COVID-19: Therapeutics and interventions currently under consideration.

With the emergence of COVID-19 extensive research began to identify medications, candidate compounds and other therapeutic approaches. The complex virology of COVID-19 may provide multiple potential target points for antiviral therapy, and vaccines; extensive global research is underway to exploit these potential opportunities. The complex pathophysiology, pulmonary and extrapulmonary disease, and immune mediated effects such as cytokine storm, make medical management more challenging than many viral illnesses. Non medication based interventions including hyperbaric oxygen (HBOT), extracorporeal membrane oxygenation (ECMO), aggressive dialysis, and other interventions, all with various degrees of clinical success, and will be discussed in this section. Several antivirals approved for other clinical indications were studied for repurposing against COVID-19, which we highlight, again with varying results. In addition to therapeutics, concern was raised over potential risks associated with ACE inhibitors and ARB use, which is presented. Often the timing of the medication determined its clinical benefit as will be discussed with dexamethasone and other medications. As such, this Therapeutics Review will present prominent and/or promising medications and therapeutic approaches with the caveats that 1. To date, none are FDA approved beyond emergency use authorization (EUA), and 2. Although a comprehensive look at various classes of interventions, it is by no means a complete list of every compound trialed against COVID-19. Recognizing the knowledge basis upon which we treat COVID-19 patients, develop therapeutics, and vaccines continues to evolve as new information is presented, every effort nevertheless has been made to provide as timely information as possible. It is hoped that the information shared can help guide the clinician in terms of potential options to treat this complex group of patients.

The inkjet cleaner "Hurricane"--another GhB recipe.

Gamma hydroxybutyrate (GHB) is widey used as a sexual enhancement drug, a euphoriant, muscle building agent, a sleep aid, a weight loss agent, and as a date rapeagent. Precursor ingredients such as gammabutyrolactone (GBL) and GHB recipes are available, especially via the Internet. This is a report of an organic inkjet cleaner containing a GHB precursor 1,4-butanediol and butylenegycol. A 26-y-o male fell unconscious during work being unresponsive, with constricted pupils, and convulsing, he did not respond to naloxone. A bottle labeled "Hurricane" was found in his pocket. Five h later the patient awoke and was subsequently discharged with all vitals normal. The patient had recently purchased "Hurricane" as a sleep aid and to treat his panic attacks. It is an organic product with active ingredients similar to ink jet cleaner, the key ingredient being 1,4butanediol, which is metabolized to GHB. In spite of legislative changes restricting GHB, the precursors remain available and continue a public health threat.

Preparing for an era of weapons of mass destruction (WMD)--are we there yet? Why we should all be concerned. Part II.

September 11, 2001 demonstrated dramatic voids in national preparedness, and catalyzed massive efforts to identify and remedy vulnerabilities. Since Part I of this series appeared in August 2002, significant improvements have been achieved especially in bioterrorism and chemical terrorism for first responders and emergency medicine, law enforcement, and public health (surveillance). Such efforts manifested benefits during the SARS outbreaks and monkeypox cases of 2003. Nevertheless, emerging infectious diseases will continue to pose a threat if we do not remain vigilant and continue to invest in training, surveillance, and treatments. As expected, many poison centers and toxicologists have taken leadership roles nationwide. In regions where such leadership existed, preparedness levels are strong and collaborations resulted in the development of valuable response plans and training, including the Advanced Hazardous Life Support (AHLS) and Basic Disaster Life Support (BDLS) courses. Early success notwithstanding, experts suggest that current national preparedness has improved slightly from "1" (9/11) to "3" out of "10". Increasingly it has become evident that the nuclear threat, including radiation terrorism, is significant, against which the US remains inadequately prepared. Arguably the nuclear threat-whether accidental or planned-remains our highest consequence vulnerability, and we must rapidly improve our readiness across disciplines. Special populations including the elderly and children remain marginalized in preparedness protocols. Local vulnerabilities including chemical manufacturing and transportation--not just a risk for terrorism but industrial accidents--continue unabated. Our early success is not an endpoint; much work remains and time is fleeting. This report examines vulnerabilities that must be addressed to enhance preparedness.

Dying to be thin: a dinitrophenol related fatality.

2, 4-dinitrophenol (DNP) was originally used as an explosive and later introduced in the 1930's to stimulate metabolism and promote weight loss. It's also a component of pesticides still available globally. Concerns about hyperpyrexia lead to DNP being banned as a dietary aid in 1938. A 22-y-old male presented to the Emergency Department (ED) with a change in mental status 16 h after his last dose of DNP. On admission he was diaphoretic and febrile with an oral temperature of 102 F, but lucid and cooperative. He became agitated and delirious. Intravenous midazolam was initiated with mechanical cooling. Pancuronium was administered later and the patient was intubated. Over the next hour the patient became bradycardic, then asystolic, and despite resuscitative efforts, died. Advertisements claim DNP safe at the dose our patient ingested. It is widely available and with the potential to cause severe toxicity is an understudied public health concern.

A nationwide survey of poison control centers comparing 1999 to 1998 triage and management of asymptomatic children who ingested tricyclic antidepressant.

Triage of asymptomatic, unintentional pediatric (< 6y) tricyclic antidepressant (TCA) exposures has been based upon single cases or small studies involving large dose, symptomatic ingestions. This study evaluated patterns of triage for asymptomatic pediatric TCA exposures as practiced nationally by regional centers and compared them to 1998 patterns. It also evaluated the role of activated charcoal in the management of these exposures. Surveys were sent to the 30 certified regional Poison Control Centers that responded to our 1998 survey. Twenty-two centers responded (73%). Fourteen (63%) referred to a health care facility based upon mg/kg, compared to 6 (20%) in 1998. Of the 14, 6 referred at doses >5 mg/kg compared to 2 (6.6%) in 1998. If referred to an emergency department, 18 (82%) recommended activated charcoal compared to 1 (3.3%) in 1998. The lowest toxic dose reported in the literature is 6.7 mg/kg. This is consistent with poison control data during the past 6y where no child became toxic at doses < 5 mg/kg. This survey demonstrated significant changes in triage patterns for asymptomatic pediatric TCA exposures.

Selected tricyclic antidepressant ingestions involving children 6 years old or less.

OBJECTIVE: According to the annual report of the American Association of Poison Control Centers, tricyclic antidepressant (TCA) ingestions accounted for 15,708 exposures in 1998, of which 70% (all age groups) were treated at health care facilities (HCFs), with an estimated 2,022 children less than 6 years of age exposed. The study objective was to evaluate the manifestations, referral patterns, HCF management, and medical outcomes in pediatric patients 6 years old or less with TCA ingestions reported to a regional poison control center. METHODS: All TCA (amitriptyline, clomipramine, desipramine, doxepin, imipramine, nortriptyline) ingestions from January 1, 1993, to December 31, 1997, involving patients aged 6 years or less managed by the poison control center were evaluated for dose, symptoms, treatments, disposition, and outcome. RESULTS: Forty-four of 48 patients (92%) were asymptomatic. All were single-drug exposures. Forty-three patients (90%) ingested a TCA dose that was less than the normally prescribed pediatric dose (5 mg/kg). Of the five children ingesting >5 mg/kg (range 5-9.4 mg/kg), only one (5.3 mg/kg) was mildly symptomatic (drowsy) prior to admission. Thirty-one of the 48 (65%) were sent to the emergency department (dose range 0.59-9.4 mg/kg). Fourteen of the 31 were admitted for 12-24-hour observation and none subsequently developed symptoms. Twenty-three (74%) received activated charcoal (AC). There was no difference in outcome between the children who did and did not receive AC. CONCLUSIONS: No case of significant toxicity occurred in the children who experienced unintentional TCA ingestions in this study population. None of the children in the study had toxicity at doses <5 mg/kg. Further study is necessary to develop clinical guidelines for the appropriate referral of unintentional ingestions of TCA involving children.