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GI/Hepatic > Constipation and IBS > Flashcards

Constipation and IBS Flashcards

1
Q

What is the definition of constipation?

A

Described by < 3 bowel movements per week, stool size or consistency, or sensation of incomplete defecation

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2
Q

What are the mechanical causes of constipation?

A

Colorectal cancer
Colon, rectal or anal stricture
Intestinal pseudo-obstruction
Megacolon

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3
Q

What are the neurologic disease causes of constipation?

A

Spinal cord lesion
Stroke
Parkinson’s disease
MS

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4
Q

What are the metabolic disturbance causes of constipation?

A 
Hypercalcemia
Hypokalemia (severe)
Hypomagnesemia
Hypothyroidism (severe)
Uremia
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5
Q

What medications can cause constipation?

A 
Opioids
Anticholinergics
Ca Channel blockerws
Anticonvulsants
Antidepressants
Antispasmodics
Antihistamines
Antiemetics (zofran)
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6
Q

What is acute constipation?

A

Usually treatable with lifestyle changes (diet, fluid intake, exercise) and OTC treatment

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7
Q

What is chronic constipation?

A

Often requires Rx treatment if patient does not respond to lifestyle changes and OTC treatment

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8
Q

What is opioid induced bowel dysfunction?

A

constellation of GI symptoms including N/V, OIC (most common), abdominal cramping, bloating, and abdominal pain

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9
Q

What is OIC?

A

Opioid induced constipation

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10
Q

What are the nonpharmacological therapies for treatment of constipation?

A 
Increase fiber in diet (25-40g/day)
Increase fluid intake (6-8 glasses of water per day)
Increase exercise (3-5d/wk)
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11
Q

How does insoluble fiber work?

A

Insoluble fiber reduces the risk of colon cancer by increasing transit through the colon and decreasing the time carcinogens are in contact with the mucosa. It also dilutes the carcinogenic substance

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12
Q

How does soluble fiber work?

A

Soluble fiber has been shown to decrease cholesterol by binding to bile acids in the intestines
It also regulates blood glucose by slowing stomach emptying resulting in a steadier rate of carb absorption in the small bowel

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13
Q

What are the saline osmotic laxatives?

A

Mag Citrate
Mag hydroxide
Mag Sulfate
Sodium phosphate

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14
Q

What is the onset of action for saline osmotic laxatives?

A

Fast (15min - 3 hours)

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15
Q

What are osmotic laxatives?

A

Glycerin
Lactulose
PEG

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16
Q

What is the onset of action for glycerin?

A

Fast (w/in 1 hour)

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17
Q

What is the onset of action for lactulose?

A

1-2 days (may require multiple doses)

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18
Q

What is the onset of action for PEG?

A

1-3 days

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19
Q

What are stimulant laxatives?

A

Bisacodyl

Senna

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20
Q

What is the onset of action for bisacodyl?

A 
6-12 hours (oral)
1 hour (supp.)
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21
Q

What is the onset of action for senna?

A

6-12 hours

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22
Q

What are the bulk forming laxatives?

A

Psyllium
Wheat dextrin
Calcium polycarbophil
Methylcellulose

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23
Q

What is the onset of action for bulk-forming laxatives?

A

12-72 hours

Less effective in drug-induced constipation

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24
Q

What is a stool softener?

A

Doc sodium

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25
Q

What is the onset of action for doc sodium?

A

1-6 days

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26
Q

What is a chloride channel activator?

A

Amitiza

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27
Q

What is Amitiza’s MOA?

A

Activates chloride channels in colon to draw fluid into colon

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28
Q

What is Amitiza FDA approved for?

A

CIC in adults
IBS-C
Chronic OID

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29
Q

What is the onset of action for amitiza?

A

w/in 24 hours

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30
Q

What preg category is amitiza?

A

C but animal studies suggest the potential for fetal death

Women should have (-) test prior to starting and should use BC while taking

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31
Q

What are common ADRs of Amitiza?

A

HA
Diarrhea
Nausea
Dyspnea

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32
Q

What is a guanylate cylase-C agonist?

A

Linzess

Trulane

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33
Q

What is the MOA of Linzess and Trulance?

A

Increases chloride secretion into intestinal lumen increasing intestinal fluid and decreases transit time (also decreases visceral pain by inhibiting afferent nerve activity)

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34
Q

What is Linzess FDA approved for?

A

CIC in adults

IBS-C

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35
Q

What is the onset of action for Linzess?

A

w/in 1-2 days

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36
Q

What is Linzess/Trulance contraindicated for?

A

Peds up to age 6 (avoid 6-17yo)

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37
Q

What are ADRs for Linzess?

A

GI (diarrhea, flatulence, ab distension)

HA

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38
Q

What is Trulance FDA approved for?

A

CIC in adults

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39
Q

What is the onset of action for Trulance?

A

1-2 days

40
Q

What are the ADRs for Trulance?

A

GI (diarrhea, flatulence abdominal distension)

41
Q

What are the peripheral opioid antagonists?

A

Methylnaltrexone
Naloxegol
Alvimopan
Naldemedine

42
Q

What is the MOA of peripheral opioid antagonists?

A

Blocks opioid binding to the mu, kappa, and gamma receptors in the periphery

  • Does not cross BBB
  • Does not affect opioid analgesic effects or induce opioid withdrawal
43
Q

What is methylnaltrexone FDA approved for?

A

Chronic OIC in both cancer and noncancer pain

44
Q

What is the onset of action for methylnaltrexone?

A

30-60 minutes in responding patients

45
Q

What enzyme metabolizes methylnaltrexone?

A

Substrate of CYP 2D6 (minor)

46
Q

What are the ADRs of methylnaltrexone?

A

GI (ab pain, flatulence, nausea)

47
Q

What is naloxegol FDA approved for?

A

Chronic OIC in noncancer pain

48
Q

What is the OOO for naloxegol?

A

6-12 hours

49
Q

How is naloxegol metabolized?

A

Substrate for CYP 3A4 and P-gp resulting in several drug interactions

50
Q

What is are the ADRs for naloxegol?

A

GI (ab pain, diarrhea, flatulence, N/V, HA

51
Q

What is alvimopan FDA approved for?

A

Treatment of post-op ileus

52
Q

What is the OOO of alvimopan?

A

4-7 hours

53
Q

What are the ADRs for alvimopan?

A

Hypokalemia

Dyspepsia

54
Q

What is naldemedine FDA approved for?

A

Tx of Chronic OIC in noncancer pain

55
Q

What is the OOO of naldemedine?

A

4-24 hours

56
Q

How is naldemedine metabolized?

A

Subwstrate of CYP 3A4 (major) and P-gp resulting in potential for several drug interactions

57
Q

What are the ADRs for naldemedine?

A

Ab pain
Diarrhea
Nausea

58
Q

What is a combination peripheral opioid antagonist and opioid agonist?

A

Targinig ER (Oxycodone/Naloxone)

59
Q

What is the MOA of Targinig ER?

A

Naloxone which has a high affinity for opioid receptors in the GI tract, displaces oxycodone from GI tract opioid receptors making oxycodone available for transport to the brain where it exerts its opioid effect. With less opioid binding in the GI tract there will be less opioid inducing constipation

60
Q

What is Targinig ER FDA approved for?

A

Treatment of moderate to severe pain requiring daily, around the clock, long term opioid treatment

61
Q

Can Naloxone cross the BBB?

A

Yes - while it has very high first pass hepatic metabolism it still crosses the BBB and can reverse the analgesic effects of opioids

62
Q

What is IBS?

A

Characterized by altered bowel habits AND abdominal pain for at least 3 months

63
Q

What are the types of IBS?

A

IBS-constipation predominant (IBS-C)
IBS-diarrhea dependent (IBS-D)
IBS-mixed constipation/diarrhea

64
Q

When is IBS prevalent?

A

3-4th decade

Usually resolves 6-7th decade

65
Q

What are the physiologic abnormalities in IBS?

A

Altered GI reactivity (motility, secretion) to luminal (food, distention, inflammation, bacteria) or environmental (psychosocial stress) stimuli, resulting in diarrhea and/or constipation
Hypersensitive GI tract with enhanced visceral perception and pain
Dysregulation of the brain-GI axis

66
Q

What is encompassed by the brain-GI axis?

A

Enteric nervous system (including afferent and efferent innervation)
CNS
HPA axis
Serotonin - 80% of all serotonin found in GI tract; increases peristalsis and secretory reflexes

67
Q

How do we diagnose IBS?

A

Symptom based criteria since there is no diagnostic test

68
Q

What are alarm symptoms?

A 
Rectal bleeding
Anemia
Weight loss
Fever
FH of colon cancer
Onset of sx after age 50
Major change in sx
69
Q

What do we do if there are alarm sx present?

A

Rule out other dz

Always test for celiac dz

70
Q

What are the non-pharma and CAM treatment for IBS?

A 
Exclude dietary triggers
Exercise for 30-60min 5 d/wk
Psychological treatment (hypnosis, cognitive behavioral therapy, psychotherapy) Acupuncture
Chinese, indian, tibetan herbs
Peppermint oil - anispasmodic; 
Melatonin
71
Q

What are the Pharm tx for IBS?

A

Treat gut dysmotility AND pain

72
Q

What is the MOA of antispasmodic agents?

A

Inhibit muscarinic cholinergic receptors on smooth muscle

73
Q

What are the ADRs for antispasmodic agents?

A

Anticholinergic

74
Q

What are antispasmodic agents?

A

Hyoscyamine
Dicyclomine
Clindinium chlordiazepoxide

75
Q

What is the MOA of TCA’s?

A

Reduce sensitivity of peripheral nerves or to changes that occur in the brain (anticholinergic)
Reduce pain and normalize GI transit time

76
Q

What is an example of TCAs?

A

Amitriptyline

77
Q

When will benefits be seen for TCAs?

A

w/in 2 weeks - if not seen by 4 weeks DC

78
Q

How long should TCAs be used to treat IBS?

A

at least 6 months

79
Q

When should TCAs not be used for IBS?

A

IBS-C or mixed d/t the consitpating effects of TCAs

80
Q

What is the potential MOA of SSRIs on IBS?

A

Decreases visceral hypersensitivity

81
Q

What are ADRs of SSRIs?

A

Zoloft/prozac: diarrhea
Paxil: constipation or diarrhea
Celexa/Lexapro: useful for all IBS

82
Q

What are SNRIs shown to be effective for in IBS?

A

Cymbalta and Effexor have been shown to be effective in reducing pain in other chronic conditions, but data is lacking

83
Q

What do 5-HT3 receptor antagonists treat?

A

IBS-D for both diarrhea and pain

84
Q

Which 5-HT3 receptor antagonist is only approved for women with severe IBS-D?

A

Lotronex

85
Q

What are two 5-HT3 receptor antagonists used for IBS-D?

A

Lotronex

Zofran

86
Q

What is the peripheral mu-opioid receptor agonist?

A

Viberzi

87
Q

What is the MOA of Viberzi?

A

Mixed locally acting, kappa-opioid agonist, and a delta-opioid receptor antagonist (very little oral absorption)

88
Q

What is Viberzi approved for?

A

IBS-D to improve diarrhea with ab pain

89
Q

How is Viberzi metabolzied?

A

Substrate of several enzymes
Inhibits P-gp
Several potential drug interactions

90
Q

What are the ADRs for Viberzi?

A

Nausea
Constipation
Rare pancreatitis (EtOH drinkers)

91
Q

What antibiotic is used for IBS?

A

Xifaxan

92
Q

What is Xifaxan FDA approved for?

A

IBS-D

93
Q

What is Xifaxan used off-label for?

A

Tx of C. diff colitis

94
Q

What are other FDA indications for Xifaxan?

A

Traveler’s diarrhea

Hepatic encephalopathy prophylaxis

95
Q

What are probiotics most useful for?

A

Bloating

GI/Hepatic (7 decks)

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