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Constipation: The Latest and Greatest Rosene Pirrello, RPh Solomon Liao, MD Objectives By the end of this session, participants will be able to:     Prevent constipation Select the appropriate laxative Select the appropriate enema Treat 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) 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      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    Intermittent nausea    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?      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:       5-HT3 receptor antagonists   Scopolamine, atropine, hyoscine Phenothiazines Tricyclic antidepressants Antiparkinsonian agents Antihistamines 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   “diarrhea” started 2 days ago     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  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 considerations  Renal patients: avoid Mg, Phos  Liver patients: Lactulose  Geriatric patients: don’t like sweet  Avoid fiber laxatives   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  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 motility  Onset: 40% laxation within 24 hrs  Dose: 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 Antagonist  FDA: Post-op ileus    Onset: 48 hrs Dose:     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  Lots of causes of constipation     Including drugs Ounce of Prevention Choice of laxatives – practical considerations Naloxegol is first line peripheral opioid antagonist