IBD drugs

Question 1

what are the 5-ASA drugs and suffix to look for? and what disease are they used for

Answer 1

Sulfasalazine*
Mesalamine
Olsalazine*
Balsalazide*

“sala”

Ulcerative Colitis

Question 2

What is the Janus Kinase Inhibitor and what disease is it used for

Answer 2

Tofacitinib

Ulcerative Colitis

Question 3

What are the 3 TNF-a Inhibitors and what disease is it used for

Answer 3

Adalimumab
Golimumab
Infliximab

Ulcerative Colitis

Question 4

What is the one a-4 Integrin inhibitors and what disease are they used for

Answer 4

Vedolizumab

used for Ulcerative Colitis

Question 5

What are first line therapy drugs that are not covered in this lecture that are used for both Ulcerative Colitis and Crohns disease

Answer 5

Steroids, Immune Modulators, and even antibiotics also utilized as first-line therapy but not officially indicated, and covered elsewhere in the Curriculum

Question 6

What are the IL-12/23 inhibitors and what disease are they used for

Answer 6

Ustekinumab

Question 7

what TNF-a Inhibitors are used for Crohns disease

Answer 7

Adalimumab
Certolizumab
Infliximab

Question 8

what are the 2 a-4 integrin inhibitors used in Crohns disease

Answer 8

Natalizumab

Vedolizumab

Question 9

What are the 5-ASA agents mechanism of action

Answer 9

Inhibition of Prostoglandin and Leukotriene production via the arachidonic acid pathway

inhibits both Cyclooxygenase and Lipoxygenase

Reduction in PMN & macrophage chemotaxis
May also inhibit the activation of NFκB(nuclear factor kappa-light-chain-enhancer of activated B cells)
–Regulates transcription of genes for pro-inflammatory proteins

Question 10

when are all 5-ASA compounds contraindicated and when is Sulfasalazine contraindicated

Answer 10

All 5-ASA compounds contraindicated in ASA-allergic patients

•Sulfasalazine contraindicated in sulfonamide-allergic patients

Question 11

how does administration of 5-ASA effect the extent of the disease

Answer 11

Oral:Varies by agent; may be released in the distal/terminal ileum, colon, or throughout GI tract

Rectal Enemas:
May reach the splenic flexure
Do not frequently concentrate in the rectum

Rectal Suppositories:
Reach the upper rectum (15-20 cm beyond the anal verge)

Question 12

what are 5-ASA agents indications and what are the two exceptions

Answer 12

Indications (Active & Maintenance):
•Mild-to-Moderate U.C.

Except Olsalazine (only for maintenance of remission)

Except Balsalazide (only for active disease)

Question 13

Mechanism of action of TNF-a Inhibitors?

Answer 13

Binds to an neutralizes membrane-associated and soluble human TNF-α-mediated pro-inflammatory cell signaling, ultimately blocking leukocyte migration to site of inflammation:

Question 14

what is the only TNF-a inhibitor that can be given IV for IBD

Answer 14

Infliximab

Question 15

what are side effects of TNF-a inhibitors?

Answer 15

Infections make sure to test for TB pre therapy since can activate from latent phase especially Adalimumab

can cause Liver toxicity

can cause Dermatologic-related (EM, SJS, TEN)
Malignancies (various)

Question 16

when are TNF-a inhibitors used and what are their indications

Answer 16

Used after inadequate response to conventional or immunosuppressant therapy

used for active and maintenance

Question 17

Mechanism of action of a-4 integrin inhibitors

Answer 17

Limits Integrin’s-associated cell adhesion and subsequent trans-endothelial migration of leukocytes to cite of inflammation

Question 18

Side effects of a-4 Integrin inhibitors and how is this monitored

Answer 18

Infections
PML (assoc. w/ John Cunningham Virus (JCV)) –3 Risk Factors for PML:
–treatment >2 years
–prior immunosuppressant treatment
–anti-JC virus (JCV) antibodies

only has been seen in natalizumab

MRI and CSF analysis

Question 19

what are the Indications of A-4 integrin inhibitors and when is the recommended use

Answer 19

All α-4 Integrininhibitors recommended for use after inadequate response to conventional or TNF-α therapy

Natalizumab
Moderate-to-Severe C.D.
not recommended in combination with immunosuppressant’s; including TNF-α agents

•Vedolizumab
Moderate-to-Severe C.D. & U.C.

Question 20

how are a-4 integrin inhibitors dosed?

Answer 20

IV every 4 or 8 hours

Question 21

Mechanism of action for IL-12/23 inhibitors

Answer 21

Bind to P40-subunit of IL-12 & IL-23 blocking activation and differentiation of naïve T cells and activation of NK cells

thereby inhibiting production of pro-inflammatory cytokines; INFg(Th1), TNF-α, IL-17 (Th17) & IL-21, among others…

Question 22

what are side effects of IL-12/23 inhibitors

Answer 22

Infections therefore must do a TB test pre therapy

Question 23

what are the indications of IL-12/23 inhibitors and when should they be used

Answer 23

Indications (Active & Maintenance):

Moderate-to-Severe U.C. & C.D

used for For patients intolerant or inadequate response (resistant) to conventional, immune modulators, steroids or TNF-α therapy

Question 24

what is the dosing of Ustekinumab

Answer 24

SQ every 8 weeks (after single IV infusion for induction)

Question 25

Mechanism of action of JAK inhibitors

Answer 25

Bind to and inhibit free-floating and bound JAK-1 & JAK-3 (lesser extent to JAK-2)

thereby ultimately inhibiting gene transcription & more cytokine release

Question 26

what are the side effects of JAK inhibitors

Answer 26

Lymphopenia/Lymphocytosis
Neutropenia/Anemia
Increases in LDL & HDL (minimal ratio change)

Rare:
Increased risk of malignancies/serious infections
–from R.A. indication-data

Question 27

Indications and dosing of Tofacitinib?

Answer 27

Indications (Active & Maintenance):
Moderate-to-Severe U.C.

•Dosing
Tofacitinib(Xeljanz)
Administered PO BID

Question 28

what is the recommendation of use of Biologic therapies and potent immunosuppressants with JAK inhibitors

Answer 28

Not recommended

Question 29

What are the indications and dosing for steroid agents

Answer 29

Indications:
Acute and/or Severe U.C. & C.D. uncontrolled by other conventional medications

Not for maintenance of remission unless absolutely required (steroid-dependent)

•Dosing:
Use the lowest dose for shortest duration possible