: thalidomide
What are the indications of glucocorticoids?
They are indicated to induce remission of acute flares in both ulcerative colitis and Crohn’s disease.
They are NOT used for maintaining the remission, only inducing it.
How can glucocorticoids be administered?
They can be administered both topically and systemically.
What is the MOA of glucocorticoids?
They work by inhibiting the gene transcription of various inflammatory mediators (like cytokines) from inflammatory cells like: eosinophils, lymphocytes and by extension plasma cells.
This action occurs via the glucocorticoid receptor in the cytoplasm which upon activation inhibits the nuclear factor-kB (NF-kB)
What are the pharmacokinetics of sulphasalazine (ASA)?
- Sulphasalazine (Salicyl-azo-sulfapyridine) consists of two components as the scientific name suggests: 5-aminosalicylic acid and sulfapyridine connected together via an azo bond.
- It is poorly absorbed in the intestine and when it reaches the colon, the colonic bacteria split the azo-bond releasing the two components.
- One metabolite is thought to have the anti-inflammatory effect while the other has the anti-microbial effect.
- It is also used as a Disease-modifying-anti-rheumatic-drug (DMARD)
- The usual dosage in UC and acute CD is as follows:
A. Dosages that induce remission: 1-2g three to four times a day
B. Dosages that maintain remission: 500mg three to four times a day
What are the adverse effects of sulphasalazine?
Dosage-dependent side effects:
1. Nausea and vomiting
2. Anorexia
3. Headaches
4. Alopecia
5. Folate-malabsorption
Dosage-independent side effects:
1. Hypersensitivity
2. Skin rashes
3. Blurred vision
4. Hemolytic anemia
5. Agranulocytosis
6. Hepatitis
7. Fibrosing alveolitis
8. Rarely colitis
9. Male infertility
What are the contraindications of sulphasalazine?
Patients with a history of sensitivity to:
1. Sulphonamides
2. Salicylates
3. Porphyria’s
What is the MOA of azathioprine?
Azathioprine is converted to 6-Mercaptopurine which is then converted in the liver to thioguanine.
Thioguanine then inhibits purines synthesis which inhibits cellular proliferation.
What are the indications of Azathioprine?
It is indicated in the following:
1. Management of active, chronic UC
2. Maintenance therapy for CD
It is used in a dose of 2mg/kg/day
What is the MOA of Methotrexate?
It is an anti metabolite. It works by reversibly and competitively inhibiting dihydrofolate reductase.
What are the indications of methotrexate?
It’s mainly used in CD.
It can be helpful in controlling relapses of CD in patients unresponsive to either glucocorticoids or Azathioprine therapy.
