15 - GI Pharmacology III

Question 1

What is irritable bowel syndrome?

Answer 1

Irritable bowel syndrome is an idiopathic chronic relapsing disorder characterized by abdominal discomfort (pain, bloating, distension, or cramps) in association with alterations in bowel habits (diarrhea, constipation, or both)

Question 2

What is the cause of IBS?

Answer 2

The cause is uncertain and the best therapeutic strategy to treat the disease is questionable.

Question 3

What is the goal of current treatment strategies?

Answer 3

Current treatment strategies target relieving pain and improving bowel function

Question 4

Describe the basics of treatment for IBS

Answer 4

Common therapeutic strategies take advantage of loperamide to reduce diarrhea, osmotic laxatives to relieve constipation, as well as tricyclic antidepressants and antispasmodics antimuscarinics to relieve pain.

Question 5

Describe treatments that target serotonin receptors

Answer 5

• Activation of both 5-HT3 and 5-HT4 receptors stimulate motility
• 5-HT3 receptors are also responsible for relaying sensory information such as pain to the CNS

Question 6

Describe the differences in targeting 5-HT3 receptors and 5-HT4 receptors

Answer 6

• Antagonizing 5-HT3 pain receptors can be used to relieve pain and diarrhea
• Agonizing 5-HT4 receptors can be used to relieve IBS-associated constipation

Pretty much…

• 3 = block for blocking pain
• 4 = stimulate to relieve constipation

Question 7

What are the two drugs used to treat IBS?

Answer 7

• Tegaserod

- Alosetron

Question 8

What is the mechanism of action of Tegaserod

Answer 8

Partial agonist of 5-HT4 ***

This means that it is used to relieve the symptoms of constipation

Question 9

What are the adverse effects of tegaserod?

Answer 9

Note that it is NOT available for general use right now

• GI pain, dyspepsia, flatulence, nausea, vomiting, diarrhea
• MI and stroke risk

Question 10

What is the mechanism of action for alosetron?

Answer 10

Antagonist of 5-HT3 ***

This means that it blocks the receptors which send pain signals to the CNS, relieving the pain associated with IBS

It is used in IBS-diarrhea dominant cases in women

Question 11

What are the adverse effects of alosetron?

Answer 11

• Constipation in 29%
• Ischemic colitis (fatal)

This is a LAST resort drug for this reason

Question 12

What are the two distinct diseases that inflammatory bowel disease (IBD) can be divided into?

Answer 12

• Ulcerative colitis
• Crohn’s disease

Both are INFLAMMATORY diseases

Question 13

Describe Crohn’s disease

Answer 13

• Can affect anywhere in the GI tract from mouth to anus
• Most commonly seen in the ileum (small intestine)
• The site of origin is the intestinal submucose and eventually spreads to the mucosa and serosa
• Characterized by “skip lesions”

Question 14

Describe ulcerative colitis

Answer 14

• Inflammation of the GI tract in the large intestine only

- Originates in the crypts of Lieberkuhn

Question 15

What are the 6 drugs used to treat IBD that you need to know?

Answer 15

1 - Sulfasalazine
2 - Mesalamine
3 - Prednisone
4 - Azathioprine
5 - Methotrexate
6 - Infliximab

Question 16

Which two are aminosalicylates?

Answer 16

• Sulfasalazine

- Mesalamine

Question 17

Sulfasalazine and mesalamine are the first line treatment for which condition?

Answer 17

Mild to moderate ulcerative colitis

Question 18

What is unique about the mechanism of the two aminosalicylates?

Answer 18

They work “topically”

• This means they need to work on the top of the mucosal surface of the GI tract
• They do not work if they have been absorbed into the blood stream and reach the inflamed tissues by the blood

Question 19

Describe the action of aminosalicylates once they reach their target “topically”

Answer 19

Unknown

• May inhibite inflammatory cytokines (IL-1 and TNF-alpha)
• Scavenge free radicals
• Inhibit COX

Question 20

Which of the 6 IBD drugs is a glucocorticoid?

Answer 20

Predinsone

Question 21

Describe the treatment of IBD patients with prednisone and other glucocorticoid drugs

Answer 21

• First, steroid-responsive patients will have a decrease in IBD related symptoms and remain symptom free following the steroid treatment regimen.
• Second, steroid-dependent patients will have a relapse of IBD symptoms during a tapering period of drug administration or following the termination of treatment.
• Finally, steroid-unresponsive patients do not find relief from IBD symptoms during steroid treatment.

Question 22

What patients would you treat with glucocorticoids like prednisone?

Answer 22

Patients with moderate to severe active IBD

Question 23

Which two of the six IBD drugs are chemo drugs? Why are they effective?

Answer 23

• Axathioprine
• Methotrexate

Used for their immunosuppressive effects - they are particularly useful with steroid-dependent and steroid-unresponsive patients

Also used for the maintenance of remession for patients with IBD (axathioprine) and Crohn’s specifically (methotrexate)

Question 24

Which of the six IBD drugs is an immunoglobulin drug?

Answer 24

Inflixamab

Question 25

Describe the mechanism of infliximab

Answer 25

• It binds to and sequesters TNF-alpha
• This prevents it from stimulating inflammatory cytokines
• It therefore inhibits the inflammatory process ***

Question 26

Which patients would you treat with infliximab?

Answer 26

Patients with moderate to severe IBD