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Constipation: The Latest and Greatest
Rosene Pirrello, RPhSolomon Liao, MD
Objectives
By the end of this session, participants will be able to: Prevent constipationSelect the appropriate laxativeSelect the appropriate enemaTreat refractory opioid-induced constipation
Is She Constipated?
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 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)
1. American College of Gastroenterology Constipation Task Force
Am J Gastroenterol 2005; 100 Supp 1:S1-42. Can J Gastroenterol. 2011 Oct; 25(Supp B): 7B-10B
Causes: Concurrent Diseases
Hypothyroidism Diabetes Hypokalemia Hernia Hypercalcemia
Rectocele Anal
Fissure/Stenosis
Mucosal Prolapse
Colitis
Causes: Malignancy Intestinal obstruction
tumor in bowel wall or external compression by abdominal or
pelvic tumor Damage to
lumbosacral spinal cord cauda equina or pelvic plexus.
Causes: Misc
Inadequate food intake Low-fiber diet Dehydration Weakness Inactivity Depression Unfamiliar toilet arrangements
Pseudomyxoma Peritonei
28 year-old Ovarian cancer Subacute increased abdominal pain
Generalized, 10/10 On long acting morphine 60 mg po q12 hrs
Intermittent nausea On ondansetron 4 mg po q8 hrs prn nausea She has been eating
+ flatus, daily soft bowel movements.
How would you treat her pain?
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
Anticonvulsants Drugs with anticholinergic effects:
Scopolamine, atropine, hyoscine Phenothiazines Tricyclic antidepressants Antiparkinsonian agents Antihistamines
5-HT3 receptor antagonists Ondansetron, granisetron, dolasetron
Opioids
Opioids: Effects on the gut
Increased tone in ileocecal and anal sphincters
Reduced peristalsis in small intestine and colon
Impaired defecation reflex Reduced sensitivity to distention Increased internal anal sphincter tone
Causes: Drugs
Antacids ( Ca++ and Al+++
compounds) Diuretics Iron Vincristine Calcium Channel Blockers
Management: Prophylaxis
Encourage activity, if possible Maintain adequate oral fluid intake Create a favorable environment Anticipate constipating effects of
drugs Start a laxative prophylactically
Lung Cancer
80 year-old on long acting morphine For dyspnea and pain
“diarrhea” started 2 days ago Abdominal distention Nausea
Had been having “irregular bowel movement” before diarrhea
What do you do?
Enemas
Treatment Algorithm
Classification of Laxatives Predominantly
softening/osmotic Lactulose Sorbitol PEG (Miralax) Saline Laxatives Bulk-forming
Ca Channel Activator Lubiprostone
(Amitiza®)
Predominantly peristalsis stimulating Anthracenes (senna) Polyphenolics
(bisacodyl) Peripherally-acting
Opioid Antagonists Alvimopan (Entereg®) Methylnaltrexone
(Relistor®) Naloxegol (Movantik®)
Choice of Laxatives
Practical considerationsRenal patients: avoid Mg, PhosLiver patients: LactuloseGeriatric patients: don’t like sweet Avoid fiber laxatives
With opioids, diuretics Unable to drink sufficiently
CostDrug 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 45 year-old stage 4 colon cancer
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
Methylnaltrexone Onset: 4 to 24 hours (SC) Dose: Usually 12 mcg SC; may repeat
daily Naloxegol
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 motilityOnset: 40% laxation within 24 hrsDose: 24 mcg BID (PO)
Adjust in liver disease: Child-Pugh B Class: 16 mcg BID Child-Pugh C Class: 8 mcg BID
Whipple 58 year-old pre-op for Whipple of
pancreatic carcinoma No cardiac history Opioid naïve
Post-op PCA planned What can help prevent an ileus?
Alvimopan (Entereg) Oral Peripherally-acting Opioid AntagonistFDA: Post-op ileus
Short term hospital use only - 15 dose totalOnset: 48 hrsDose:
First dose 90 minutes prior to surgery Then 12 mg PO BID; may repeat daily for up
to 7 daysLiver disease: Class C - Avoid use1.3% MI in chronic opioid users
Lancet. 2009 ;373:1198-206.
Conclusion Lots of causes of constipation
Including drugs Ounce of Prevention Choice of laxatives – practical
considerations Naloxegol is first line peripheral
opioid antagonist