Developed nation 10-40 yrs Fast food, animal fat, refined

carbohydrate Smoking NSAIDs Stress Microflora

……???

1. 16TH chromosome……CARD15/NOD2

2. IL-23 R gene

……..+Mutations

Inflammatory bowel disease

How to treat….

Crohn’s disease

Ulcerative colitis

Pathogenesis

Actual cause unknown Immune mediated

Chronic inappropriate inflammatory response with relapse and remissions

Treatment …

1. Nutritional therapy

2. Drug treatment

Nutritional treatment

Fe and Ca supplements Vitamins Minerals Low fibre diet Low lactose diet Total parenteral nutrition regimen

(severe cases)

Mode of treatment

Active cases (for inducing remission) – steroids

Maintenance of remission phase-aminosalicylates, azathioprine

Drug treatment

1. Steroids2. Aminosalicylates3. Purine analogues

Steroids Prednisolone 40mg/day Highly effective in controlling

symptoms/inducing remission in both ulcerative colitis and crohn’s disease

DOC in moderately severe exacerbations

Hydrocortisone enema/foam---topical treatment of proctitis and distal ulcerative colitis

Steroids are discontinued after remission is induced

Mesalazine is started during steroid therapy is continued to prevent relapses

Aminosalicylates

1. Sulfasalazine 2. Mesalazine

3. Olsalazine4. Balsalazine

Sulfasalazine

5-ASA + Sulfapyridine Low solubility Poorly absorbed from

ileum Sulfapyridine-only helps

to carry 5ASA to colon without being absorbed proximally

MOA

Inhibits COX,LOX. ….Cytokines,PAF,TNF-alpha,nuclear

transcription factor(NFKB) Reduce migration of inflammatory

cells Reduce mucosal secretions

Effects

Reduce no. of stools,abdominla cramps,and fever

Use

Mild to moderate exacerbations 3-4g/day……..induce remission for

few weeks Relapse common after stoppage Maintenance therapy-1.5-2g/day…

postpones relapse as long as taken Main use –maintaining

remission

ADR

Due to sulfapyridine absorbed1. Rashes2. Fever3. Joint pain4. Hemolysis5. Blood dyscrasias6. NV,headache,malaise also7. Oligospermia8. Male infertility

Mesalazine/mesalamine

5-ASA Not effective orally- Delayed release preparations by

coating with acrylic polymer Effectively deliver to distal small

bowel and colon

Daily dose-2.4g for ulcerative colitis Primary use —maintenance of

remission Mild to moderate exacerbations

ADR

Nephrotoxic Contraindicated in renal and hepatic

impairment DI- coated mesalazine may

enhance the gastric toxicity of steroids and hypoglycemicaction of sulphonylureas

5-ASA enemas 1-2g once /twice daily…..distal

ulcerative colitis, including refractory cases

Olsalazine

2 molecules of 5-ASA linked by an azo bond

Most reliable preparation of delivery of 5-ASA to the colon

But it aggravates diarrhoea

Azathioprine

Delayed response occurs after weeks or months

Lower toxicity Moderate to severe crohn’s disease

and ulcerative colitis Useful in steroid resistant cases Good remission maintenance

property

Azathioprine---6mercapto purne in liver

Inhibit purine nucleotide----inhibit lymphocyte function esp. Tcells

Thank u……….

Gopisankar.M.G.2008 MBBS