Lower GI Pharmacology

Question 1

Best anti-diarrheal agent
Poorly penetrates the CNS
u receptor agonist

Answer 1

Loperamide (Imodium)

Question 2

Anti-diarrheal agonist

Can produce CNS effects – abuse potential given with atropine

Answer 2

Diphenoxylate (Lomotil)

Question 3

Absorbs water and increases stool bulk

Answer 3

Bulk forming and absorbents: Kaolin (clay) + pectin (Kaopectate); also fiber

Question 4

Includes bismuth which is thought to have anti-secretory, anti-inflammatory and anti-microbial effects
Use to prevent and treat traveler’s diarrhea

Answer 4

Bismuth subsalicylate (pepto bismol)

Question 5

Somatostatin analog; inhibits secretory diarrhea d/t hormone-secreting tumors of the pancreas and GI tract

Answer 5

Octreotide (Sandostatin)

Question 6

Off-label uses for Octreotide

Answer 6

Post operative dumping syndrome, variceal bleeding, other forms of diarrhea

Question 7

3 mechanims laxatives work by

Answer 7

1. enhancing the retention of intraluminal fluid by hydrophilic or osmotic mechanisms
2. decreasing net absorption or increase secretion of fluid by effects on small- and large-bowel fluid and electrolyte transport
3. altering motility

Question 8

Mechanism of dietary fiber

Answer 8

Fiber fermented by the colon bacteria produces short chain fatty acids which are somewhat prokinetic and trophic for the endothelium
Fermentation increases stool bacterial mass

**Non-fermented fiber retains water and increases stool bulk

Question 9

Inorganic salts that are not absorbed causes water retention
Bowel cleansing products

Answer 9

Milk of Magnesia (MgOH2)

Question 10

Osmotic laxative

Unabsorbed carbohydrate metabolized to short chain fatty acids by gut bacteria

Answer 10

Lactulose

Question 11

Another use of Lactulose

Answer 11

Portal-systemic encephalopathy – can decrease ammonia levels

Question 12

Not absorbed, remains in the lumen
Retain water due to osmotic grade
May be given with isotonic Na and K salts (prevent net ionic shift)

Answer 12

Polyethylene Glycol (PEG, Miralax)

Question 13

Anionic surfactant, lowers surface tension

Answer 13

Ducosate salts (bilax, colace)

Question 14

Stimulant laxatives

Cause mucosa inflammation/irritation

Answer 14

Contact cathartics

Question 15

Laxative
Diphenylmethane, Prodrug - converted by bowel esterases
Acts on large intestine

Answer 15

Bisacodyl

Question 16

Laxative
Anthraquinone cathartics, Prodrug - requires colonic bacteria
Plant derivative
Acts on large intestine

Answer 16

Senna

Question 17

Prostanoid
Activates chloride channels in the intestine to increase fluid secretion
Not absorbed and only acts in intestinal lumen
Used for adult chronic constipation and women with IBS

Answer 17

Lubiprostone

Question 18

Binds and activates guanylate cyclase C receptor on the luminal surface of intestinal epithelial cells to increase intracellular and extracellular cGMP –> chloride and bicarb secretion, extracellular cGMP may decrease visceral pain

Used for chronic idiopathic constipation, irritable bowel syndrome with constipation

Answer 18

Linaclotide

Question 19

Opioid receptor antagonist

For constipation

Answer 19

Methylnaltrexone

Question 20

5HT3 receptor antagonist used for diarrhea dominant irritable bowel syndrome (restricted use)

Answer 20

Alosetron

*Concern with increased incidence of ischemic colitis with use

Question 21

Therapeutic goals of IBD

Answer 21

1. Treat acute attacks
2. Maintain remission - long term management
3. Treat complications

Question 22

Used for mod-severe acute attacks

Disadvantage – systemic affects

Answer 22

Prednisone

Question 23

Enteric release steroid used for Crohn’s disease to target the inflamed gut –> less side effects

Answer 23

Budesonide

Question 24

5-aminosalicylate
Delayed time or pH dependent release
For mild to moderate UC (less effective for Crohn’s)

Answer 24

Mesalamine

Question 25

5-aminosalicylate

Prodrugs – converted to Mesalamine

Answer 25

Olsalazine

Sulfasalazine

Question 26

SE of Sulfasalazine

Answer 26

Related to sulfapyridine and include fever, malaise, vomiting, headache

Question 27

SE of Mesalamine

Answer 27

Relatively infrequent and minor and include headache, dyspepsia, and skin rash

Question 28

SE of Olsalazine

Answer 28

Diarrhea

Question 29

Which patients should you avoid 5-aminosalicylates in?

Answer 29

Contraindicated in patients allergic to salicylate

Question 30

Thiopurine antimetabolites for IBD

Answer 30

6-mercaptopurine

Azathioprine

Question 31

What is azathioprine metabolized to?

Answer 31

6-mercaptopurine

Question 32

SE of Azathioprine?

Answer 32

Numerous, bone marrow suppression, vomiting, jaundice, pancreatitis
Used for both UC and Crohn’s

Question 33

Dihydrofolate reductase inhibitor, off label use for Crohn’s

Answer 33

Methotrexate

Question 34

Calcineurin inhibitor off label use for ulcerative colitis

Answer 34

Cyclosporine

Question 35

Immunoglobulin against TNFalpha

Used for moderate to severe Crohn’s and UC

Answer 35

Infliximab

Question 36

SE of Infliximab

Answer 36

Lupus-like syndrome, delayed hypersensitivity, infection

Increased URI and increased incidence of non-Hodgkin lymphoma

Question 37

Recombinant human IgG1 monoclonal antibody against TNFalpha

Used for IBD

Answer 37

Adalimumab (Humira)

Question 38

A pegylated humanized antibody Fab fragment of TNFalpha monoclonal antibody
Used for IBD

Answer 38

Certolizumab pegol (Cimzia)

Question 39

Monoclonal antibody against 4-integrin

Binds 4-integrin and reduces leukocyte extravasation

Answer 39

Natalizumab (Tysabri)

Question 40

Why isn’t Natalizumab used very often?

Answer 40

Increases the risk of progressive multifocal leukoencephalopathy (PML)