Drug Treatment of Inflammatory Bowel Disease

DRUG TREATMENT OF
INFLAMMATORY BOWEL
DISEASE
Objectives
 Describe the mechanism of action,
pharmacokinetics and adverse effects
of drugs in IBD
INFLAMMATORY BOWEL DISEASE
 Ulcerative Colitis
 Crohn’s disease
Inflammatory bowel disease
 Inappropriate inflammatory response to
intestinal microbes in a genetically
susceptible host
Ulcerative colitis
- diffuse mucosal
inflammation
- limited to colon
- defined by location
(eg
proctitis;pancolitis)
Crohn’s disease
- patchy transmural
inflammation
- fistulae, strictures
- any part of GI tract

AIMS OF THERAPY
 Suppress inflammatory response
 Suppress the immune reaction

 Aminosalicylates corticosteroids
 Acute maintenance acute

Aminosalicylates
• precise MOA unknown
• act on epithelial cells
• anti-inflammatory
• modulate release of cytokines and reactive

oxygen species
Aminosalicylates
 Local effect on mucosa in reducing inflammation
Sulphasalazine
 Broken down by gut bacterial azoreductase to 5-
aminosalicylate & sulphapyridine
SULFASALAZINE
Bacterial Flora Bacterial azoreductase

(Colon)
Sulfapyridine 5-aminosalicylic Acid
Absorbed Acts through the lumen
Systemic Adverse Effect Anti-inflammatory Effect

Aminosalicylates
 5-ASA absorbed in small intestine
 Acetylated by N- acetyltransferase-1
 Excreted in urine
Indications
 Maintaining remission in UC
 Reduce risk of colorectal cancer by 75%

(long term Rx for extensive disease)
 Less effective for maintenance in CD
 Inducing remission in mild UC/CD (higher

doses)
Contraindications
/cautions
 5-ASA
- Salicylate hypersensitivity
 Sulfapyridine
- G6PD deficiency (haemolysis)
- Slow acetylator status ( risk of
hepatic and blood disorders)
Adverse effects
 Dose-related
 Idiosyncratic (rare)
- blood disorders
- skin reactions – lupus like syndrome;

Stevens-Johnson syndrome; alopecia
Blood disorders
 Agranulocytosis; aplastic anaemia;
leucopenia; neutropenia;
thrombocytopenia; methaemoglobinemia
 Patients should advised to report any

unexplained bleeding; bruising; purpura;
sore throat; fever or malaise
Steven’s Johnson syndrome
 immune-complex–
mediated
hypersensitivity
 erythema
multiforme
 target lesions,
mucosal
involvement
Newer formulations
 Mesalazine (5-ASA)
 Balsalazide (a prodrug of 5-ASA)
 Olsalazine (5-ASA dimer)

Mesalazine
 Available as
 Enteric-coated tablets (for ileal Crohn’s disease)
 Slow release tablets (for proximal bowel Crohn’s)
 Enemas, suppositories (for distal colonic disease)
 Used when sulphasalazine can not be

tolerated
Aminosalicylates
Sulfasalazine
 Oral use
Mesalamine (5-aminosalicylic acid).
 Oral delayed release capsules
 Enema
Olsalazine.
 5-ASA-n=n-5-ASA
 Bacterial flora breaks it into 5-ASA
Anti-inflammatory &
Immunosuppressive Drugs
 Corticosteroids
 Prednisolone
 Hydrocortisone
Corticosteroids
USES
 Remission Induction
 Route of Administration
Oral
Intravenous
Topical (Enema)
Indications
 Moderate to severe relapse UC & CD
 No role in maintenance therapy
 Combination oral and rectal

Immunomodulators
 Azathioprine
 Cyclosporine
 Infliximab (Anti-TNF-)
Thiopurines
Azathioprine
 MOA: inhibit ribonucleotide synthesis;

induce T cell apoptosis by modulating
cell (Rac1) signalling
Indications
 Steroid sparing agents
 Active disease CD/UC
 Maintenance of remission CD/UC
 Generally continue treatment x 3-4years

Ciclosporin
 MOA:inhibitor of calcineurin
preventing clonal expansion of T
cells
 Indicated in Severe UC
 No value in CD
Methotrexate
 MOA: inhibitor of dihyrofolate reductase;
anti-inflammatory
 Inducing remission/preventing relapse

in CD
 Refractory to or intolerant of
Azathioprine
Infliximab
 Indicated active and fistulating CD
- in severe CD refractory or intolerant
of steroids & immunosupressants
- for whom surgery is inappropriate
 MOA: anti-TNF monoclonal antibody
 Potent anti-inflammatory
Antibiotics
 Metronidazole
 Ciprofloxacin
 Clarithromycin
 “Probiotics” (administration of “healthy”

bacteria)
 Summary
Drugs for IBD
 Aminosalicylates
 Glucocorticoids
 Immunosuppressives
 Cytokine modulators
 Antibiotics
Management of UC
to induce remission
1. oral +- topical 5-ASA

2. +- oral corticosteroids
3. Azathioprine
4. iv steroids/Colectomy/ ciclosporin
(severe)
Maintaining remission
1. oral +- topical 5-ASA
2. +- Azathioprine (frequent relapses)

Management of CD
to induce remission
1. oral high dose of 5-ASA
2. +- oral corticosteroids reducing over 8/52
3. Azathioprine
4. iv steroids/ metronidazole/elemental
diet/surgery/infliximab
Maintaining remission
+- Azathioprine (frequent relapses)
Methotrexate (intolerant of
azathioprine)
Infliximab infusions (8 weekly)

Drug Treatment of Inflammatory Bowel Disease

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Drug Treatment of Inflammatory Bowel Disease

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DRUG TREATMENT OF

- any part of GI tract

 Suppress the immune reaction

 Acute maintenance acute

• act on epithelial cells

• modulate release of cytokines and reactive

Bacterial Flora Bacterial azoreductase

Sulfapyridine 5-aminosalicylic Acid

Absorbed Acts through the lumen

Systemic Adverse Effect Anti-inflammatory Effect

 Reduce risk of colorectal cancer by 75%

 Less effective for maintenance in CD

 Inducing remission in mild UC/CD (higher

- skin reactions – lupus like syndrome;

 Patients should advised to report any

 Balsalazide (a prodrug of 5-ASA)

 Olsalazine (5-ASA dimer)

 Used when sulphasalazine can not be

 No role in maintenance therapy

 Combination oral and rectal

 MOA: inhibit ribonucleotide synthesis;

 Active disease CD/UC

 Maintenance of remission CD/UC

 Generally continue treatment x 3-4years

 Inducing remission/preventing relapse

 MOA: anti-TNF monoclonal antibody

 “Probiotics” (administration of “healthy”

1. oral +- topical 5-ASA

1. oral +- topical 5-ASA

2. +- Azathioprine (frequent relapses)

1. oral high dose of 5-ASA

2. +- oral corticosteroids reducing over 8/52

+- Azathioprine (frequent relapses)

Infliximab infusions (8 weekly)

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