Abstract
Dear Editor:
A 66-year-old woman with ovarian adenocarcinoma FIGO IIIC was admitted for palliative care. She had been previously given first-line chemotherapy without efficacy and had declined further anticancer treatment. Peritoneal and pleural effusions were present. Current medication included oral morphine 10 mg 4 hourly for abdominal pain (VAS 5/10), acetylsalicylic acid 100 mg/day, oxazepam 7.5 mg twice daily, fondaparinux 2.5 mg/day subcutaneously, picosulfate 10 mg twice daily, and inhaled ipratropium and salbutamol.
Because of chronic constipation, intrarectal enema was provided but remained unsuccessful. Methylnaltrexone 8 mg was then given subcutaneously and this resulted in abundant bowel movements. Simultaneously, intractable vomiting occurred but with neither nausea nor abdominal pain. Clinical examination and abdominal x-ray were unremarkable. A total of 12 vomiting episodes occurred during the next 24 hours that were reminiscent of morphine intolerance. Thus, opioid rotation to oral hydromorphone (2 mg 4 hourly) was attempted ut aliquid. And immediate stop of vomiting was observed.
Discussion
Methylnaltrexone is a selective opioid antagonist that binds to the μ receptor. Its capacity to cross the blood-brain barrier is very limited. Absorption is rapid following subcutaneous administration, and peak concentration (Cmax) is achieved approximately 30 minutes later. 1 Its efficacy on constipation is well demonstrated. 2 Abdominal pain, nausea, flatulence, dizziness, and hyperhidrosis are known side effects but vomiting has never been reported.
Animal studies have shown opioids to have emetic as well as antiemetic properties. When methylnaltrexone was administered to dogs, emetic effect of morphine was suppressed. 3 This suggests that the antiemetic effect is bound to the activation of opioid μ peripheral receptors. Subtype μ1 receptor is localized outside of the brain and its activation has emetic properties. On the other hand, subtype μ2 receptor is localized in the brain (solitary fasciculus nucleus) and its activation has antiemetic properties. Because methylnaltrexone is an antagonist of the μ peripheral receptor, it could thus suppress the peripheral antiemetic effect of morphine but without decreasing its central antiemetic effect.4–7
In the clinical case described here, symptoms compatible with morphine intolerance (intractable vomiting without nausea prodroma) occurred immediately after methylnaltrexone injection and only stopped following rotation from morphine to hydromorphone. Methylnaltrexone administration may thus have modified μ receptors' affinity, thereby exacerbating the emetic property of morphine.