Thursday, 17 October 2013

Opioids And Constipation

Today's post from (see link below) talks about a problem that takes many people by surprise after they are prescribed opioids for neuropathic pain and that is constipation. Almost everybody who needs to take opioid medication suffers from constipation and it's often difficult to treat properly. Your doctor will very often give you a side prescription to help with the constipation but if not, you will need to find something that helps you best. It's important to note that if diet change and exercise don't work then you may need laxatives of one sort or another but you should be careful to follow the instructions very carefully. You shouldn't take laxatives on a permanent basis, they can damage your bowels and make them dependent on the laxative. Best to work with your doctor on this one.

All About Opioids and Opioid-Induced Constipation (OIC) 
This Opioid-Induced Constipation (OIC) information section was written by Peter Crosta (MA) for Medical News Today,

Although opioids are very effective for treating and managing pain, their use frequently results in opioid-induced constipation (OIC). Treatment options for OIC may be as simple as changing diet or as complicated as requiring several medicines and laxatives.
How can changing lifestyle factors treat OIC?

Changing lifestyle factors is usually the first recommendation that physicians make for the prevention or treatment of constipation. This includes:
Increasing dietary fiber
Increasing fluid intake
Increasing exercise or physical activity
Increasing time and privacy for toileting

Changes in lifestyle, however, may not be possible for many patients. In addition, these changes may be ineffective in treating OIC. If there is a concurrent underlying disease or medicine that is causing constipation, the disease may need to be treated separately or another treatment regimen may have to be considered. 

What drugs or medicines treat OIC?

OIC treatment usually requires additional medicines to be prescribed along with the opioid painkillers that are causing the constipation. Withholding the opioid treatment is ill-advised because it results in a decrease in the patient's quality of life. Often, laxatives and/or cathartics are prescribed at the same time as the opioid painkillers so that treatment for the constipation beings immediately. A cathartic accelerates defecation, while a laxative eases defecation, usually by softening the stool; some medicines are considered to be both laxatives and cathartics.

For the treatment of OIC, doctors may prescribe:
Osmotic laxatives - increase the amount of water in the gut, increasing bulk and softening stools.
Emollient or lubricant cathartics - soften and lubricate stools.
Bulk cathartics - increase bulk and soften stools.
Stimulant cathartics - directly counteract the effect of the opioid medications by increasing intestinal motility, helping the gut to push the stools along.
Prostaglandins or prokinetic drugs - change the way the intestines absorb water and electrolytes, and they increase the weight and frequency of stools while reducing transit time.
Other medicines block the effects of opioids on the bowel to reverse opioid-induced constipation.

Although the treatments listed above are usually successful in treating OIC, sometimes a physician will recommend rectal intervention. As discussed, prophylaxis with laxatives are/or cathartics is considered usual - as some clinicians assume [constipation] to be virtually universal in patients who are prescribed opioid analgesics1.

Rectal interventions are indicated if the appropriate oral measures have been ineffective2. Rectal intervention means the following treatments:
Enemas (micro and larger volume)
Rectal irrigation (sometimes known as colonic irrigation)
Manual evacuation

The first choice rectal intervention for uncomplicated constipation is glycerine suppositories2. If these are ineffective, then a stimulant enema might be administered. Oral and rectal stimulant laxatives should be avoided if there is possible or proven bowel obstruction. Gentle rectal measures can sometimes be effective in emptying the rectum and lower colon. Oral softening agents are useful if the obstruction is incomplete. It should be remembered that constipation can cause bowel obstruction.

If none of the rectal laxatives above prove adequate to remove impacted faeces, rectal irrigation with normal saline can be performed3. Manual evacuation should be used as a last resort when all other methods of bowel management have been shown to be ineffective.
Combination therapy

Constipation is a known side effect of opioid analgesics and should be addressed before opioid therapy begins. As opioid-induced constipation can be severe and adversely impact quality of life and compliance with therapy, prophylaxis with laxatives is considered to be the best approach. A British Pain Society survey conducted in March 2009 showed that nearly half of GPs (44%) surveyed believe that the negative impact of such side effects is the key factor in patient non-compliance with prescribed opioid treatments.

Concurrent management on initiation of opioids frequently includes recommending certain lifestyle or dietary adjustments (as listed above) and initiating a scheduled regimen of laxatives. Laxative and cathartic therapy may be needed throughout opioid therapy and beyond. Effective management requires a composite of strategies, including behavioral and lifestyle changes (diet, activity, and fluid intake, as appropriate).

However medications used to manage opioid-induced constipation, such as laxatives, do not address the underlying opioid receptor-mediated cause of constipation and are often ineffective4.
Newer targeted treatments for opioid induced constipation

Methylnaltrexone (available as Relistor(R)) helps restore bowel function in patients who have advanced illness and receive opioids for pain relief. Methylnaltrexone is delivered via subcutaneous injection and specifically targets opioid-induced constipation. When given alongside opioid therapy, it is designed to displace the opioid from binding to peripheral receptors in the gut, decreasing the opioid's constipating effects and inducing laxation.

Methylnaltrexone is a peripherally acting mu-opioid receptor antagonist that decreases the constipating effects of opioid pain medications in the gastrointestinal tract without diminishing their ability to relieve pain.

Methylnaltrexone blocks peripheral opioid receptors in the gut and unlike other opioid antagonists has restricted ability to cross the blood-brain barrier. As a result, it antagonizes only the peripherally located opioid receptors in the GI tract, so it's action reverses opioid-induced constipation without precipitating withdrawal symptoms or affecting or reversing the central analgesic effects of opioids5.

Another new medication for severe pain (long-term pain that can be experienced as a result of conditions such as back pain, arthritis and osteoarthritis)6, are tablets combining prolonged release oxycodone, an opioid which treats pain, and prolonged release naloxone, a compound which counteracts the potential negative effects of the opioid on the GI function (available as TarginactTM). This novel combination has been proven to provide equivalent pain relief to oxycodone alone, whilst significantly improving bowel function7. Naloxone is an opioid receptor antagonist that, when taken orally, has negligible systemic bioavailability8 providing a full inhibitory effect on local opioid receptors in the gut - counteracting opioid-induced constipation - without impacting on the centrally acting analgesic efficacy of oxycodone.

* Image borrowed from Wyeth library

1. Hanks G, Cherny N, Fallon M. Symptom Management. The management of pain: Opioid Analgesic Therapy. In Oxford textbook of Palliative Medicine, 3rd Ed. Oxford University Press, 2003.

2. Cancer - a cpomprehensive clinical guide, By David L. Morris, John Henry Kearsley, Christopher John Hacon Williams

3. Oxford textbook of palliative medicine, By Derek Doyle, Geoffrey Hanks, Nathan I. Cherny, Kenneth Calman

4. Reimer K, Hopp M, Zenz M, Maier C, Holzer P, Mikus G, Bosse B, Smith K, Buschmann-Kramm C, Leyendecker P: Meeting the Challenges of Opioid-Induced Constipation in Chronic Pain Management - A Novel Approach.

Pharmacology 2009;83:10-17 (DOI: 10.1159/000165778)

5. Ho et al. 2003; Kurz and Sessler 2003; Schmidt 2001; Foss 2001

6. Severe pain, which can be adequately managed only with opioid analgesics

7. Vondrackova D, Leyendecker P, Meissner W. et al. Analgesic efficacy and safety of oxycodone in combination with naloxone as prolonged release tablets in patients with moderate to severe chronic pain.J Pain. 2008; 9(12): 1144-1154.

Meissner W, Leyendecker P, Müller-Lissner S, et al. A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation. Eur J Pain. 2008; doi:10.1016/j.ejpain.2008.06.012.

Simpson K, Leyendecker P, Hopp M, et al. Fixed-ratio combination oxycodone/naloxone compared with oxycodone alone for the relief of opioid-induced constipation in moderate-to-severe non-cancer pain. Curr Med Res Opin. 2008; 24(12): 3503-3512.

8. Nadstawek J, Leyendecker P, Hopp M, et al. Patient assessment of a novel therapeutic approach for the treatment of severe, chronic pain. Int J Clin Pract. 2008; 62: 1159-116.

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