IBD and IBS

Question 1

What is IBD (Irritable Bowel Disease)?

Answer 1

• A severe anti-inflammatory disorder affecting the lower GI tract. Inflammation is destructive and very painful.
• ->Perforation can occur, which can be fatal.

2 Main Types of IBD:
-Crohns Disease
-Ulcerative Colitis
(Treatment addressing both inflammation and activating the immune response)

Question 2

What are Aminosalicylates?

Answer 2

• Discovered in the 1930’s (originally used to treat rheumatoid arthritis)
• Mechanism isn’t fully understood (causes anti- inflammation)

Question 3

Mesalamine:

Answer 3

5-aminosalicyclic acid (5-ASA)

• ->Anti-inflammatory activity
• Inhibits inflammatory mediators including TNFalpha and MAY inhibit COX (there are likely other mechanisms that contribute)

*Acts locally, and therefore targets the colon.

Strategies: Prodrug cleaved in the colon, enteric coating dissolved in the colon, microspheres release drug slowly, as well as rectal administration.

Question 4

Sulfasalzine

Answer 4

5-ASA + Sulfapyridine

• 2 molecules separated in the colon by bacteria.
• Efficacy largely due t 5-ASA, and the adverse effects are largely due to Sulfapyridine (acts as the drugs escort)

Question 5

Asacol and Saloflak (5-ASA EC):

Answer 5

Delayed release of 5-ASA (released based on pH)

• -The drug can’t be released in the stomach due to it’s low pH
• Begins releasing drug in the terminal ileum (Small Intestine) and continues through the the rectum.

Question 6

5- ASA ER (Pentasa):

Answer 6

Extended Release (ER) Microsphere 
-->Release 5-ASA all the way throughout the small intestine to the rectum.

Question 7

Suppositories:

Answer 7

Effects may extend to the upper rectum.

Question 8

Enema:

Answer 8

Enema’s reach much further than suppositories- up to the distal colon

Question 9

Side Effects of Rectal’s (Suppositories and Enema)

Answer 9

• Gastrointestinal (worse with Sulfasalazine)

- Headache

Question 10

TNF-alpha Inhibitors:

Answer 10

TNFalpha plays a major role in mediating inflammation.

• ->Appears to be very important in IBD
• Different types in drugs, including Monoclonal Antibodies & Corticosteroids

Question 11

Infliximab:

Answer 11

Monoclonal antibodies bind to TNF-alpha and prevent it from interacting with it’s receptor..

Side Effects:

• Opportunistic Infections and Immunosuppressive effects may increase risk of infection.
• Reactivation of TB can occur (should be screened)
• Hypersensitivity reactions (Acute or Delayed)
• Infliximab is chimeric (animal/ human) while others are human mabs.
• -In theory, there may be a higher risk of reactions with infliximab
• Malignancies- due to reduced immune surveillance (TNF-alpha lyses tumour cells)
• Extent of risk is still unclear.

Question 12

Prednisone, Budesonide

Answer 12

Oral corticosteroids

• Budesonide has low bioavailability, therefore tends to act locally in the GI tract.
• -Has a lower efficacy than Prednisone

Adverse Effects:
-Numerous serious side effects with systemic agents like Prednisone (fewer with Budesonide)

Question 13

Azathioprine:

Answer 13

-Converted to a structural analogue of guanine.
“False Nucleotides” halts DNA/ RNA synthesis.
-Lymphocytes rely on de novo purine synthesis (synthesis of complex molecules from simple sugars or amino acids, as opposed to recycling after partial degradation.

-Is more susceptible to actions of anti- metabolites.

Adverse Effects: Related to effects on the immune system (Infection, Cancer), as well as related to rapidly dividing cells (Bone Marrow Suppression and Gastrointestinal)

Question 14

Methotrexate:

Answer 14

Folate antagonist

–Significant adverse effects

Question 15

Antibiotics/ Probiotics to treat IBD:

Answer 15

Acute Complications:
–>Antibiotics for the management of acute complications (infections)

–>Chronic management: Theory is that an imbalance of pro and anti inflammatory bacteria contribute to IBD

Question 16

What is Irritable Bowel Syndrome (IBS)?

Answer 16

Very common & challenging to treat

• -Occurs in 3 forms:
  1. IBS-C (Constipation)
  2. IBS-D (Diarrhea)
  3. Mixed
• -Abdominal pain is significant & is affected by physiological & dietary components.

-Treated with laxatives and anti- diarrheals

Question 17

Hyoscine:

Answer 17

• Anti- cholinergic (anti-spamics)
• Muscarinic Receptor Antagonist (decreases peristalsis & decreases contractions of the colon)

Side Effects: Dry Mouth, Urinary Retention & Constipation

Question 18

Pinaverium:

Answer 18

Ca2+ Antagonist

• Blocks entry of calcium into smooth muscle cells of the GI tract.
• Blocking calcium inhibits smooth muscle contraction

Side Effects include constipation and abdominal distention

SERIOUS side effects include Esophageal Irritation
-Patients should take Pinaverium with a full glass of water/ small snack to make sure it clears the esophagus.

Question 19

Linaclotide:

Answer 19

cGMP Agonist

• Increases intestinal secretions
• Reduces transmission of pain signals
• Anti-depressants are also used to treat IBS
• ->Particularly, if there is co-morbid depression and anxiety.

Question 20

TCA’s and SSRI’s:

Answer 20

Common anti-depressant drugs with anti- cholinergic effects.

• TCA is better suited for people with IBS-D
• TCA’s are more reliable than SSRI’s on the GI tract.

Question 21

Amitriptyline:

Answer 21

TCA which exhibits anti cholinergic effects.

• Off target effects
• Normally, constipation is considered an adverse effect of TCA’s but in this case, it can be used to treat IBS-D

-Can also be prescribed to treat chronic pain.

Question 22

Citalopram:

Answer 22

SSRI

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