Drugs for Lower GI Tract

Question 1

What is the clinical use for lubiprostone?

Answer 1

It is a stimulant laxative used for idiopathic chronic constipation in adults. It is approved for chronic use.

Question 2

Name the saline laxative and describe its mechanism of action.

Answer 2

Mg(OH)2: It is administered as a hypertonic solution and the osmotic pressure leads to accumulation of fluids in the GI tract and stimulation of peristalsis.

Question 3

What is the clinical use of Mg(OH)2?

Answer 3

It is used for complete evacuation in under 3 hours for things like colonoscopy prep. Also treats constipation in IBS pts.

Question 4

In which kind of patient should Mg(OH)2 be used with caution?

Answer 4

A renal insufficient patient. This laxative increases the risk of hypermagnesemia.

Question 5

Name the anti-diarrheals.

Answer 5

Loperamide (aka Immodium) and Alosetron

Question 6

Describe the mechanism of action of Loperamide (Immodium).

Answer 6

It is an opioid with low abuse potential d/t poor GI absorption. Slows intestinal transit time by stimulating mu opioid receptors in the intestinal smooth muscle.

*Loperamide- low potential for abuse

Question 7

In which kind of patient should Loperamide be avoided?

Answer 7

Patients w/ ulcerative colitis or acute bacillary/amoebic dysentery b/c of risk of toxic megacolon

Question 8

What is the clinical use of Loperamide?

Answer 8

It treats diarrhea in pts w/ IBS

Question 9

What is the clinical use of Alosetron?

Answer 9

Diarrhea in women, predominantly IBS

Question 10

What is a rare but serious side effect associated with Alosetron?

Answer 10

Ischemic colitis

Question 11

Describe the mechanism of action of Alosetron.

Answer 11

It’s a 5-HT3 receptor antagonist. It decreases colonic motility via enteric and CNS blockade of the 5-HT3 receptors.

Question 12

Name the stimulant laxative and describe its mechanism of action.

Answer 12

Lubiprostone: Cl- channel activator that increases intestinal fluid secretion resulting in increased BMs. Binds to the CIC-2 Cl- channel inducing secretion of Cl- into lumen where Na+ will seek to bind the Cl- for isoelectricity, dragging water with it.

*when stimulated, you use lube ;)

Question 13

Name the mesalamine and its mechanism of action.

Answer 13

Sulfasalazine: The mechanism is not fully understood but it seems to interfere w/ intermediates in inflammatory pathways. It is only effective topically, not systemically.

Question 14

What is the clinical use for sulfasalazine?

Answer 14

It is first-line tx for ulcerative colitis

Question 15

What side effects are associated with sulfasalazine use?

Answer 15

40% of patients can’t tolerate this drug. It can cause n/d, headaches, hypersensitivity, and bone marrow suppression

Question 16

Name the corticosteroid discussed in lecture and its clinical use.

Answer 16

Prednisone: Used for episodic IBD (**not long-term tx) to rapidly reduce ulceration and cause initial remission by decreasing inflammatory response.

Question 17

Name the thiopurine anti-metabolite and its clinical use.

Answer 17

Azathioprine: Long-term immunosuppression therapy for IBD.

Question 18

What are the side effects and drawbacks associated with azathioprine?

Answer 18

It may take 3-6 months to reach maximal effect and polymorphisms can greatly impact efficacy and side effects of this drug. Typical side effects include bone marrow suppression**, pancreatitis, elevated LFTs, rashes, fever, and nausea

Question 19

Name the TNFa inhibitor and its clinical use.

Answer 19

Infliximab: Approved for use in ulcerative colitis.

Question 20

Describe the mechanism of infliximab.

Answer 20

It is an antibody to TNF-alpha that binds to TNF-alpha effectively blocking its inflammatory effects at TNF receptors

Question 21

What side effect is associated with infliximab use?

Answer 21

Increased infections