IBD Pharm

Question 1

What are the main classes of drugs used to threat IBD?

Answer 1

• 5-ASA (aminosalicylates)
• TNF-α inhibitors
• α-4 integrin inhibitors
• IL-12/23 inhibitors
• JAK inhibitors
• steroids/immune modulators and abx as well

Question 2

What is the mechanism of action for 5-ASA?

Answer 2

inhibits both COX and LIPOX

-inhibit arachadonic acid -> prostaglandin and leukotriene -> decreased inflammation

Question 3

What are the inidcations for 5-ASA drugs?

Answer 3

Active and maintenance of UC only (mild/moderate -> first line)

Question 4

What suffix is associated with 5-ASA drugs?

Answer 4

“-sala-“

Question 5

What is sulfasalazine?

(anything special?)

Answer 5

5-ASA drug (IBD -> UC only)

sulfapyridine carrier:

• generates side effects
• contraindicated in sulfa alergies

Question 6

What is mesalamine?

(anything special?)

Answer 6

5-ASA (IBD -> UC only)

• single 5-ASA, no carrier
• multiple routes of administration (oral, rectal enema, suppositories)

Question 7

What is olsalazine?

(anything special?)

Answer 7

5-ASA drug (IBD -> UC only)

-two 5-ASA

Question 8

What is balsalazide?

(anything special?)

Answer 8

5-ASA drug (IBD -> UC only)

inert carrier

Question 9

What side effects are associated with 5-ASA drugs?

Answer 9

• mild CNS
• mild GI

Question 10

What are contrainidications for 5-ASA drugs?

Answer 10

• ASA allergies
• sulfa allergies (sulfasalazine only)

Question 11

What is the mechanism of action for TNF-α inhibitors?

Answer 11

Binds TNF-α, inhibiting its pro-inflammatory effects and upregulation of surface adhesion molecules

Question 12

What is the general indications for TNF-α inhibitors?

Answer 12

moderate to severe UC and/or CD (which one varies per drug)

used after inadequate response to other drugs

Question 13

What is adalimumab?

(indications)

Answer 13

TNF-α inhibitor

indicated for:

-active/maintenance of UC and CD (moderate to severe -> doesn’t respond to others)

Question 14

What is infliximab?

(indications)

Answer 14

TNF-α inhibitor

indicated for:

• active/maintenance CD (moderate to severe)
• active/maintenance UC (severe only)
• only with inadequate response to other treatment

Question 15

What is golimumab?

(indications)

Answer 15

TNF-α inhibitor

indicated for:

• active/maintenance UC only (moderate to severe)
• only with inadequate response to other treatment

Question 16

What is certolizumab?

(indications)

Answer 16

TNF-α inhibitor

indicated for:

• active/maintenance CD (moderate to severe)
• only with inadequate response to other treatment

_{<strong>C</strong>erto… and <strong>C</strong>rohns both start with <strong>C</strong>}

Question 17

What are side effects of TNF-α inhibitors?

Answer 17

• TB reactivation
• elevated LFTs
• EM/TEN/SJS (rare)

Question 18

What is the mechanism of α-4 integrin inhibitors?

Answer 18

-bind and block α-4 integrins, inhibiting leukocytes migration

Question 19

What is natalizumab?

(inidcations)

Answer 19

α-4 integrin inhibitor

• active/maintenance for CD only (moderate-to-severe)
• inadequate response to other treatements

Question 20

What is vedolizumab?

(indications)

Answer 20

α-4 integrin inhibitor

• active/maintenance for CD and UC (moderate-to-severe)
• inadequate response to other treatements

_{make the letter ‘V’ with your finger, you are holding up the number two and this treats both UC/CD}

Question 21

What black box warning is associated with α-4 integrin inhibitors?

Answer 21

PML (progressive multifocal leukoencephalopathy) from JCV virus reactivation

-specific monitoring and education is required to prescirbe/take (TOUCH program)

Question 22

What side effects are associated with α-4 integrin inhibitors?

Answer 22

• infusion reactions
• anti-medication Ab formation
• increased risk for malignancy (rare)

Question 23

What is the mechanism of action for IL-12/23 inhibitors?

Answer 23

bind p-40 subunit that is common to IL-12 and IL-23 receptors, inhibiting their function

• inhibits Th₁₇ and NK differentiation
• inhibits proinflammatory cytokine release

Question 24

What is ustekinumab?

(indications)

Answer 24

IL-12/23 inhibitor

• active/maintenance of CD and UC (moderate-to-severe)
• only with inadequate response to other treatment

Question 25

What are the side effects of IL-12/23 inhibitors?

Answer 25

- TB reactivation - injection site reaction - increased risk of malignancy (rare)

Question 26

What is the mechanism of action for JAK inhibitors?

Answer 26

bind and inhibit intracellular **JAKs (1 and 3)** which are involved in **cytokine signaling** -strong effect on JAK 3 which is involved in IL-4 signaling, **particularly inhibiting Th₂ differentiation** (-\> UC only)

Question 27

What is tofacitinib? | (indications)

Answer 27

JAK inhibitor - active and maintenance of UC only (moderate-to-severe) - only with inadequate response to other treatment

Question 28

What are side effects of JAK inhibitors?

Answer 28

- lymphopenia/lymphocytosis - neutropenia/anemia - increased LDL and HDL - increased risk of malignancy (rare)

Question 29

What drugs should be avoided while taking biologics?

Answer 29

other biologic medications

Question 30

What is the order that drugs should be used with progressively treatment resistant IBD?

Answer 30

First line: - **5-ASA (UC only)** - **abx** - **steroids**/immune modulators Second line: -**TNF-α inhibtors** Third line: - **JAK inhibitors** (UC only) - **IL-12/23 inhibitors** (both) - **α-4 integrin inhibitors** (both)