23. Lower GI Pharm (irritable bowel)

Question 1

What is irritable bowel syndrome (IBS)?

Answer 1

Very common
Challenging to treat
Constipation (IBS-C), diarrhea (IBS-D), or mixed

Bowel symptoms managed as noted (laxatives or anti-diarrheals)
Abdominal pain very hard to treat

Slides 4-7

Question 2

What drugs are used for IBS and pain?

Answer 2

Antispasmodics:
Anticholinergics
Calcium antagonists (GI tracts)

Question 3

What are anticholinergics?

Answer 3

Hyoscine
Muscarinic (M) receptors stimulate peristalsis in the GI tract (rest and digest)
Blocking M receptors inhibits contractions of the colon

Side effects: dry mouth, urinary retention, constipation (usual anticholinergic affects)

Slides 8-9

Question 4

What are calcium antagonists?

Answer 4

Pinaverium
Blocks entry of Ca into smooth muscle cells of the GI tract
Ca plays critical role in smooth muscle contraction
Therefore blocking Ca inhibits smooth muscle contraction

Side effects: constipation, abdominal distension, esophageal irritational

Slides 10-11

Question 5

What is linaclotide?

Answer 5

Cyclic guanosine monophosphate (cGMP) agonist

Increases intestinal secretions
Reduces transmission of pain signals

Slide 12

Question 6

What is inflammatory bowel disease (IBD)?

Answer 6

Sever inflammation (and it’s destructive)

Can involve anywhere along the GI tract

2 major types:
Ulcerative colitis (limited time colon)
Crohn’s disease 

Inflammation can destroy intestinal mucosa (painful)

Complications like bleeding, perforation, sepsis

Slides 16-19

Question 7

What is used to treat inflammatory bowel disease (IBD)?

Answer 7

Aminosalicylates
Corticosteroids
Immunosuppressants
TNF inhibitors

Inflammation and immune responses are the key processes in the disease

Question 8

What are aminosalicylates used in IBD?

Answer 8

5-aminosalicylic acid (5-ASA or mesalamine)

Anti-inflammatory activity, inhibits inflammatory mediators including tumour necrosis factor (TNFα), also may inhibit cyclooxygenase (COX)

Prodrugs cleaves to colon, enteric coating dissolved in colon, microspheres releasing drug slowly, rectal administration

Side effects: GI (worse than sulfasalazine), headache,

Slides 20-27

Question 9

What is the prodrug aminosalicylates?

Answer 9

Sulfasalazine

5-ASA + sulfapyridine
2 molecules separated in colon by bacteria

Slide 23

Question 10

What is enteric coating in aminosalicylates?

Answer 10

Enteric coating (EC)
5-ASA EC
Delayed release of 5-ASA, based on pH (drug not released in low pH of stomach)
Begin releasing drug in terminal ileum, continue through to rectum

Slide 24

Question 11

What are extended release (ER) microspheres in aminosalicylates?

Answer 11

5-ASA ER
Release 5-ASA throughout the small intestine to rectum

Slides 25-26

Question 12

What are corticosteroids used in IBD?

Answer 12

Prednisone, budesonide
Budesonide has low oral bioavailability (intended to act locally in GI tract

Anti inflammatory effects

Side effects: numerous with systemic agents like prednisone, fewer side effects with budesonide

Slides 30-31

Question 13

What is microbiota with health and disease?

Answer 13

Increasing recognition of the role of bacteria in general health, both good and bad bacteria
Small intestinal bacteria overgrowth is a phenomena where there is excess bacteria in the gut

Many ways to treat IBS may be to target gut bacteria with an antibiotics (rifaximin)

Slides 34-37