GI Motility 3 Flashcards
1
Q
Definition of what?
- A chronic functional disorder of the gastrointestinal tract characterized by chronic abdominal pain and altered bowel habits in the absence of an organic disease
A
Irritable Bowel Syndrome (IBS)
2
Q
What are the 5 sxs of IBS?
A
- Abdominal pain
- Distention
- Bloating
- Indigestion
- Various symptoms of defecation
3
Q
What are the 3 “subcategories” of IBS?
A
- pain associated with diarrhea (IBS-D)
- pain associated with constipation (IBS-C)
- pain and diarrhea alternating with constipation (IBS-M)
4
Q
- What is the initial tx of IBS-C (Constipation)
- If the initial tx fails, what is the next option?
A
- 1st: soluble fiber (Psyllium/ispaghula)
- 2nd: trial of polyethylene glycol (PEG)
5
Q
What is the last option for tx of IBS-C?
A
Tegaserod
6
Q
Which drug?
- Osmotic laxative
- Improves constipation, but not abdominal pain
A
Polyethylene Glycol (PEG)
7
Q
What 2 ADEs limit the use of Polyethylene Glycol (PEG)?
A
- Bloating
- Abdominal discomfort
8
Q
Which drug?
Prostanoic acid derivative
- stimulates the type 2 chloride channel (ClC-2) in the small intestine
- increases chloride-rich fluid secretion into the intestine
- stimulates intestinal motility and shortens intestinal transit time
A
Lubiprostone (Amitiza)
9
Q
Lubiprostone (Amitiza)
- Used in the treatment of what?
- Approved for tx of women over what age w/ IBS-C?
- Efficacy for men w/ IBS is what?
- Reduce dose to daily in pts w/ what condition?
A
- Tx: chronic constipation
- >18 y/o
- men: unproven
- severe hepaic impairment
10
Q
Lubiprostone (Amitiz)
Chloride Channel Activator
- May cause what symptom due to delayed gastric emptying?
- Lasted as category C for pregnancy
- Should be avoided in women of what age?
A
- nausea
- child bearing age (increased fetal loss in guinea pigs)
11
Q
Which drug?
- Stimulates intestinal fluid secretion and transit time
- Use in patients with persistent constipation despite PEG
A
Linaclotide (Linzess)
( Guanylate Cyclase-C Agonist )
12
Q
Which drug?
•Significant improvement in secondary endpoints of abdominal pain/discomfort, bloating, straining, stool consistency, number of CSBMs (complete & spontaneous bowel movements) per week, compared with placebo
A
Linaclotide (Linzess)
( Guanylate Cyclase-C Agonist )
13
Q
What is the most common side effect of Linaclotide (Linzess)?
( Guanylate Cyclase-C Agonist )
A
Diarrhea
14
Q
Which drug?
- –Guanylate cyclase-C agonist on the luminal surface of intestinal epithelium
- –Increase in cyclic guanosine monophosphate (cGMP) concentrations
- –Results in chloride and bicarbonate secretion into the intestinal lumen
- –Intestinal fluid increases and GI transit time is accelerated
A
Plecanatide (Trulance)
(Guanylate Cyclase-C Agonist)
15
Q
What does Plecanatide tx?
A
IBS-C (Chronic idiopathic constipation)
16
Q
What is the boxed warning for Plecanatide (Trulance)?
A
Risk of serious dehydration in pediatric patients
17
Q
Plecanatide (Trulance) is not recommended in what patients?
A
Pregnancy
18
Q
ADE’s of which drug?
A
- –Diarrhea
- –Dizziness
- –UTI
- –Increased ALT/AST
- –Sinusitis
19
Q
Which drug?
•Stimulates the release of neurotransmitters and increases colonic motility
A
Tegaserod
(Serotonin 5-HT4 Receptor Agonist)
20
Q
Which drug?
- Increased number of cardiovascular deaths observed in post-marketing studies
- voluntarily removed from the market except in the emergency situation
A
Tegserod
(Serotonin 5-HT4-Receptor Agonist)
KNOW THIS***
21
Q
Which drug?
•Emergency treatment of IBS with constipation and chronic idiopathic constipation in women < 55 yo
A
Tegaserod
(Serotonin 5-HT4 Receptor Agonist)
22
Q
What is the initial therapy for IBS-D (diarrhea)
A
Loperamide
23
Q
Loperamide (used for IBS-D), decreases stool frequency and consistency, but does NOT tx what 3 sxs?
A
- bloating
- abdominal discomfort
- global IBS sxs
24
Q
How should Loperamide be administered?
A
45 mins before a meal on regularly scheduled doses
25
**Which drug?**
•A mixed mu-opioid receptor agonist, delta-opioid receptor antagonist and kappa opioid receptor agonist
**Eluxadoline** (Viberzi)
(tx for IBS-D
26
**Which drug?**
* Acts locally to reduce abdominal pain and diarrhea
* Acts without constipating side effects
**Eluxadoline** (Viberzi)
27
**Which drug?**
_Contraindications:_
* –biliary disorders, pancreatitis, severe liver impairment (Child-Pugh Class C) and heavy alcohol use
* –patients who do not have a gallbladder due to a high incidence of severe acute pancreatitis noted in post-marketing surveillance
Eluxadoline (Viberzi)
28
**ADE's of which drug?**
* –nausea, constipation, and abdominal pain
* –pancreatitis developed in 0.3 percent of patients with either biliary disorders (spasm of the sphincter of Oddi and biliary sludge) or alcohol use
* –CNS depression
**Eluxadoline** (Viberzi)
29
**Eluxadoline (Viberzi)**
* Has potential for what?
* Adjustment is needed in what condition?
* Abuse potential
* mild hepatic impairment
30
What is 2nd line therapy for IBS-D? (3 drugs)
**Bile acid sequestrants**
* Cholestyramine
* Colestipol
* Colesevelam
31
**IBS-D tx w/ second line therapy**
* Up to 50% of pts w/ functional diarrhea and IBS-D have what other condiiton?
Bile Acid Malabsorption
32
What are the 4 SE of Bile Acid Sequestrants
(2nd line therapy for IBS-D)
**Gastrointestinal SEs**
* Bloating
* Flatulance
* Abdominal discomfort
* Constipation
33
5-HT3 receptors activate _which pain sensation_ via _which neurons from the gut_ to the spinal cord & CNS?
* Activate visceral pain sensation via extrinsic sensory neurons
34
Inhibition of afferent GI 5-HT3 receptors may reduce unpleasant visceral afferent sensation, including which 3 sxs?
* nausea
* bloating
* pain
35
Name the 4 5-HT3 Antagonists
* Ondanetron
* Granisetron
* Dolasetron
* Palonosetron
36
Blockage of central 5-HT3 receptors reduces the central response to which type of stimulation?
visceral afferent
37
* 5-HT3 receptor blockage on the terminals of enteric cholinergic neurons inhibits what?
* Especially in what location? --\> increasing colonic transit time
* inhibits colonic motility
* left colon
38
**Which drug for IBS-D?**
* Approved for the treatment of women with severe IBS in whom diarrhea is the predominant symptom ("diarrhea-predominant IBS")
* Efficacy in men has not been established
**Alosetron**
| (5-HT3 Receptor Antagonists)
39
**PK & PD of which drug?**
* highly potent and selective antagonist of the 5-HT3 receptor
* rapidly absorbed from the gastrointestinal tract
* undergoes extensive hepatic cytochrome P450 metabolism with renal excretion of most metabolites
* binds with higher affinity and dissociates more slowly from 5-HT3 receptors than other 5-HT3 antagonists, which may account for its long duration of action
**Alosetron**
| (5-HT3 Receptor Antagonists)
40
**Which drug?**
* Reduces IBS-related lower abdominal pain, cramps, urgency, and diarrhea
* Leads to a reduction in the mean number of bowel movements per day and improvement in stool consistency
**Alosetron**
| (5-HT3 Receptor Antagonist)
41
**Which drug?\*\***
* Restricted to women with severe diarrhea-predominant IBS who have not responded to conventional therapies and who have been educated about the relative risks and benefits
* Requires FDA-approved restricted-use program
**Alosetron for IBS-D**
(5-HT3 Receptor Antagonist)
***KNOW THIS\*\*\*\****
42
**Alosetron for IBS-D**
* Which symptom occurs in up to 30% of pts w/ diarrhea-predominant IBS, requiring discontinuation of the drug in 10%?
* Episodes of what are sometimes fatal have been reported in 3/1000?
* Constipation
* ischemic colitis
43
**Tx of chronic abdominal pain in IBS**
* Which treatment is helpful?
**Tricyclic antidepressants**
| (Amitriptyline or Desipramine)
44
**Which drug?**
* may alter central processing of visceral afferent information
* reduces stool frequency & liquidity (anticholinergic properties)
* may alter receptors for enteric neurotransmitters such as serotinin, affecting visceral afferent sensation
Tricyclic Antidepressants
| (Amitriptyline or Desipramine)
45
What are the 2 commonly used agents for Antispasmodics (Anticholinergics)?
(For IBS)
* Dicyclomine
* Hyoscymine
46
Antispasmodics work primarily through which activities?
(For IBS)
Anticholinergic activities
47
**Which drug? (for IBS)**
* Inhibit muscarinic cholinergic receptors in the enteric plexus and on smooth muscle
* low doses w/ minimal autonomic effects
* infrequently used
Antispasmodics (Anticholinergics)
* dicyclomine
* hyoscymine
48
Higher doses of Antispasmodics (dicyclomine & hyoscymaine) have additional effects such as what? (4)
**Significant additional anticholinergic effects**
* dry mouth
* visual disturbances
* urinary retention
* constipation
49
