Miscellaneous : Gastroenterology / Proctology
Oral Naloxone to Prevent or Reverse Opioid-Induced Constipation
Opioid analgesics are the cornerstone of pain management for moderate-to-severe cancer pain and, increasingly, chronic non-cancer pain. The use of opioids is commonly associated with dose-limiting constipation that seriously impacts patients' quality of life. Agents currently used to manage opioid-induced constipation (OIC), such as laxatives, do not address the underlying opioid receptor-mediated cause of constipation and are often ineffective. A novel approach for selectively and locally antagonizing the gastrointestinal effects of opioids involves the coadministration of a mu-opioid receptor antagonist with negligible systemic availability, such as oral naloxone. Combination therapy with prolonged-release (PR) oxycodone plus PR naloxone has been shown to provide effective analgesia while preventing or reducing constipation. This novel strategy has the potential to significantly improve the quality of life of patients suffering from chronic pain, affording patients the benefit of full analgesia, without the burden of OIC. 1
In a controlled trial involving 202 patients with chronic pain under stable oral prolonged-release (PR) oxycodone therapy (40, 60 or 80mg/day), patients were randomized to receive PR oral naloxone (10, 20, 40mg/day) or placebo. No loss of analgesic efficacy with naloxone was observed; mean pain intensity scores were comparable for placebo and all doses of naloxone and remained unchanged during treatment. Naloxone 20 mg and 40 mg significantly improved bowel function at the end of the maintenance phase compared with placebo. The 2:1 oxycodone/naloxone ratio was identified as the most suitable. The conclusion: co-administration of PR oral naloxone and PR oral oxycodone is associated with a significant improvement in bowel function compared with PR oral oxycodone alone, with no reduction in the analgesic efficacy of oxycodone. 2
A small double-blind, randomized, placebo-controlled study of 9 patients evaluated the effects on constipation and analgesia of low doses of oral naloxone (4 mg, 2 mg, or placebo) given three times daily in patients taking stable doses of opioids with complaints of constipation. All the patients who received oral naloxone had some improvement in their bowel frequency. Two patients experienced partial reversal of analgesia, and one patient had complete reversal of analgesia. Patients using high doses of opioids appeared to be the most vulnerable to reversal of analgesia by oral naloxone. 3
To prevent systemic opioid withdrawal symptoms, therapy should be started with low doses and patients carefully monitored during titration. 4
Oral naloxone, particularly when formulated as an extended release preparation, may provide an option for relief of opioid-induced constipation in patients who desire to avoid subcutaneous injections of methylnaltrexone.
1 Pharmacology. 2009;83(1):10-7.
Meeting the challenges of opioid-induced constipation in chronic pain management - a novel approach
Click here to access the PubMed abstract of this article.
2 Eur J Pain. 2009 Jan;13(1):56-64
A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation.
Click here to access the PubMed abstract of this article.
3 J Pain Symptom Manage. 2002 Jan;23(1):48-53
Low-dose oral naloxone reverses opioid-induced constipation and analgesia.
Click here to access the PubMed abstract of this article.
4 Pain 2000 Jan;84(1):105-9.
Oral naloxone reverses opioid-associated constipation.
Click here to access the PubMed abstract of this article.
Glyceryl Trinitrate Suppository For Anal Fissure: Safety and Efficacy
A double-blind placebo-controlled clinical trial concluded that use of glyceryl trinitrate 0.2% suppositories represents a new, promising, and effective treatment for chronic anal fissure.
Dis Colon Rectum. 2008 May 10. [Epub ahead of print]
Safety and efficacy of new glyceryl trinitrate suppository formula: first double blind placebo-controlled clinical trial.
Click here to access the PubMed abstract of this article.
Topical Amitriptyline/Ketamine for Analgesia in Refractory Proctodynia
Idiopathic proctodynia, an enigmatic pain syndrome affecting the perianal region, can be persistent, relatively refractory to treatment, and associated with considerable psychological distress. Lehman and Sciallis of the Department of Dermatology, Mayo Clinic, presented the case of a patient with a long history of severe proctodynia that had been resistant to a range of topical and systemic treatments. With the use of topical amitriptyline hydrochloride 2.5% and ketamine hydrochloride 0.5% cream, the patient's pain resolved rapidly, leading to a substantially improved quality of life.
J Drugs Dermatol. 2008 Sep;7(9):887-9.
Effective use of topical amitriptyline hydrochloride 2.5% and ketamine hydrochloride 0.5% for analgesia in refractory proctodynia.
Click here to access the PubMed abstract of this article.
Short Chain Fatty Acid Enemas for Short-Term Treatment of Chronic Radiation Proctitis
Radiation proctitis is a common complication of abdominal and pelvic radiotherapy. Short chain fatty acids are the main energy source of colonocytes and their use may be impaired in chronic radiation proctitis. A prospective, randomized, double-blind trial compared short chain fatty acid enemas with placebo in 19 patients with chronic radiation proctitis. After five weeks, short chain fatty acid-treated patients showed a significant decrease in the number of days with rectal bleeding from the previous week and an improvement of endoscopic score. The study concluded that short chain fatty acid enemas can accelerate the process of healing in chronic radiation proctitis, but treatment has to be continuous if a complete and sustained clinical, endoscopic, and histologic response is to be obtained.
Dis Colon Rectum. 1999 Jun;42(6):788-95; discussion 795-6.
Short chain fatty acids are effective in short-term treatment of chronic radiation proctitis: randomized, double-blind, controlled trial.
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Am J Gastroenterol. 1996 Sep;91(9):1814-6
Evaluation of short-chain fatty acid enemas: treatment of radiation proctitis.
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Topical Metronidazole 10% Decreases Posthemorrhoidectomy Pain and Improves Healing
Oral metronidazole has been demonstrated to decrease postoperative pain after open diathermy hemorrhoidectomy. A prospective, randomized trial at the Georgia Colon and Rectal Surgical Clinic in Atlanta, Georgia investigated the efficacy of topical metronidazole 10% vs. placebo, applied to the surgical site, in reducing postoperative pain and promoting wound healing after Harmonic Scalpel hemorrhoidectomy. In the metronidazole group, postoperative edema was ranked significantly lower and overall wound healing ranked significantly better than in controls. The study concluded that topical 10% metronidazole significantly reduces post-hemorrhoidectomy discomfort on postop days 7 and 14. Postoperative edema is reduced and overall healing is improved, compared with placebo.1
A separate double-blind, randomized trial evaluated the effect of topical metronidazole 10% versus placebo, applied to surgical site, in reducing postoperative and post-defecation pain after hemorrhoidectomy. Findings indicated that topical 10% metronidazole significantly reduces post-hemorrhoidectomy discomfort. 2
1 Dis Colon Rectum 2004 May;47(5):711-6
Topical metronidazole (10 percent) decreases posthemorrhoidectomy pain and improves healing.
Click here to access the PubMed abstract of this article.
2 Dis Colon Rectum. 2008 Feb;51(2):235-8. Epub 2008 Jan 4
Topical Metronidazole can Reduce Pain after Surgery and Pain on Defecation in Postoperative Hemorrhoidectomy.
Click here to access the PubMed abstract of this article.
