IBD And IBS Pharm (Segars)

Question 1

Name the 5-ASAs and which IBD condition used for:

Answer 1

Sulfasalazine, Mesalamine, Olsalazine, Balsalazide

Question 2

What is the MOA of 5-ASA’s?

Answer 2

Inhibition of PG and LT (TxA) production via AA pathway –> reduction in PMN and macrophage chemotaxis

Question 3

When are 5-ASAs contraindicated?

Answer 3

Contraindicated in ASA-allergic pts

Sulfasalazine contraindicated in sulfonamide-allergic pts

Question 4

Name the TNF-a inhibitors

Answer 4

Adalimumab, Infliximab, Golimumab, and Certolizumab

Question 5

MOA of TNF-a inhibitors?

Answer 5

Neutralize membrane-associated and soluble human TNF-a-mediated pro-inflamm cell signaling

Inhibit expression of pro-inflamm genes

Question 6

Side effects of TNF-a inhibitors?

Answer 6

INFECTIONS –> need TB testing pre-therapy

Question 7

Indications for adalimumab?

Answer 7

Moderate-to-severe UC and CD, including infliximab failures

Question 8

Indications for infliximab?

Answer 8

Moderate-to-severe UC and CD

Question 9

Indications for Golimumab?

Answer 9

UC ONLY

Question 10

Indications for Certolizumab?

Answer 10

Moderate-to-severe CD ONLY

Question 11

How is Infliximab administered?

Answer 11

IV infusion every 8 weeks

The rest (Adalimumab, Golimumab, and Certolizumab) are SubQ

Question 12

What are the a-4 integrin inhibitor drugs?

Answer 12

Natalizumab and Vedolizumab

Question 13

VCAM1 and MAdCAM-1 are targets of this a-4 integrin inhibitor:

Answer 13

Natalizumab

Vedolizumab targets MAdCAM-1

Question 14

MOA of a-4 integrin inhibitors?

Answer 14

Limits integrins-associated cell adhesion, transendothelial migration, and immune cell activation within inflamed tissue

Question 15

Major side effect of a-4 integrin inhibitors?

Answer 15

INFECTIONS –> PML (associated w/ JCV)

3 risk factors for PML: 1) Tx > 2 yrs, 2) Prior immunosuppressant tx, 3) anti-JC virus Abs

Question 16

Indications for Natalizumab?

Answer 16

Moderate-to-severe Tx-resistant CD and maintenance therapy to prevent relapse

Question 17

Indications for Vedolizumab?

Answer 17

Moderate-to-severe tx-resistant CD AND UC and maintenance therapy to prevent relapse

Question 18

Dosing of Natalizumab? Vedolizumab?

Answer 18

Natalizumab –> IV infusion every 4 weeks

Vedolizumab –> IV infusion every 8 weeks

Question 19

Name a IL-12/23 inhibitor

Answer 19

Ustekinumab

Question 20

MOA of IL-12/23 inhibitors?

Answer 20

Bind to specific subunit of IL-12/23 receptor located on surface of T cells and NK cells –> inhibit signal transduction-related activities and production of pro-inflamm Th1 and Th17 cells

Question 21

Side effects of IL-12/23 inhibitors?

Answer 21

INFX –> TB testing pre-tx recommended

Question 22

Indications for IL-12/23 inhibitors?

Answer 22

Moderate-to-severe tx-resistant CD (active disease and maintenance)

Question 23

Adverse effects of steroids?

Answer 23

Increase glucose, BP and lipid profile
GI distress
Fluid retention/edema/swelling of face and extremities
Increased appetite/fat distribution
Insomnia/jittery/nervous/anxious/psychoses
Bone defects

Question 24

Dosing for steroids?

Answer 24

Use the lowest dose for shortest duration possible

Question 25

List the anti-muscarinics for IBS and indications

Answer 25

Hyoscyamine, Dicyclomine, and CLidinium/chlordiazepoxide

For abdominal pain/spasms

Question 26

MOA of the anti-muscarinics?

Answer 26

Competitively inhibit autonomic, post-ganglionic cholinergic receptors –> decrease GI motility and spasms (pain)

Question 27

List the anti-diarrheals used in IBS

Answer 27

Loperamide

Diphenoxylate (bismuth)

Question 28

MOA of Loperamide?

Answer 28

Interferes w/ peristalsis by a direct action on circular and longitudinal muscles of intestinal wall, slowing motility

Also may directly inhibit fluid and electrolyte secretion and/or increase water-absorption

Question 29

Side effects of Loperamide?

Answer 29

Constipation, dizziness, drowsiness, and urinary retention –> Anti-cholinergic

Question 30

MOA of Diphenoxylate?

Answer 30

Believed to exert effect locally and centrally on GI smooth m. cells; inhibits GI motility and slows excess GI propulsion

Question 31

5-HT3 antagonist for IBS?

Answer 31

Alosetron

Question 32

Side effects of Alosetron?

Answer 32

ISCHEMIC COLITIS

Constipation

Question 33

Indication for Alosetron?

Answer 33

Women w/ chronic, severe IBS-D not responsive to other conventional therapies (efficacy in men not established)

Question 34

The IBS agents for diarrhea?

Answer 34

Anti diarrheal –> Loperamide and Diphenoxylate
Opioid agonists/antagonists –> Eluxadoline
5-HT3 antagonists –> Alosetron

Question 35

MOA of Eluxadoline?

Answer 35

Agonist –> Mu and Kappa opioid receptors in GI tract –> slow peristalsis and delay digestion

Antagonist –> Delta opioid receptors in GI tract –> decrease secretions of stomach, pancreas, and biliary tract

Question 36

IBS drugs for constipation?

Answer 36

Guanylate cyclase-C agonists --> Linaclotide
Selective chloride (C2) channel activators --> Lubiprostone

Question 37

MOA of Linaclotide?

Answer 37

Bind to Guanylate cyclase-C on luminal surface of intestinal epithelium (agonist) –> increase IC/EC cGMP –> stimulate secretion of Cl/HCO3 into intestinal lumen via activation of CFTR channels –> increased intestinal fluid and accelerated transit

Question 38

MOA of Lubiprostone?

Answer 38

Activate specific ClC-2 Chloride channels in luminal cells of intestinal epithelium –> produce Cl-rich intestinal fluid secretion w/out altering serum [electrolyte]

PGE1 derivative