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1.
Toxicol Rep ; 12: 574-577, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38798988

ABSTRACT

Phenobarbital is a long-acting barbiturate used to treat alcohol withdrawal and epilepsy. Acute overdoses present with varying levels of central nervous system depression and large overdoses can be life threatening. Phenobarbital is an attractive candidate for enhanced elimination using urinary alkalinization given it is a weak acid with a long half-life and extensive urinary elimination. Limited human data exist regarding use of urine alkalinization for the treatment of phenobarbital overdose. We present a fourteen-year-old female who was treated with urinary alkalinization alone following an intentional ingestion of 3800 mg (84.4 mg/kg) of phenobarbital tablets. Urine drugs of abuse screening was preliminary positive for barbiturates and confirmed to be phenobarbital only. The initial serum phenobarbital concentration, drawn nine hours post-ingestion, was 97.4 mcg/ml (normal range 15-40 mcg/ml). Urinary alkalinization with sodium bicarbonate was started approximately 12 h post-ingestion and stopped at 72 h post-ingestion; clinical toxicity resolved by hospital day 5. The infusion was titrated to a urinary pH of greater than 7.5. Serial serum and urine phenobarbital measurements were obtained to determine elimination half-life and urinary excretion. The elimination half-life while undergoing urinary alkalinization was 81.3 h. Prior to initiation of urinary alkalinization, the urine phenobarbital concentration was 37 mcg/ml. Approximately 8.75 h after initiation, it was greater than 200 mcg/ml at a urine pH of 8.5. Urinary alkalinization appeared to augment urinary phenobarbital excretion, though with no discernible effect on elimination half-life and unclear clinical benefit. Further research is needed to better characterize the clinical effects of urinary alkalinization for phenobarbital overdose.

2.
J Emerg Med ; 66(4): e457-e462, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38461132

ABSTRACT

BACKGROUND: Opioid overdose is a major cause of mortality in the United States. In spite of efforts to increase naloxone availability, distribution to high-risk populations remains a challenge. OBJECTIVE: To assess the effects of multiple different naloxone distribution methods on patient obtainment of naloxone in the emergency department (ED) setting. METHODS: Naloxone was provided to patients in three 12-month phases between February 2020 and February 2023. In Phase 1, physicians could offer patients electronic prescriptions, which were filled in a nearby in-hospital discharge pharmacy. In Phase 2, physicians directly provided patients with take-home naloxone at discharge. In Phase 3, distribution was expanded to allow ED staff to hand patients take-home naloxone at time of discharge. The total number of prescriptions, rate of prescription filling, and amount of take-home naloxone kits provided to patients were then statistically analyzed using 95% confidence intervals (CI) and chi-squared testing. RESULTS: In Phase 1, 348 naloxone prescriptions were written, with 133 (95% CI 112.5-153.5) filled. In Phase 2, 327 (95% CI 245.5-408.5) take-home naloxone kits were given to patients by physicians. In Phase 3, 677 (95% CI 509.5-844.5) take-home naloxone kits were provided to patients by ED staff. There were statistically significant increases in naloxone distribution from Phase 1 to Phase 2, and Phase 2 to Phase 3. CONCLUSIONS: Take-home naloxone increases access when compared with naloxone prescriptions in the ED setting. A multidisciplinary approach combined with the removal of regulatory and administrative barriers allowed for further increased distribution of no-cost naloxone to patients.


Subject(s)
Drug Overdose , Opioid-Related Disorders , Pharmacy , Humans , United States , Naloxone/therapeutic use , Narcotic Antagonists/therapeutic use , Opioid-Related Disorders/drug therapy , Drug Overdose/drug therapy , Emergency Service, Hospital , Analgesics, Opioid/therapeutic use
3.
BMC Public Health ; 24(1): 923, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38553721

ABSTRACT

BACKGROUND: The opioid overdose crisis is one of the worst public health crises ever to face the US and emerging evidence suggests its effects are compounded by the presence of drug adulterants. Here we report our efforts to characterize the adulterants present within the local fentanyl supply of San Diego County, obtained from undifferentiated drug samples seized by local law enforcement over the calendar year 2021. METHODS: Thirty-two participating local law enforcement agencies across San Diego submitted 4838 unknown individual illicit drug samples (total of 312 kg) to the San Diego County Sheriff's Department Regional Crime Laboratory for identification. RESULTS: Qualitative analysis of these samples via FTIR and GC-MS identified methamphetamine (38.7%), fentanyl (20.8%), diacetylmorphine (heroin) (10.2%), codeine (5.8%) and alprazolam (4.3%) as the most common illicit substances and the presence of 52 unique adulterants. The most common adulterants included 4-methylaminoantipyrine (4-MAAP) (10.9%), mannitol (9%), acetaminophen (8.5%), methamphetamine (4.2%), diacetylmorphine (heroin) (3.6%), tramadol (1.9%), and xylazine (1.7%). Several additional pharmacologically active adulterants and contaminants of interest were also identified. CONCLUSION: This analysis is vital for public health use and harm reduction efforts at the level of the individual consumer. Continued direct surveillance of the drug supply is necessary for the detection of potentially harmful adulterants that may pose serious threats to the public.


Subject(s)
Drug Overdose , Illicit Drugs , Methamphetamine , Humans , Fentanyl/analysis , Heroin , Law Enforcement , Drug Contamination , Analgesics, Opioid
5.
Clin Toxicol (Phila) ; 61(11): 974-981, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37966491

ABSTRACT

INTRODUCTION: Mushrooms containing amatoxin are found worldwide and represent a challenging poisoning for the clinician and consulting poison center. This study evaluates the experience of a large poison system with possible amatoxin-containing mushroom ingestion calls. METHODS: A 10-year retrospective review of the California Poison Control System database was performed for amatoxin mushroom ingestion calls resulting in hospitalization. Cases found were abstracted and data statistically analyzed for association with a composite endpoint of death, liver transplant, and/or the need for dialysis. RESULTS: Amatoxin-containing mushroom calls are infrequent with the vast majority (98.4 percent) coming from Northern California during the rainier first and fourth quarters (October through March) of the year. Elevated initial aminotransferase activities and international normalized ratios were predictive of the composite negative outcome. The mortality plus liver transplant and hemodialysis composite rate was 8.2 percent, consistent with current literature. CONCLUSION: The California Poison Control System has relatively few amatoxin-containing mushroom ingestion calls that result in hospitalization but those that are reported mostly occur in Northern California. Treatment bias towards the sickest patients may explain the association of intravenous fluid use or treatment with acetylcysteine or silibinin with meeting the composite outcome. The initial presence of elevated hepatic aminotransferase activity and international normalized ratios are poor prognostic indicators and are likely reflective of late presentation, an advanced toxic phase of amatoxin poisoning, and/or delays in time to obtain poison center consultation.


Subject(s)
Agaricales , Mushroom Poisoning , Poisons , Humans , Retrospective Studies , Mushroom Poisoning/epidemiology , Mushroom Poisoning/therapy , California/epidemiology , Transaminases
6.
Am J Emerg Med ; 74: 197.e5-197.e7, 2023 12.
Article in English | MEDLINE | ID: mdl-37805370

ABSTRACT

A 48-year-old male intentionally ingested "gopher killer" containing strychnine as a, suicide attempt. He rapidly developed generalized muscle spasms with opisthotonos followed by cardiovascular collapse. He was resuscitated, treated with 24 h of, neuromuscular paralysis, and was discharged on hospital day 10 without sequelae. A blood strychnine concentration obtained five hours post ingestion was 2.2 mg/L. Strychnine poisoning is exceedingly rare in the modern United States and this report contains a video recording of the classic exam findings.


Subject(s)
Poisoning , Strychnine , Male , Humans , United States , Middle Aged , Spasm , Suicide, Attempted , Disease Progression , Poisoning/therapy
7.
Pediatr Emerg Care ; 39(10): 776-779, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37725768

ABSTRACT

OBJECTIVES: Rattlesnake envenomations are uncommon, and the majority occur in adults. Although Crotalidae equine immune F(ab') 2 antivenom (F(ab') 2 AV; trade name ANAVIP) was introduced in 2018, no pediatric specific studies of F(ab') 2 AV have been reported to date. The objective of this study was to evaluate the clinical performance and adverse effects of F(ab') 2 AV in children. METHODS: A single-center, retrospective chart review was performed on patients with rattlesnake envenomation presenting to a children's hospital between October 2018 and August 2022. Inclusion criteria were age younger than 18 years and F(ab') 2 AV use. Exclusion criteria were other antivenom use at any time and presentation beyond 24 hours postenvenomation.Demographic characteristics, hemoglobin, platelet count, fibrinogen, international normalized ratio, number of F(ab') 2 AV vials used, infusion-related complications, and clinical outcomes were collected. RESULTS: Twenty-six patients, 19 males and 7 females, with a mean age of 7.7 years (0.67 to 16 years) met inclusion criteria. Fourteen (54%) were treated with only the initial 10 vial F(ab') 2 AV doses. Twelve patients were given additional doses with a median additional vials of 10 (4-34 vials; interquartile range, 8.75-12 vials). The median total vials given for all patients was 10 (10-44 vials; interquartile range, 10-20 vials).Two patients developed acute infusion reactions. Both were treated by slowing the infusion rate and with medications (diphenhydramine, corticosteroids). No delayed reactions were noted. No patients required blood products or surgical interventions.After discharge, no complications, recurrent symptoms, return visits, or readmissions were reported. Follow-up by chart review or phone was obtained for 18 patients, and no postdischarge complications were noted. Seven patients had postdischarge hematologic laboratory evaluations and all were normal. CONCLUSIONS: Although limited by small sample size and postdischarge follow-up, F(ab') 2 AV was well tolerated in our series of pediatric patients, consistent with prior studies of all age groups.


Subject(s)
Snake Bites , Adult , Male , Female , Humans , Child , Animals , Horses , Adolescent , Snake Bites/drug therapy , Snake Bites/complications , Antivenins/adverse effects , Retrospective Studies , Aftercare , Immunoglobulin Fab Fragments/therapeutic use , Patient Discharge
8.
Am J Emerg Med ; 70: 210.e5-210.e8, 2023 08.
Article in English | MEDLINE | ID: mdl-37236864

ABSTRACT

Human exposures to "fire color changing" agents containing copper salts (CS) are rare. We report the case of an intentional mixed CS ingestion with resulting corrosive gastrointestinal injury absent classic laboratory abnormalities. A 23-year-old male with a history of bipolar disorder presented to the emergency department two hours after intentional ingesting an unknown quantity of the fire colorant "Mystical Fire," which contains cupric sulfate (CuSO4) and cupric chloride (CuCl2). He subsequently developed nausea and abdominal pain and had several episodes of vomiting. Physical examination was notable for diffuse abdominal tenderness without peritoneal signs. Laboratory evaluation was without signs of hemolysis, metabolic derangements, or acute kidney or liver injury. He was noted to have a methemoglobin concentration of 2.2%, which did not require treatment. Serum copper testing was within normal limits. Abdominal CT imaging showed no significant findings. Endoscopy was performed and revealed diffuse esophagitis and gastritis. The patient was started on a proton pump inhibitor and discharged. In this case, the absence of classic laboratory findings of copper did not rule out the presence of gastrointestinal injury. Further investigation is needed to determine the most effective means of ruling out clinically significant CS ingestions.


Subject(s)
Caustics , Male , Humans , Young Adult , Adult , Salts , Copper , Endoscopy, Gastrointestinal , Eating
9.
J Emerg Med ; 64(2): 186-189, 2023 02.
Article in English | MEDLINE | ID: mdl-36813645

ABSTRACT

BACKGROUND: The Komodo dragon (Varanus komodoensis) is the world's largest living lizard and exists in private captivity worldwide. Bites to humans are rare and have been proposed to be both infectious and venomous. CASE REPORT: A 43-year-old zookeeper was bitten on the leg by a Komodo dragon and suffered local tissue damage with no excessive bleeding or systemic symptoms to suggest envenomation. No specific therapy was administered other than local wound irrigation. The patient was placed on prophylactic antibiotics and on follow-up, which revealed no local or systemic infections, and no other systemic complaints. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although venomous lizard bites are uncommon, prompt recognition of possible envenomation and management of these bites is important. Komodo dragon bites may produce not only superficial lacerations but also deep tissue injury, but are unlikely to produce serious systemic effects; whereas Gila monster and beaded lizard bites may cause delayed angioedema, hypotension, and other systemic symptoms. Treatment in all cases is supportive.


Subject(s)
Bites and Stings , Lizards , Animals , Humans , Adult
10.
J Emerg Med ; 64(2): 255-258, 2023 02.
Article in English | MEDLINE | ID: mdl-36806431

ABSTRACT

BACKGROUND: Ethyl chloride is commercially available as a DVD/VCR cleaner, and can be found as a gasoline additive and topical anesthetic. There is an emerging trend of recreational huffing to enhance sexual relations. Neurotoxicity from repeated abuse is uncommon. CASE REPORT: A 36-year-old man with a history of intermittent ethyl chloride use for 15 years presented to the Emergency Department with an inability to walk for 4 days after frequent use for 1 week. The patient reported a rapid titration of inhalation from zero to eight cans of 4.6 oz ethyl chloride aerosol per day over a 1-week period. Initial vital signs were heart rate 88 beats/min, blood pressure 147/60 mm Hg, temperature 37.2°C (99°F), and respiratory rate 16 breaths/min. Physical examination was notable for slurred speech, ptosis, a wide-based and ataxic gait with short strides, inability to stand without support, loss of toe/finger proprioception, horizontal and vertical nystagmus, and dysmetria on coordination testing. Strength and sensation were preserved. His work-up included computed tomography and magnetic resonance imaging of the brain, cervical, thoracic, and lumbar spine that demonstrated no acute abnormalities. On hospital day 9, the patient was able to ambulate with mild difficulty. WHY SHOULD AN EMERGENY PHYSICIAN BE AWARE OF THIS?: Toxicity from excessive ethyl chloride huffing has been rarely reported. The toxicity was characterized with cerebellar findings, no attributable laboratory abnormalities, and no radiographic abnormalities on computed tomography/magnetic resonance imaging. The neurotoxicity resolved with supportive care. This case of excessive huffing of ethyl chloride presenting with neurotoxicity and ataxia further characterizes a rare complication of ethyl chloride toxicity that is gaining popularity.


Subject(s)
Cerebellar Ataxia , Ethyl Chloride , Neurotoxicity Syndromes , Male , Humans , Adult , Neurotoxicity Syndromes/etiology , Ataxia , Anesthetics, Local
11.
J Pharm Pract ; 36(1): 117-119, 2023 Feb.
Article in English | MEDLINE | ID: mdl-34159832

ABSTRACT

BACKGROUND: Although the 3 to 4 gram per 24 hours dose recommended for daily use are generally safe, case reports and some series raise concerns about nonacute excessive doses in some individuals. OBJECTIVE: To assess the safety of dosing more than 4 grams of acetaminophen in a 24-hour period in hospitalized patients and develop a method to evaluate the ongoing practice of acetaminophen dosing. Methods: We performed a retrospective chart review of supratherapeutic doses of acetaminophen over a 2-year period. Outcomes included death and the need for liver transplant. A "best practices alert" (BPA) was then developed in our EMR when more than 4 grams of acetaminophen was either prescribed or administered in a 24- hour period. Twelve months of alerts were then retrospectively reviewed and evaluated. RESULTS: 152 cases of dosing more than 4 grams were initially identified. No cases of death related to liver failure or liver transplant were found in any of these patients. 482 cases were identified after a BPA was put in place where the alert was overridden. There were no deaths and no cases that required liver transplantation due to liver failure. The majority of overrides were due to the allowed window of timing for nursing administration of acetaminophen for scheduled doses and overlap with as needed dosing. CONCLUSION: Supratherapeutic dosing of acetaminophen in our patients did not lead to death or liver transplant. A BPA in our EMR has allowed better evaluation of patterns of acetaminophen use at our university health system.


Subject(s)
Analgesics, Non-Narcotic , Drug Overdose , Liver Failure , Humans , Acetaminophen , Retrospective Studies , Patients
12.
J Am Coll Emerg Physicians Open ; 3(6): e12859, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36474706

ABSTRACT

Introduction: Pediatric organophosphate insecticide poisonings are rare in the United States, and life-threatening toxicity is rarely seen. We report 2 accidental ingestions of the organophosphate insecticide coumaphos that resulted in life-threatening symptoms. Case Reports: A 7-year-old boy and 10-year-old girl both presented from home after accidental ingestion of 1 "spoonful" of coumaphos 20% liquid (Asuntol; Bayer de Mexico, S.A. de C.V., Mexico D.F., Mexico). There were no other known ingestions. Both became rapidly symptomatic, with the boy developing dyspnea, vomiting, and depressed mental status and the girl developing headache and nausea. Soon afterward, the boy had witnessed cardiopulmonary arrest and the girl developed altered mental status and flaccid paralysis. Both were treated initially with atropine, but required no additional doses. On arrival to the pediatric intensive care unit (ICU), both patients received pralidoxime with subsequent plasma exchange and continuous venovenous hemodiafiltration (CVVHDF). Transient anemia, coagulopathy, transaminitis, and hyperglycemia developed in both patients. The girl was extubated on hospital day 6 and the boy on hospital day 11. The girl's course was complicated by aspiration pneumonia and an isolated seizure. The boy's course was complicated mainly by anoxic brain injury, associated seizures, neuroagitation, spasticity, and autonomic instability. The girl was discharged on hospital day 16 and remains asymptomatic 32 days after ingestion. As of 90 days after ingestion, the boy remains admitted to inpatient rehabilitation. Discussion: The clinical benefit of pralidoxime, plasma exchange, and CVVHDF is uncertain in these cases. The optimal treatment regimen for organophosphate insecticide toxicity remains poorly defined.

13.
Toxicol Rep ; 9: 2018-2019, 2022.
Article in English | MEDLINE | ID: mdl-36561949

ABSTRACT

The Green Bush Viper, Atheris squamigera, is native to West and Central Africa and has few well reported envenomations. Bite victims experience dizziness, nausea, headache, regional lymphadenopathy, and localized edema. Most reports also detail severe effects including thrombocytopenia, coagulopathy, hemolysis, hemorrhage, or renal failure. Fatalities are reported, but poorly described. There is no specific antivenom for A. squamigera, but non-species specific antivenom has been reported helpful in several cases. We report the case of a 36-year-old woman who was bitten by a green bush viper and was treated with several non-species specific antivenoms. There were no complications to antivenom administration and the patient experienced a milder envenomation than detailed in previous reports.

14.
Toxicol Rep ; 9: 1725-1727, 2022.
Article in English | MEDLINE | ID: mdl-36561956

ABSTRACT

Introduction: Though acetaminophen overdoses are common, acetaminophen induced methemoglobinemia is rare and it is thought to be due to oxidative stress from reactive metabolites. However, few prior cases of sulfhemoglobinemia in the setting of acetaminophen overdose have been reported. We report a case of mixed methemoglobinemia and sulfhemoglobinemia in the setting of a large, isolated acetaminophen ingestion. Case report: A 30-year-old African American male presented after intentionally ingesting 50 tablets of 500 mg acetaminophen two days prior. He was cyanotic and tachypneic. Peripheral oxygen saturation was 78 % on room air and minimally improved with high-flow oxygen. He was noted to have leukocytosis, thrombocytopenia, anion gap metabolic acidosis with lactic acidemia, acute kidney injury, transaminitis, hyperbilirubinemia, and coagulopathy. Arterial partial pressure of oxygen was normal. Methemoglobin and sulfhemoglobin concentrations were 8.5 % and 5.2 %, respectively. Along with intravenous N-acetylcysteine, methylene blue was administered without clinical improvement. Hemolytic anemia was subsequently noted. Glucose-6- phosphate dehydrogenase (G6PD) deficiency was then confirmed with a quantitative assay and genetic testing. He also received one dose of intravenous metoclopramide. The patient ultimately required eight units of packed red blood cells and several weeks of hemodialysis before discharge on hospital day 43. Discussion: Acetaminophen is structurally related to compounds known to cause methemoglobinemia and sulfhemoglobinemia. We hypothesize that these dyshemoglobinemias were triggered by acetaminophen-induced oxidative stress. The role of G6PD deficiency in the formation of sulfhemoglobinemia is unclear. Acetaminophen overdoses presenting with methemoglobinemia should prompt concern for underlying G6PD deficiency. Coincidental sulfhemoglobinemia should be considered if the clinical presentation is more severe than the methemoglobin concentration alone would suggest. Use of methylene blue in this case, despite the low measured methemoglobin percentage, which likely triggered hemolytic anemia; methylene blue use in a similar circumstance should be weighed carefully against the risk of harm.

15.
J Emerg Med ; 63(1): 58-61, 2022 07.
Article in English | MEDLINE | ID: mdl-35933263

ABSTRACT

BACKGROUND: Diethylene glycol (DEG) is an industrial solvent with many uses, including brake fluids. It has also caused mass poisonings after use as an inappropriate substitute for propylene glycol or glycerin, though individual ingestions are rare. Like other toxic alcohols, DEG is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase, with toxicity likely mediated by the resulting metabolites. Fomepizole, an alcohol dehydrogenase inhibitor, is used to prevent metabolite formation with other toxic alcohol exposures. Fomepizole is recommended for DEG poisoning, though supporting clinical evidence is limited. CASE REPORT: A 31-year-old man presented after ingestion of DEG-containing brake fluid and hydrocarbon-containing "octane booster." He was noted to be clinically intoxicated, with a mildly elevated anion gap metabolic acidosis and no osmolar gap. DEG level was later found to be elevated, consistent with his ingestion. He was treated with fomepizole alone, with resolution of metabolic acidosis and clinical findings over the next 2 days. No delayed neurologic sequelae were present at 52-day follow-up. Our case provides additional evidence supporting the use of fomepizole for DEG poisoning. Consistent with other toxic alcohols, DEG poisoning, especially early presentations, may benefit from empiric fomepizole administration. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: DEG poisoning is potentially life threatening, but treatable if identified early. An ingestion can be toxic despite a normal osmolar gap, leading to false reassurance. Finally, it is rare, so emergency physicians must be made aware of its potential dangers.


Subject(s)
Acidosis , Poisoning , Acidosis/chemically induced , Acidosis/drug therapy , Adult , Alcohol Dehydrogenase/therapeutic use , Aldehyde Dehydrogenase/therapeutic use , Antidotes/pharmacology , Antidotes/therapeutic use , Eating , Ethylene Glycol , Ethylene Glycols , Fomepizole/therapeutic use , Glycerol/therapeutic use , Humans , Male , Octanes/therapeutic use , Poisoning/therapy , Propylene Glycols/therapeutic use , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Solvents/therapeutic use
16.
Pediatr Rep ; 13(4): 613-623, 2021 Nov 15.
Article in English | MEDLINE | ID: mdl-34842797

ABSTRACT

Despite significant prevention efforts, childhood poison exposures remain a serious public health challenge in the United States. This study aimed to assess annual trends of pharmaceutical vs. non-pharmaceutical poison exposures in the US among children 0-19 years and compare the odds of death by children's age group. Poison exposure and fatality data were retrospectively extracted from 2009 to 2019 National Poison Data System (NPDS) annual reports for children in all reported age groups. Overall, there was a significant reduction in the annual population-adjusted poison exposures in children (annual percentage change = -2.54%, 95% CI = -3.94% to -1.15%, p < 0.01), but not in poisoning-related fatalities. Children 0-5 had similar odds of dying from exposure to non-pharmaceuticals vs. pharmaceuticals. The odds of children 6-12 dying from non-pharmaceuticals vs. pharmaceuticals was 2.38 (95% CI = 1.58, 3.58), χ2 = 18.53, p < 0.001. In contrast, the odds of children 13-19 dying from pharmaceuticals vs. non-pharmaceuticals was 3.04 (95% CI = 2.51, 3.69), χ2 = 141.16, p < 0.001. Suicidal intent accounted for 40.63% of pharmaceutical deaths in children 6-12, as well as 48.66% of pharmaceutical and 31.15% of non-pharmaceutical deaths in children 13-19. While a significant decline in overall childhood poison exposures was reported, a decrease in poisoning-related fatalities was not observed. Children in different age groups had contrasting relative odds of death from pharmaceutical and non-pharmaceutical exposures. Among older children, a greater proportion of poisoning-related deaths was due to intentional suicide. These findings provide evidence of age-specific trends in childhood poison exposure risk and directions for future poison prevention efforts and behavioral health partnerships.

17.
Bioorg Med Chem Lett ; 39: 127854, 2021 05 01.
Article in English | MEDLINE | ID: mdl-33631370

ABSTRACT

p300 and CREB-binding protein (CBP) are essential for a multitude of cellular processes. Dysregulation of p300/CBP histone acetyltransferase activity is linked to a broad spectrum of human diseases including cancers. A novel drug-like spirohydantoin (21) has been discovered as a selective orally bioavailable inhibitor of p300/CBP histone acetyltransferase. Lead compound 21 is more potent than the first-in-class lead A-485 in both enzymatic and cellular assays and lacks the off-target inhibition of dopamine and serotonin transporters, that was observed with A-485.


Subject(s)
CREB-Binding Protein/antagonists & inhibitors , Drug Discovery , E1A-Associated p300 Protein/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Hydantoins/pharmacology , Spiro Compounds/pharmacology , Administration, Oral , Biological Availability , CREB-Binding Protein/metabolism , Dose-Response Relationship, Drug , E1A-Associated p300 Protein/metabolism , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/metabolism , Humans , Hydantoins/administration & dosage , Hydantoins/metabolism , Molecular Structure , Spiro Compounds/administration & dosage , Spiro Compounds/metabolism , Structure-Activity Relationship
19.
J Med Toxicol ; 17(1): 48-50, 2021 01.
Article in English | MEDLINE | ID: mdl-32710249

ABSTRACT

INTRODUCTION: Studies of acute hypersensitivity reactions in pediatric populations receiving Crotalidae Polyvalent Immune Fab (CPIF) are complicated by small size, wide age ranges, and diverse definitions of such reactions. METHODS: This is a retrospective chart review of patients aged 13 years or younger treated with CPIF for Crotalid envenomation from November 2006 to 2016. The primary outcome was the presence of an acute hypersensitivity reaction to CPIF and was defined as the development of any of the following symptoms within 3 hours of initiation of CPIF infusion: urticaria, wheezing or respiratory distress, angioedema, hypotension, nausea, and/or vomiting. Demographics, CPIF dose to control and total dose, bite location, level of care, and length of stay were also recorded. RESULTS: Thirty-four patients were ultimately treated with CPIF. Ages ranged from 10 months to 13 years. Twenty-one patients (60%) were male, 24 (70.6%) were admitted to the ICU, and the median length of stay was 2 days with a range of 1-11 days. Zero patients developed an acute hypersensitivity reaction to CPIF. CONCLUSION: Acute hypersensitivity reactions to CPIF did not occur in this cohort. Such reactions are rare with the use of CPIF in pediatric patients.


Subject(s)
Antivenins/adverse effects , Crotalid Venoms/antagonists & inhibitors , Crotalinae , Drug Hypersensitivity/epidemiology , Immunoglobulin Fab Fragments/adverse effects , Snake Bites/drug therapy , Adolescent , Age Factors , Animals , Child , Child, Preschool , Crotalid Venoms/immunology , Drug Hypersensitivity/diagnosis , Drug Hypersensitivity/immunology , Female , Humans , Infant , Male , Prevalence , Retrospective Studies , Risk Assessment , Risk Factors , Snake Bites/diagnosis , Snake Bites/epidemiology , Snake Bites/immunology , Time Factors , Treatment Outcome
20.
J Emerg Med ; 59(2): 224-226, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32565170

ABSTRACT

BACKGROUND: Methohexital is a short-acting barbiturate used for procedural sedation in the emergency department (ED). As with other sedatives, adverse effects with methohexital include excess sedation and hypotension, but this agent can also lower the seizure threshold. We report a patient who developed a generalized seizure after administration of methohexital. CASE REPORT: A 60-year-old man presented to the ED by ambulance with chest pain and shortness of breath. Paramedics had administered adenosine for supraventricular tachycardia without conversion before arrival to the ED. He had no history of seizures. His initial vital signs in the ED included heart rate of 189 beats/min with a supraventricular rhythm, blood pressure 137/108 mm Hg, respiration 22 breaths/min, and oxygen saturation of 98% on room air. It was decided to attempt synchronized electrical cardioversion, and methohexital 1 mg/kg (120 mg) was administered over 2 min for moderate sedation. Within 15 s of methohexital administration, the patient developed a generalized seizure that lasted for 90 s. After seizure termination, he was successfully cardioverted, returned to his previous baseline level of consciousness within 20 min, and discharged without further problems with a follow-up referral to neurology. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Methohexital is a short-acting barbiturate used for moderate sedation. Its adverse effects are unique in that it can lower the seizure threshold in some patients. Alternative agents for sedation should be considered in individuals with possible seizure disorders.


Subject(s)
Conscious Sedation , Methohexital , Anesthetics, Intravenous , Humans , Hypnotics and Sedatives , Male , Methohexital/adverse effects , Middle Aged , Seizures/chemically induced
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