IBD And IBS

Question 1

Inflammatory Bowel Disease

Answer 1

Severe inflammatory disorder affecting the lower GI tract

• inflammation is destructive and painful
• perforation can occur, which can be fatal

Question 2

Two types of IBD

Answer 2

Crohn’s Disease

Ulcerative colitis

Question 3

IBD treatment addresses

Answer 3

Inflammation and immune response

Question 4

Drug classes for IBD (4)

Answer 4

Aminosalicylates
TNF inhibitors
Corticosteroids
Immunosuppressants

Question 5

Aminosalicylates example

Answer 5

5-Aminosalicylic Acid (5-ASA)
- also known as mesalamine
Extended Release Microspheres (5-ASA ER)

Question 6

Aminosalicylates mechanism

Answer 6

• Inhibit inflammatory mediators

- may also inhibit cyclooxygenase

Question 7

Aminosalicylates pharmacokinetics

Answer 7

• act locally (target colon)
• strategies: Prodrug cleaved in colon, enteric coating dissolved in colon, microspheres release drug slowly, rectal administration.

Question 8

Aminosalicylates Prodrug

Answer 8

Sulfasalazine

Question 9

Sulfasalazine mechanism

Answer 9

5-ASA + sulfapyridine

• two molecules separated in colon by bacteria
• efficacy largely due to 5-ASA
• adverse effects due to sulfapyridine

Question 10

Extended Release Microspheres mechanism

Answer 10

Release 5-ASA throughout the small intestine to rectum

Question 11

Rectal Suppositories

Answer 11

Suppositories effects may extend to the upper rectum (10-15cm)

Question 12

Rectal (Enema)

Answer 12

Enemas reach further than suppositories, up to the distal colon

Question 13

Aminosalicylates Side Effects

Answer 13

Gastrointestinal (worse with sulfasalazine)
Headache
Other rare ones but serious harms

Question 14

TNF alpha inhibitors

Answer 14

TNF alpha is a key mediator of inflammation

Appears to be particularly important in IBD

Question 15

TNF alpha inhibitor example

Answer 15

Monoclonal antibodies

Infliximab

Question 16

TNF alpha inhibitors mechanism

Answer 16

MAbs bind to TNF and prevent it from interacting with its receptor

Question 17

TNF alpha inhibitors side effects

Answer 17

Opportunistic infections

• Immunosuppressive effects may increase the risk (réactivation of tuberculosis)
• Hypersensitivity reactions: acute or delayed, infliximab is chimeric (animal/human)
• malignancies: due to reduced immune surveillance, TNF lyses tumor cells

Question 18

Corticosteroids mechanisms

Answer 18

Anti-inflammatory effects
Immunosuppressive
Prednisone and Budesonide

Question 19

Corticosteroids routes

Answer 19

Oral, rectal, parenteral

Question 20

Corticosteroids side effects

Answer 20

• Numerous serious side effects with systemic agents like Prednisone
• Fewer with Budesonide

Question 21

Immunosuppressants example

Answer 21

Antimetabolites

- Azathioprine

Question 22

Azathioprine mechanism

Answer 22

• converted to a structural analogue of guanine
• “false nucleotide” halts DNA/RNA synthesis
• Immune cells (lymphocytes) rely on de novo purine synthesis: therefore more susceptible to actions of metabolites

Question 23

Immunosuppressants side effects

Answer 23

Infection
Cancer
Bone marrow suppression
Gastrointestinal

Question 24

Cyclosporine mechanism

Answer 24

Inhibits T-cell activation by inhibiting IL-2

Question 25

Cyclosporine is difficult to use because..

Answer 25

Narrow margin for safety Many drug interactions Significant adverse effects

Question 26

Other Immunosuppressants

Answer 26

Methotrexate Folate antagonist - significant adverse effects

Question 27

Irritable Bowel Syndrome

Answer 27

Very common, challenging to treat - Constipation, diarrhea or mixed - abdominal pain - psychological, dietary components

Question 28

Antispasmodics

Answer 28

- anticholinergics | - calcium antagonists

Question 29

Anticholinergics example

Answer 29

Hyoscine

Question 30

Anticholinergics mechanism

Answer 30

Muscarinic receptors stimulate peristalsis in the GI tract | - blocking M receptors inhibits contractions of the colon

Question 31

Anticholinergic side effects

Answer 31

- Dry mouth - urinary retention - constipation

Question 32

Calcium antagonist example

Answer 32

Pinaverium

Question 33

Calcium antagonists mechanism

Answer 33

Blocks entry of Calcium into smooth muscle cells of the GI tract - calcium plays a role in smooth muscle contraction

Question 34

Calcium Antagonists side effects

Answer 34

- constipation - Abdonminal distension Serious: esophageal irritation - patients should take with a full glass of water/small snack to make sure drug clears the esophagus

Question 35

IBS managing pain and constipation (drug name)

Answer 35

Linaclotide - cGMP agonist: increases intestinal secretions and reduces transmission of pain signals

Question 36

Anti-depressants used in treatment of IBS

Answer 36

- tricyclic antidepressants | - serotonin selective reuptake inhibitors

Question 37

Tricyclics antidepressant used in IBS

Answer 37

Amitriptyline

Question 38

Tricyclics antidepressant side effects

Answer 38

- exhibit side effects similar to anticholinergic (dry mouth, constipation, and urinary retention) - Better for use in IBS-D than SSRI's

Question 39

SSRI example

Answer 39

Citalopram

Question 40

SSRI use in IBS

Answer 40

Typically used to treat IBS-C but the effects on the GI are not as reliable as TCA