Lecture 3 Part 2: LOWER GI Drugs (MOST QUESTIONS)

Question 1

What are the 2 Stimulant laxative prototype drugs?

What is their general MOA?

Answer 1

1. Lubiprostrone
2. Linaclotide

MOA: Cl- channel activators
- incr intestinal fluid secretion –> incr # of BMs –> SOFT/Semi fluid stools in 6 hrs

Question 2

Specific MOA for Lubiprostone?

Answer 2

DIRECTLY activates Cl C2 channel

Question 3

Specific MOA for Linaclotide?

Answer 3

Activates the CTFR channel via cGMP

Question 4

AEs for Lubiprostone & Linaclotide?

Answer 4

Both S/E = Diarrhea but worse in Linaclotide

Lubiprostone = N/, abd pain & distention

Question 5

Uses for BOTH Lubiprostone & Linaclotide?

Answer 5

IBS-C

Question 6

CI for Linaclotide?

Answer 6

Pediatric Patients –> incr mortality in mice

Question 7

What is the saline/osmotic laxative prototype drug? MOA?

Answer 7

Magnesium Hydroxide

MOA: incr stool freq/loosens it –> WATERY EVACUATION in 1-3 HOURS (faster than stimulant)

Question 8

How is Magnesium Hydroxide administered as a saline/osmotic laxative? Effects?

Answer 8

Admin by mouth as hypertonic solution –> osmotic pressure –> acculm of intestinal fluids –> stimulates peristalsis

Question 9

Why must caution be used for Magnesium Hydroxide in renal insufficiency?

Answer 9

Incr risk of HYPERmagnesemia

Question 10

Uses for Magnesium Hydroxide?

Answer 10

1. IBS-C
2. Colonoscopy prep
   - give cathartic dose –> complete evacuation in < 3 hrs

Question 11

What are the 2 Anti-diarrheal prototype drugs?

Answer 11

1. Loperamide (Immodium)

2. Alosetron

Question 12

MOA for Loperamide (Immodium)?

Use?

Answer 12

Mu opioid rec agonist in intestinal smooth muscle –> SLOWS GI transit time

DOESNT HELP w/PAIN

Use = IBS-D

Question 13

AEs for Loperamide (Immodium)?

Answer 13

Constipation (duh)

Can cross BBB, at high dose –> CNS toxicity but not big problem w/Loperamide (Immodium)

Question 14

Why must you avoid Loperamide (Immodium) in pts w/UC, acute bacillary and amoebic dysentery?

Answer 14

Risk of toxic megacolon

Question 15

MOA for Alosetron?

Answer 15

5-HT3 receptor antagonist –> decrease motility in colon

Question 16

3 Major AEs a/w Alosetron?

Answer 16

1. Ischemic Colitis**
2. Constipation (duh again)
3. Toxic megacolon

Question 17

When/what population can Alosetron be used for?

Answer 17

When std therapies fail –> use Alosetron for WOMEN w/ IBS-D

Question 18

What type of drug is Sulfasalazine?

Answer 18

Mesalamine (5-ASA)

Question 19

What form of Sulfasalazine is most effective and where?

Answer 19

Topical = Most effective form

Most effective at delivering 5-ASA to SI

Question 20

Why can some patients not tolerate Sulfasalazine?

Note: new formulations better tolerated

Answer 20

Sulfapyridine moiety

Question 21

For what dz is Sulfasalazine the 1st line Tx?

Answer 21

UC

Question 22

Why are corticosteroids (prednisone) used for IBD?

NOTE: THEY CANNOT BE USED LONG TERM

Answer 22

Steroids decrease the inflammatory response –> rapidly reduce ulceration & cause remission

Question 23

What type of drug is Azathioprine?

MOA for Azathioprine?

Answer 23

immunosuppressive

Thiopurine anti-metabolite –> blocks DNA synthesis

Question 24

Major AEs for Azathioprine?

Answer 24

Bone marrow suppression**

Others: pancreatitis, Incr LFTs, rash, fever, N/, toxic metabolite

Question 25

Azathioprine is used for long term therapy of IBD but what is the drawback?

Answer 25

Clinical response can take weeks to months

Question 26

What type of drug is Infliximab?
MOA for Infliximab?

Note: for both UC & Crohn’s

Answer 26

TNF alpha inhibitor

infliximab binds to TNF alpha –> blocks inflammatory effects