GI Motility 3 Flashcards
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
Irritable Bowel Syndrome (IBS)
What are the 5 sxs of IBS?
- Abdominal pain
- Distention
- Bloating
- Indigestion
- Various symptoms of defecation
What are the 3 “subcategories” of IBS?
- pain associated with diarrhea (IBS-D)
- pain associated with constipation (IBS-C)
- pain and diarrhea alternating with constipation (IBS-M)
- What is the initial tx of IBS-C (Constipation)
- If the initial tx fails, what is the next option?
- 1st: soluble fiber (Psyllium/ispaghula)
- 2nd: trial of polyethylene glycol (PEG)
What is the last option for tx of IBS-C?
Tegaserod
Which drug?
- Osmotic laxative
- Improves constipation, but not abdominal pain
Polyethylene Glycol (PEG)
What 2 ADEs limit the use of Polyethylene Glycol (PEG)?
- Bloating
- Abdominal discomfort
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
Lubiprostone (Amitiza)
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?
- Tx: chronic constipation
- >18 y/o
- men: unproven
- severe hepaic impairment
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?
- nausea
- child bearing age (increased fetal loss in guinea pigs)
Which drug?
- Stimulates intestinal fluid secretion and transit time
- Use in patients with persistent constipation despite PEG
Linaclotide (Linzess)
( Guanylate Cyclase-C Agonist )
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
Linaclotide (Linzess)
( Guanylate Cyclase-C Agonist )
What is the most common side effect of Linaclotide (Linzess)?
( Guanylate Cyclase-C Agonist )
Diarrhea
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
Plecanatide (Trulance)
(Guanylate Cyclase-C Agonist)
What does Plecanatide tx?
IBS-C (Chronic idiopathic constipation)
What is the boxed warning for Plecanatide (Trulance)?
Risk of serious dehydration in pediatric patients
Plecanatide (Trulance) is not recommended in what patients?
Pregnancy
ADE’s of which drug?
- –Diarrhea
- –Dizziness
- –UTI
- –Increased ALT/AST
- –Sinusitis
Which drug?
•Stimulates the release of neurotransmitters and increases colonic motility
Tegaserod
(Serotonin 5-HT4 Receptor Agonist)
Which drug?
- Increased number of cardiovascular deaths observed in post-marketing studies
- voluntarily removed from the market except in the emergency situation
Tegserod
(Serotonin 5-HT4-Receptor Agonist)
KNOW THIS***
Which drug?
•Emergency treatment of IBS with constipation and chronic idiopathic constipation in women < 55 yo
Tegaserod
(Serotonin 5-HT4 Receptor Agonist)
What is the initial therapy for IBS-D (diarrhea)
Loperamide
Loperamide (used for IBS-D), decreases stool frequency and consistency, but does NOT tx what 3 sxs?
- bloating
- abdominal discomfort
- global IBS sxs
How should Loperamide be administered?
45 mins before a meal on regularly scheduled doses
Which drug?
•A mixed mu-opioid receptor agonist, delta-opioid receptor antagonist and kappa opioid receptor agonist
Eluxadoline (Viberzi)
(tx for IBS-D
Which drug?
- Acts locally to reduce abdominal pain and diarrhea
- Acts without constipating side effects
Eluxadoline (Viberzi)
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)
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)
Eluxadoline (Viberzi)
- Has potential for what?
- Adjustment is needed in what condition?
- Abuse potential
- mild hepatic impairment
What is 2nd line therapy for IBS-D? (3 drugs)
Bile acid sequestrants
- Cholestyramine
- Colestipol
- Colesevelam
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
What are the 4 SE of Bile Acid Sequestrants
(2nd line therapy for IBS-D)
Gastrointestinal SEs
- Bloating
- Flatulance
- Abdominal discomfort
- Constipation
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
Inhibition of afferent GI 5-HT3 receptors may reduce unpleasant visceral afferent sensation, including which 3 sxs?
- nausea
- bloating
- pain
Name the 4 5-HT3 Antagonists
- Ondanetron
- Granisetron
- Dolasetron
- Palonosetron
Blockage of central 5-HT3 receptors reduces the central response to which type of stimulation?
visceral afferent
- 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
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)
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)
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)
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****
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
Tx of chronic abdominal pain in IBS
- Which treatment is helpful?
Tricyclic antidepressants
(Amitriptyline or Desipramine)
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)
What are the 2 commonly used agents for Antispasmodics (Anticholinergics)?
(For IBS)
- Dicyclomine
- Hyoscymine
Antispasmodics work primarily through which activities?
(For IBS)
Anticholinergic activities
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
Higher doses of Antispasmodics (dicyclomine & hyoscymaine) have additional effects such as what? (4)
Significant additional anticholinergic effects
- dry mouth
- visual disturbances
- urinary retention
- constipation
