Antipsychotics for the treatment of sympathomimetic toxicity: A systematic review.

OBJECTIVE: Benzodiazepines 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. METHODS: We 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. RESULTS: 6539 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. CONCLUSION: This 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.

Experimental treatments for cocaine toxicity: a difficult transition to the bedside.

Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. Although there is no true antidote to cocaine toxicity, current management strategies address the life-threatening systemic effects, namely hyperthermia, vasospasm, and severe hypertension. Clinicians rely on rapid cooling, benzodiazepines, and α-adrenergic antagonists for management, with years of proven benefit. Experimental agents have been developed to more effectively treat acute toxicity. Pharmacodynamic approaches include antipsychotics that are thought to interfere with cocaine's actions at several neurotransmitter receptors. However, these medications may worsen the consequences of cocaine toxicity as they can interfere with heat dissipation, cause arrhythmias, and lower the seizure threshold. Pharmacokinetic approaches use cocaine-metabolizing enzymes, such as butyrylcholinesterase (BChE), cocaine hydrolase (CocH), and bacterial cocaine esterase (CocE). Experimental models with these therapies improve survival, primarily when administered before cocaine, although newer evidence demonstrates beneficial effects shortly after cocaine toxicity has manifested. CocE, a foreign protein, can induce an immune response with antibody formation. When enzyme administration was combined with vaccination against the cocaine molecule, improvement in cocaine-induced locomotor activity was observed. Finally, lipid emulsion rescue has been described in human case reports as an effective treatment in patients with hemodynamic compromise because of cocaine, which correlates well with its documented benefit in toxicity due to other local anesthetics. A pharmaceutical developed from these concepts will need to be expedient in onset and effective with minimal adverse effects while at the same time being economical.

Relative addictive potential of opioid analgesic agents.

Opioid overdoses and deaths continue to be a problem in the USA with a significant portion related to prescribed opioid analgesic agents. The role of pharmacogentic factors in opioid addiction is an active area of research. While all opioid analgesic agents have some addictive potential, it is clear that there are some with greater addictive potential. Oxycodone is the most widely abused opioid analgesic and it appears to predispose to chronic use with high likability by users. Fentanyl and hydromorphone are both very lipophilic allowing rapid penetration into the CNS, but are not rated as highly as other agents. Providers should consider the risk of addiction with the opioids they prescribe and give those with a lower addictive potential.

Safety and efficacy of pharmacologic agents used for rapid tranquilization of emergency department patients with acute agitation or excited delirium.

Introduction: Management of patients with acute agitation or aggressive behavior can pose a significant challenge to health-care providers in emergency departments. Areas covered: This article provides a comprehensive review of the pharmacologic properties, efficacy, and safety profiles of select intramuscular (IM) sedative agents (i.e., antipsychotics, benzodiazepines, and ketamine) for rapid tranquilization. Expert opinion: Using antipsychotics and benzodiazepines - whether a single agent or combined - will have similar efficacy in producing sedation. But there are differences in the time to sedation depending on which agent is used. Based upon the available studies, droperidol (5-10 mg IM) and midazolam (5-10 mg IM) have the fastest onset of sedation when either is used as a single agent. When combination therapy is used, using midazolam with an antipsychotic agent, instead of lorazepam, may result in faster sedative effect. QT prolongation and torsades de pointes are uncommon adverse drug effects of antipsychotic administration. Ketamine is often reserved as a second-line agent when antipsychotics and benzodiazepines fail to produce the desired tranquilization. However, ketamine (5 mg/kg IM) is more frequently associated with airway compromise requiring endotracheal intubation. A low-dose of ketamine (2 mg/kg IM) may reduce the risk of airway compromise while providing adequate sedation.

Just the Facts: Management of cyclopeptide mushroom ingestion.

A 54-year-old woman prepares dinner around 8:00 pm that includes mushrooms that she picked from her yard. The next morning, around 8:00 am, the woman (patient), her daughter, and son-in-law all develop abdominal cramps, violent vomiting, and diarrhea. They present to the emergency department and are admitted for dehydration and intractable vomiting with a presumed diagnosis of food poisoning. Twenty-four hours later, they appear well with stable vital signs and improved symptoms. Four hours later, 36 hours post-ingestion, the patient becomes lethargic. A venous blood gas reveals pH, 7.1; PCO2, 16 mmHg; and her AST was 3140 units/L with an ALT of 4260 units/L and an INR of 3.7.

The role of take-home naloxone in the epidemic of opioid overdose involving illicitly manufactured fentanyl and its analogs.

INTRODUCTION: There has been an exponential increase in overdose fatalities as illicitly manufactured fentanyl and its analogs (IMF) are becoming more prevalent in the illicit drug supply. In response, overdose education and naloxone distribution (OEND) programs have been implemented throughout the United States as a harm reduction strategy. However, there are increasing reports that higher naloxone doses or repeat administration might be required for overdose victims involving IMF. AREAS COVERED: In this article, we provide a comprehensive review of the epidemiology, public health impact, and pharmacologic properties of IMF. The pharmacokinetic properties of currently available take-home naloxone (THN) kits, the role of THN as a harm reduction strategy and available data on its clinical use are discussed. Implications of occupational IMF exposure for first responders are also described. EXPERT OPINION: THN administration by a bystander is an effective harm reduction intervention. However, there is growing evidence that higher dose or multiple administrations of naloxone are required to fully reverse IMF related toxicity. Recently, the US Food and Drug Administration approved THN kits with a concentrated naloxone dose that produce high bioavailability. However, limited presence of OEND programs and cost of these new devices impede their accessibility to the general public.

The Evolution of Recommended Naloxone Dosing for Opioid Overdose by Medical Specialty.

INTRODUCTION: Opioid abuse and opioid overdose deaths have increased significantly over the past decade. Naloxone is a potentially life-saving medication that can reverse opioid-induced respiratory depression, though precipitated opioid withdrawal can pose acute risks to the patient and medical personnel. The optimal naloxone dose is unclear and few studies address this question. METHODS: A convenience sample of commonly available references were queried for the recommended IV naloxone dose. When dosing recommendations were different for opioid-tolerant patients these were also recorded. RESULTS: Twenty-five references were located. 48% recommended a starting dose ≤ 0.05 mg while 36% recommend a dose ten-fold higher. More than half of medical toxicology and general medical sources recommended a low-dose strategy with a starting dose lower than 0.05 mg IV. CONCLUSION: There are variations in the recommended doses for naloxone with ranges spanning an order of magnitude. Further exploration is needed to determine the dose that balances reversal of respiratory depression with mitigation of withdrawal.

Electromyographic and laboratory findings in acute Solanum torvum poisoning.

CONTEXT: Solanum torvum berries, known as susumber or turkey berries, are prepared as part of traditional Jamaican dishes usually served with cod and rice. Poisoning is rare. Although toxic compounds have never been definitively isolated, previous reports suggest toxicity results from inhibition of acetylcholinesterases. We present a case of susumber berry poisoning with detailed electromyographic studies and laboratory analysis. CASE DETAILS: A 54-year-old woman presented to the Emergency Department (ED) complaining of vision, speech, and gait changes; emesis; and diffuse myalgias following consumption of susumber berries. The physical examination demonstrated an intact, lucid mental status, miosis, opsoclonus, severe dysarthria, dysmetria, mild extremity tenderness and weakness, and inability to ambulate. Her symptom constellation was interpreted as a stroke. DISCUSSION: Electromyography demonstrated a pattern of early full recruitment as well as myotonia during the period of acute toxicity. Additionally, solanaceous compounds, in particular solasonine and solanidine, were identified in leftover berries and the patient's serum. Store-bought commercial berries and subsequent serum samples were free of such toxic compounds. EMG studies, together with a laboratory analysis of berries or serum can assist in the differential diagnosis of stroke, and provide both a prognostic screening and confirmation of suspected glycoside toxicity.