Alcohol in metabolism

The 2018 Lancet LowBack Pain Series, comprising 3 papers written by 31 authors from disparate disciplines and 12 different countries, raised unprecedented awareness of the rising global burden of low back pain partly attributable to poor quality health care. Many people with low back pain get the wrong care, causing harm to millions across theworld andwasting valuable health care resources. Based upon an up-to-date, evidence-based synthesis, the series described current guideline recommended care of low back pain, and new strategies that show promise, but require further testing, to reduce low value care. We also proposed a series of actions needed to reverse the alarming global rise in low back pain disability. A better understanding of low back pain in different cultures and changes to the way care for low back pain is delivered and the way clinicians are reimbursed are key to reversing this problem. To reach all relevant stakeholders, we devised a well-planned and thorough media strategy to facilitate promotion of the series. This included not only Lancet staples such as a Lancet social media card, structured press release, and Lancet podcast distributed to about 2000 journalists but also email banners, country media focal points who could provide country-specific information, a set of global key messages that were modified for country-level use, a twitter hashtag of the series, #LowBackPain, and a schedule of suggested tweets to be used by authors over the 48 hours before and after the publication of the series. The series was alsomade free to download (see https://www.thelancet.com/ series/low-back-pain). The success of this approach is evident by the unprecedented media coverage it received with all 3 articles achieving Altmetric scores in the 99th percentile. There was media coverage in at least 17 countries including wall-to-wall coverage in the United Kingdom, Australia, and Denmark. Furthermore, interest in The Lancet Low Back Pain Series has persisted as evident by continued attention from major media outlets. For example, The Economist published an article entitled “Back pain is a massive problem which is badly treated” on 18 Jan 2020, accompanied by a “Leader” (editorial opinion) on the topic. This review, invited to coincide with a plenary at the 2020 World Congress on Pain, outlines and discusses some of the main messages from The Lancet Low Back Pain Series, with a focus on pertinent positive and negative developments since it was published.

The Lancet Series call to action to reduce low value care for low back pain: an update.

Background The present paper provides an updated review of both the large number of new/novel/emerging psychoactive substances (NPS) and their associated psychopathological consequences. Focus was here given on identification of those NPS being commented in specialised online sources and the related short-/long-term psychopathological and medical ill-health effects. Methods
 NPS have been identified through an innovative crawling/navigating software, called the ‘NPS.Finder®’, created in order to facilitate the process of early recognition of NPS online. A range of information regarding NPS, including chemical and street names; chemical formula; three-dimensional image and anecdotally reported clinical/psychoactive effects, were here made available. Results
 Using the ‘NPS.Finder®’ approach, a few thousand NPS were here preliminarily identified, a number which is about 4-fold higher than those figures suggested by European and international drug agencies. NPS most commonly associated with the onset of psychopathological consequences included here synthetic cannabinoids/cannabimimetics; new synthetic opioids; ketamine-like dissociatives; novel stimulants; novel psychedelics and several prescription and over-the-counter medicines. Conclusions
 The ever-increasing changes in terms of recreational psychotropics' availability represent a relatively new challenge for psychiatry, as the pharmacodynamics and pharmacokinetics of many NPS have not been thoroughly understood. Health/mental health professionals should be informed about the range of NPS; their intake modalities; their psychoactive sought-after effects; the idiosyncratic psychotropics' combinations and finally, their medical and psychopathological risks.

/pdf/new-emerging-psychoactive-substances-and-associated-17g7jl7dcz.pdf

New/emerging psychoactive substances and associated psychopathological consequences.

There is a high prevalence of painful diabetic polyneuropathy (pDPN) with around one-third of all patients with diabetes suffering from pDPN. pDPN has debilitating consequences, with a major impact on morbidity and quality of life. Unfortunately, there is no globally licenced pharmacotherapy that modulates the underlying disease mechanisms to prevent or halt the progression of diabetic neuropathy. The cornerstone of treatment therefore remains optimising glycaemic control and cardiovascular risk factors, and symptom control. Evidence from placebo-controlled studies has shown that antidepressants and anticonvulsants are effective for alleviating pDPN. Current clinical guidelines recommend the treatment of pDPN through the use of amitriptyline (tricyclic antidepressant), duloxetine (serotonin norepinephrine reuptake inhibitor), gabapentin and pregabalin (α2-δ ligands), tramadol and tapentadol (μ receptor agonists and norepinephrine reuptake inhibitors) and topical agents such as capsaicin (transient receptor potential V1 receptor desensitizer), although the latter is known to cause degeneration of small nerve fibers. pDPN can be difficult to treat, which frustrates healthcare providers, patients and caregivers. There is an additional need for clinical trials of novel therapeutic agents and optimal combinations for the management of pDPN. This article reviews the pharmacological management of pDPN, emerging therapies, the difficulties of placebo response in clinical trials and novel proposed biomarkers of treatment response.

Treating Pain in Diabetic Neuropathy: Current and Developmental Drugs.

### What you need to know

A 65 year old woman presents with continuous dull back ache and leg pain over the past four years. She underwent lumbar decompression surgery three months ago, but the pain persists. She has no neurological deficits. She is on treatment for hypertension and chronic kidney disease and cannot take non-steroidal anti-inflammatory drugs. She has tried paracetamol, codeine, tramadol, and amitriptyline for her pain in the past with little benefit. You offer a trial of pregabalin and ask her to follow up if she feels dizzy or is not able to tolerate the drug. 

Pregabalin and gabapentin, collectively gabapentinoids, are primarily anticonvulsant drugs. Over the past decade, they have been increasingly prescribed for pain.1 They are recommended for neuropathic pain in adults23 (table 1), but are commonly used off-label for other pain disorders such as low back pain, sciatica, and migraine.910 Pregabalin was one of the highest selling drugs globally in 2017.11 In 2018, more than 14 million prescriptions of pregabalin and gabapentin were issued in England.12 This increase in gabapentinoid prescribing may be driven by a desire to avoid opioid analgesics.13

View this table:

Table 1 
Approved indications for pregabalin and gabapentin



Pregabalin and gabapentin were reclassified as Class C drugs in the UK in April 2019 following an increase in the number of deaths caused by gabapentinoid misuse and addiction.14 Under the UK’s Misuse …

https://www.bmj.com/content/bmj/369/bmj.m1315.full.pdf

Pregabalin and gabapentin for pain.

The gabapentinoids gabapentin and pregabalin have been related to addiction citing pharmacovigilance data, some case presentations and increasing reports mainly from methadone maintenance treatment programs or emergency medicine. Most of these reports were based on patients with another current or previous substance use disorder (SUD). According to the ICD-10 dependence criteria, physical dependence (withdrawal symptoms, tolerance) was reported most frequently alongside regular use of gabapentinoids. Far less patients showed key symptoms of behavioral dependence (craving, loss of control, or addictive behavior). 

Through a literature review, we found 2 and 13 case reports about gabapentionoid-seeking behavior or craving for gabapentin and pregabalin, respectively. Those patients without a history of another SUD, but being behaviorally dependent on gabapentinoids, deemed more appropriate to reflect the true addictive power of these drugs. We found solely 4 such cases, all referring to pregabalin and none for gabapentin. Taking into account that gabapentinoids have become widely distributed and easily obtainable via the internet or black-markets, one would expect many more of these cases, if gabapentinoids had considerable addictive power. Moreover, we are not aware of any patient who sought detoxification treatment owing to the misuse of gabapentinoids. Unlike for traditional psychoactive drugs, there is only very scarce evidence for gabapentinoids to be misused in a long-term manner and to be rewarding and reinforcing in animal experiments. Further, we assessed the hazardous potential of gabapentin and pregabalin in relation to that of traditional substances of abuse. Altogether, we support the view that gabapentinoids are quite rarely addictive in the general population. In patients with a history of SUD, however, gabapentinoids (notably pregabalin) should avoided or, if thought to be beneficial, administered with caution by using a strict prescription and therapy monitoring.

/pdf/on-the-addictive-power-of-gabapentinoids-a-mini-review-36w5bkrhfm.pdf

On the addictive power of gabapentinoids: a mini-review.

It is unusual for purpura to emerge as a result of drinking alcohol Such a peculiarity was observed in a 55-year-old man with a 30-year history of heavy alcohol use The Caucasian patient was studied for 11 years during several detoxification treatments During the last 2 years of that period, purpuric rashes were newly observed The asymptomatic purpura was limited to both lower limbs, self-limiting with abstinence, and reoccurring swiftly with alcohol relapse This sequence was observed six times, suggesting a causative role of alcohol or its metabolites A skin biopsy revealed histological features of purpura pigmentosa progressiva (termed Schamberg’s disease) Additionally, alcoholic fatty liver disease markedly elevated serum immunoglobulins (immunoglobulin A and immunoglobulin E), activated T-lymphocytes, and increased C-reactive protein In addition, moderate combined (cellular and humoral) immunodeficiency was found Unlike the patient’s immunoglobulin A level, his serum immunoglobulin E level fell in the first days of abstinence, which corresponded to the time of purpura decline Systemic vasculitis and clotting disorders were excluded The benign character of the purpura was supported by missing circulating immune complexes or complement activation An alcohol provocation test with vinegar was followed by the development of fresh “cayenne pepper” spots characteristic of Schamberg’s disease This case report demonstrates that Schamberg’s disease can be strongly related to alcohol intake, in our patient most likely as a late complication of severe alcoholism with alcoholic liver disease Immunologic disturbances thereby acquired could have constituted a basis for a hypersensitivity-like reaction after ingestion of alcohol Schamberg’s disease induction by vinegar may point to an involvement of acetate, a metabolite of ethanol

/pdf/recurrent-purpura-due-to-alcohol-related-schamberg-s-disease-2kykryoo34.pdf

Recurrent purpura due to alcohol-related Schamberg’s disease and its association with serum immunoglobulins: a longitudinal observation of a heavy drinker

Katrin Isbruch

Papers

On the addictive power of gabapentinoids: a mini-review.

Recurrent purpura due to alcohol-related Schamberg’s disease and its association with serum immunoglobulins: a longitudinal observation of a heavy drinker