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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
What are the 3 specific indications for the use of the anti-constipation agent, Lubiprostone?
- **Constipation** predominant IBS (**IBS-C**) - Chronic **idiopathic** constipation (**CIC**) - **Opioid-induced constipation** (**OIC**) --\> **chronic pain, NON-cancer/past cancer adults\*\*\*\*\***
26
What are the 3 peripheral opioid antagonists used for constipation?
- Methyl**naltrexone** - Naloxegol - Alvim**op**an
27
What is the MOA for the peripheral opioid antagonists used for constipation?
Antagonists at peripheral **mu-opioid** receptors
28
What is the specific indication for the 3 peripheral opioid receptor antagonists used for constipation?
- **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
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**?
Alvimopan
30
Which anti-constipation agent carries a risk of **MI** with use? Because of this what is the restriction on its use?
- **Alvimopan** - **REMS** program requires use **only** in approved facility for **max of 15 doses**
31
What are the 5 laxative/cathartic agents used that are **bulk forming** agents?
- **Dietary fiber/bran** - Psyllium - Methyl**cellulose/**Carboxymethyl**cellulose** - Calcium polycarbophil
32
How many days does it take to see the efficacy of the **bulkforming** laxative agents?
2-4 days
33
Are there drug-drug interactions with the bulk forming agents, if so which ones specifically? What is recommended for dosing these agents?
- **LOTS! ---\>** Mainly w/ **psyllium** and the **celluloses** - Recommendation similar to antacids, take **2 hours after other meds**
34
Which 2 agents belong to the stool softener category?
1) **Docusate 'salts'** 2) **Mineral oil**
35
Stool softening agents are also known as what kind of laxatives?
- **Surfactant** or **Emollient** laxatives
36
How do stool softeners work?
- Anionic **surfactants** = soften/lubricate feces by reducing surface tension - Mineral oil is hydrocarbon-based, is indigstible and penetrates stool thereby softening it
37
When is the efficacy of Stool Softeners seen (i.e., how many days)?
- In **1-3 days** - Minimal laxative effect; softening mainly
38
Which 5 agents belong to the **stimulant** class of laxatives/cathartic agents?
1. Bisacodyl 2. Castor oil 3. Glycerin 4. Senna 5. Sodium Picosulfate
39
What is the MOA of the **stimulant class** of laxatives?
- **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
Castor oil, part of the stimulant class of laxatives is hydrolyzed into what?
**Ricinoleic acid** ---\> promotes H2O/electrolyte accumulation in GI
41
Which laxative agent is associated with urine discoloration (yellow-brown/red-pink)?
**Senna** (stimulant class)
42
Sodium picosulfate (**stimulant**) contains magnesium oxide/anhydrous citric acid and is converted into?
Magnesium citrate (**osmotic**)
43
What is the efficacy of the stimulant class of laxatives (i.e., how long to work)? Which agent in the class has soonest onset?
- Usually **12-36 hours** - **Sooner** w/ **glycerin**
44
What are the contraindications and cautions for the use of the stimulant class of laxatives?
- **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
Which laxative agents are given the evening before colonscopy?
- **Sodium Picosulfate** (stimulant) - Large dose of **PEG-3350 = Osmotic**
46
What are the 2 agents in the **saline** class of laxatives?
1) **Magnesium** salts 2) Sodium **phosphate**
47
What drug interactions must be accounted for when using Saline Agents as laxatives?
Diuretics (**electrolyte** balance)
48
Caution must be taken when using Saline Agents as laxatives in patients with which conditions?
- Renal disease (**electrolytes**) - CHF/HTN (**sodium**)
49
What are the 4 agents part of the Osmotic class of laxatives?
1. Lactulose 2. Magnesium Citrate 3. Sorbitol 4. PEG-3350
50
What is the MOA of the laxative, Sorbitol?
Non-absorbably sugar hydrolyzed to SCFA's retaining fluid in GI (increased motility)
51
Which osmotic agent is also used for severe liver disease patients w/ hyperammonemia? Why?
- **Lactulose** - Change in pH **traps ammonia in the GI**!
52
Adverse effects with osmotic agents used as laxatives?
- Electrolyte disturbances; **watch closely** - Abdominal pain/distention/flatulence
53
What is polyethylene glycol (PEG-3350) used for?
- **Large** doses for **bowel prep prior to GI scopes**, radiological procedures or surgery - **Small** doses for **constipation**
54
What is the efficacy of large doses vs. smaller doses of osmotic agents as laxatives?
- **Large doses** = 1-3 **hours** - **Smaller doses** = 0.5 to 3 **days**
55
Which laxative/cathartic agent is a tri-hydroxyl alcohol that functions as an **irritant (stimulant), osmotic**, and **lubricant** agent?
Glycerin

GI II Exam 1. (25 decks)

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