Christopher D. Rosenbaum

Here today, gone tomorrow…and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines.

Despite their widespread Internet availability and use, many of the new drugs of abuse remain unfamiliar to health care providers. The herbal marijuana alternatives, like K2 or Spice, are a group of herbal blends that contain a mixture of plant matter in addition to chemical grade synthetic cannabinoids. The synthetic cathinones, commonly called “bath salts,” have resulted in nationwide emergency department visits for severe agitation, sympathomimetic toxicity, and death. Kratom, a plant product derived from Mitragyna speciosa Korth, has opioid-like effects, and has been used for the treatment of chronic pain and amelioration of opioid-withdrawal symptoms. Salvia divinorum is a hallucinogen with unique pharmacology that has therapeutic potential but has been banned in many states due to concerns regarding its psychiatric effects. Methoxetamine has recently become available via the Internet and is marked as “legal ketamine.” Moreover, the piperazine derivatives, a class of amphetamine-like compounds that includes BZP and TMFPP, are making a resurgence as “legal Ecstasy.” These psychoactives are available via the Internet, frequently legal, and often perceived as safe by the public. Unfortunately, these drugs often have adverse effects, which range from minimal to life-threatening. Health care providers must be familiar with these important new classes of drugs. This paper discusses the background, pharmacology, clinical effects, detection, and management of synthetic cannabinoid, synthetic cathinone, methoxetamine, and piperazine exposures.

Herbal medicines for the management of opioid addiction: safe and effective alternatives to conventional pharmacotherapy?

Striking increases in the abuse of opioids have expanded the need for pharmacotherapeutic interventions. The obstacles that confront effective treatment of opioid addiction — shortage of treatment professionals, stigma associated with treatment and the ability to maintain abstinence — have led to increased interest in alternative treatment strategies among both treatment providers and patients alike. Herbal products for opioid addiction and withdrawal, such as kratom and specific Chinese herbal medications such as WeiniCom, can complement existing treatments. Unfortunately, herbal treatments, while offering some advantages over existing evidence-based pharmacotherapies, have poorly described pharmacokinetics, a lack of supportive data derived from well controlled clinical trials, and severe toxicity, the cause for which remains poorly defined. Herbal products, therefore, require greater additional testing in rigorous clinical trials before they can expect widespread acceptance in the management of opioid addiction.

Kinetics and efficacy of an organophosphorus hydrolase in a rodent model of methyl-parathion poisoning.

OBJECTIVES Organophosphorus (OP) pesticides exert a tremendous health burden, particularly in the developing world. Limited resources, the severity of intentional OP ingestions, and a paucity of beneficial therapies all contribute to the morbidity and mortality of this broad class of chemicals. A novel theoretical treatment for OP poisoning is the use of an enzyme to degrade the parent OP in the circulation after poisoning. The aims of this study were to determine the pharmacokinetics and efficacy of an OP hydrolase (OpdA) in a rodent model of severe methyl-parathion poisoning. METHODS Two animal models were used. First, Wistar rats were administered two different doses of the hydrolase (0.15 and 1.5 mg/kg), and the ex vivo hydrolytic activity of plasma was determined by a fluorometric method. Second, an oral methyl-parathion animal poisoning model was developed to mimic severe human poisoning, and the efficacy of postpoisoning OpdA (as measured by survival to 4 and 24 hours) was determined. RESULTS The half-life of OpdA in the Wistar rat was dependent on the dose administered and ranged between 45.0 and 57.9 minutes. The poisoning model of three times the lethal dose to 50% of the population (3 x LD(50)) of methyl-parathion resulted in 88% lethality at 4 and 24 hours. Using a single dose of 0.15 mg/kg OpdA 10 minutes after poisoning resulted in 100% survival at 4 hours (p = 0.001 vs. placebo), but 0% at 24 hours postpoisoning (p = NS vs. placebo). CONCLUSIONS The OP hydrolase OpdA exhibits pharmacokinetics suitable for repeated dosing and increases short-term survival after severe methyl-parathion poisoning.

Non-muscarinic therapeutic targets for acute organophosphorus poisoning.

Organophosphorus (OP) pesticides are a broad class of acetylcholinesterase inhibitors that are responsible for tremendous morbidity and mortality worldwide, contributing to an estimated 300,000 deaths annually. Current pharmacotherapy for acute OP poisoning includes the use of atropine, an oxime, and benzodiazepines. However, even with such therapy, the mortality from these agents is as high as 40%. It is increasingly recognized that not all OPs are the same. Significant differences exist in their toxicity, lipophilicity, and response to oxime therapy. Other non-muscarinic effects of OP pesticides exist, such as acute and chronic neuromuscular junction failure and central respiratory failure. In part because most of the mortality from these chemicals takes place in the developing world, little National Institutes of Health (NIH) research has been directed towards these agents. However, the similar mechanism of action of OP pesticides and the military nerve agents, along with increasing concerns about chemical terrorism has lead to the formation of the NIH Countermeasures Against Chemical Threats (CounterACT) Program. As part of the CounterACT Program, the NIH has recently designated six OP pesticides as “threat agents”. This concept paper describes some of the knowledge gaps related to non-muscarinic effects of OP pesticides and highlights needed areas of further research. Leveraging the current NIH interest in these chemicals to medical necessities in the developing world offers the possibility of delivering new therapeutics where they are needed on a daily basis.

Intersection of chronic pain treatment and opioid analgesic misuse: causes, treatments, and policy strategies

Treating chronic pain in the context of opioid misuse can be very challenging. This paper explores the epidemiology and potential treatments for chronic pain and opioid misuse and identifies educational and regulation changes that may reduce diversion of opioid analgesics. We cover the epidemiology of chronic pain and aberrant opioid behaviors, psychosocial influences on pain, pharmacological treatments, psychological treatments, and social treatments, as well as educational and regulatory efforts being made to reduce the diversion of prescription opioids. There are a number of ongoing challenges in treating chronic pain and opioid misuse, and more research is needed to provide strong, integrated, and empirically validated treatments to reduce opioid misuse in the context of chronic pain.

Current practices for mental health follow-up after psychiatric emergency department/psychiatric emergency service visits: a national survey of academic emergency departments

OBJECTIVE The objective was to describe continuity of care approaches for psychiatric emergencies in the emergency department. METHODS A national survey of all 138 academic emergency departments in the United States was conducted. RESULTS Most emergency physicians (81%) had no systematic method for identifying psychiatric emergency patients with high recidivism. In order to promote outpatient care, sites commonly reported using intensive interventions, including scheduling outpatient appointments prior to discharge (72%) and in-house case management (64%). CONCLUSION While systematic identification of repeat psychiatric emergency patients was uncommon, emergency departments reported using a variety of fairly intensive strategies to promote continuity of care with outpatient mental health services.

Nasopharyngeal Necrosis After Chronic Opioid (Oxycodone/Acetaminophen) Insufflation

Nasopharyngeal necrosis resulting from narcotic insufflation is a recognized phenomenon, but cocaine use is more commonly associated with this pathology than opioid abuse. Physical exam findings associated with severe tissue destruction are not routinely seen on physical examination or available in the medical literature. We present a case of chronic oxycodone/acetaminophen insufflation and images of a defect in the soft palate.

Readiness to change alcohol and illicit drug use among a sample of emergency department patients

Objective: This study sought to (1) provide estimates of alcohol and illicit drug use, alone and in combination, among a sample of adult emergency department patients and (2) examine readiness to change. Methods: Consecutive emergency department patients ≥18 years of age from a large regional hospital in Camden, NJ, were enrolled from May to December 2005. Patients provided information on alcohol and illicit drug use, as well as on interest in quitting each of these substance classes. Results: Of the 1549 subjects surveyed, 98 (6%) indicated weekly use of both alcohol and illicit drugs, and 58 (4%) indicated problems associated with use of both substance classes. Problem users of illicit drugs felt that quitting drugs was more important, that they were more ready and that they were more confident in quitting than problem users of alcohol. Conclusion: Problem use of multiple substances was relatively common in this emergency department sample. A substantial proportion of problem users of both substance classes were highly motivated to quit the use of one, but not the other, substance class. Further longitudinal and clinical trial research is needed to study the implications of multiple substance use, motivation to change and cessation.

Oxymorphone Insufflation Associated with Acute Sensorineural Hearing Loss: Case Files of the University of Massachusetts Medical Toxicology Fellowship

A37-year-oldmale was found supine andminimally responsive in his mother’s basement. Emergency medical services reported miotic pupils, bradypnea, and depressed mental status that improved significantly after administration of naloxone 1 mg intramuscularly. In the emergency department, the patient had stable vital signs and normal mental status. He reported having consumed alcohol earlier, then snorting crushed Opana® (oxymorphone: Endo Pharmaceuticals Inc; Chadds Ford, PA, USA) shortly before being found unresponsive. The patient purchased the oxymorphone on the Internet and was unsure if he used the immediateor the extended-release formulation. In the emergency department, the patient felt well, except for acute subjective bilateral hearing loss described as feeling like he was “in a tunnel.” He denied any associated trauma, headaches, changes in vision, tinnitus, or ataxia. His physical examwas unremarkable except for subjective bilateral hearing loss observed by both the patient and the examiners. No formal audiologic testing was performed. What Is the Differential Diagnosis of Sensorineural Hearing Loss?

Minocycline Toxicity: Case Files of the University of Massachusetts Medical Toxicology Fellowship

Keywords Minocycline .Tetracycline .Blueskinpigmentation .BlackbonediseaseCase PresentationA 61-year-old man was brought to the emergency department(ED) for shortness of breath, fatigue, frequent falls, and bluishdiscoloration of his skin. The primary care physician trans-ferred the patient due to concern for cyanosis. On presentationto the ED, the patient was oriented but appeared fatigued. Thepatient was afebrile and had the following vital signs: bloodpressure 161/88 mmHg, pulse 71/min, respiratory rate 16/min,and oxygen saturation 100 % on room air by fingertip pulseoximetry. On physical exam, pupils were 4 mm and reactivebilaterally, extraocular movements were intact, and there wasno nystagmus. Anicteric sclerae were notable for blue pigmen-tation (Fig. 1). Heart sounds were regular, without murmurs,rubs, or gallops. Lung sounds were clear to auscultation bilat-erally. Other thanataxia, the neurological exam was unremark-able. The skin had a generalized bluish tinge, especially on thearms,withdarkerpigmentationonthecheeks(Figs. 2,3and4).There was acne on the back and facial rosacea. Bluish discol-oration was also noted under the proximal nail beds (Fig. 5).When questioned about the skin discoloration, the patient andhisfamilymembersdescribedaninsidiousonset.Photographsof the patient from years ago confirmed that this was notcongenital. Medical history included acne, orthostatichypotension, and Parkinsons disease, for which a deep brainstimulator had been surgically implanted. A comprehensivemedication list was not immediately available; however, thepatientdeniedanyrecentmedicationadditionsoradjustments.The patientwasunemployed, denied anyrecent travel, andnoother members of his household were complaining of fatigueor similar blue skin discoloration.What is the Differential Diagnosis of these SkinChanges?When developing a differential diagnosis (see Table 1) forbluish skin discoloration, one must determine if the patienthas cyanosis. A significant toxicologic cause of blue skinappearance from cyanosis is methemoglobinemia. A carefulhistory may help differentiate between acquired versus con-genital methemoglobinemia. Recent exposure to dapsone,benzocaine, lidocaine, nitrates, or aniline dye raises suspi-cion foracquired methemoglobinemia. Sulfhemoglobinemiashould be considered in patients with a positive methemo-globin reading on co-oximetry, but who do not respond tomethylene blue treatment. Oxidizing agents that may causemethemoglobinemia can also produce sulfhemoglobinemiain the presence of sulfur compounds, such as sulfonamidederivatives, hydrogen sulfide, or gastrointestinal sources [1].Causes of noncyanotic skin discoloration are extensive.Metal deposition (e.g., silver, gold, bismuth) causes blueskin pigmentation. Chronic or improper exposure to silvercan result in a silvery blue or gray skin discoloration knownas argyria. Argyria is caused by silver deposition in the skin,specifically within fibroblasts, macrophages, and in the ex-tracellular matrix. These skin changes are often most signif-icant in sun-exposed areas [2]. Similarly, chrysiasis refers to