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GI II Exam 1. > Lecture 13: Treatment for IBD > Flashcards

Lecture 13: Treatment for IBD Flashcards

1
Q

What are the 2 MOA for the 5-ASA agents used for UC?

A

- Inhibition of PG and LT production via arachidonic acid pathway

  • Reduction in PMN and macrophage chemotaxis
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2
Q

What are the four 5-ASA agents used for treating UC?

A
  1. Sulfasalazine*
  2. Mesalamine
  3. Olsalazine*
  4. Balsalazide*

* indicates the drug is converted to mesalamine

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3
Q

What are the structural ingredients of Sulfasalazine?

A

Sulfapyridine + 5-ASA

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4
Q

What are the structural ingredients of Mesalamine?

A

Single 5-ASA

*Think ‘M’ for mono-

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5
Q

What are the structural ingredients of Olsalazine?

A

2 molecules of 5-ASA

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6
Q

What are the structural ingredients of Balsalazide?

A

Inert carrier + 5-ASA

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7
Q

How does the formulation of 5-ASA as a rectal suppository vs. rectal enema differ in the distribution of the drug in the colon for treatment?

A
  • Enemas may reach the splenic flexure
  • Suppository may reach the upper rectum
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8
Q

What are the contraindications for using 5-ASA drugs in treating UC?

A
  • ALL 5-ASA’s are contraindicated in patients allergic to aspirin (ASA)
  • Sulfasalazine is contraindicated in sulfonamide-allergic pts
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9
Q

What are the indications for using 5-ASA drugs in the treatment of UC (i.e., severity of disease and patients in which state of disease)?

What are the 2 exceptions?

A
  • Indicated for active dz and maintanence in pts w/ Mild-to-Moderate UC
  • Olsalazine used only for maintenance of remission
  • ‘B’alsalazide use only for ‘A’ctive disease (‘A’ and ‘B’ go together)
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10
Q

What are the 4 TNF-α inhibitors used for the treatment of IBD?

There are 2 that are only used for UC or CD, which are they?

A
  1. Adalimumab (CD and UC)
  2. Golimumab (UC only!)
  3. Infliximab (CD and UC)
  4. Cetrolizumab (CD only!)
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11
Q

What is the MOA of the TNF-α inhibitors used in the treatment of IBD?

A

Binds to and neutralizes TNF-α mediated pro-inflammatory cell signaling, ultimately blocking leukocyte migration to sites of inflammation

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12
Q

What are adverse effects of using TNF-α inhibitors for IBD?

Because of these what must be done before using?

A
  • Infections –> Must do TB testing prior to therapy!
  • Hepatotoxicity –> increased enzymes (get LFT prior to)
  • Headache/arthralgias/fatigue
  • Rare = EM, SJS, TEN (dermatologic conditions) and malignancies
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13
Q

TNF-α inhibitors to be used in the treatment of IBD only after what?

A

AFTER inadequate response to conventional or immunosuppressant therapy

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14
Q

What are the indications for using TNF-α inhibitors as a treatment of IBD (i.e., severity of dz and disase state of pt)?

A
  • Can be used for active dz or maintenance
  • Pts with moderate-to-severe
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15
Q

Of the TNF-α inhibitors for IBD which is the only one that can be administered via IV for a maintenance does and how often?

A

Infliximab infusion every 8 weeks

*The ‘I’ can remind you of IV*

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16
Q

Which 5-ASA agent used for UC has mutliple routes of administration and what are they?

A
  • Mesalamine (single 5-ASA)
  • pH-dependent released in terminal ileum and colon
  • Time-dependent; controlled release
  • Rectal enema
  • Rectal suppository
17
Q

What are the α-4 integrin inhibitors used for IBD and differentiate which is for UC, CD, or both.

A
  • Vedolizumab (UC and CD) –> think ‘V’ = versatile
  • Natalizumab (CD only)
18
Q

What is the MOA of the α-4 integrin inhibitors used in the tx of IBD?

A

Limits intergrin’s-associated cell adhesion and subsequent transendothelial migration of leukocytes to site of inflammation

19
Q

What is a specific adverse effect related to Natalizumab used for treating IBD?

A

Progressive multifocal leukoencephalopathy (PML)

20
Q

What are the 3 risk factors for PML associated with Natalizumab in the treatment of CD?

A

1) Treatment >2 years
2) Prior immunosuppressant treatment
3) anti-JC virus (JCV) antibodies

21
Q

Before using natalizumab for the treatment of CD, what kind of screening is recommended due to risks of PML?

A
  • Gadolinium-enhanced MRI of the brain
  • When indicated CSF analysis for JC viral DNA
22
Q

What are the indications for using the α-4 integrin inhibitors for treatment of IBD (i.e., severity of dz and disease state of patient)?

A
  • Used for active dz and management
  • Moderate-to-severe IBD
23
Q

Using α-4 integrin inhibitors for the treatment of IBD should only be done after what?

A

Inadequate response to conventional or TNF-α therapy

24
Q

What is the route of administration and how does the maintenance dosing for Natalizumab vs. Vedolizumab differ?

A
  • Natalizumab –> IV every 4 weeks
  • Vedolizumab –> IV every 8 weeks
25
Q

Which agent is an IL-12/23 inhibitor used for IBD and which type specifically?

A

Ustekinumab —> CD

26
Q

What is the MOA for the IL-12/23 inhibitor, Ustekinumab, used in the treatment of CD?

A
  • Binds P40-subunit of IL-12/23 blocking activation and differentiation of naive T cells and activation of NK cells
  • Inhibits production of pro-inflammatory cytokines
27
Q

Which serious adverse effect exists with IL-12/23 inhibitors, specifically Ustekinumab, used in the treatment of CD?

A

Infections –> TB test needed pre-therapy!

28
Q

What is the indication for using Ustekinumab for CD (i.e., severity of dz and state of disease in pt)?

A
  • Indicated for active dz and maintenance
  • Moderate-to-severe CD
29
Q

When would it be appropriate to use Ustekinumab for the treatment of CD (i.e., only after what)?

A

Pts intolerant or inadequate response (resistant) to conventional, immune modulators, steroids or TNF-α therapy

*NEVER in conjunction w/ these agents

30
Q

Which routes of administration exist for Ustekinumab and what is the dosing schedule for each?

A
  • IV as a single infusion for induction
  • SQ every 8 weeks for maintenance
31
Q

What is the Janus Kinase (JAK) inhibitor used for treatment of IBD?

Which form of IBD specifically?

A
  • Tofacitnib
  • UC only!
32
Q

What are some of the adverse effects of the JAK-inhibitor, Tofacitinib used for UC?

A
  • Lymphopenia/Lymphocytosis
  • Neutropenia/Anemia
  • Fatigue
  • Increases in LDL and HDL
33
Q

What is the indication for using Tofacitinib in the tx of UC (i.e., severity of dz and disease state of patient)?

A
  • Used for active dz and maintenance
  • Moderate-to-severe UC
34
Q

What is the recommendation for using Tofacitinib with other drugs when treating UC?

A

Concomitant use of biologic therapies or potent immunosuppressant’s is NOT recommended

35
Q

What is the route of administration for Tofacitinib and the dosing schedule?

A

Administered PO 2x/day (BID)

36
Q

What are the indications for using steroid agents in treating IBD?

Can they be used for maintenance of remission?

How should they be dosed if used?

A
  • Acute and/or severe UC and CD uncontrolled by other conventional meds
  • NOT for maintenance of remission unless absolutely required (steroid-dependent)
  • Use the LOWEST dose for shortest duration possible

GI II Exam 1. (25 decks)

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