Gi_Test 2: Maloney_Drugs For Ibd (Chron's & Uc)

Front 1

Proinflammatory triggers stimulate T cells and Macrophages to secrete what?

(leading to inflammation)

Back 1

Cytokines (TNFa)

AA metabolites (PG, LT)

Growth Factors

Oxygen radicals

Front 2

UC vs. CD

Restricted to colon
Continuous lesion
Superficial layers
Th2 cells predominate

Back 2

UC

Front 3

UC vs. CD

Any part of GI tract
Patchy lesions
Superficial and deep layers
Th1 cells predominate
Can develop **FISTULAS**

Back 3

CD

Front 4

Where do prostaglandins and
leukotrienes come from?

Back 4

Arachidonic Acid

Front 5

Differentiate between remission and the acute phase (active disease) of IBD

Back 5

• Active = pain, bloating, bloody diarrhea—use Rx to induce remission

Front 6

MOA:

Blocks BOTH cyclooxygenase and lipoxygenase = ↓PGs and ↓LTs

Back 6

5-Aminosalicytes

Note:
**Inhibition of lipoxygenase has MOST beneficial treatment effect!**

Front 7

Drug Class?

Sulfasalazine
Olsalazine
Balsalazide
Mesalamine (oral and rectal)

Back 7

5-Aminosalicytes

"-sala"

Front 8

"-sala"

Back 8

5-Aminosalicytes

Front 9

↓lipoxygenase = ↓ ______ ?

Back 9

Leukotrienes

(This ↓inflammation and PMN chemotaxis)

Front 10

Which 5-ASA agent can be given as both a rectal suppository and enema?

Back 10

Mesalamine

Front 11

These drugs have:

- Topical effect on the GI tract

- Block the production of leukotrienes

Back 11

5-ASA

Front 12

NSAIDs have not been shown
to be beneficial in IBD. What
does this imply?

Back 12

Getting rid of PGs (by blocking COX-1) does not help in IBD.

Blocking leukotrienes DOES help!

Front 13

How do you prevent
systemic absorption of
5-ASA agents?

Back 13

Give as:

-Rectal suppository

-Enema

-Time released capsule

-Conjugated to a carrier

Front 14

Explain conjugated carriers of 5-ASA used to increase absorption in the colon

Back 14

Sulfasalazine – carrier is sulfapyridine

Olsalazine – carrier is another molecule of 5-ASA

Balsalazide – carrier is an inert molecule

These form an AZO BOND (N=N) which is cleaved by BACTERIAL AZOREDUCTASE in the colon. Then, they are absorbed!

Front 15

What is the rationale for
conjugating 5-ASA with
sulfapyridine?

Back 15

We don't want 5-ASA being absorbed in the small intestine. We need it to be absorbed in the lower GI/ Colon!

Front 16

Rectal enema
Azo bond
Asacol
Pentasa

Back 16

Front 17

Compare the ability of 5-ASA compounds to induce remission and maintain remission in IBD

Back 17

Sulfasalazine/mesalamine = 1st Line/DOC** for BOTH inducing AND maintain remission in Mild-Moderate UC/CD

- Sulfasalazine has the best evidence for inducing remission with CD (vs mesalamine)

Front 18

Clincal Use:

Mild to moderately active ulcerative colitis
- Induce remission
- Maintenance of remission

Back 18

5-ASA

Front 19

Compare the ability of 5-ASA compounds to treat mild to moderate IBD and severe IBD

Back 19

They don't treat severe IBD!!!

-Give corticosteroids to induce remission

-Immunosuppressants to maintain remission

Front 20

sulfasalazine vs. mesalamine

Side Effects:

Male infertility

Back 20

sulfasalazine

**d/t the sulfapyridine released**

(Remember, sulfasalazine is conjugated with sulfapyridine to increase colon absorption.. When the AZO BOND is cleaved, sulfasalazine blocks leukotriene formation and sulfapyridine causes SEs)

Front 21

sulfasalazine vs. mesalamine

Side Effects:

o Skin rash
o Hemolytic anemia
o Agranulocytosis
o Pulmonary complications
o Hepatitis
o Pancreatitis*

Back 21

sulfasalazine

**Hypersensitivity reaction from the sulfapyridine released**

Front 22

sulfasalazine vs. mesalamine

Side Effects:

-Folic Acid Deficiency

Back 22

sulfasalazine

Front 23

sulfasalazine vs. mesalamine

–Adverse Effects
o Headache
o Dyspepsia
o Skin rash
o Diarrhea

Back 23

mesalamine

Front 24

Clinical Use:

o Clinical Use
- Moderate to severely active ulcerative colitis or Crohn’s disease

***Induce remission***
o Mild to moderate UC or CD: 2nd line choice**

- Severe and/or steroid resistant or dependent UC or CD: 1st line choice**

**Not effective for maintaining remission**

Back 24

Corticosteroids

Front 25

A patient with a history of Crohn's Disease is not currently on any medications and is believed to have a fistula. How can you treat?

Back 25

Add Metronidazole (ABX)

Front 26

A 35-year-old female is diagnosed
with ulcerative colitis. A trial of
sulfasalazine is ineffective. She
continues to have 3-5 bloody stools
per day. What can you do for her?

Back 26

Steroids to reduce inflammation

Front 27

Drug Class?

Prednisone
Methyprednisolone
Hydrocortisone
Budesonide

Back 27

Corticosteroids

Front 28

What is the main problem with
the use of corticosteroids
(especially long term)?

Back 28

SIDE EFFECTS!

Front 29

What is the potential
advantage of budesonide
vs. prednisone?

Back 29

Less Side Effects!!

Front 30

Name the Corticosteroid:

- Controlled ileal release formula

-High affinity for the glucocorticoid receptor

-80-90% is eliminated by first pass
metabolism in the liver

***Works topically***

**NO SYSTEMIC CONCENTRATION**

**LESS SIDE EFFECTS**

Back 30

Budesonide

Front 31

Clincal Use:

- Moderate to severely active ulcerative colitis or Crohn’s disease

- Oral, rectal, or parenteral

- Induce remission

**Not effective at maintaining remission**

Back 31

Corticosteroids

Front 32

This corticosteroid NOT used systemically—d/t HIGH affinity for MC receptors—do NOT want activation here, as it may alter electrolytes

Back 32

Hydrocortisone enema

Front 33

What corticosteroid has been shown to prolong time to relapse in pts with CD in medically induced remission

Back 33

Budesonide

Front 34

Describe Steroid Responsive Patients with IBD

Back 34

- Clinical improvement 1-2 weeks

-Remain in remission when drug tapered slowly over weeks or months

Front 35

Describe Steroid Dependent Patients with IBD

Back 35

- Clinical improvement 1-2 weeks

- Relapse when steroid dose is tapered

Front 36

General Class of drugs?

**Thiopurine analogs**
- Azathioprine
- 6-Mercaptopurine

**Methotrexate**

**Cyclosporine**

Back 36

Immunosuppressive Agents

Front 37

If a person is unresponsive to steroids,
or is steroid dependent, or has severe
disease and goes into remission with
steroids, what else can you do?

Back 37

Try Immunosuppressive Agents

Front 38

Why are Azathioprine and 6-mercaptopurine good for maintaining remission?

Back 38

take SIGNIFICANTLY longer for onset of action in inducing remission
~3-6 months

MTX and Cyclosporine can take a few weeks and aren't as good for maintenance ---> better for INDUCING REMISSION

Front 39

What are the TNF-a inhibitors for IBD?

Back 39

Infliximab**

Adalimumab

Certolizumab Pegol

(Monoclonal antibodies to TNF-a)

Front 40

MOA:

- Binds to membrane bound TNF-α on MΦ or activated T cells and induces cell death

- Binds to soluble TNF-α and prevents it from binding to the TNF receptor on target cells

- This prevents the inflammatory effects of TNF-α in IBD

Back 40

Infliximab**

Front 41

What is entanercept? Is it useful in IBD?

Back 41

Etanercept= the RA Rx

It is a Recombinant TNF-α receptor– not effective for treating IBD

Front 42

Clinical Use:

- For inducing remission in patients UNRESPONSIVE to steroids

- For reducing steroid use in pts that are steroid dependent

- For MAINTENANCE therapy in severe IBD after inducing remission with steroids

- Fistulizing Crohn’s disease

Back 42

Immunosuppressant Agents

Front 43

Clinical Use:

**Moderate to severe Crohn’s disease**
• Induce remission
• Maintain remission

**Fistulizing Crohn’s disease**

**Moderate to severe ulcerative colitis**
• Induce remission
• Maintain remissio

Back 43

Biological Response Modifiers- TNF-α inhibitors

(Infliximab is especially helpful in UC!!)

Front 44

Many patients with CD need dosage
adjustments or lose their response to
infliximab. Why might that be?

Back 44

Development of antibodies to infliximab (remember, it's 25% mouse) as the drug gets into the serum

**Adalimumab** can be used in
patients who have lost response to,
or are intolerant to infliximab

Front 45

You have induced remission with steroids in a patient that had been diagnosed with Severe UC. What drug can you give next to maintain remission?

Back 45

infliximab !!

Great for inducing and maintaining remission in severe/moderate UC

Front 46

A 34-year-old male suffering from severe IBD is not responding to first-line therapy. The patient is being switched to an agent that frequently causes nephrotoxicity. Which of the following agents was he most likely switched to?

A. azathioprine
B. cyclosporine
C. etanercept
D. methotrexate
E. infliximab
F. sulfasalazine

Back 46