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GI II Exam 1. > Lecture 12: Treatments for Diarrhea, Abdominal Pain, and Constipation > Flashcards

Lecture 12: Treatments for Diarrhea, Abdominal Pain, and Constipation Flashcards

1
Q

What are the 3 Opioid Agonists used to treat diarrhea?

A
  1. Loperamide
  2. Diphenoxylate
  3. Eluxadoline
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2
Q

What is the MOA of Loperamide as an Anti-diarrheal?

A
  • Interferes w/ peristalsis (slows transit time)
  • Direct action on circular and longitudinal ms. of intestinal wall
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3
Q

What is one of the serious side-effects related to Loperamide?

A

Cardiac toxicities leading to death

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4
Q

Which anti-diarrheal agent is given with a small amount of atropine to discourage abuse/OD’s?

A

Diphenoxylate (opioid agonist)

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5
Q

MOA of Diphenoxylate?

A
  • Exerts effects locally and centrally on GI smooth muscle cells
  • Inhibits GI motility
  • Slow excess GI propulsion
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6
Q

What is the MOA of the anti-diarrheal Eluxadoline?

A
  • Agonist at opioid mu and kappareceptors inGI tract –> slows peristalsis/delays digestion
  • Antagonist at delta opioid receptors in GI –> ↓ stomach, pancreas and biliary secretion
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7
Q

Eluxadoline (opioid agonist) is indicated for use in which patients?

A

IBS-D (diarrhea predominant subtype)

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8
Q

What is the the most serious adverse effect associated with Eluxadoline?

Which patients are most at risk?

A
  • Hepatic/pancreatic toxicity
  • Pancreatitis = high-risk in pts w/o GB –> DEATHs have occurred
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9
Q

The anti-diarrheal, Eluxadoline, is contraindicated in which 5 conditions?

A

1) Biliary duct obstruction
2) Sphincter of Oddi dysfunction
3) Alcoholism
4) Hx of Pancreatitis
5) Severe hepatic impairment

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10
Q

Therapy with the anti-diarrheal, Eluxadoline, should be stopped if what develops?

A

Severe constipation develops and lasts 4+ days

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11
Q

What is the 5-HT3 antagonist used as an anti-diarrheal?

A

Alosetron

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12
Q

What is the only indication for using the antidiarrheal, Alosetron?

A

Chronic, severe IBS-D that is NOT responsive to other conventional therapies

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13
Q

What is a major adverse effect related to the anti-diarrheal, Alosetron?

If which side effect develops should therapy be stopped?

A
  • Ischemic colitis (black box warning!)
  • Constipation is an adverse effect and if this occurs, STOP THERAPY!
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14
Q

What are the regulations for prescribing the anti-diarrheal, Alosetron due to one of its severe adverse effects?

i.e., what must both the doc and pt do

A
  • No refills w/o a follow up exam!
  • Doc must enroll in prescribing program
  • Doc and pt must sign a risk-benefit statement and agree to adhere to therapy plans
  • Additional self-training and testing by Docs to learn to appropriately Dx IBS required!
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15
Q

What are the contraindications for the anti-diarrheal, Alestron?

A

Hx of Active:

  • GI obstruction, perforation, stricture, adhesion or toxic megacolon
  • Diverticulitis, Chron Dz, or UC
  • Impaired intestinal circulation, thrombophlebitis or a hypercoagulable state
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16
Q

What is the Cl- Channel Inhibitor used as an Anti-diarrheal?

A

Crofelemer

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17
Q

What is the MOA of the anti-diarrheal, Crofelemer?

A

- Inhibits Cl- secretion by blocking:

- cAMP-stimulated CFTR channels and

- Calcium-activated (CaCC) chloride channels

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18
Q

What is the specific indication for using the anti-diarrheal, Crofelemer?

A

Non-infectious diarrhea in HIV/AIDS pts. on anti-retroviral tx

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19
Q

Which drug class is used for abdominal pain/spasms associated with IBS?

A

Anti-muscarinics

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20
Q

What are the 4 antimuscarinics used for abdominal pain/spasms associated w/ IBS?

A
  • Hyoscyamine
  • Dicyclomine
  • Clindinium/Chlordiazepoxide
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21
Q

What is the guanylate cyclase-c agonist used for constipation and it’s two MOA?

A
  • Linaclotide
  • Binds GC-C on luminal surface of intestinal epithelium and increases intra/extracellular [cGMP]
  • Stimulates secretion of Cl-/HCO3- into intestinal lumen via activation of CFTR ion channels
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22
Q

What are the indication for use of the anti-constipation agent, Linaclotide?

A
  • Constipation predominant IBS (IBS-C)
  • Chronic idiopathic constipation (CIC)
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23
Q

What is the Selective Chloride (C2) Channel Activator used for treatment of constipation?

A

Lubiprostone

*“Lubi“-prostone –> “Lubes up the GI”

24
Q

What is the MOA for the anti-constipation drug, Lubiprostone?

A
  • A bicyclic FA, PGE-1 derivative
  • Increases intestinal fluid secretion by activating GI specific chloride channels (CIC-2) in luminal cells of intestinal epithelium
25
Q

What are the 3 specific indications for the use of the anti-constipation agent, Lubiprostone?

A
  • Constipation predominant IBS (IBS-C)
  • Chronic idiopathic constipation (CIC)
  • Opioid-induced constipation (OIC) –> chronic pain, NON-cancer/past cancer adults*****
26
Q

What are the 3 peripheral opioid antagonists used for constipation?

A
  • Methylnaltrexone
  • Naloxegol
  • Alvimopan
27
Q

What is the MOA for the peripheral opioid antagonists used for constipation?

A

Antagonists at peripheral mu-opioid receptors

28
Q

What is the specific indication for the 3 peripheral opioid receptor antagonists used for constipation?

A
  • Opioid-induced constipation (OIC) –> chronic pain, non-cancer/past cancer adults –> Methylnaltrexone and Alvimopan
  • Alvimopan = hospital use ONLY –> for accelerating time to GI recovery following bowel resection surgery (prevention of postoperative ileus)
29
Q

Which peripheral opioid antagonist is for hospital use only and is used to accelerate time to GI recovery post-surgery and for prevention of post-op ileus?

A

Alvimopan

30
Q

Which anti-constipation agent carries a risk of MI with use?

Because of this what is the restriction on its use?

A
  • Alvimopan
  • REMS program requires use only in approved facility for max of 15 doses
31
Q

What are the 5 laxative/cathartic agents used that are bulk forming agents?

A
  • Dietary fiber/bran
  • Psyllium
  • Methylcellulose/Carboxymethylcellulose
  • Calcium polycarbophil
32
Q

How many days does it take to see the efficacy of the bulkforming laxative agents?

A

2-4 days

33
Q

Are there drug-drug interactions with the bulk forming agents, if so which ones specifically?

What is recommended for dosing these agents?

A
  • LOTS! —> Mainly w/ psyllium and the celluloses
  • Recommendation similar to antacids, take 2 hours after other meds
34
Q

Which 2 agents belong to the stool softener category?

A

1) Docusate ‘salts’
2) Mineral oil

35
Q

Stool softening agents are also known as what kind of laxatives?

A
  • Surfactant or Emollient laxatives
36
Q

How do stool softeners work?

A
  • Anionic surfactants = soften/lubricate feces by reducing surface tension
  • Mineral oil is hydrocarbon-based, is indigstible and penetrates stool thereby softening it
37
Q

When is the efficacy of Stool Softeners seen (i.e., how many days)?

A
  • In 1-3 days
  • Minimal laxative effect; softening mainly
38
Q

Which 5 agents belong to the stimulant class of laxatives/cathartic agents?

A
  1. Bisacodyl
  2. Castor oil
  3. Glycerin
  4. Senna
  5. Sodium Picosulfate
39
Q

What is the MOA of the stimulant class of laxatives?

A
  • Irritant to enterocytes, GI smooth m. –> inflammation
  • Na+/K+- ATPase inhibition and/or increase in prostaglandin synthesis/secretion (via cAMP/cGMP)
  • Promote water/electrolyte accumulation in GI
40
Q

Castor oil, part of the stimulant class of laxatives is hydrolyzed into what?

A

Ricinoleic acid —> promotes H2O/electrolyte accumulation in GI

41
Q

Which laxative agent is associated with urine discoloration (yellow-brown/red-pink)?

A

Senna (stimulant class)

42
Q

Sodium picosulfate (stimulant) contains magnesium oxide/anhydrous citric acid and is converted into?

A

Magnesium citrate (osmotic)

43
Q

What is the efficacy of the stimulant class of laxatives (i.e., how long to work)?

Which agent in the class has soonest onset?

A
  • Usually 12-36 hours
  • Sooner w/ glycerin
44
Q

What are the contraindications and cautions for the use of the stimulant class of laxatives?

A
  • Contraindications = GI obstruction, Ileus, or impaction (don’t want to irritate bowel in these pts!)
  • Caution = several of these agents pass into breast milk
45
Q

Which laxative agents are given the evening before colonscopy?

A
  • Sodium Picosulfate (stimulant)
  • Large dose of PEG-3350 = Osmotic
46
Q

What are the 2 agents in the saline class of laxatives?

A

1) Magnesium salts
2) Sodium phosphate

47
Q

What drug interactions must be accounted for when using Saline Agents as laxatives?

A

Diuretics (electrolyte balance)

48
Q

Caution must be taken when using Saline Agents as laxatives in patients with which conditions?

A
  • Renal disease (electrolytes)
  • CHF/HTN (sodium)
49
Q

What are the 4 agents part of the Osmotic class of laxatives?

A
  1. Lactulose
  2. Magnesium Citrate
  3. Sorbitol
  4. PEG-3350
50
Q

What is the MOA of the laxative, Sorbitol?

A

Non-absorbably sugar hydrolyzed to SCFA’s retaining fluid in GI (increased motility)

51
Q

Which osmotic agent is also used for severe liver disease patients w/ hyperammonemia?

Why?

A
  • Lactulose
  • Change in pH traps ammonia in the GI!
52
Q

Adverse effects with osmotic agents used as laxatives?

A
  • Electrolyte disturbances; watch closely
  • Abdominal pain/distention/flatulence
53
Q

What is polyethylene glycol (PEG-3350) used for?

A
  • Large doses for bowel prep prior to GI scopes, radiological procedures or surgery
  • Small doses for constipation
54
Q

What is the efficacy of large doses vs. smaller doses of osmotic agents as laxatives?

A
  • Large doses = 1-3 hours
  • Smaller doses = 0.5 to 3 days
55
Q

Which laxative/cathartic agent is a tri-hydroxyl alcohol that functions as an irritant (stimulant), osmotic, and lubricant agent?

A

Glycerin

GI II Exam 1. (25 decks)

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