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1

Treatment of Ulcerative Colitis and Crohn’s Disease
5 drugs

1. Aminosalicylates
2. Corticosteroids
3. Antibiotics
4. Immunosuppresive agents
5. Biological Agents

2

Drugs that are used for treatment are based on?
4

1. Severity of disease
2. Ulcerative colitis
3. Crohn’s disease location of lesions
4. Exacerbation vs. maintenance therapy

3

Drugs used for treatment of inflammatory bowel disease
1. Aminosalicylates
-used how? 2
2. Corticosteroids
-Used how?
-Should not be used for what?

1.
-Mild to moderate UC and CD exacerbations
-Maintenance of remission
2.
-Treatment of UC and CD acute exacerbations
-Should not be used chronically to maintain remission

4

Drugs used for treatment of inflammatory bowel disease
1. Antibiotics
-Used for?
2. Immunosuppresive agents
-Used for?

1. Acute exacerbations and maintenance of remission
2. To maintain remission

5

Drugs used for treatment of inflammatory bowel disease
1. IV cyclosporine
used for?
2. Immune modifiers used for?

1. Severe active steroid refractory UC

2. Maintain remission in steroid refractory UC and CD

6

Treatment Options for Crohn’s and Ulcerative Colitis:
Describe treatment of Distal UC
1. Mild
2. Moderate
3. Severe
4. Remission

Severity of Disease
Distal UC

1. Mild
Oral/rectal aminosalicylate or rectal corticosteroid

2. Moderate
Oral Aminosalicylate and oral/rectal steroids and/or immunosuppressive

3. Severe
IV corticosteroids with/without IV cyclosporine

4. Remission
Oral/rectal aminosalicylate with/without oral immunosuppressive

7

Treatment Options for Crohn’s and Ulcerative Colitis:
Describe treatment of Extensive UC?
1. Mild
2. Moderate
3. Severe
4. Remission

Extensive UC
1. Mild- Oral Aminosalicylate

2. Moderate- Oral Aminosalicylate and oral steroids and/or immunosuppressive

3. Severe- IV corticosteroids with/without IV cyclosporine

4. Remission- Oral/rectal aminosalicylate with/without oral immunosuppressive

8

Treatment Options for Crohn’s and Ulcerative Colitis:
Describe treatment of CD?
1. Mild
2. Moderate
3. Severe
4. Remission

CD
1. MIld- Oral Aminosalicylate with/without antibiotics

2. Moderate- Oral Aminosalicylate and oral steroid and/or immunosuppressive

3. Severe- IV corticosteroids with/without IV cyclosporine

4. Remission- Oral Aminosalicylate with/without oral immunosuppressive

9

What are the Aminosalicylates?
4

1. Sulfasalazine (Azulfidine)
2. Mesalamine (Asacol, Pentasa)
3. Olsalazine (Dipentum)
4. Basalazide (Colazal)

10

Aminosalicylates clinical uses
2

1. Induce and maintain remission in UC
2. Efficacy in Crohn’s is not well established, but often used as 1st line tx of Crohn’s involving the colon or distal ileum.

11

Aminosalicylates forms of administration?
3

1. PO
2. Enema
3. Suppository

12

Aminosalicylates: Sulfasalazine (Asulfidine)
1. Preg cat?
2. Converted to what in the proximal colon?
3. Take how many times daily?
4. Contraindication?

1. Pregnancy cat. B (Sulfapyridine-mesalamine compound)

2. Converted to mesalamine in the proximal colon

3. Tablets administered 4 times daily

4. Contraindicated in sulfa allergy

13

Aminosalicylates: Mesalamine (Asacol, Pentasa)
1. Preg cat?
2. Poorly absorbed in the GI tract so works primarily like a topical agent with what kind of effects?
3. Describe the four ways of administration?

1. B
2. limited systemic SE and drug interactions
3.
-Oral tablets (Asacol)
released in the distal ileum and colon

-Oral capsules (Pentasa)
released in the proximal small intestine and throughout the colon

-Enema
Can reach distal and sigmoid colon, administered at bedtime
Rectal suppositories

-Primarily used for UC proctitis

14

Aminosalicylates: Basalazide (Colazal)
1. Preg cat?
2. Converted to mesalanine where?

Olsalazine (Dipentum)
1. Preg cat?
2. Converted to mesalanine where?


These 2 drugs are not used as much as the others due to the increased cost but no added efficacy
Both are poorly absorbed in the GI tract so work primarily like a topical agent with limited systemic SE and drug interactions

Basalazide (Colazal)
1. Pregnancy cat. B
2. Converted to mesalamine in the proximal colon

Olsalazine (Dipentum)
1. Pregnancy cat. C
2. Converted to mesalamine in the proximal colon

15

MOA Aminosalicylates
3

1. Blocks prostaglandin production
2. Perhaps interferes with production of inflammatory cytokines
3. May inhibit natural killer cells, lymphocytes and macrophages


Exact mechanism unknown

16

Contraindications to Aminosalicylates
3

1. Aspirin or other salicylate allergy
2. Glucose-6-phosphate dehydrogenase deficiency
3. Sulfasalazine is contraindicated with a history of sulfa allergy

17

Dosing of Aminosalicylates?
1. What must we dose at?
2. SE increase with what?

1. Must be used at max doses for maximum therapeutic benefit


2. Side effects increase as the dose increases


-Dosing varies from once daily to four times daily depending on the formulation

18

Side effects of sulfasalazine 5


Severe rxns? 5


What do we need to supplement with?

1. Worst side effect profile of all the aminosalicylates
2. Nausea, Vomiting
3. Photosensitivity, oligospermia
4. Skin discoloration
5. Decreased folate levels

Severe:
1. Steven-Johnson syndrome,
2. crystalluria,
3. pancreatitis,
4. hepatitis,
5. bone marrow suppression


Need to take a folic acid supplement

19

What do we need to monitor with Sulfasalazine and how often? 2



Periodically what else? 2

1. CBC with differential,
2. LFTs prior to therapy then every other week for 3 months, then every month for 3 months, then quarterly


Periodic renal and LFTs

20

Side effects of mesalamine & it’s compounds

Mesalamine 4

Olsalazine 1

Balsalazide 1

Rarely these can be associated with what?

Mesalamine
1. Headache,
2. malaise,
3. abdominal pain and
4. diarrhea

Olsalazine
1. Similar to mesalamine but has more severe secretory diarrhea

Balsalazide
Similar to mesalamine
1. If capsules opened and sprinkled in food may cause staining of the teeth

Rarely can be associated with renal impairment

21

Mesalamine
No specific recommendations on how frequent to monitor these labs
-Which ones? 3

1. Renal function prior to and during therapy
2. CBC
3. Hepatic function

22

Corticosteroids
1. Used for what?
2. Short term side effects? 6
3. Long term side effects? 5

1. Used for acute exacerbations
Not used for maintaining remission
2. Short term side effects
-Increased glucose levels,
-increased appetite,
- insominia, anxiety,
- tremors,
-increased fluid retention,
-increased blood pressure

Long term side effects
-Decreased bone mineral density,
-fat redistribution,
-ulcers from decreased prostaglandin production,
-hypertriglyceridemia,
-hirsutism

23

Prednisone (Deltasone) and Prednisolone (Prelone) are most commonly used oral medications
1. Initial dose? then what?
2. IV formulas? 2

1. 40-60mg/d initially
Taper with patients response

2. IV – Hydrocortisone (Solu-Cortef) and Methylprednisolone (Solumedrol)

24

1. Budesonide (Entocort) is what?
-It is used how for treatment?

Budesonide (Entocort)
1. Controlled release with limited systemic absorption
-Has been used as the treatment of choice in patients with mild to moderate CD in combo with 5-ASA or as mono therapy

25

What are the topical steriods?
3


What is this used to treat?

1. Cortenema,
2. Cortifoam,
3. Anusol-HC suppositories
-Hydrocortisone enemas, foam or suppositories

1. For IBD involving the rectum/sigmoid colon
Sometimes referred to as topical

26

Antibiotics are generally used for the treatment of what?

1. Used generally for treatment of Crohn’s disease that does not respond to 5-ASAs after 3-4 weeks or if the patient is intolerant to 5-ASAs

Efficacy in Ulcerative colitis has not been established

27

What antibiotics are used in the treatment of Crohn's?
2

1. Cipro
2. Metronidazole (Flagyl)

28

1. Why do we use cipro for crohns?
2. May take up to how long for remission?

1. May have some immunosuppressive properties
2. May take up to 6 weeks for remission

29

1. HOw should we administer Flagyl?
2. May have what kind of properties?
3. May take how long to respond to therapy?
4. Duration of therapy may be up to how long?

1. Start at a higher dose and decrease after response is noted
2. Likely also has some immunosuppressive properties
3. May take 1-2 months for response to therapy
4. Duration of therapy may be up to 12 months

30

What are the Immune modifiers?
4

1. Azathioprine
2. 6-mercaptopurine
3. Methotrexate
4. Infliximab