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