Constipation:
The Latest and Greatest
Rosene Pirrello, RPh
Solomon Liao, MD
Objectives
By the end of this session, participants will be
able to:
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Prevent constipation
Select the appropriate laxative
Select the appropriate enema
Treat refractory opioid-induced
constipation
Is She Constipated?
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64 year-old recently started on Lasix for
mild diastolic heart failure
Usually bowel movement every other
day
Now bowel movement every 2-3 days
and “harder” stools
What would you recommend, if
anything?
Definition
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What is your definition of constipation?
“unsatisfactory defecation characterized by
infrequent stool, difficult stool passage or
both” (1)
“reduced frequency or ease of stool passage
from what is deemed the normal or expected
pattern for that individual” (2)
American College of Gastroenterology Constipation Task Force
Am J Gastroenterol 2005; 100 Supp 1:S1-4
2.
Can J Gastroenterol. 2011 Oct; 25(Supp B): 7B-10B
1.
Causes: Concurrent Diseases
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Hypothyroidism
Diabetes
Hypokalemia
Hernia
Hypercalcemia
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Rectocele
Anal
Fissure/Stenosis
Mucosal Prolapse
Colitis
Causes: Malignancy
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Intestinal obstruction
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tumor in bowel wall or
external compression by abdominal or pelvic
tumor
Damage to
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lumbosacral spinal cord
cauda equina or
pelvic plexus.
Causes: Misc
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Inadequate food intake
Low-fiber diet
Dehydration
Weakness
Inactivity
Depression
Unfamiliar toilet arrangements
Pseudomyxoma Peritonei
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28 year-old Ovarian cancer
Subacute increased abdominal pain
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Intermittent nausea
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Generalized, 10/10
On long acting morphine 60 mg po q12 hrs
On ondansetron 4 mg po q8 hrs prn nausea
She has been eating
+ flatus, daily soft bowel movements.
How would you treat her pain?
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A) Increase her opioids
B) Add a non-opioid pain medicine
C) Give her an enema
D) Start antibiotics
E) Obtain an pain consult for a nerve
block
Causes: Common Palliative
Care Drugs
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Anticonvulsants
Drugs with anticholinergic effects:
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5-HT3 receptor antagonists
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Scopolamine, atropine, hyoscine
Phenothiazines
Tricyclic antidepressants
Antiparkinsonian agents
Antihistamines
Ondansetron, granisetron, dolasetron
Opioids
Opioids: Effects on the gut
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Increased tone in ileocecal and anal
sphincters
Reduced peristalsis in small intestine
and colon
Impaired defecation reflex
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Reduced sensitivity to distention
Increased internal anal sphincter tone
Causes: Drugs
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Antacids ( Ca++ and Al+++ compounds)
Diuretics
Iron
Vincristine
Calcium Channel Blockers
Management: Prophylaxis
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Encourage activity, if possible
Maintain adequate oral fluid intake
Create a favorable environment
Anticipate constipating effects of drugs
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Start a laxative prophylactically
Lung Cancer
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80 year-old on long acting morphine
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“diarrhea” started 2 days ago
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For dyspnea and pain
Abdominal distention
Nausea
Had been having “irregular bowel
movement” before diarrhea
What do you do?
Enemas
• Fleets
• Mineral oil
• Tap water
• Soap sod
• Lactulose
• Milk & Molasses
• Harris flush
• Flushing colonoscopy
Treatment Algorithm
1st line: Prevention or Treatment
• Senna
• Bisacodyl
• MOM
2nd line: Add or change to
• PEG
• Lactulose
• Sorbitol
3rd line: Rescue therapy
• Suppository
• Enemas
4th Line: Refractory therapy
• Peripheral opioid antagonist
• Chloride channel activator
Classification of Laxatives
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Predominantly
softening/osmotic
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Lactulose
Sorbitol
PEG (Miralax)
Saline Laxatives
Bulk-forming
Ca Channel Activator
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Lubiprostone
(Amitiza®)
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Predominantly peristalsis
stimulating
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Anthracenes (senna)
Polyphenolics (bisacodyl)
Peripherally-acting Opioid
Antagonists
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Alvimopan (Entereg®)
Methylnaltrexone (Relistor®)
Naloxegol (Movantik®)
Choice of Laxatives
Practical considerations
 Renal patients: avoid Mg, Phos
 Liver patients: Lactulose
 Geriatric patients: don’t like sweet
 Avoid fiber laxatives
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With opioids, diuretics
Unable to drink sufficiently
Cost
Drug
Supply
UCI Cost
Senna
100 tabs
$1.87
Bisacodyl
100 tabs
$1.16
MOM
355 mL
$1.77
PEG
526 g
$9.33
Lactulose
946 mL
$9.01
Sorbitol
960 mL
$5.42
Fleets enema
1 enema
$0.72
Methylnaltrexone
12 mg / SC daily
$62.12
Naloxegol
25 mg / PO daily
$7.18
Alvimopan
12 mg / PO BID
$114.32 = $228.64 daily
Lubiprostone
24 mcg / PO BID
$4.82
= $9.64 daily
Colon Cancer
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45 year-old stage 4 colon cancer
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Peritoneal & small bowel metastases
No bowel movement for 5 days
Abdominal pain and distention
Nausea but no vomiting
Normal active bowel sounds
No response to enemas
What do you do?
Peripherally-acting Opioid Antagonist
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Methylnaltrexone
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Onset: 4 to 24 hours (SC)
Dose: Usually 12 mcg SC; may repeat daily
Naloxegol
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Onset: 4 to 24 hours (PO)
Dose: 25 mg daily 1 hour before a meal
(12.5 mg daily for CrCl <60)
Lubiprostone (Amitiza)
Chloride channel activator: increases
intestinal fluid secretion and motility
 Onset: 40% laxation within 24 hrs
 Dose: 24 mcg BID (PO)
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Adjust in liver disease:
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Child-Pugh B Class: 16 mcg BID
Child-Pugh C Class: 8 mcg BID
Whipple
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58 year-old pre-op for Whipple of
pancreatic carcinoma
No cardiac history
Opioid naïve
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Post-op PCA planned
What can help prevent an ileus?
Alvimopan (Entereg)
Oral Peripherally-acting Opioid Antagonist
 FDA: Post-op ileus
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Onset: 48 hrs
Dose:
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Short term hospital use only - 15 dose total
First dose 90 minutes prior to surgery
Then 12 mg PO BID; may repeat daily for up to
7 days
Liver disease: Class C - Avoid use
1.3% MI in chronic opioid users
Lancet. 2009 ;373:1198-206.
Conclusion
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Lots of causes of constipation
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Including drugs
Ounce of Prevention
Choice of laxatives – practical
considerations
Naloxegol is first line peripheral opioid
antagonist