Inflammatory Bowel Disease Treatment

Question 1

What is UC?

Answer 1

mucosal inflammatory condition confined to rectum & colon

Question 2

What is Crohn’s?

Answer 2

transmural inflammation from mouth to anus

Question 3

What does therapy for UC or Crohn’s depend on?

Answer 3

Anatomic location, the severity, responsiveness, goal of therapy, & drug toxicity

Question 4

Malaise & fever are uncommon in what form of IBD?

Answer 4

UC

Question 5

What is the distribution of UC vs Crohn’s?

Answer 5

Crohn’s = discontinuous

UC = continuous

Question 6

Aphthous or linear ulcers are common in which form of IBD?

Answer 6

Crohn’s

Question 7

What features are common in Crohn’s?

Answer 7

Ileal involvement 
Strictures
Fistulas 
Granulomas 
Linear clefts 
Cobblestone appearance

Question 8

What feature is common in UC?

Answer 8

Crypt abscesses

Question 9

What is the goal of pharmacologic therapy for IBD?

Answer 9

Relieve the inflammatory process & induce remission

Question 10

What is the action of azo compounds (end in “salazine”)?

Answer 10

Reduce absorption of the parent drug from the small intestine

Question 11

Azo compounds: Where are high concentrations of active drug made available?

Answer 11

Terminal ileum & colon

Question 12

What are examples of mesalamine compounds?

Answer 12

Pentasa

Asacol & apriso

Lialda

Rowasa (enema), canasa (suppositories)

Question 13

What does pentasa act on?

Answer 13

small intestine

Question 14

What does anacol & apriso act on?

Answer 14

distal ileum & proximal colon

Question 15

What does lialda act on?

Answer 15

colon

Question 16

What does rowasa & canasa act on?

Answer 16

rectum & sigmoid colon

Question 17

5-ASA is derived from what 2 pathways?

Answer 17

Cyclooxygenase & lipoxygenase

Question 18

What is the MOA of 5-ASA?

Answer 18

Interferes w/ production of inflammatory cytokines

Inhibit cellular functions

Question 19

What is the efficacy of 5-ASA on UC vs Crohn’s?

Answer 19

UC: induces & maintains remission, considered 1st line for mild-mod disease

Crohn’s: efficacy unproven (many still use as 1st line for mild-mod disease involving the colon or distal ileum)

Question 20

What is the action of the controlled-release oral formulation of budesonide?

Answer 20

Releases in the distal ileum & colon, where it is absorbed

Question 21

How do you treat mod-severe active IBD?

Answer 21

Glucocorticoids

Question 22

Have higher doses of glucocoricoids been shown to be more efficacious?

Answer 22

Nope

Question 23

What is a con of glucocorticoids?

Answer 23

Not useful for maintaining remission

- Aminosalicylates or immunosuppressive agents should be used

Question 24

Purine antimetabolites have ___________ properties

Answer 24

immunosuppressive

Question 25

6-mercaptopurine undergoes biotransformation via...

Answer 25

competing catabolic enzymes - xanthine oxidase & thiopurine methyltransferase

Question 26

Active 6-thioguanine nucelotides are concentrated in cells resulting in...

Answer 26

prolonged 1/2 life

Question 27

Prolonged kinetics of 6-thioguanine nucelotide results in a delay of...

Answer 27

17 weeks before onset of therapeutic benefit from oral azathioprine or 6-MP

Question 28

What are ADEs of azathioprine & 6-mercaptopurine (purine analogs)?

Answer 28

Bone marrow depression Hepatic toxicity Increased risk of lymphoma

Question 29

Describe the drug interaction w/ allopurinol

Answer 29

Reduces xanthine oxide catabolism of the purine analogs --> increased active 6-thioguanine nucleotides

Question 30

What has an important role in the pathogenesis of IBD?

Answer 30

Luminal bacteria | Fungi & viruses

Question 31

What is the role of abx on IBD?

Answer 31

Treats micro abscesses Decreases bacterial translocation Treats septic complications Induces remission

Question 32

What has been hypothesized to have a role in the development of Crohn's?

Answer 32

Mycobacterial infection

Question 33

What is the MOA of methotrexate?

Answer 33

Inhibit dihydrofolate reductase enzyme Interfere w/ interleukin Stimulate release of adenosine Stimulate death of T lymphocytes

Question 34

What are ADEs of methotrexate?

Answer 34

Bone marrow depression Alopecia Mucositis Peripheral neuropathy when used for prolonged periods Hepatic damage in pts w/ psoriasis

Question 35

What reduces the risk of ADEs of methotrexate?

Answer 35

Folate supplementation

Question 36

Those on methotrexate & who have renal insufficiency, are at increased risk for what?

Answer 36

Hepatic accumulation & toxicity

Question 37

What is the MOA of anti-tumor necrosis factor?

Answer 37

Dysregulation of helper T cell type 1 response & regulatory T cells

Question 38

What is an example of anti-tumor necrosis factor therapy?

Answer 38

Monoclonal antibodies to human TNF

Question 39

Anti-tumor necrosis agents prevent the cytokine from binding to...

Answer 39

its receptors

Question 40

Anti-tumor necrosis agents: the Fc portion of human IgG1 promotes...

Answer 40

antibody-mediated apoptosis

Question 41

What fraction of pts will eventually lose response despite higher doses or more frequent injections of anti-tumor necrosis agents?

Answer 41

1/3

Question 42

What causes the loss of response in anti-tumor necrosis agents?

Answer 42

May be due to development of antibodies to the TNF antibody

Question 43

What are ADEs of anti-tumor necrosis agents?

Answer 43

Infection Risk of serious infections increased w/ concomitant coricosteroids Antibodies to the antibody (less likely in concomitant therapy w/ immunomodulators) Delayed serum sickness-like rxn

Question 44

Concomitant treatment w/ anti-TNF agents & immunomodulators may increase the risk of what?

Answer 44

lymphoma

Question 45

What are integrins?

Answer 45

Adhesion molecules on the surface of leukocytes

Question 46

Integrins may interact w/ what?

Answer 46

Selectins (another class of adhesion molecules, on the surface of the vascular endothelium)

Question 47

What is the MOA of integrins?

Answer 47

Allows circulating leukocytes to adhere to the vascular endothelium & move through the vessel wall into the tissue

Question 48

What is anti-integrin therapy (natalizumab) used for?

Answer 48

Mod-severe Crohn's who have failed other therapies through a carefully restricted program

Question 49

What are ADEs of anti-integrin therapy (natalizumab)?

Answer 49

acute infusion rxns small risk of opportunistic infections

Question 50

What should you monitor w/ anti-integrin therapy?

Answer 50

Brain MRI, mental status, progressive multifocal leukoencephalopathy