GI: Diarrhea, Abdominal Pain, and Constipation

Question 1

What 5 drug classes can be sed for diarrhea?

Answer 1

1. Prostaglandin Inhibitors
   - Bismuth
2. Opioid Agonists
   - loperamide, diphenoxylate, eluxadoline
3. 5HT3 antagonists
   - alosetron
4. Cl Channel Inhibitors
   - Crofelemer

Question 2

Does loperamide cross the BBB?

Answer 2

No, so no need to worry about addiction as much

-watch for cardiac toxicities though!

Question 3

MOA for loperamide and diphenoxylate?

Answer 3

Interferes with peristalsis, so it slows transit time

-increases segmental peristalsis, so increases bulk

Question 4

Side effects for Mu Opioids (loperamide and diphenoxylate)?

Answer 4

Anticholinergic (Dry as a cracker, hot as a hare, mad as a hatter, red as a beet.. you get it)

Question 5

What is given with diphenoxylate to prevent addiction?

Answer 5

Can cross BBB, so give with small dose of atropine to avoid overdose

Question 6

MOA for Eluxadoline?

Answer 6

Mu and Kappa agonist
-slows peristalsis

Antagonist at Delta opioid receptors
-stomach, pancreas, biliary secretions decreased

Question 7

When would you prescribe eluxadoline?

Answer 7

IBS, diarrhea predominant

Question 8

Side effects for Eluxadoline?

Answer 8

Hepato/pancreatotoxicity
-pancreatitis is especially high risk in those without gallbladder

CNS related
-sedation, euphoria, impaired cognition

Question 9

If a patient doesnt have a gallbladder, what do you need to watch out for in a patient taking eluxadoline?

Answer 9

Pancreatitis

-deaths have occurred due to this

Question 10

What are some contraindications to taking eluxadoline?

Answer 10

1. Biliary obstruction
2. alcoholism
3. pancreatitis
4. Severe hepatic impairment (liver disease, cirrhosis)

Question 11

If a patient is taking eluxadoline and has constipation for more than 4 days, what should you do?

Answer 11

Stop the therapy!

Question 12

What is the indication for alosetron?

Answer 12

Chronic, severe IBS-D that is unresponsive to other therapies (especially in women)

Question 13

Say a patient has IBS-D, and has tried all other conventions to stop it and all have failed.. what would you presribe?

Answer 13

Alosetron

Question 14

Side effects for Alosetron?

Answer 14

1. Ischemic Colitis
   - pts must have follow up to get again, patients at significant risk!
2. GI related
   - constipation, dyspepsia

Question 15

Contraindications for alosetron?

Answer 15

History or current:

• GI obstruction, perf, toxic megacolon
• diverticulitis, Chrons, UC
• Severe constipation
• -STOP IMMEDIATELY

Question 16

What drug is derived from the dark red sap of the Croton lechleri tree?

Answer 16

Crofelemer

-Cl- channel blocker

Question 17

MOA of Crofelemer?

Answer 17

Inhibits Cl- secretion by blocking cAMP stimulated CFTR

-less Cl- means less water.. so bulks up the stool

Question 18

If an HIV/AIDs patient comes in with diarrhea that is caused by their antiretroviral therapy what should you prescribe?

Answer 18

Crofelemer

Question 19

Side effects for crofelemer?

Answer 19

GI issues
-abdominal distention, elevated AST/ALT

Infections
-respiratory/urinary

Question 20

Agents used for Abdominal pain, mainly IBS related?

Answer 20

Antimuscarinic agents

1. Hyoscamine
2. Dicyclomine

Question 21

MOA of hyoscamine and Dicyclomine?

Answer 21

they are antimuscarinic agents, so competitively inhibit post ganglionic cholinergic receptors

Question 22

Side effects of hyoscamine and Dicyclomine?

Answer 22

They are antimuscarinic agents, so Dry as a cracker, hot as a hare, mad as a hatter, red as a beet.. you get it

Question 23

Drugs used for constipation

Answer 23

1. Laxatives
2. Peripheral Opioids
   - methylnaltrexone, naloxegol, alvimopan
3. Guanylate Cyclase Agonists
   - Linaclotide
4. Selective Cl (C2) channel activators
   - lubiprostone

Question 24

MOA of Methylnaltrexone, naloxegol, and alvimopan?

Answer 24

They are peripheral mu-opioid receptor antagonists

-so block the effects to relieve constipation

Question 25

If a patient is taking and opioid and are constipated.. what should you prescribe?

Answer 25

A mu opioid antangonist -Methylnaltrexone, naloxegol, or alvimopan or Lubiprostone

Question 26

If you are wanting to accelerate GI recovery for a patient following bowel resection surgery with an anastomosis.. what would you prescribe?

Answer 26

Alvimopan

Question 27

What is a warning when taking alvimopan?

Answer 27

can cause MI | -Max of 15 doses according to REMS program

Question 28

MOA for LIncaclotide?

Answer 28

Activates guanylate cyclase-c for constipation | -stimulates CFTR ion channel, more Cl- in lumen, water will follow to relieve constipation

Question 29

When would you prescribe lincaclotide?

Answer 29

1. IBS-C | 2. Chronic Idiopathic Constipation

Question 30

MOA of lubiprostone?

Answer 30

A prostaglindin E derivative for constipation -activates ClC-2 channels, Cl- out and water will follow to relieve constipation First three letters are Lub(e), so it helps things slide out

Question 31

Indications for Lubiprostone?

Answer 31

1. IBS-C (women) 2. Chronic Idiopathic Constipation 3. Opoid induced constipation

Question 32

What are the bulk forming agents used in diarrhea?

Answer 32

Fiber/Bran Psyllium Cellulose agents Calcium Polcarbophil

Question 33

Adverse effects of bulk forming agents?

Answer 33

Bloating and obstruction -must drink lots of water Also interactions with drugs!

Question 34

What agents are used as stool softeners? how do they work?

Answer 34

1. Docusate salts 2. Mineral Oil Work to lubricate feces and decrease fluid resorption from GI tract

Question 35

Which agents are used as stimulants (irritants) for laxatives?

Answer 35

``` Senna Bisacodyl Castor Oil Glycerin Sodium Picosulfate ```

Question 36

Which stimulate is used for pre-colonoscopy bowel prep?

Answer 36

Sodium picosulfate

Question 37

MOA of stimulants?

Answer 37

1. Irritate the enterocytes, leads to inflammation - causes Na/K inhibition and can increase prostaglindin synthesis 2. Promote water/electorlyte accumulation in GI

Question 38

What is castor oil hydrolyzed to?

Answer 38

ricinoleic acid

Question 39

Which of the stimulates acts as a tri-hydroxyl alcohol and functions as an irritant, osmotic agent, and lubricant?

Answer 39

Glycerin

Question 40

When is the effect of stimulants noticed?

Answer 40

12-36 hours

Question 41

Which stimulant can cause red/brown urine?

Answer 41

Senna

Question 42

What are the two saline agents used as laxatives?

Answer 42

1. Magnesium salts (mag. sulfate, mag. hydroxide) | 2. Sodium Phosphate

Question 43

How do the saline agents work?

Answer 43

Magnesium/phosphate is poorly absorbed, so created a hyperosmolar solution to retain water in GI tract

Question 44

What drugs do saline agents interact with?

Answer 44

diuretics

Question 45

What are the contraindications in someone taking a saline agent as a laxative?

Answer 45

``` Renal Disease (electrolytes) CHF/HTN ```

Question 46

What are the osmotic agents used as a laxative?

Answer 46

lactulose Magnesium Citrate Sorbitol Polyethylene Glycol Effects seen in 1-3 hours in large doses

Question 47

What can lactulose be used for besides as a laxative?

Answer 47

Severe liver disease (Hepatic Encephalopathy) causing hyperammonemia, as it changes pH to trap ammonia in GI

Question 48

What are the adverse effects of osmotic agents?

Answer 48

Can cause severe dehydration fro electrolyte disturbances | -so watch at risk populations!

Question 49

Which osmotic agents is used in large doses for bowel prep?

Answer 49

Polyethylene glycol | -smaller doses for constipation