8. Aminosalicylates
Local effect on mucosa in reducing inflammation
Sulfasalazine contains sulfapyridine and 5-aminosalicylic acid 5-ASA. The 5-
ASA accounts for its therapeutic benefits for IBD. Its exact mechanism of
action is unknown, but topical application to the intestinal mucosa suppresses
proinflammatory cytokines and other inflammatory mediators.
When given orally, 5-ASA alone is absorbed before it reaches the lower GI tract
where it is needed. When combined with sulfapyridine, 5-ASA reaches the
colon. However, many people are unable to tolerate sulfapyridine.
Newer preparations have been developed to deliver 5-ASA to the terminal
ileum and colon olsalazine(Dipentum), mesalamine (Pentasa) and balsalazide
(Colazal) These drugs are as effective as sulfasalazine and are better tolerated
when administered orally
10. Sulfasalazine
Oral use
Mesalamine (5-aminosalicylic acid)
{Asacol & Pentasa } timed released
need PH >7.
Oral delayed release capsules
Enema
Olsalazine.
5-ASA-n=n-5-ASA
Bacterial flora breaks it into 5-ASA
(COLON)
Aminosalicylates
11. Mesalamine
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
12. Indications
Inducing remission in mild UC/CD (higher
doses)
Maintaining remission in UC
Less effective for maintenance in CD
14. Antimicrobials are used to treat CD, although no
specific infectious agent has been discovered.
Metronidazole (Flagyl), ciprofloxacin (Cipro) and
clarithromycin(Biaxin) have been used successfully
with CD, but have not been shown to be as effective for
UC.
21. Immunomodulator agents
Thiopurines (Azathioprine & 6-mercaptopurine).
Methotrexate.
calcineurin inhibitors (Cyclosporine & Tacrolimus)
Immune modifiers: uses
• Can be used to reduce or eliminate corticosteroid dependence in patients with IBD.
• Can be used in selected patients with IBD when 5-ASAs and corticosteroids are
either ineffective or insufficient to control.
• Can be used to maintain remission in CD and in UC when 5-ASAs fail.
• Are an alternative treatment for CD relapses after corticosteroid therapy.
• Can be used for corticosteroid dependence, to maintain remission and allow
withdrawal of corticosteroids.
• Either thiopurines or methotrexate can be used concurrently with biologic therapy to
enhance effectiveness and reduce the likelihood of antibody formation.
22. Thiopurines
Are given orally and take 3-6 months to
exhibit full effectiveness.
Azathioprine
Inhibit ribonucleotide synthesis; induce T
cell apoptosis by modulating cell (Rac1)
signalling
23. Indications
Steroid sparing agents
Active disease CD/UC
Maintenance of remission CD/UC
Generally continue treatment x 3-4years
24. Caclineurine Inhibitors
Ciclosporin
MOA:inhibitor of calcineurin preventing clonal
expansion of T cells
In UC
Use of CSA is limited to acute (corticosteroid-
refractory) severe colitis.
No value in CD
Tacrolimus in CD.
25. Methotrexate
MOA: inhibitor of dihyrofolate reductase;
anti-inflammatory
Inducing remission/preventing relapse
in CD
Refractory to or intolerant of
Azathioprine
26. Safety and Toxicity Considerations
1. Feagan BG, et al. Cochrane Database Syst Rev. 2012;10:CD000544. 2. Gisbert JP, et al. Inflamm Bowel Dis.
2007;13(5):629-638. 3. World MJ, et al. Nephrol Dial Transplant. 1996;11(4):614-621. 4. Kotlyar D, et al, Clinical
Gastroenterology and Hepatology. 2015;13:847–858. 5. Lichtenstein GR, et al. Am J Gastroenterol.
2009;104(2):465-483. 6. Methotrexate injection USP [package insert]. Lake Forest, IL: Hospira, Inc.; 2011.
Mesalamine1 5-ASA AZA/6-MP4 MTX5-6
Low incidence of
adverse effects
Diarrhea,
headache, nausea
most common
Abdominal pain
Dyspepsia
Acute tolerance
syndrome
Nephrotoxicity
Pancreatitis
Incidence of kidney
impairment occurs in
less than 1 in 200
(<0.5%) patients
treated with 5-ASA2
Pancreatitis (4%)
Allergy (2%)
Bone marrow
suppression (4%)
Liver toxicity (9%)
Serious infection (2%)
Nausea/vomiting
Bone marrow
suppression
Liver scarring
Clinically important
interstitial nephritis
occurs in 1 in 500
patients―50% of cases
occur in the first year,
and others may occur
many years later3
Increased risk of
lymphoma
Nonmelanoma skin
cancer
Abnormal Pap smears
Contraindicated if
attempting pregnancy
28. Biologics
Infliximab (Remicade) is the first major biologic drug
therapy (immunomodulator) to be approved for the
treatment of IBD. Infliximab is a monoclonal antibody
to the cytokine tumor necrosis factor. It is given IV to
induce and maintain remission in patients with active
CD and in patients with draining fistulas who do not
respond to conventional drug therapy
31. Ongoing Therapeutic Monitoring
• Periodic kidney function w/urine + blood tests
Mesalamines
• Bone health issues
Corticosteroids
• TPMT, CBC, LFT during therapy
Thiopurines
• CBC, LFT, renal function during therapy, alcohol avoidance, pregnancy prevention
Methotrexate
• Consider annual TB test
• Coccidiomycosis + histoplasmosis testing for patients living or who have lived in high
prevalence regions
Anti-TNF
• Monitor for PML, LFTs, TB screening according to local practice, infection,
neurological symptoms
Anti-Integrin
TPMT, thiopurine methyltransferase; CBC, complete blood count; LFT, liver function tests;
TB, tuberculosis; TNF, tumor necrosis factor.
32. Treatment Concepts
Treatment paradigms and therapeutic options for IBD have evolved rapidly
over the past decade.
1) An increased emphasis on dual therapy to reduce immunogenicity,
improve efficacy and preserve durability.
2) Emerging use of therapeutic drug monitoring to optimize response and
guide management of loss of response.
3) Increased emphasis on mucosal healing as an important treatment goal as
it correlates with surgical-free outcomes with minimal intestinal damage and
patient disability.
. Mucosal healing (i.e. absence of ulceration or erosion) is important in the clinical
management of IBD—achieving mucosal healing has been unequivocally associated
with better outcomes and has become an important treatment goal.
35. ULCERATIVE COLITIS- MANAGEMENT
a) Topical aminosalicylate
alone (suppository or
enema
b) ?ADD PO
aminosalicylate to a topical
aminosalicylate OR
c) consider an PO
aminosalicylate alone
a) PO Aminosalicylate
- High induction
dose .
b) ?ADD topical
Aminosalicylate OR
PO beclometasone
dipropionate
- If no improvement 72 hrs
despite IV Hydrocortisone
OR
-Symptoms worsen to
pancolitis:
a) ADD IV Ciclosporin to IV
steroids
36. Management of CD
to induce remission
1. oral high dose of 5-ASA
1. +- oral corticosteroids reducing over 8/52
2. Azathioprine
3. iv steroids/ metronidazole/elemental
diet/surgery/infliximab
38. Crohn’s Disease Therapies
Therapy is modified according to severity at presentation or failure at prior step
Pentasa
Biologics or
Thiopurine +
Corticosteroid
Biologics +
Thiopurine +
Corticosteroid
Disease Severity
at Presentation
Severe
Moderate
Mild
Biologics or
Thiopurine
Pentasa
Biologics
Induction
Maintenance
For terminal ilium or colonic lesions only
39. Sequential Therapies for UC
Therapy is stepped up according to severity at presentation or failure at prior step
Aminosalicylate
Aminosalicylate
or Thiopurine +
Corticosteroid
Biologics +
Thiopurine +
Corticosteroid
Disease Severity
at Presentation
Severe
Moderate
Mild
Aminosalicylate
or Thiopurine
Aminosalicylate
Biologics
Induction
Maintenance
Colectomy
42. Surgery in CD
Surgical options are:
— Drainage of abscesses
— Segmental resection
— Bowel-sparing stricturoplasty
— Ileorectal or ileocolonic anastomosis
— Ileocolic resection .
— Temporary diverting ileostomy/colostomy in severe perianal
fistula
— Laparoscopic ileocecal resection
43. Surgery in UC
— Total proctocolectomy plus permanent ileostomy.
— Ileal pouch–anal anastomosis (IPAA).
— Segmental resection can be considered for localized
neoplasms in the elderly, or in patients with extensive
comorbidity.
44. UC
Indications for Surgery:
Unresponsive to medical treatment
Significantly affecting quality of life
Growth retardation in Children
Life-threatening complications...
Bleeding
Toxic Megacolon
Impending perforation
Carcinoma
45. Total Proctocolectomy
-The colon and rectum are removed and the anus closed. The terminal ileum is brought out through the
abdominal wall and a permanent ileostomy formed.
Ileorectal Anastomosis
-The colon is resected, leaving a rectal stump. The terminal ileum is then anastomosed to this stump.
This is an early alternative to total proctocolectomy, however, it has several problems. The remaining
rectum is often still affected by the disease, and further treatment, even eventual resection, is often
required. There is also a significant incidence of rectal cancer among clients who had this surgery.
Ileal Pouch-Anal Anastomosis
-Also known as the J pouch; prevents the need for an ostomy and preserves the rectal sphincter muscle.
The rectal mucosa is excised and the colon is removed. An ileoanal reservoir is then created in the anal
canal, and a temporary loop ileostomy is formed. After healing has taken place, the ileostomy is
reversed and stool drains into the reservoir, which is created by suturing two loops of bowel together.
Continental ileostomy or Kock Pouch
-A procedure in which a reservoir or pouch is constructed from a loop of ileum. This allows stool to be
stored intra-abdominally until it is drained through a nipple valve made from an intussucepted portion
of ileum. This has advantages because the client does not need to wear an external pouch, has minimal
skin problems, and usually has no leakage of stool or flatus. The client drains the pouch several times a
day using a catheter, usually when a feeling of fullness occurs.
47. Mediterranean Diet
Primarily plant-based foods
(fruits and vegetables, whole grains, legumes and nuts)
Replace butter with healthier fats (olive oil)
Herbs and spices instead of salt
Limit red meat (beef and pork) to
no more than a few times a month
Fish, chicken, and turkey at least twice a week
48. Other Dietary Considerations
Eat smaller, more frequent meals
Drink plenty of fluids
Consider multivitamin once daily
Talk to a dietitian
Probiotics once daily
Dairy, gluten, excessive caffeine /
carbonation can exacerbate symptoms
49. Lifestyle Changes
Stress Management
− Exercise (20 minutes / day)
− Relaxation and breathing exercises (yoga and meditation)
Smoking Cessation / avoid second hand smoke exposure
Avoid unnecessary antibiotic exposure
Utilize Patient Education Resources (CCFA)
50. Final Thoughts
Early diagnosis / avoid treatment delays
Treating IBD patients is a collaborative approach
between primary care and GI and other specialists
Increase patient satisfaction
Aminosalicylates- in 1977 S Kalsi demonstrated that 5-aminosalicylic acid (5-ASA) and mesalazine was the therapeutic compound in sulfasalazine
Corticosteriods-
Immune supperessive drugs- azathioprine, methotrixate, tacrolimus
Biologic- Infliximab
Treatment of acute UC- NICE
1) mild to moderate first presentation or inflammatory exacerbation of proctitis or proctosigmoiditis:
a) offer a topical aminosalicylate[1] alone (suppository or enema
b) consider adding an oral aminosalicylate[2] to a topical aminosalicylate or
c) consider an oral aminosalicylate[2] alone 2) mild to moderate first presentation or inflammatory exacerbation of left-sided or extensive ulcerative colitis: a) offer a high induction dose of an oral aminosalicylate b) consider adding a topical aminosalicylate or oral beclometasone dipropionate 3) ACUTE SEVERE COLITIS: Consider adding intravenous ciclosporin[6] to intravenous corticosteroids or consider surgery
for people:
-who have little or no improvement within 72 hours of starting intravenous
corticosteroids or
-whose symptoms worsen at any time despite corticosteroid treatment
