The clinical pharmacology of buprenorphine: extrapolating from the laboratory to the clinic.
TL;DR: Studies characterizing buprenorphine's pharmacodynamic actions, including its safety, abuse liability, withdrawal suppression and withdrawal precipitation capacity, physical dependence potential, cross-tolerance and duration of action as well as a review of the pharmacological profile of bupenorphine/naloxone combinations are reviewed.
About: This article is published in Drug and Alcohol Dependence.The article was published on 2003-05-21. It has received 199 citations till now. The article focuses on the topics: Buprenorphine & Clinical pharmacology.
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TL;DR: The neurobiological and genetic basis of addiction, its terminology and diagnosis, the evidence on addiction rates during opioid treatment of chronic pain and the implications of biological mechanisms in formulating rational opioid treatment regimes are reviewed.
Abstract: Throughout the long history of opioid drug use by humans, it has been known that opioids are powerful analgesics, but they can cause addiction. It has also been observed, and is now substantiated by multiple reports and studies, that during opioid treatment of severe and short-term pain, addiction arises only rarely. However, when opioids are extended to patients with chronic pain, and therapeutic opioid use is not confined to patients with severe and short-lived pain, compulsive opioid seeking and addiction arising directly from opioid treatment of pain become more visible. Although the epidemiological evidence base currently available is rudimentary, it appears that problematic opioid use arises in some fraction of opioid-treated chronic pain patients, and that problematic behaviors and addiction are problems that need to be addressed. Since the potentially devastating effects of addiction can substantially offset the benefits of opioid pain relief, it seems timely to reexamine addiction mechanisms and their relevance to the practice of long-term opioid treatment for pain. This article reviews the neurobiological and genetic basis of addiction, its terminology and diagnosis, the evidence on addiction rates during opioid treatment of chronic pain and the implications of biological mechanisms in formulating rational opioid treatment regimes.
412 citations
Cites background from "The clinical pharmacology of bupren..."
...Both of these drugs provide protection from withdrawal for approximately 24–48 h, while their analgesic effects last only 4–8 h, so that a major difference between pain and addiction treatment using these agents is that dosing is more frequent for pain (Fishman et al., 2002; Walsh and Eissenberg, 2003; Johnson et al., 2005)....
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TL;DR: The issues associated with the management of acute pain in patients receiving OAT are highlighted and theoretical and empirical findings that suggest unique requirements for opioid analgesia for such patients are described.
Abstract: More patients with opioid addiction are receiving opioid agonist therapy (OAT) with methadone and buprenorphine. As a result, physicians will more frequently encounter patients receiving OAT who develop acutely painful conditions, requiring effective treatment strategies. Undertreatment of acute pain is suboptimal medical treatment, and patients receiving long-term OAT are at particular risk. This paper acknowledges the complex interplay among addictive disease, OAT, and acute pain management and describes 4 common misconceptions resulting in suboptimal treatment of acute pain. Clinical recommendations for providing analgesia for patients with acute pain who are receiving OAT are presented. Although challenging, acute pain in patients receiving this type of therapy can effectively be managed.
390 citations
TL;DR: An overview of how food reinforcement and behavioral choice theory are related to eating is provided to show how this theoretical approach may help organize research on eating from molecular genetics through treatment and prevention of obesity.
Abstract: Eating represents a choice among many alternative behaviors. The purpose of this review is to provide an overview of how food reinforcement and behavioral choice theory are related to eating and to show how this theoretical approach may help organize research on eating from molecular genetics through treatment and prevention of obesity. Special emphasis is placed on how food reinforcement and behavioral choice theory are relevant to understanding excess energy intake and obesity and how they provide a framework for examining factors that may influence eating and are outside of those that may regulate energy homeostasis. Methods to measure food reinforcement are reviewed, along with factors that influence the reinforcing value of eating. Contributions of neuroscience and genetics to the study of food reinforcement are illustrated by using the example of dopamine. Implications of food reinforcement for obesity and positive energy balance are explored, with suggestions for novel approaches to obesity treatment based on the synthesis of behavioral and pharmacological approaches to food reinforcement.
363 citations
TL;DR: The self-administration model has reliably identified medications to treatment opioid dependence, and the recent data with modafinil suggest that the human laboratory model also identifies medications to treat cocaine dependence.
Abstract: Rationale
Laboratory animal and human models of drug self-administration are used to evaluate potential pharmacotherapies for drug abuse, yet the utility of these models in predicting clinically useful medications is variable.
254 citations
Cites background from "The clinical pharmacology of bupren..."
...Buprenorphine’s antagonist-like properties attenuate the effects of heroin and other mu agonists, while its agonistlike properties likely contribute to its improved compliance compared to conventional mu antagonists (see Walsh and Eissenberg 2003)....
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TL;DR: The buprenorphine plus naloxone combination product should provide additional safeguards for use in office-based practice by decreasing risk of diversion, and office- based treatment should expand the availability of services to opioid dependent patients.
236 citations
References
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Journal Article•
TL;DR: It has been shown that buprenorphine is a partial agonist of the mu type which both suppressed and precipitated abstinence in the morphine-dependent dog while morphine and propoxyphene are stronger agonists.
Abstract: Three different syndromes produced by congeners of morphine have been identified in the nondependent chronic spinal dog. These syndromes have been attributed to interaction of agonists with three distinguishable receptors (mu, kappa and sigma). Morphine is the prototype agonist for the mu receptor, ketocyclazocine for the kappa receptor and SKF-10,047 for the sigma receptor. The morphine syndrome (mu) in the dog is characterized by miosis, bradycardia, hypothermia, a general depression of the nociceptive responses and indifference to environmental stimuli. Ketocyclazocine (kappa) constricts pupils, depresses the flexor reflex and produces sedation but does not markedly alter pulse rate or the skin twitch reflex. SKF-10,047 (sigma), in contrast to morphine and ketocyclazocine, causes mydriasis, tachypnea, tachycardia and mania. The effects of these three drugs can be antagonized by the pure antagonist naltrexone, indicating that they are agonists. Further, chronic administration of morphine, ketocyclazocine and SKF-10,047 induces tolerance to their agonistic effects. Morphine suppresses abstinence in morphine-dependent dogs while ketocyclazocine does not. Ketocyclazocine at best precipitated only a liminal abstinence syndrome in the morphine-dependent dog, indicating that it had little affinity for the morphine receptor. Ketocyclazocine thus appears to be a selective agonist at the kappa receptor. Further, it has been shown that buprenorphine is a partial agonist of the mu type which both suppressed and precipitated abstinence in the morphine-dependent dog while morphine and propoxyphene are stronger agonists. Apomorphine and SKF-10,047 produce similar pharmacologic effects suggesting that sigma activity may involve a dopaminergic mechanism.
2,879 citations
TL;DR: Buprenorphine has potential for treating narcotic addiction since it is acceptable to addicts, is long-acting, produces a low level of physical dependence such that patients may be easily detoxified, is less toxic than drugs used for maintenance therapy, and blocks the effects of narcotics.
Abstract: Buprenorphine was evaluated for its abuse potential and utility in treating narcotic addiction. The drug was morphine-like but was 25 to 50 times more potent than morphine and was longer-acting. Little if any physical dependence of clinical significance was produced by buprenorphine. The effects of morphine to 120-mg doses were blocked by buprenorphine, a blockade that persisted for 29 1/2 hours. In man, buprenorphine has less intrinsic activity than morphine, and as such, as a low abuse potential. Moreover, the drug has potential for treating narcotic addiction since it is acceptable to addicts, is long-acting, produces a low level of physical dependence such that patients may be easily detoxified, is less toxic than drugs used for maintenance therapy, and blocks the effects of narcotics.
749 citations
TL;DR: The purpose of this study was to characterize the acute effects of buprenorphine, an opioid partial (μ‐agonist, across a wide range of doses in comparison to methadone.
Abstract: Objective
The purpose of this study was to characterize the acute effects of buprenorphine, an opioid partial (μ-agonist, across a wide range of doses in comparison to methadone.
Method
Healthy adult male volunteers, who had experience with but were not physically dependent on opioids, participated while residing on a closed research unit. Four subjects received buprenorphine (0, 1, 2, 4, 8, 16, and 32 mg sublingually and five subjects received methadone (0, 15, 30, 45, and 60 mg orally) in ascending order at 1-week intervals. Physiologic, subjective, and behavioral measures were monitored for 96 hours after drug administration.
Results
Both drugs produced typical opioid agonist effects (positive mood, sedation, respiratory depression, and miosis), some of which persisted for 24 to 48 hours. A plateau was observed for the dose effects of buprenorphine on subjective measures and respiratory depression. Pharmacokinetic data revealed that plasma concentrations of buprenorphine were linearly related to dose, indicating no limits on sublingual absorption in this dose range.
Conclusions
This study shows a plateau on buprenorphine effects, consistent with its partial agonist classification, and that single doses of buprenorphine up to 70 times the recommended analgesic dose are well tolerated by nondependent humans.
Clinical Pharmacology and Therapeutics (1994) 55, 569–580; doi:10.1038/clpt.1994.71
715 citations
TL;DR: Buprenorphine was as effective as methadone, 60 mg/d, and both were superior to methad one, 20 mg/D, in reducing illicit opioid use and maintaining patients in treatment for 25 weeks.
Abstract: Objective. —To assess the efficacy of buprenorphine for short-term maintenance/detoxification. Design. —A randomized, double-blind, parallel group study comparing buprenorphine, 8 mg/d, methadone, 60 mg/d, and methadone, 20 mg/d, in a 17-week maintenance phase followed by an 8-week detoxification phase. Setting. —Outpatient facilities at the Addiction Research Center, Baltimore, Md. Patients. —One hundred sixty-two volunteers seeking treatment for opioid dependence. Intervention. —In addition to the medication, counseling using a relapse prevention model was offered but not required. Primary Outcome Measures. —Retention time in treatment, urine samples negative for opioids, and failure to maintain abstinence. Results. —Throughout the maintenance phase, retention rates were significantly greater for buprenorphine (42%) than for methadone, 20 mg/d (20%,P Conclusions. —Buprenorphine was as effective as methadone, 60 mg/d, and both were superior to methadone, 20 mg/d, in reducing illicit opioid use and maintaining patients in treatment for 25 weeks. (JAMA. 1992;267:2750-2755)
533 citations