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MJ- P2 E2 > GI Motility 3 > Flashcards

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)

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2
Q

What are the 5 sxs of IBS?

A
  • Abdominal pain
  • Distention
  • Bloating
  • Indigestion
  • Various symptoms of defecation
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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)
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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)
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5
Q

What is the last option for tx of IBS-C?

A

Tegaserod

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6
Q

Which drug?

  • Osmotic laxative
  • Improves constipation, but not abdominal pain
A

Polyethylene Glycol (PEG)

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7
Q

What 2 ADEs limit the use of Polyethylene Glycol (PEG)?

A
  • Bloating
  • Abdominal discomfort
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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)

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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
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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)
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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 )

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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 )

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13
Q

What is the most common side effect of Linaclotide (Linzess)?

( Guanylate Cyclase-C Agonist )

A

Diarrhea

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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)

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15
Q

What does Plecanatide tx?

A

IBS-C (Chronic idiopathic constipation)

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16
Q

What is the boxed warning for Plecanatide (Trulance)?

A

Risk of serious dehydration in pediatric patients

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17
Q

Plecanatide (Trulance) is not recommended in what patients?

A

Pregnancy

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18
Q

ADE’s of which drug?

A
  • –Diarrhea
  • –Dizziness
  • –UTI
  • –Increased ALT/AST
  • –Sinusitis
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19
Q

Which drug?

•Stimulates the release of neurotransmitters and increases colonic motility

A

Tegaserod

(Serotonin 5-HT4 Receptor Agonist)

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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
Q

Which drug?

•A mixed mu-opioid receptor agonist, delta-opioid receptor antagonist and kappa opioid receptor agonist

A

Eluxadoline (Viberzi)

(tx for IBS-D

26
Q

Which drug?

  • Acts locally to reduce abdominal pain and diarrhea
  • Acts without constipating side effects
A

Eluxadoline (Viberzi)

27
Q

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
A

Eluxadoline (Viberzi)

28
Q

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
A

Eluxadoline (Viberzi)

29
Q

Eluxadoline (Viberzi)

  • Has potential for what?
  • Adjustment is needed in what condition?
A
  • Abuse potential
  • mild hepatic impairment
30
Q

What is 2nd line therapy for IBS-D? (3 drugs)

A

Bile acid sequestrants

  • Cholestyramine
  • Colestipol
  • Colesevelam
31
Q

IBS-D tx w/ second line therapy

  • Up to 50% of pts w/ functional diarrhea and IBS-D have what other condiiton?
A

Bile Acid Malabsorption

32
Q

What are the 4 SE of Bile Acid Sequestrants

(2nd line therapy for IBS-D)

A

Gastrointestinal SEs

  • Bloating
  • Flatulance
  • Abdominal discomfort
  • Constipation
33
Q

5-HT3 receptors activate which pain sensation via which neurons from the gut to the spinal cord & CNS?

A
  • Activate visceral pain sensation via extrinsic sensory neurons
34
Q

Inhibition of afferent GI 5-HT3 receptors may reduce unpleasant visceral afferent sensation, including which 3 sxs?

A
  • nausea
  • bloating
  • pain
35
Q

Name the 4 5-HT3 Antagonists

A
  • Ondanetron
  • Granisetron
  • Dolasetron
  • Palonosetron
36
Q

Blockage of central 5-HT3 receptors reduces the central response to which type of stimulation?

A

visceral afferent

37
Q
  • 5-HT3 receptor blockage on the terminals of enteric cholinergic neurons inhibits what?
  • Especially in what location? –> increasing colonic transit time
A
  • inhibits colonic motility
  • left colon
38
Q

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
A

Alosetron

(5-HT3 Receptor Antagonists)

39
Q

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
A

Alosetron

(5-HT3 Receptor Antagonists)

40
Q

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
A

Alosetron

(5-HT3 Receptor Antagonist)

41
Q

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
A

Alosetron for IBS-D

(5-HT3 Receptor Antagonist)

KNOW THIS****

42
Q

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?
A
  • Constipation
  • ischemic colitis
43
Q

Tx of chronic abdominal pain in IBS

  • Which treatment is helpful?
A

Tricyclic antidepressants

(Amitriptyline or Desipramine)

44
Q

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
A

Tricyclic Antidepressants

(Amitriptyline or Desipramine)

45
Q

What are the 2 commonly used agents for Antispasmodics (Anticholinergics)?

(For IBS)

A
  • Dicyclomine
  • Hyoscymine
46
Q

Antispasmodics work primarily through which activities?

(For IBS)

A

Anticholinergic activities

47
Q

Which drug? (for IBS)

  • Inhibit muscarinic cholinergic receptors in the enteric plexus and on smooth muscle
  • low doses w/ minimal autonomic effects
  • infrequently used
A

Antispasmodics (Anticholinergics)

  • dicyclomine
  • hyoscymine
48
Q

Higher doses of Antispasmodics (dicyclomine & hyoscymaine) have additional effects such as what? (4)

A

Significant additional anticholinergic effects

  • dry mouth
  • visual disturbances
  • urinary retention
  • constipation
49
Q
A

MJ- P2 E2 (19 decks)

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