Sympathomimetic Toxicity Research Articles

Evaluation of the Clinical and Paraclinical Symptoms of Children Intoxicated With Amphetamines in Akbar Hospital of Mashhad, Iran 2021-2022.

Amphetamine poisoning in children is a significant public health concern due to its potential for severe adverse effects on physical and mental health. In this article, we describe a case series of 29 children under the age of 14 presenting with sympathomimetic toxidrome due to confirmed amphetamine poisoning. In this cross-sectional study, children (1 month to 14 years old) who were hospitalized in the emergency and pediatric departments of Imam Reza and Akbar Hospital in Mashhad from the beginning of April 2021 to September 2022 were identified with the diagnosis of amphetamine poisoning. Their demographic, clinical, and paraclinical (laboratory and electrocardiogram) information, which was included in the relevant checklists, were analyzed and reported. Out of 29 children included in the study, 18 (62%) were male and the rest were female. The average age of children was 44.75 ±43.9 months; most of them were less than 4 years old. In all patients, glasgow coma scale (GCS) was 15. In 25.92% of cases (8 patients) blood pressure was above the 90% percentile for age and sex, 82.60% (24 cases) were tachycardia, 72.41% crying (21 cases), 86.20% were restless (25 cases), 10.34% tremor (3 cases), 10.34% had body pain (3 cases), and 6.89% (2 cases) had delusions. None of the subjects had a seizure. The serum level of creatine phosphokinase was on average 771.99 ± 966 units/L. All children had an increase in creatine phosphokinase (CPK) and 25.9% of children had an increase in CPK to more than 1000 units/L. Based on the results, in children with symptoms such as restlessness, crying, and tachycardia, poisoning with amphetamine group substances should be included in the differential diagnosis list, and also measuring CPK and investigating the possible occurrence of rhabdomyolysis in cases of poisoning of children with amphetamine seems necessary.

Methamphetamine Poisoning After "Plugging" Intentional Recreational Rectal Use

BackgroundMethamphetamine is a commonly used illicit substance. The route of administration is usually parenteral, oral ingestion, or snorting. A less common route of administration is placing in the rectum. Case ReportA 28-year-old man presented to the emergency department with acute methamphetamine toxicity within 30 min after intentional rectal administration of methamphetamine for recreational purposes. The patient had hypertension, tachycardia, drug-induced psychosis, elevated creatine kinase, and required rapid sequence intubation and admission to the intensive care unit. Our patient had no clinical evidence of bowel ischemia or injury at the time of discharge. Why Should an Emergency Physician Be Aware of This?Rectal administration of methamphetamine is known as “plugging,” “booty bumping,” “keestering,” and “butt whacking.” The rectal administration of methamphetamine has the increased risk of severe acute methamphetamine toxicity, as rectal administration bypasses first-pass metabolism, allowing for a more acute onset and higher bioavailability of methamphetamine compared with oral administration. There is the potential for mesenteric ischemia and bowel injury after rectal methamphetamine. Close clinical monitoring for bowel and rectal ischemia or injury are recommended, in addition to management of the sympathomimetic toxidrome.

Basic approach to poisoning focusing “Toxidrome”

Background: The term “toxidrome” is derived from the term “toxic syndrome.”A toxidrome is a constellation of signs and symptoms that are seen with particular classes of poisons. Methods: A systematic review of English literature was done with search item naming toxidrome and or basic approach to poisoning. Search engine was multiple leaded by pubmed having mesh term of toxidrome. The journal sites of asiajol and banglajol was also searched for related topics. Personal communication with toxicology related paper was also applied during the process. Results: All of the toxidromes can be identified using the a quick “toxicological physical exam.” No laboratory tests are necessary! The toxicologic physical exam focuses on the following components: Vital Signs, behavior like sleepy, normal, euphoric, agitated ? Pupils whether small, normal, big? Mucus membranes like checking the axillae whether it is dry, normal, wet?Bowel sounds to see whether it is decreased, normal, increased? There are 7 toxidromes that the emergency physician should be able to recognize and treat.These include: The anticholinergic toxidrome, cholinergic toxidrome, opioid toxidrome, opioid withdrawal toxidrome, sedative-hypnotic toxidrome, sedative-hypnotic withdrawal toxidrome, and sympathomimetic toxidrome. Beside these, two additional toxidrome has recently been introduced, one is serotonergic toxidrome and neuroleptic malignant toxidrome. Patients who take several substances may have a mixed toxidrome. For example, a patient who “speedballs” cocaine and heroin may have features of both the opioid and sympathomimetic toxidromes. Conclusion: Like all clinical syndromes, patients almost never exhibit every single feature of a particular toxidrome. When diagnosing a patient with a specific toxidrome you are looking for the one which best fits. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 185-186

Characterization of Nonfatal Opioid, Cocaine, Methamphetamine, and Polydrug Exposure and Clinical Presentations Reported to the Toxicology Investigators Consortium Core Registry, January 2010-December 2021.

To characterize and compare opioid-only, cocaine-only, methamphetamine-only, opioid-and-cocaine exposure, and opioid-and-methamphetamine exposure and to examine clinical presentations, leading to a better understanding of overdose effects involving these drug exposures. We examined drug exposures in the Toxicology Investigators Consortium (ToxIC) Core Registry from January 2010 to December 2021, a case registry of patients presenting to participating healthcare sites that receive a medical toxicology consultation. Demographic and clinical presentations of opioid-only, cocaine-only, methamphetamine-only, and opioid-and-cocaine exposure, and opioid-and-methamphetamine exposure consultations were described; differences between single and polydrug exposure subgroups were calculated to determine statistical significance. Clinical presentations associated with exposures were evaluated through calculated adjusted relative risk. A total of 3,883 consultations involved opioids, cocaine, methamphetamine, opioid-and-cocaine exposure, or opioid-and-methamphetamine exposure. Opioid-only (n = 2,268, 58.4%) and methamphetamine-only (n = 712, 18.3%) comprised most consultations. There were significant differences in clinical presentations between exposure subgroups. Opioid-and-cocaine exposure consultations were 8.15 times as likely to present with a sympathomimetic toxidrome than opioid-only. Conversely, opioid-and-cocaine exposure and opioid-and-methamphetamine exposure were 0.32 and 0.42 times as likely to present with a sympathomimetic toxidrome compared to cocaine-only and methamphetamine-only consultations, respectively. Opioid-and-cocaine exposure was 0.67 and opioid-and-methamphetamine exposure was 0.74 times as likely to present with respiratory depression compared to opioid-only consultations. Similarly, opioid-and-cocaine exposure was 0.71 and opioid-and-methamphetamine exposure was 0.78 times as likely to present with CNS depression compared to opioid-only consultations. Used in combination, opioids and stimulants may mask typical clinical presentations of one another, misattributing incorrect drugs to overdose in both clinical treatment and public health surveillance.

Duloxetine overdose causes sympathomimetic and serotonin toxicity without major complications

Objective Duloxetine is a commonly used antidepressant that is a serotonin and norepinephrine reuptake inhibitor. We aimed to investigate the frequency and severity of clinical effects following duloxetine overdose. Methods We undertook a retrospective review of duloxetine overdoses (>120 mg) admitted to two tertiary toxicology units between March 2007 and May 2021. Demographic information, details of ingestion (dose, co-ingestants), clinical effects, investigations (ECG parameters including QT interval), complications (coma [GCS < 9], serotonin toxicity, seizures and cardiovascular effects), length of stay [LOS] and intensive care unit [ICU] admission were extracted from a clinical database. Results There were 241 duloxetine overdoses (>120 mg), median age 37 years (interquartile range [IQR]: 25–48 years) and there were 156 females (65%). The median dose was 735 mg (IQR: 405–1200 mg). In 177 patients, other medications were co-ingested, most commonly alcohol, paracetamol, quetiapine, diazepam, ibuprofen, pregabalin and oxycodone. These patients were more likely to be admitted to ICU (12 [7%] vs. none; p = 0.040), develop coma (16 [9%] vs. none; p = 0.008) and hypotension [systolic BP < 90 mmHg] (15 [8%] vs. one; p = 0.076). Sixty four patients ingested duloxetine alone with a median dose of 840 mg (180–4200 mg). The median LOS, in the duloxetine only group, was 13 h (IQR:8.3–18 h), which was significantly shorter than those taking coingestants, 19 h (IQR:12–31 h; p = 0.004). None of these patients were intubated. Six patients developed moderate serotonin toxicity, without complications and one had a single seizure. Tachycardia occurred in 31 patients (48%) and mild hypertension (systolic BP > 140 mmHg) in 29 (45%). One patient had persistent sympathomimetic toxicity, and one had hypotension after droperidol. Two patients of 63 with an ECG recorded had an abnormal QT: one QT 500 ms, HR 46 bpm, which resolved over 3.5 h and a second with tachycardia (QT 360 ms, HR 119 bpm). None of the 64 patients had an arrhythmia. Conclusion Duloxetine overdose most commonly caused sympathomimetic effects and serotonin toxicity, consistent with its pharmacology, and did not result in coma, arrhythmias or intensive care admission, when taken alone in overdose.

Comparison of clinical characteristics between meth/amphetamine and synthetic cathinone users presented to the emergency department

Background Synthetic cathinones (SC) are popular new psychoactive substances that produce sympathomimetic toxicity. Meth/amphetamine and SC have similar chemical structures and pharmacological effects. We aimed to compare the clinical characteristics between meth/amphetamine and SC users presenting to the emergency department (ED). Methods This retrospective observational cohort study included patients who presented to six EDs from May 2017 to April 2021 with symptoms that related to recreational drug use and whose urine toxicology tests were positive only for meth/amphetamine or SC through liquid chromatography-tandem mass spectrometry. Results There were 379 patients who tested positive only for meth/amphetamine (MA group), and 87 patients tested positive only for SC (SC groups). Patients in the MA group were older than those in the SC group (median (IQR); MA: 37.0 (30–43.7), SC: 25.0 (21.0–32.7), p < 0.001). There were no significant between-group differences in the sex distribution and initial chief complaints. Compared with the MA group, the SC group had more cases of tachycardia (≥ 135/min; MA: 29 (8.2%), SC:16 (19.0%), p = 0.0031) and hyperthermia (≥ 38 °C; MA: 31 (8.2%), SC:18 (20.7%), p = 0.001). Besides, the SC group had significantly higher levels of creatinine kinase (CK, IU/L; MA: 263 (115–601), SC: 497 (206–9216), p = 0.008) as well as a higher risk of rhabdomyolysis (CK > 1000; MA:32 (8.4%), SC: 16 (18.4%), p = 0.006) and severe rhabdomyolysis (CK > 10,000; MA:10 (2.6%), SC:10 (11.5%), p = 001). Multivariable logistic regression analyses indicated SC group in comparison with the MA group (adjusted odds ratio: 2.732, 95% confidence interval: 1. 250–5.972, p = 0.012) was an association with the risk of rhabdomyolysis. Conclusion Our findings demonstrate that tachycardia, hyperthermia, and rhabdomyolysis were more common among cathinone users than among meth/amphetamine users presented to EDs.

Drugs of Abuse

The term “drugs of abuse” lacks a formal medical definition. Historically, discussions of drugs of abuse focused on “street drugs”; however, the adverse effects of the nonmedical use of prescription medications, such as opiates, benzodiazepines, and therapeutic amphetamines, are increasingly seen. The purpose of this review is to aid the clinician in identifying and treating a broad representation of drugs of abuse, which may include those illicitly produced in laboratories (e.g., methamphetamine), diverted pharmaceuticals (oxycodone), and herbal products (marijuana). This review covers stimulants, hallucinogens, cannabinoids, and sedative-hypnotics. Figures show substances ranked according to weighted harm score on a normalized scale from 0 being no harm to 100 being extreme harm to self and others, a treatment algorithm for sympathomimetic toxicity, a treatment algorithm for sedative-hypnotic overdose, and a treatment algorithm for opioid overdose. Tables list commonly abused sympathomimetic agents, modern novel drugs of abuse, commonly abused sedative-hypnotic agents, commonly abused opiates, and pitfalls of the drug screen. This review contains 4 highly rendered figures, 6 tables, and 90 references. Key Words: street drugs, prescription medications, opiates, benzodiazepines, amphetamines, stimulants, hallucinogens, oxycodone, marijuana, overdose

Pediatric Methamphetamine Toxicity: Clinical Manifestations and Therapeutic Use of Antipsychotics-One Institution's Experience.

Methamphetamine toxicity is common in the Southwestregion of the UnitedStates and presents diagnostic and treatment challenges in the pediatric population. The aim of our study was to characterize signs and symptoms of methamphetamine toxicity in pediatric patients, highlighting manifestations unique to this population. Additionally, our study sought to evaluate treatment modalities, specifically antipsychotics, in this population with the intent to characterize their adverse effects. This is a retrospective review ofpediatric patients (age > 2months ≤ 18years) at a tertiary care pediatric hospital with ICD-9 or ICD-10 codes suggestive of stimulant exposure between September 1, 2010, and July 31, 2017. Patients with clinical manifestations of sympathomimetic toxicity and confirmation of methamphetamine on urine drug testing via GC/MS were included. Nature, source, and route of exposure along with clinical manifestations including signs, complications, treatments utilized, and adverse events related to treatment were recorded. Specifically, adverse effects following administration of antipsychotics were studied. Seventy-nine patientsmet inclusion criteria: median age 2.0years. Typical manifestations of sympathomimetic toxicitywere common, including tachycardia (93.4%), hypertension (85.7%), agitation (79.7%), and abnormal motor activity (55.8%). The prominence of gastrointestinal signs (26.3%) and unique abnormal motor activity were notable. The most common treatments were intravenous fluids (96.1%) and benzodiazepines (77.9%). Antipsychotics were administered in 40.5% of cases, with haloperidol used in the majority. No patients developed seizures, dystonia, torsades de pointes, or hyperthermia after antipsychotic administration. Pediatric patients with methamphetamine toxicity commonlymanifest sympathomimetic signs.Antipsychoticswere often used as an adjunct treatment in this cohort of patients, and no adverse events were reported. Clinicians should be aware of prominent gastrointestinal signs and abnormal motor activity and neurologic manifestations unique to pediatric patients that will assist in making the correct diagnosis in cases of suspected methamphetamine toxicity.

Toxicity from illegitimate slimming agents – a 10-year case series at a tertiary toxicology laboratory in Hong Kong

Context This retrospective case-series study aims to provide an overview of the clinical, biochemical and analytical findings in patients who presented with toxicity related to the use of illegitimate slimming agents in Hong Kong from the perspective of a tertiary referral toxicology laboratory. Methods All clinical cases referred to the Hospital Authority Toxicology Reference Laboratory, Hong Kong with clinical suspicion of illegitimate slimming agent-related toxicity between January 2008 and December 2017 were reviewed retrospectively. The use of illegitimate slimming agents included the use of (1) deregistered slimming agents, (2) drug analogues that were not registered drugs, (3) registered drugs not approved for the indication of weight reduction (whether prescribed by a doctor or not), and (4) prescription-only slimming agents without a doctor’s prescription. Patients taking registered weight-reducing drugs prescribed by a doctor were excluded. Patient demographics, clinical features, relevant laboratory investigations, and toxicological findings were analyzed. Results From 2008 to 2017, a total of 346 patients were analytically confirmed by our laboratory to have clinical toxicity related to the use of illegitimate slimming agents. The median age of the patients was 27 years and 92.5% of the patients were female. The most common clinical presentations included psychiatric features, sympathomimetic toxicity, hypokalemia, and abnormal thyroid function tests. Fatal or severe clinical toxicity was observed in 10% of the cases. The major classes of drugs detected on our analytical platforms were stimulants (e.g., sibutramine), laxatives (e.g., anthraquinones), diuretics (e.g., hydrochlorothiazide), and thyroid hormones (e.g., animal thyroid tissue). These illegitimate slimming agents were obtained from various sources including the Internet, over-the-counter in community pharmacy, or unspecified local sources. Discussion and conclusions The use of slimming agents is common worldwide; apart from taking registered slimming agents prescribed by registered practitioners, many users obtain slimming agents from various illegitimate sources. The unregulated use of these drugs can be associated with significant clinical toxicity. This study provides a current landscape of illegitimate slimming agent toxicity in Hong Kong to frontline clinicians and other toxicology professionals. Collaboration between clinicians, laboratories, and government authorities would be imperative to prevent further health adversities related to the misuse of these agents.

Heroin Adulterated with the Novel Synthetic Cannabinoid, 5F-MDMB-PINACA: A Case Series.

IntroductionHeroin can be adulterated with various substances that may or may not have pharmacological effects. Here we report a case series of 8 patients who presented to the emergency department after overdose with intravenous heroin preparation adulterated with the synthetic cannabinoid methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (5F-MDMB-PINACA).Case SeriesExcept for one patient, all of them presented with a typical initial opioid toxidrome consisting of central nervous system and respiratory depression along with pinpoint pupils. Naloxone was given to them, triggering severe agitation and combative behavior along with overlapping features of anticholinergic and sympathomimetic toxidrome. All patients required multiple doses of benzodiazepines. Three were successfully treated with physostigmine.Discussion5F-MDMB-PINACA is a synthetic cannabinoid that was added to heroin in samples obtained from patients reported in this case series. Patients demonstrated significant agitation after receiving naloxone for opioid toxidrome, presumably because of the removal of the depressant effect of opioids, which unmasked the excitatory effects of the synthetic cannabinoids. Three patients required physostigmine along with the benzodiazepines for control of their agitation, urine retention and abnormal vitals, suggesting the possibility of an anticholinergic toxidrome to have developed in these patients.ConclusionHeroin contaminated with 5F-MDMB-PINACA exhibits variable severities of anticholinergic effects, some on presentation and others only after opiate antagonism.

Safety and Efficacy of an On-Site Intensive Treatment Protocol for Mild and Moderate Sympathomimetic Toxicity at Australian Music Festivals.

Serotonin and sympathomimetic toxicity (SST) after ingestion of amphetamine-based drugs can lead to severe morbidity and death. There have been evaluations of the safety and efficacy of on-site treatment protocols for SST at music festivals. The study aimed to examine the safety and efficacy of treating patients with SST on-site at a music festival using a protocol adapted from hospital-based treatment of SST. The study is an audit of presentations with SST over a one-year period. The primary outcome was need for ambulance transport to hospital. The threshold for safety was prospectively defined as less than 10% of patients requiring ambulance transport to hospital.The protocol suggested patients be treated with a combination of benzodiazepines; cold intravenous (IV) fluid; specific therapies (cyproheptadine, chlorpromazine, and clonidine); rapid sequence intubation; and cooling with ice, misted water, and convection techniques. One patient of 13 (7.7%) patients with mild or moderate SST required ambulance transport to hospital. Two of seven further patients with severe SST required transport to hospital. On-site treatment may be a safe, efficacious, and efficient alternative to urgent transport to hospital for patients with mild and moderate SST. The keys to success of the protocol tested included inclusive and clear education of staff at all levels of the organization, robust referral pathways to senior clinical staff, and the rapid delivery of therapies aimed at rapidly lowering body temperature. Further collaborative research is required to define the optimal approach to patients with SST at music festivals.

PROLONGED LYSERGIC ACID DIETHYLMIDE INDUCED SEROTONIN SYNDROME

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Serotonin syndrome (SS) is a life threatening condition which may often be difficult to diagnose. The increasing incidence of SS is attributable to the wide use of selective serotonin reuptake inhibitors, opioids, and recreational drugs like Lysergic Acid Diethlymide (LSD) which act primarily through 5-HT2 serotonin receptors1. Severe cases often require aggressive intervention in the Intensive Care Unit (ICU) to manage hyperthermia, ventilation, seizures, delirium, rhabdomyolysis, and autonomic instability; however, frequently used analgesics in the ICU such as Fentanyl also contribute to increasing serotonergic levels, thereby, prolonging SS2. CASE PRESENTATION: A 28 year old male visiting from Europe with an unknown medical history was brought in to the hospital after sudden onset of diaphoresis, agitation, and confusion at a restaurant. He presented in status epilepticus with combative behavior leading to intubation, sedation, and paralysis. Seizure control required multiple agents. Initial objective data revealed no electrolyte or metabolic abnormalities, and negative toxicology. Imaging of the brain and infectious workup was unremarkable. Within hours, the patient became hyperthermic and hypertensive; pertinent exam findings included clonus and hyperreflexia. Based on these findings, SS versus sympathomimetic toxicity were the highest on our differential diagnosis. Treatment with cyproheptadine was initiated. The hospital course was prolonged and complicated by aspiration pneumonia, multiple deep vein thrombosis, and prolonged delirium. Higher amounts of Fentanyl and Propofol were required to maintain adequate sedation. The patient remained hypertensive, febrile, with signs of hyperreflexia, and clonus for seven days. Fentanyl was discontinued due to potential serotonergic additive effects. Rapid clinical signs of improvement were observed. It was ultimately discovered that the patient was using lysergic acid diethylamide (LSD). DISCUSSION: LSD is a widely used hallucinogen and a recognized cause of SS³. In the ICU, patients can be exposed to multiple serotonergic agents including opiates and antiemetics, thus, it is imperative clinicians are aware of which agents precipitate and prolong the course of SS. Moreover, each individual’s risk for developing and recovering from SS is dependent on several factors including age, liver, renal function, and genetic polymorphisms in the cytochrome P450 pathway. A thorough review of medications in the ICU may prevent further complications and result in a faster and favorable prognosis. CONCLUSIONS: Our case demonstrates a unique presentation of SS with a favorable outcome due to early suspicion of the diagnosis, recognition of serotonergic agents, and aggressive intervention. Reference #1: Wacker, D. (2017). Crystal Structure of an LSD-Bound Human Serotonin Receptor. Cell, 168(3), pp.377-389.e12. Reference #2: Greenier, E. (2014). Serotonin syndrome: fentanyl and selective serotonin reuptake inhibitor interactions. American Association of Nurse Anesthetists, 82(5), pp.340-5. Reference #3: Halberstadt, A. (2017). Hallucinogenic Drugs: A New Study Answers Old Questions about LSD. Current Biology, 27(4), pp.R156-R158. DISCLOSURES: No relevant relationships by Sujith Puskoor, source=Web Response No relevant relationships by Rebecca Saunders, source=Web Response No relevant relationships by Anita Singh, source=Web Response

Syrian rue seeds interacted with acacia tree bark in an herbal stew resulted in N,N-dimethyltryptamine poisoning

Introduction: Illicit substance use is an increasing problem all over the world, especially in adolescents and young adults. It is a challenge to make a definitive diagnosis of a specific substance in a poisoning case without toxicology laboratory confirmation. We confirmed the presence of N,N-dimethyltryptamine (DMT) by liquid chromatograph tandem mass spectrometer (LC/MS/MS) in biologic samples from two patients who presented with signs and symptoms consistent with sympathomimetic toxicity following the consumption of an herbal stew.Case: Two patients consumed an herbal stew together developed DMT poisoning from the interaction between Syrian rue seeds containing alkaloids with monoamine oxidase inhibitor (MAOI) activity and Acacia tree bark containing DMT. Patients’ blood and spot urine was analyzed by LC/MS/MS which revealed the presence of DMT (case 1 urine: 1206 ng/mL, serum: 25 ng/mL; case 2 urine: 478 ng/mL, serum: undetectable) and harmaline (case 1 urine: 1564 ng/mL, serum: 3.3 ng/mL; case 2 urine: 1230 ng/mL, serum: undetectable).Discussion: The diagnosis of DMT poisoning is confirmed by the presence of DMT and harmaline in patients’ serum and urine. Case 1 exhibited more severe signs and symptoms (e.g., altered consciousness, rhabdomyolysis, and elevated liver enzyme) than case 2. This may be explained by the presence of psychoactive DMT levels in the blood of case 1 whereas DMT was undetected in the blood of case 2.Conclusions: Consumption of an herbal stew composed of Syrian rue seeds and Acacia tree bark may be equivalent to taking a combination of DMT and MAOI, which may precipitate a sympathomimetic syndrome. Physicians should be aware that unusual clinical presentations may be the result of drug-drug interactions from a mixed herbal preparation.

Antipsychotics for the treatment of sympathomimetic toxicity: A systematic review

ObjectiveBenzodiazepines are often recommended first-line for management of cocaine and amphetamine toxicity while antipsychotic treatment is discouraged due to the potential for lowering seizure threshold, prolonging the QT interval, and decreasing heat dissipation. We performed a systematic review including animal and human studies to elucidate the efficacy and safety of antipsychotics in managing sympathomimetic toxicity specifically evaluating the effect of treatment on mortality, seizures, hyperthermia, and cardiovascular effects. MethodsWe searched MEDLINE, Embase, BIOSIS Previews, Web of Science, Scopus, CENTRAL and gray literature from inception to 31 May 2017 to answer: Can antipsychotics be used safely and effectively to treat cocaine or amphetamine toxicity? Citations were screened by title and abstract. Additional citations were identified with citation tracking. Data were extracted from full-texts. Results6539 citations were identified; 250 full-text articles were assessed. Citation tracking identified 2336 citations; 155 full texts were reviewed. Seventy-three papers were included in this review. In 96 subjects with cocaine toxicity treated with an antipsychotic, there were three deaths, two cardiac arrests, two seizures, and one episode of hyperthermia. In 330 subjects with amphetamine toxicity treated with an antipsychotic, there were two episodes of coma and QT prolongation and one episode of each: hypotension, NMS, cardiac arrest, and death. ConclusionThis systematic review represents an exhaustive compilation of the available evidence. There is neither a clear benefit of antipsychotics over benzodiazepines nor a definitive signal of harm noted. We encourage clinicians to adapt treatment based on specific circumstances and characteristics of their individual patients.

Drugs of Abuse

The term “drugs of abuse” lacks a formal medical definition. Historically, discussions of drugs of abuse focused on “street drugs”; however, the adverse effects of the nonmedical use of prescription medications, such as opiates, benzodiazepines, and therapeutic amphetamines, are increasingly seen. The purpose of this review is to aid the clinician in identifying and treating a broad representation of drugs of abuse, which may include those illicitly produced in laboratories (e.g., methamphetamine), diverted pharmaceuticals (oxycodone), and herbal products (marijuana). This review covers stimulants, hallucinogens, cannabinoids, and sedative-hypnotics. Figures show substances ranked according to weighted harm score on a normalized scale from 0 being no harm to 100 being extreme harm to self and others, a treatment algorithm for sympathomimetic toxicity, a treatment algorithm for sedative-hypnotic overdose, and a treatment algorithm for opioid overdose. Tables list commonly abused sympathomimetic agents, modern novel drugs of abuse, commonly abused sedative-hypnotic agents, commonly abused opiates, and pitfalls of the drug screen. This review contains 4 highly rendered figures, 5 tables, and 89 references

A case series involving young children presenting with accidental ingestion of amphetamine based stimulants

•Attention Deficity Hyperactivity Disorder (ADHD) affects adults and children.•Stimulant prescribing for ADHD is increasing.•Overdose of amphetamine based stimulants results in a sympathomimetic toxidrome.•Lisdexamfetamine dimesylate is the first prodrug stimulant developed to treat ADHD.

Sympathomimetic Toxidromes and Other Pharmacological Causes of Acute Hypertension.

Acute drug-induced hypertension, sympathomimetic toxicity, and other hyperadrenergic states can be caused by both xenobiotic toxicity and withdrawal. This manuscript is a selective review of the recent literature regarding pharmacologic causes of hypertensive emergencies and other hyperadrenergic states. We will discuss designer stimulants, alpha2 and baclofen agonist withdrawal, and the clinical entity known as posterior reversible encephalopathy syndrome (PRES). Additionally, we examine the controversial "unopposed alpha" phenomenon which may result from use of beta-adrenergic antagonist in the presence of stimulant toxicity. These topics encompass clinical situations and disease entities that are increasingly encountered and are often either unanticipated or under-recognized.

Pharmacology of MDMA- and Amphetamine-Like New Psychoactive Substances.

New psychoactive substances (NPS) with amphetamine-, aminoindan-, and benzofuran basic chemical structures have recently emerged for recreational drug use. Detailed information about their psychotropic effects and health risks is often limited. At the same time, it emerged that the pharmacological profiles of these NPS resemble those of amphetamine or 3,4-methylenedioxymethamphetamine (MDMA). Amphetamine-like NPS induce psychostimulation and euphoria mediated predominantly by norepinephrine (NE) and dopamine (DA) transporter (NET and DAT) inhibition and transporter-mediated release of NE and DA, thus showing a more catecholamine-selective profile. MDMA-like NPS frequently induce well-being, empathy, and prosocial effects and have only moderate psychostimulant properties. These MDMA-like substances primarily act by inhibiting the serotonin (5-HT) transporter (SERT) and NET, also inducing 5-HT and NE release. Monoamine receptor interactions vary considerably among amphetamine- and MDMA-like NPS. Clinically, amphetamine- and MDMA-like NPS can induce sympathomimetic toxicity. The aim of this chapter is to review the state of knowledge regarding these substances with a focus on the description of the in vitro pharmacology of selected amphetamine- and MDMA-like NPS. In addition, it is aimed to provide links between pharmacological profiles and in vivo effects and toxicity, which leads to the conclusion that abuse liability for amphetamine-like NPS may be higher than for MDMA-like NPS, but that the risk for developing the life-threatening serotonin syndrome may be increased for MDMA-like NPS.

No major role of norepinephrine transporter gene variations in the cardiostimulant effects of MDMA

PurposeMethylenedioxymethamphetamine (MDMA, ecstasy) is used recreationally and frequently leads to sympathomimetic toxicity. MDMA produces cardiovascular and subjective stimulant effects that were shown to partially depend on the norepinephrine transporter (NET)-mediated release of norepinephrine and stimulation of α1-adrenergic receptors. Genetic variants, such as single-nucleotide polymorphisms (SNPs), of the NET gene (SLC6A2) may explain interindividual differences in the acute stimulant-type responses to MDMA in humans.MethodsWe characterized the effects of common genetic variants of the SLC6A2 gene (rs168924, rs47958, rs1861647, rs2242446, and rs36029) on cardiovascular and subjective stimulation after MDMA administration in 124 healthy subjects in a pooled analysis of eight double-blind, placebo-controlled studies.ResultsCarriers of the GG genotype of the SLC6A2 rs1861647 SNP presented higher elevations of heart rate and rate-pressure product after MDMA than subjects with one or no G alleles. Subjects with a C allele in the SLC6A2 rs2242446 SNP presented higher elevations of the heart rate after MDMA administration compared with the TT genotype. Subjects with the AA genotype of the SLC6A2 rs36029 SNP presented higher elevations of mean arterial pressure and rate pressure product after MDMA administration than carriers of the G allele. The SLC6A2 rs168924 and rs47958 SNPs did not alter the response to MDMA.ConclusionsGenetic polymorphisms of the SLC6A2 gene weakly moderated the acute cardiovascular response to MDMA in controlled studies and may play a minor role in adverse cardiovascular events when MDMA is used recreationally.

Intoxications in the STRIDA project involving a panorama of psychostimulant pyrovalerone derivatives, MDPV copycats

Context: An increasing number of new psychoactive substances (NPS) of different chemical classes have become available through marketing and sale over the Internet. This report from the Swedish STRIDA project presents the prevalence, laboratory results, and clinical features in intoxications involving 11 stimulant pyrovalerone NPS derivatives over a 5-year period.Study design: Case series of consecutive patients with admitted or suspected intake of NPS presenting to Swedish hospitals for emergency treatment from January 2011 to March 2016.Patients and method: Blood and urine samples were collected from intoxicated patients presenting to hospitals all over Sweden. Analyses of NPS and other drugs of abuse were performed by immunochemical and liquid chromatography–mass spectrometry multi-component methods. Clinical data were collected during consultation with the Swedish Poisons Information Centre (PIC), and retrieved from medical records. The study involved analytically confirmed cases with 11 pyrovalerone drugs.Results: During the study period, 114 intoxications were detected that involved any of 11 new pyrovalerone drugs. In addition to these new pyrovalerone derivatives, 3,4-methylenedioxypyrovalerone (MDPV) was detected in 17 of the cases and α-pyrrolidinovalerophenone (α-PVP) in 45 cases. Identification was made according to forensic standards and comprised the following substances: 4F-α-PVP, α-PHP, PV8, 4Me-PPP, α-PBP, 4F-PV8, α-PPP, MDPHP, α-PVT, 4Cl-α-PVP, and 4F-α-PHP. The three most frequently detected drugs were α-PBP, MDPHP, and 4F-α-PVP. The age range of patients was 16–66 (median 30) years and 84% were males. The substance concentrations in urine and serum were highly variable, ranging from 1 ng/mL to 300 µg/mL. Poly-drug use was common with only 8 of 114 cases (7%) involving one pyrovalerone drug. The additional substances comprised other NPS and classical psychoactive drugs. The patients showed a variety of clinical signs; agitation, delirium, hallucinations, excessive motor activity, seizures, tachycardia, hypertension, and/or hyperthermia.Conclusions: In analytically confirmed NPS-related intoxications, 11 new pyrovalerone derivatives in addition to MDPV and α-PVP were found. The clinical features were consistent with a sympathomimetic toxidrome, but the urine and serum concentrations were highly variable. The results demonstrated that many novel pyrovalerone stimulants were introduced on the recreational NPS drugs market. Analytical investigations were necessary to obtain this information.