In this issue of the Scandinavian Journal of Pain, Stephen Butler, former chief of the famous Bonica Pain Clinic at the University of Washington in Seattle, reviews new knowledge of buprenorphine [1]. During the four decades after buprenorphine became available for clinical use persistent misunderstandings have existed in textbooks and in reviews in medical literature. These misunderstandings have misled clinicians and patients so that optimal uses of this drug were reduced. This problem continues to this day [1].
The first serious misunderstanding was that buprenorphine is not an addicting drug. It was marketed as a drug for moderate to severe pain with low risk of misuse or abuse. Clinicians and addicted persons soon discovered that this is not true. I was surprised and very disappointed to discover soon after the sublingual buprenorphine was available in Norway, already in 1983–84, that one of my patients sold his sublingual buprenorphine tablets on the illegal market. Addicted persons dissolved the sublingual tablets and injected the drug. So buprenorphine was soon moved on to the narcotic drug list.
There are other misunderstandings about buprenorphine, mostly based on animal data. These misunderstandings came into textbooks on pharmacology and pain as “medical truths” about 30 years ago. They have been difficult to get out of textbooks and guidelines. They continue to live on in teachings to medical students and postgraduate training.
It is by now a well-known fact that animal models of pain and analgesia are unreliable as predictors of clinical effects in patients with pain. In clinical practice there is no bell-shaped dose-response curve and there is no plateau on the dose-relief response curve of buprenorphine. There is also no antagonist effect from buprenorphine on other mu-opioid agonists such as morphine or oxycodone. On the contrary, there may be supra-additive or synergistic effects between buprenorphine and morphine, and between buprenorphine and oxycodone – for references, see [2].
Buprenorphine is an agonist on the mu-, the delta, and the ORL- 1 receptors. Buprenorphine is an antagonist at the kappa-receptor. Active metabolites have different effects on the four opioid receptors; all except the norbup-3-glu are analgesic. Buprenorphine itself is not a respiratory depressant or sedative, but some of its active metabolites are. Buprenorphine and its active metabolites are not excreted by the kidney, so that buprenorphine may be used in patients with advanced renal failure.
Buprenorphine has a slow onset-time and a prolonged offset-time. These properties are mostly advantageous. However, when treating strong acute pain, the long onset-time may be a slight disadvantage. It makes buprenorphine less than an ideal opioid for IV patient-controlled-analgesia (PCA). For the same reason it is also not a good alternative for treating so called “break-through-pain”. The agonist effect of buprenorphine on the ORL-1 receptor reduces reward-effects and slows the development of tolerance to the analgesic effects.
Buprenorphine is an excellent alternative for treating chronic pain, especially chronic neuropathic pain and cancer pain when pain is constantly present. Chronic pain in the elderly patients, who often have components of neuropathic pain and often have reduced renal function, is a well documented indication for buprenorphine. The 7-day transdermal buprenorphine patch is well tolerated and easily administered to such patients [3].
Treatment of the opioid-abuse disease with buprenorphine is now a well established indication for buprenorphine. Its slow onset (less “kick-effect”), and its prolonged offset-time reduces the likelihood of acute withdrawal problems and reduces the “craving” of opioids – for references see Stephen Butler’s well documented review [1].
Caveat
Buprenorphine, a potent mu-agonist, may induce or maintain opioid addiction. Illegally obtained high-dose transmucosal buprenorphine, intended for treatment of addiction, is dissolved and injected by opioid abusers, even in the Nordic countries. This is a clear reminder to us all that any mu-opioid receptor agonist is always potentially an abuse-drug. Buprenorphine must always be prescribed to pain-patients with the same strict precautions as any other potent opioid. And the patients, their drug use, and pain condition must be conscientiously monitored [4].
Buprenorphine is now a thoroughly studied drug. It is about time we get rid of the many misunderstandings and false myths around this useful opioid drug.
DOI of refers to article: http://dx.doi.org/10.1016/j.sjpain.2013.05.004.
References
[1] Butler S. Buprenorphine–clinically useful but often misunderstood. Scand J Pain 2013;4:148–52.Search in Google Scholar
[2] Kress HG. Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine. Eur J Pain 2009;13:219–30.Search in Google Scholar
[3] Breivik H, Ljosaa TM, Stengaard-Pedersen K, Persson J, Aro H, Villumsen J, Tvinnemose D. A 6-months, randomised, placebo-controlled evaluation of efficacy and tolerability of a low-dose 7-day buprenorphine transdermal patch in osteoarthritis patients naive to potent opioids. Scand J Pain 2010;1:122–41.Search in Google Scholar
[4] Breivik H, Gordh T, Butler S. Keeping an open mind: Achieving balance between too liberal and too restrictive prescription of opioids for chronic non-cancer pain: Using a two-edged sword. Scand J Pain 2012;3:1–4.Search in Google Scholar
© 2013 Scandinavian Association for the Study of Pain
