Toxicology

2002 annual report of the American association of poison control centers toxic exposure surveillance system ¹

Nerium oleander L. is a medicinal plant, used for the treatment of cancers and hyperglycemia across the world, especially in Indian sub-continent, Turkey, Morocco, and China. Although clinical studies supporting its pharmacological effects remain critically underexplored, accidental and intentional consumption of any part of the plant causes fatal toxicity in animals and humans. While the polyphenolic fraction of oleander leaves has been attributed to its pre-clinical pharmacological activities, the presence of diverse cardiac glycosides (especially oleandrin) causes apoptosis to cancer cells in vitro and results in clinical signs of oleander poisoning. Thus, the dual pharmacological and toxicological role of oleander is a perplexing dichotomy in phytotherapy. The current investigative review, therefore, intended to analyze the intrinsic and extrinsic factors that likely contribute to this conundrum. Especially by focusing on gut microbial diversity, abundance, and metabolic functions, oleander-associated pharmacological and toxicological studies have been critically analyzed to define the dual effects of oleander. Electronic databases were extensively screened for relevant research articles (including pre-clinical and clinical) related to oleander bioactivities and toxicity. Taxonomic preference was given to the plant N. oleander L. and synonymous plants as per ‘The World Flora Online’ database (WCSP record #135196). Discussion on yellow oleander (Cascabela thevetia (L.) Lippold) has intentionally been avoided since it is a different plant. The review indicates that the gut microbiota likely plays a key role in differentially modulating the pharmacological and toxicological effects of oleander. Other factors identified influencing the oleander bioactivities include dose and mode of treatment, cardiac glycoside pharmacokinetics, host-endogenous glycosides, plant material processing and phytochemical extraction methods, plant genotypic variations, environmental effects on the phytochemical quality and quantity, gene expression variations, host dietary patterns and co-morbidity, etc. The arguments proposed are also relevant to other medicinal plants containing toxic cardiac glycosides.

Anticonvulsants are frequently prescribed, and exposures are commonly reported to American Association of Poison Control Centers sites. The purpose of this study was to describe the epidemiology of fatalities associated with oral anticonvulsant use, including patient demographics, specific medications, and the circumstances surrounding the deaths.

This was a retrospective analysis of cases coded with oral anticonvulsants as a single substance and associated with a fatal outcome reported to the AAPCC National Poison Data System from 2000 to 2019. Polydrug ingestions and parenteral exposures were excluded. Patient characteristics, circumstances of the ingestion, specific medication, and chronicity of use were described.

We identified 126 cases that were classified as fatalities associated with single anticonvulsant use. The five most implicated anticonvulsants were carbamazepine, gabapentin, lamotrigine, phenytoin, and valproic acid. The majority (68.3%) of fatal cases were suicides. Phenytoin was implicated in eight (89%) adverse reactions and seven (70%) therapeutic errors. Valproic acid caused one (11.1%) adverse reaction and was associated with one (10%) therapeutic error. Three (75%) unintentional fatalities were caused by carbamazepine.

The plurality (42.1%) of fatal ingestions occurred in acute-on-chronic use. An additional 40 (31.7%) were acute. Chronic use accounted for 15 (11.9%) of fatal exposures, including 5/10 of fatalities attributed to therapeutic error. The chronicity of medication use was unknown in 18 (14.3%) of fatal ingestions.

Narrative summaries were available in 14 cases. Four of the patients presented to the emergency department with minimal symptoms. The other 10 had varying degrees of central nervous system (CNS) depression. Seizures were observed in six cases. Hyperammonemia was reported in seven of nine valproic acid ingestions.

Fatalities associated with isolated anticonvulsant use are uncommon and typically occur following intentional overdoses. Fatal adverse reactions and therapeutic errors are most associated with phenytoin use and disproportionately affect elderly patients.

The current study inspects the impact of nilotinib (Nil) on liver damage caused by acetaminophen (APAP). Adult male mice were pre-treated with nilotinib (Nil,5 and 10 mg/kg) orally once daily for 7 days followed by a single intraperitoneal administration of acetaminophen (APAP, 200 mg/kg) on the 7th day.

The results indicated that nilotinib significantly decreased APAP-induced elevation of biochemical markers (ALT, AST, ALP, LDH, ɤ GT, and total bilirubin). Additionally, nilotinib significantly increased hepatic GSH and SOD content, while decreased MDA content. Nil significantly suppressed the expression of HIF-1α and VEGF. Histopathological examination of hepatic tissue from Nil-treated mice revealed that Nil reduced acetaminophen-induced necrosis.

El uso de medicamentos para aliviar los síntomas del «resfriado común» en los niños es muy frecuente. A la falta de evidencia científica que avale su utilidad se suma la potencial toxicidad, habiéndose descrito intoxicaciones graves e incluso letales. El objetivo de este estudio es describir las características clínico-epidemiológicas de los pacientes atendidos en un servicio de urgencias pediátricas por sospecha de intoxicación no intencionada por anticatarrales.

Estudio analítico-observacional de los pacientes con edad inferior a 18 años atendidos en un servicio de urgencias pediátricas por sospecha de intoxicación no intencionada por un medicamento anticatarral, entre julio-2012 y junio-2020. Se clasificó la gravedad según el Poisoning Severity Score (PSS): PSS-0 = sin toxicidad; PSS-1 = toxicidad leve; PSS-2 = moderada; PSS-3 = grave; PSS-4 = letal. Si la intoxicación se produjo en el transcurso de un tratamiento con el medicamento, se determinó si la edad del paciente estaba incluida en las indicaciones terapéuticas según ficha técnica.

Se recogieron 63 casos. Los medicamentos implicados fueron: anticongestivos y mucolíticos (31; 49,2%), antitusígenos (26; 41,2%), broncodilatadores orales (6; 9,5%). Se clasificaron según gravedad en: PSS-0 = 40 (63,5%), PSS-1 = 21 (33,3%), PSS-2 = 1 (1,6%) y PSS-3 = 1 (1,6%). En 29 pacientes (46%) existía antecedente de uso terapéutico; de estos, en 15 casos (51,7%) la edad del paciente era inferior a la recomendada en ficha técnica. En 14 pacientes (22,2%) la intoxicación se produjo por error en la dosis administrada por los cuidadores.

Aunque la evidencia científica no recomienda medicamentos anticatarrales en niños, se siguen produciendo intoxicaciones no intencionadas por estos fármacos, en ocasiones moderadas o graves.

The use of medications to relieve the symptoms of the “common cold” in children is very frequent. In addition to the lack of scientific evidence supporting its usefulness, there is evidence of potential toxicity, and serious and even fatal cases of intoxication have been described. The objective was to describe the clinical and epidemiological characteristics of the patients treated in a paediatric emergency department for suspected unintentional intoxication by a cold medicine.

Observational and analytical study of patients aged less than 18 years managed in a paediatric emergency department for suspected unintentional poisoning by a cold medicine between July 2012 and June 2020. We classified severity according to the Poisoning Severity Score (PSS): PSS-0 = no toxicity; PSS-1 = mild toxicity; PSS-2 = moderate; PSS-3 = severe; PSS-4 = lethal. If the intoxication occurred while the patient was in active treatment with the drug, we determined whether the patient's age was in the applicable range established in the therapeutic indications provided in the summary of product characteristics.

The study included data for 63 cases. The drugs involved were decongestants and mucolytics (31; 49.2%), antitussives (26; 41.2%) and oral bronchodilators (6; 9.5%). The distribution by severity was 40 cases with PSS-0 (63.5%), 21 with PSS-1 (33.3%), 1 with PSS-2 (1.6%) and 1 with PSS-3 (1.6%). In 29 patients (46.0%) there was a history of therapeutic use; in 15 of these cases (51.7%) the age was lower than recommended in the summary of product characteristics. In 14 patients (22.2%) the intoxication was due to administration of the wrong dose by caregivers.

Although scientific evidence does not support the use of cold medicines in children, unintentional intoxications by these drugs keep happening, in some cases causing moderate or severe symptoms.

There are 5000–10,000 snake envenomations annually in the United States. Fortunately, few are fatal. In this study we review the epidemiology of fatal snakebites.

Native snakebite cases from the American Association of Poison Control Centers (AAPCC) National Poison Data System from 1989 to 2018 were reviewed. Additional cases that were not reported to the AAPCC were identified by reviewing Wikipedia and by searching PubMed and online news outlets using various combinations of relevant keywords.

We identified 101 fatal bites from native snakes. Rattlesnakes accounted for 74 (90.2%) of the 82 deaths for which the species was known or which occurred where rattlesnakes are the only native crotalids. There were five fatalities attributed to copperheads, two due to cottonmouths, and one caused by an eastern coral snake. Males were disproportionately affected. The median age for victims was 40 years old. In cases for which data were available, many of the snake interactions were intentional, e.g. religious services, animal husbandry, and attempting to kill the snake.

Death following envenomation from a native U.S. snake is unlikely, particularly if medical attention is sought promptly. Rattlesnake envenomations are more likely to be fatal than bites from other species. Intentionally engaging with a venomous snake raises the risk of incurring a fatal bite, as does concurrent alcohol or drug use. Age less than 12 years old does not appear to be a risk factor for a fatal outcome, while elderly patients may have a slightly increased risk of death.

Reported tramadol toxicity emphasizes the necessity to recognize its mechanism of toxicity, particularly to the brain tissue. Aim: This study aimed to evaluate the protective effect of vitamin C (Vit C) in cerebrocortical toxicity mediated by tramadol in rats using biochemical and histological parameters.

Forty-eight albino rats were randomly divided into eight groups, (n = 6/group) as follow: the control group received normal saline and vitamin C group received vitamin C (200 mg/kg per oral). Tramadol 50, 100, 150 groups received tramadol in doses of (50, 100 and 150 mg/kg per oral, respectively); Tramadol 50+ Vit C, 100+ Vit C, 150+ Vit C groups received vitamin C (200 mg/kg per oral) plus tramadol in doses of (50, 100 and 150 mg/kg per oral, respectively). Rats had received vitamin C and tramadol daily for 30 days. Blood and brain tissues samples were harvested for biochemical, histopathological, immunohistochemical and electron microscopic examinations.

Tramadol administration leads to a significant elevation of MDA, NO levels and a significant decrease in antioxidants parameters (CAT, SOD and GSH) in the tissues of cerebral cortices in rats which were directly proportional to the dose of tramadol. In histological investigations, tramadol-treated groups showed pyknotic pyramidal cells, multiple red neurons and shrinking red neurons with hallows around it and apoptotic cells were detected. These biochemical abnormalities and histological impairment were ameliorated in groups with tramadol low doses by the co-treatment with vitamin C.

vitamin C has antioxidant and anti-apoptotic potentials against tramadol neurotoxicity via suppression of oxidative stress, lipid peroxidation, structural abnormalities, and down-regulation of p53 and overexpression of Bcl2 in the nervous tissues.