Acute Methylenedioxypyrovalerone Toxicity.

The objective of this study was to characterize the acute clinical effects, laboratory findings, complications, and disposition of patients presenting to the hospital after abusing synthetic cathinone. We conducted a retrospective multicenter case series of patients with synthetic cathinone abuse by searching for the terms bath salts, MDPV, methylenedioxypyrovalerone, mephedrone, methcathinone, methylone, methedrone, and cathinone within the "agent" field of a national clinical toxicology database (ToxIC). The medical records of these patients were obtained and abstracted by investigators at each study site. Patients with confirmatory testing that identified a synthetic cathinone in either blood or urine were included in the series. Patients who had either an undetectable synthetic cathinone test or no confirmatory testing were excluded. A data abstraction sheet was used to obtain information on each patient. We entered data into an Excel spreadsheet and calculated descriptive statistics. We identified 23 patients with confirmed synthetic cathinone exposure--all were positive for methylenedioxyprovalerone (MDPV). Eighty-three percent were male and 74 % had recreational intent. The most common reported clinical effects were tachycardia (74 %), agitation (65 %), and sympathomimetic syndrome (65 %). Acidosis was the most common laboratory abnormality (43 %). Seventy-eight percent of patients were treated with benzodiazepines and 30 % were intubated. Ninety-six percent of patients were hospitalized and 87 % were admitted to the ICU. The majority (61 %) of patients was discharged home but 30 % required inpatient psychiatric care. There was one death in our series. The majority of patients presenting to the hospital after abusing MDPV have severe sympathomimetic findings requiring hospitalization. A number of these patients require inpatient psychiatric care after their acute presentation.

Profiles of importance, readiness and confidence in quitting tobacco use.

OBJECTIVE: This study examined whether rulers of importance, readiness and confidence (IRC) in quitting smoking could be used to identify subgroups of smokers, with the future goal of potentially tailoring interventions to specific readiness profiles. METHODS: Consecutive emergency department patients ≥18 years old were considered for enrolment. Participants provided information on their tobacco use and motivation to quit smoking using 10-point IRC rulers. We used latent profile analysis on the IRC rulers to identify subgroups of smokers and examined associations between profile membership and participant's nicotine dependence and demographics. RESULTS: A total of 1549 patients were screened, yielding a sample of 609 tobacco users. According to statistical fit indices, a four-profile solution fits best: 32% displayed maximum importance and readiness with strong confidence, 43% of the sample displayed relatively average levels of all three variables, 17% displayed below average importance with least favourable readiness and confidence and 7% displayed least favourable importance and readiness but relatively high confidence. Profiles were then shown to differ on nicotine dependence and educational level. CONCLUSIONS: Four distinct profiles of IRC responses were observed. Identifying and describing these patterns has the potential to enhance future targeted intervention efforts and has implications for theory development.

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.

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.

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.

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.

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.

Timing and frequency of physostigmine redosing for antimuscarinic toxicity.

We sought to determine how frequently antimuscarinic-poisoned patients receiving physostigmine receive multiple doses of physostigmine, the length of time between physostigmine doses, and what impact multiple doses of physostigmine have on the disposition and total length of hospital stay. We performed a retrospective chart review of patients given physostigmine for likely antimuscarinic toxicity. A total of 45 patients met inclusion criteria. We abstracted patient demographics, vital signs, physical exam findings, electrocardiograms, the timing and dose of physostigmine, the implicated antimuscarinic agents, and disposition from the hospital. We counted the number of patients who required multiple physostigmine doses and calculated the time to repeat dosing. Fourteen of the 45 patients (31%) given physostigmine for antimuscarinic toxicity received multiple doses: nine patients (20%) received two doses, three patients (6.6%) received three doses, and two patients (4.4%) received four doses. Less than 5.5 h elapsed between sequential physostigmine doses, and less than 6.5 h elapsed between the first and last dose. Forty-five percent of patients receiving one dose of physostigmine were discharged from the emergency department (ED) and 36% of patients receiving more than one dose of physostigmine were discharged from the ED. Whether admitted or discharged, there was no statistically significant difference in the length of hospital stay between patients receiving one or multiple doses of physostigmine. Repeated physostigmine administration is not frequently needed in medication-induced antimuscarinic toxicity. Patients are not likely to require further physostigmine redosing more than 6.5 h from their first dose.