A 72-year-old man comes to the office due to constipation. His stools have become increasingly hard, small-volume, and difficult to pass. This has been associated with bloating but not vomiting. Symptoms have not improved despite fiber supplementation, polyethylene glycol, and bisacodyl. The patient was recently diagnosed with metastatic pancreatic cancer and was prescribed palliative chemotherapy 2 months ago. His cancer causes severe abdominal pain, which requires high-dose oxycodone to control. Vital signs are within normal limits. The abdomen is mildly distended with decreased bowel sounds. Which of the following medications acts as a µ-opioid receptor antagonist that could alleviate this patient's constipation without inducing withdrawal symptoms?

Question

A 72-year-old man comes to the office due to constipation.  His stools have become increasingly hard, small-volume, and difficult to pass.  This has been associated with bloating but not vomiting.  Symptoms have not improved despite fiber supplementation, polyethylene glycol, and bisacodyl.  The patient was recently diagnosed with metastatic pancreatic cancer and was prescribed palliative chemotherapy 2 months ago.  His cancer causes severe abdominal pain, which requires high-dose oxycodone to control.  Vital signs are within normal limits.  The abdomen is mildly distended with decreased bowel sounds.  Which of the following medications acts as a µ-opioid receptor antagonist that could alleviate this patient's constipation without inducing withdrawal symptoms?

Quizplus · Accepted Answer

11ec160b_3bd4_199c_9249_151c708bdfcc_MD0001_00 This patient has opioid-induced constipation (OIC). Opiates (eg, oxycodone) exert their analgesic effects by binding to opiate receptors in the central and peripheral nervous systems, reducing nociceptive transmission and the perception of pain. Constipation, the most common side effect of opiate therapy, occurs due to the activation of µ-opiate receptors in the gastrointestinal tract. This results in decreased intestinal peristaltic activity and inhibition of ion and fluid secretion, leading to desiccated, pellet-like stool. Unlike many other opiate side effects, tolerance to constipation does not readily occur. Therefore, all patients on opiate therapy should be considered for prophylactic laxative therapy (eg, docusate, polyethylene glycol, bisacodyl). Those with refractory OIC may benefit from methylnaltrexone, a peripherally acting µ-opioid receptor antagonist that reverses the anti-peristaltic effect of opiates. It does not cross the blood-brain barrier; therefore, it does not induce opiate-related withdrawal symptoms, allowing for treatment of OIC without disrupting analgesic effects. (Choices A and B) Diphenoxylate and loperamide are both opiate-based medications designed to inhibit peristalsis in the gastrointestinal tract. These medications are used to treat diarrhea and would worsen this patient's constipation. (Choice C) Lubiprostone is a chloride channel agonist that increases intestinal secretions. Although it is not a µ-opioid receptor antagonist, it can be used to treat OIC and would not put patients at risk for opiate-related withdrawal. (Choice E) Naloxone is also an opioid receptor antagonist; however, unlike methylnaltrexone, naloxone crosses the blood-brain barrier. It induces symptoms of withdrawal and reversal of analgesia and is used to treat acute opioid toxicity (eg, respiratory depression, somnolence). Educational objective: Constipation is the most common side effect of opiate therapy and occurs due to the binding of µ-opioid receptors in the gastrointestinal tract, which decreases intestinal motility and inhibits ion and fluid secretion. Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist that does not cross the blood-brain barrier, can alleviate opioid-induced constipation without inducing opiate-related withdrawal symptoms. __________ References: Opioid-induced constipation: advances and clinical guidance. (http://www.ncbi.nlm.nih.gov/pubmed/26977281)

A 72-Year-Old Man Comes to the Office Due to Constipation