Journal of Medical Toxicology最新文献

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are therapies for type 2 diabetes whose use expanded sharply after semaglutide's 2021 approval for obesity. Although gastrointestinal effects are well described, national patterns of acute GLP-1 RA exposures are poorly characterized. This study evaluated trends in GLP-1 RA exposures reported to U.S. poison centers, focusing on demographic shifts, exposure circumstances, and clinical outcomes before and after the 2021 FDA approval.

Methods: We analyzed human GLP-1 RA exposures reported to the National Poison Data System from 2012 to 2023, using July 1, 2021, to define pre- and post-approval periods. Demographics, exposure characteristics, therapies, and medical outcomes were compared using standardized statistical tests. Quarterly call counts were modeled with segmented Poisson regression to assess changes in reporting trajectory.

Results: A total of 10,033 exposures were identified (3,113 pre-approval; 6,920 post-approval). Semaglutide predominated post-approval (64.2%). The exposed population shifted younger and more female. Most cases were unintentional therapeutic errors with mild gastrointestinal symptoms. The proportion managed in or referred to a health care facility increased from 23.0% to 33.5% (RR = 1.46, [95% CI: 1.36, 1.57], p < 0.001). Segmented Poisson modeling demonstrated a significant inflection in call volume, with semaglutide exposures increasing an additional 9.9% per quarter after approval.

Conclusions: GLP-1 RA exposures rose sharply following semaglutide's weight-loss approval, accompanied by increased health care utilization despite generally mild clinical effects. Although multiple factors likely contributed to these trends, improved patient counseling and clearer poison center guidance may help reduce preventable therapeutic errors and unnecessary emergency evaluation.

Introduction: Hexahydrocannabinol (HHC) is a semi-synthetic hydrogenated derivative of delta-9-tetrahydrocannabinol (THC). HHC emerged within global markets in 2021and has been detected within unregulated cannabis products.

Case report: A 32-year-old male presented to hospital 1.5 h following ingestion of a single gummy, which had been sold as a THC product. Symptoms included nausea, vomiting, slurred speech, a subjective feeling of whole-body numbness, and an inability to move his head. Examination revealed an apparent dissociative state, sinus tachycardia (118 beats per minute), mydriasis, confusion, and tachypnoea (24 breaths per minute). There was no objective focal neurological deficit. Investigations including haematology and biochemistry were normal. Management was supportive and symptoms resolved within eight hours of ingestion. Serum analysis revealed the HHC isomers 9R-hexahydrocannabinol (9R-HHC) and 9 S-hexahydrocannabinol (9 S-HHC). No other pharmaceutical or psychoactive substance was detected.

Discussion: HHC can be manufactured using cannabidiol as a precursor and can be administered via inhalation, orally and sublingually. The 9R-HHC isomer is the primary psychoactive component. HHC is rapidly absorbed, crosses the blood-brain-barrier and is hepatically metabolised. User reports of HHC adverse effects include anxiety, nausea, and "paralysing effects". Cases of HHC exposure reported in the literature describe palpitations, chest tightness, 'respiratory pause', seizures, dysarthria, dyskinesia, hallucinations, mydriasis, myalgias and acute psychosis. This case of analytically confirmed HHC exposure describes multi-system toxicity including gastrointestinal effects, and dissociative-like neurological effects, and serves as a reminder of the dangers of unregulated products sold within the illicit drug market.

Background: Salicylate toxicity remains a significant cause of morbidity and mortality. At therapeutic levels, most salicylic acid (SA) is albumin-bound, but in overdose, the free fraction rises, driving toxicity. Albumin supplementation has been hypothesized as a strategy to reduce free SA, yet quantitative data are limited.

Methods: An in vitro model was developed to assess albumin's binding capacity for salicylic acid across overdose-relevant concentrations. Solutions of SA (SA30 ≈30 mg/dL, SA50 ≈50 mg/dL, SA100 ≈100 mg/dL, SA120 ≈120 mg/dL) were combined with albumin ranging from 1-8 g/dL, representing subphysiologic to supraphysiologic concentrations. One solution (SA120-A) was prepared at pH 7.0 to evaluate binding in acidic environments. Free SA was quantified in each sample.

Results: Increasing albumin reduced free salicylate under all conditions. From 1-8 g/dL, free SA decreased by 38.56 mg/dL (95% CI [37.62, 39.49] at SA50, 38.49 mg/dL (95% CI [37.77, 39.20] at SA100, 38.83 mg/dL (95% CI [37.85, 39.81] at SA120 (pH 7.4), and 52.77 mg/dL (95% CI [51.54, 54.01] at SA120 (pH 7.0). Correction of hypoalbuminemia (1-4 g/dL) reduced free SA by 11.33 mg/dL (95% CI [11.14, 11.53] at SA30, 21.07 mg/dL (95% CI [20.19, 21.94] at SA50, 18.40 mg/dL (95% CI [18.12, 18.68] at SA100, 18.27 mg/dL (95% CI [16.93, 19.61] at SA120 (pH 7.4), and 21.40 mg/dL (95% CI [21.00, 21.80] at SA120-A (pH 7.0). Increasing albumin further to 8 g/dL reduced free SA by an additional 17.49 mg/dL (95% CI [17.42, 17.56] at SA50, 20.09 mg/dL (95% CI [19.62, 20.55] at SA100, 20.57 mg/dL (95% CI [20.18, 20.95] at SA120 (pH 7.4), and 31.37 mg/dL (95% CI [30.12, 32.62] at pH 7.0. SA30 fell below quantification beyond 5 g/dL.

Conclusion: Albumin addition reduced free salicylate, supporting its potential as a "protein sink" in salicylate toxicity. Further research is needed to determine the clinical relevance and safety of this theoretical intervention.

Introduction: 2,4-dinitrophenol (DNP) is an uncoupler of oxidative phosphorylation and is highly toxic in overdose.

Case report: We present a case of an 18-year-old female who survived an acute-on-chronic DNP overdose resulting in hypermetabolic state and widespread ST depression with associated troponin I elevation. Serial DNP levels are plotted for this patient, demonstrating first order kinetics with a half-life of 18 h.

Discussion: Survival in this case may be attributed to early management of hyperthermia and hypermetabolic state, as well as the acute-on-chronic nature of the overdose. Human pharmacokinetic data for DNP in overdose are rare, as are cases with ST-segment changes.

The 2025 ACMT Ward and Ryan Donovan Memorial Fund lecture was presented by Daniel Ciccarone, MD, MPH from Department of Family and Community Medicine at the University of California San Francisco (UCSF). This article is an edited version of his keynote address during ACMT's 2025 Annual Scientific Meeting. During the course of his talk, Dr. Ciccarone discussed polysubstance use in the "Fentanyl-plus" era. The epidemiology and economics of the four waves of opioid overdose deaths were examined, and promising harm reduction strategies to assist in reducing overdose mortality were highlighted.