Transdermal Buprenorphine, Opioid Rotation to Sublingual Buprenorphine, and the Avoidance of Precipitated Withdrawal: A Review of the Literature and Demonstration in Three Chronic Pain Patients Treated With Butrans.

Published July 13, 2013

Am J Ther. 2013 Jul 10;
Kornfeld H, Reetz H

Buprenorphine is an opioid, used in the United States and abroad for both analgesia and addiction, with unique opioid receptor binding properties. There are several pharmacological features of buprenorphine that make it an emerging option for the long-term treatment of chronic pain-its respiratory suppression ceiling effect, its efficacy in neuropathic pain and hyperalgesic states, and its decreased suppression of the immune and endocrine systems compared with other long-acting opioids. Previous studies have shown that high-dose sublingual buprenorphine is an effective treatment of chronic pain patients not responding to other opioids. Guidelines for the introduction of sublingual buprenorphine, termed buprenorphine induction, include an opioid-free “withdrawal” period of 12-48 hours to avoid an anticipated and accelerated opioid withdrawal, a syndrome described in this article as precipitated withdrawal. The requirement of a period of opioid abstinence before buprenorphine use may present a significant barrier to its adoption for chronic pain. We present a case series of a novel method of sublingual buprenorphine introduction without an induction period, using the recently Food and Drug Administration-approved low-dose transdermal buprenorphine (Butrans; Purdue Pharma L.P.) as a bridge medication. In these cases, buprenorphine was started in opioid-dependent chronic noncancer pain patients who had taken short-acting opioid medications within hours of the initiation of the rotation. This method avoids the painful abstinence period and did not result in precipitated withdrawal or other significant adverse effects. HubMed – addiction

Association between prescribing hypnotics for parents and children in Norway.

Arch Dis Child. 2013 Jul 11;
Holdø I, Handal M, Skurtveit S, Bramness JG

To describe the dispensing of the hypnotic alimemazine to children aged 0-3 years and investigate the association between dispensing of alimemazine to children and dispensed hypnotics to their parents.An observational cohort study linking information from the Medical Birth Registry of Norway and the Norwegian Prescription Database. Hypnotics dispensed to parents in a 1-year period before pregnancy was associated with dispensed alimemazine for children aged 0-3 years.All children born in Norway in 2008 (N=59 325) and their mothers and fathers were included.Dispensed alimemazine to children during the first 3 years of life.Three percent of children received alimemazine. Dispensed hypnotics to mothers increased the risk of the child receiving a prescription for alimemazine, OR of 2.3 (1.7-3.0) for boys and 1.7 (1.2-2.4) for girls. When both parents had been dispensed prescriptions for hypnotics, the risk increased nearly threefold. A dispensed alimemazine prescription was also associated with dispensed prescriptions for antidepressants to both mother and father, mother’s smoking, the child’s gender and child’s prescriptions for antibiotics, respiratory drugs and dermatological steroids.Dispensed alimemazine to children under 3 was associated with parents’ previous use of hypnotics, indicating that factors other than the child’s health influence the use of hypnotic drugs in infancy and toddler years. The frequent usage of alimemazine in children below 3 years and the association with parents’ use of hypnotics should concern prescribing doctors. HubMed – addiction

Hypothesizing that designer drugs containing cathinones (“bath salts”) have profound neuro-inflammatory effects and dangerous neurotoxic response following human consumption.

Med Hypotheses. 2013 Jul 8;
Blum K, Foster Olive M, Wang KK, Febo M, Borsten J, Giordano J, Hauser M, Gold MS

Consensus in the most recent literature indicates that psychoactive “bath salts” is a relatively new drug-combination that was added to Schedule I classification in October 2011. Common ingredients include the cathinone analogs: mephedrone and methylenedioxypyrovalerone (MDPV). The mechanism of action of these synthetic cathinone analogs has not yet been well studied. We propose an intensive systematic investigation to determine the potential for cathinones to produce neurotoxic effects in various brain regions. In spite of a lack of evidence, for neurotoxicity there are number of horrific cases now on record that suggest intensification of research is needed. For example, a suicide by hanging had high 3,4-MDPV concentration while a driver under the influence had the highest reported methylone (MEPH) concentration. More interestingly, there have been consistent case reports indicating delayed responses, including: severe agitation with possible psychosis, suicidal ideation, rhabdomyolysis, hypertension, tachycardia, and death. In animal studies, amphetamine (AMPH), methamphetamine (METH) and cocaine release dopamine (DA), similarly to the action of cathinone and particular cathinone analogues. Two components of bath salts, MEPH and MDPV produce opposite effects at human dopamine transporter (hDAT) comparable to METH and cocaine, respectively. Moreover, it has already been found by others that MEPH is almost as potent as METH; and MDPV is much more potent than cocaine with longer lasting effects. It has been conjectured correctly that bath salts containing MDPV and MEPH (or a similar drug) might be expected both, to initially release DA and subsequently prevent its reuptake via hDAT. The null hypothesis, that cathinones do not cause neurotoxicity to dopamine nerve endings of the striatum, seems parsimonious and requires intensive investigation. Our hypothesis is that when consumed by humans, cathinones may induce neurotoxic pathways involving the neuro-glial-microglia and/or specific inflammation, that may help explain the clinically observed delayed response. We intend to explore this hypothesis utilizing a novel proteomic and biomarker technique developed by scientists at the McKnight Brain Institute, University of Florida as well as magnetic-resonance imaging across pre-frontal orbital cortex-cingulate gyrus and mesolimbic pathways of the brain of rodents. HubMed – addiction

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