Inflammatory bowel Diseases

1. Recent Advances in Management of
Inflammatory Bowel Diseases
Mrs. Priyanka Namdeo
Assistant Professor
Department of Pharmacology

4. Inflammatory Bowel Diseases

5. ULCERATIVE COLITIS
• Limited to the large intestine (colon) and the
rectum.
• The inflammation occurs only in the innermost
layer of the lining of the intestine.
• Usually begins in the rectum and lower colon, but
may also spread continuously to involve the entire
colon.
CROHN’S DISEASE
• Transmural inflammation (inflammation may
extend through the entire thickness of the bowel
wall) of GI mucosa affect any part of the GI tract.
• Most commonly affects the end of the small
intestine (the ileum) where it joins the beginning of
the colon.
• Appear in “patches,” affecting some areas of the
GI tract while leaving other sections completely
untouched.

6. EPIDEMIOLOGY
 In the United States, it is currently estimated that about 1 –1.3 million people suffer from IBD.
 Ulcerative colitis is slightly more common in males, while Crohn’s disease is more frequent in women.
 The peak age of onset of UC and CD is between 15 and 30 years.
 The male to female ratio for UC is 1:1 and for CD is 1.1–1.8
 The risk of UC in smokers is 40% that of nonsmokers.
 Smoking is associated with a twofold increased risk of CD.
 If a patient has IBD, the lifetime risk that a first-degree relative will be affected is ~10%.

7. Etiology

8. Pathophysiology
ALTERED MUCOSAL IMMUNE RESPONSE
- Dietary and bacterial antigens penetrate into the intestinal wall and activates the immune system.
- This causes increased production of pro-inflammatory mediators which will lead to inflammation of
the mucosal layer.
Inflammation

9. Diagnosis
1. Physical Examination
2. Endoscopy
3. Biopsy
4. Radiology
5. Blood Test
MANAGEMENT The goal of treatment is to:
• Improve and maintain patients’ general well-being
• Treat acute disease:
– Eliminate symptoms and minimize
side effects and long-term adverse effects
– Reduce intestinal inflammation and if possible heal the mucosa
• Prevent complications, hospitalization, and surgery
• Maintain good nutritional status

10. Thiopurines • Azathioprine and 6-mercaptopurine
FOR CROHN’S DISEASE- 50 % patients respond and 1/2 -2/3 of them will maintain that response
FOR ULCERATIVE COLITIS- use of azathioprine is largely based on its established efficacy in CD rather any proven
benefit in UC
Methotrexate
FOR CROHN’S DISEASE- MTX 25 mg/wk IM, induced remission in 40% vs 20% in placebo at 8 weeks
- MTX 15 mg/wk IM / SC for 1-4 yrs. 65% maintained remission vs 40% in placebo group
- Oral MTX was not found effective • Used as alternative to thiopurines
FOR ULCERATIVE COLITIS - Not effective
Antibiotics
FOR CROHN’S DISEASE- Metronidazole: useful in healing perineal fistulas. Benefit not seen in active luminal crohn’s
disease.
- Ciprofloxacin: showed benefit in perianal fistula and in treatment of luminal disease.
- Rifaximin 800 mg bd Vs placebo : 62% vs 43% remission at 12 wks
FOR ULCERATIVE COLITIS - Antibiotics not effective in UC except in suppurative complications
Cyclosporine
FOR CROHN’S DISEASE - Only high doses are effective at unacceptably high cost of side effects. Other less
hazardous medications are preferred.
FOR ULCERATIVE COLITIS - Only 1 study showed response in 9 of 11 patients in 7 days with IV cyclosporine
4mg/kg/day • 50% patients required colectomy in 6 months

11. Biological therapy for IBD
Biological therapy is the use of biological agents, (e.g., antibodies and cytokines)
Anti TNF therapy is more effective when treatment is initiated early in the disease.
• Combination therapy with infliximab and azathioprine is more effective than either alone
Adalimumab • Advantages over infliximab: – induces remissions more frequently than placebo in adult patients with
CD who cannot tolerate IFX
Golimumab • Latest approval, May 2013
• Moderate to severe Ulcerative colitis (UC) with an inadequate response or intolerant to prior treatment or requiring
continuous steroid therapy
• Other anti-TNF-α antibodies in terms of its ability to inhibit both TNF-α-mediated cytotoxicity and TNF-α-mediated
endothelial cell activation.
Certolizumab pegol • Approved in April 2008

12. Anti adhesion molecules
• Natalizumab : Approved by FDA in 2008
- Humanized monoclonal antibody against α4- integrin, Inhibits leukocyte migration into
inflammed tissue , inhibits lymphocyte trafficking into site of inflammation
• Vedolizumab : Approved by FDA in 2014 for Crohn’s disease and ulcerative colitis. Gut
selective, no effect on CNS
Anti interleukins
• Ustekinumab: Human anti IL-12/IL-23 monoclonal antibody
Janus Kinase (JAK) inhibitor
Janus kinase (JAK) signal inhibitors: As most of the available biological therapies are directed at
the blockage of only one cytokine, JAK family of kinases mediate signal transduction activity for
multiple cytokines
Tofacitinib: oral JAK inhibitor showed promise for UC and CD with response rates 30-80%
Nutritional therapy
• Dietary pattern has effect on intestinal microbial enterotype
• Alteration of microbiome with diet may be a strategy to prevent or manage crohn’s disease

13. GPAT ORIENTATION
GPAT.…. Graduate Pharmacy Aptitude Test.
 Important for admission in Master courses.(M.Pharm, M.tech)
 B.Pharm completed & final year B. Pharm students ONLY are eligible for appearing in GPAT
Exam.
 B. Pharm 1st year to 3rd year students are NOT ELIGIBLE.
 Online GPAT conducted by AICTE, New Delhi
 125 MCQ’s (each for 4 marks) - 3 hrs duration – negative marking (wrong answer - 1 mark
deduction).
 No deduction of marks if not attempted.
 GPAT score is valid for ONE YEAR ONLY from the date of announcement of the result.
 There is no provision for re-grading/re-checking or re-totaling. PAYAL H. PATIL 2

15. How to start?
Refer Syllabus 1st.
Use following types of books - (1) Fundamental and basic concepts (2) Problem oriented-the one’s used for GPAT
Previous questions papers - GATE- A companion(by Inamdar madam) helpful to understand Logic behind answer
and type of questions frequently asked.
Keep contact with some experts and GPAT experienced persons.
Start from the basic chapters.(like study nomenclature method, basic rings, types of receptors, chemical &
Pharmacological classification of drugs, etc.
Refer 2 or 3 books, keep 1 book as standard and add to it points from other.
Note down or mark the probable concepts(definitions, unit, dimensions, theories, formulae, etc.
Solve problems as much as possible.
Use tricks in solving problems.
Self assessment-most important.
Continue the self assessment until getting a very good score.
Solve more and more problems, discover more and more new tricks…
REMEMBER….. “ No study No problems,
less study more problems,
more study few problems….”

16. What to refer ?

17. SUBJECTS