ABSTRACT
Zopiclone is a sedative-hypnotic that is increasingly being used for insomnia, especially among patients with depression. The side effects of zopiclone include nausea, vomiting, headache, giddiness, sedation, altered mental status, and coma. Here, we describe a rare case of a patient with underlying depression who overdosed on zopiclone, resulting in a presentation of drowsiness and dyspnea. A diagnosis of methemoglobinemia was made only through astute observation of the presence of a saturation gap, poor oxygen saturation despite high flow oxygen supplementation, and the arterial blood gas sample appearing chocolate brown in color. Treatment of such patients usually includes the gold standard of methylene blue. However, in our case, there was a risk of serotonin syndrome as the patient was on a serotonergic antidepressant prior. As such, an alternative treatment with ascorbic acid was utilized instead. Methemoglobinemia, while uncommon, should always be suspected in patients who present with zopiclone overdose as it can be life-threatening and is easily treatable.
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Vitamin D3 (VD3) is a fat-soluble vitamin that can accumulate in the body and lead to toxicity by increasing 25(OH) D levels when consumed in large amounts. Maintaining 25(OH) D levels greater than 30 ng/mL is crucial for overall health due to the significant role of vitamin D in the body. The most common causes of VD3 intoxication are manufacturing errors or self-administration. Currently, there is no definitive data on the dose and duration of VD3 consumption that leads to toxicity. The maximum daily doses of VD3 that can be tolerated without causing adverse effects are not established. The maximum recommended amount for long-term supplementation is 2,000 units per day. Vitamin D3 toxicity (VDT) can present in various scenarios, ranging from asymptomatic to gastrointestinal, and in severe cases with neuropsychiatric and life-threatening symptoms. We report the case of a 29-year-old man who presented with symptoms of VDT following an accidental overdose of VD3 over 2 weeks.
Subject(s)
Cholecalciferol , Vitamin D , Male , Humans , Adult , VitaminsABSTRACT
Beta-blocker and calcium-channel blocker overdoses are associated with severe morbidity and mortality; therefore, it is important to recognize and appropriately treat individuals with toxicity. The most common clinical findings in toxicity are bradycardia and hypotension. In addition to supportive care and cardiac monitoring, specific treatment includes administration of calcium salts, vasopressors, and high-dose insulin euglycaemia treatment. Other advanced treatments (e.g. ECMO) may be indicated depending on the severity of toxicity and specific agents involved.
Subject(s)
Calcium Channel Blockers , Calcium , Humans , Vasoconstrictor Agents , Adrenergic beta-Antagonists/therapeutic useABSTRACT
INTRODUCTION: Methotrexate (MTX) is a folic acid antagonist used to treat different immunological or proliferative illnesses because of its anti-proliferative and anti-inflammatory effects. MTX Toxicity is considered a severe problem. Although acute toxicity related to high-dose administration (doses ≥500 mg/m2) can be predicted based on the given dose, chronic toxicity still has no specific factors to predict it, so treatment depends on the history and symptoms of toxicity. MTX was initially used for oncology indications with high cyclic doses, then expanded to non-oncology indications with different low doses and frequencies. This significant change in doses resulted in dosing errors that contributed to MTX toxicity reports. Measures to prevent the toxicity of MTX should be implemented. CASE: A 66-year-old female patient ingested 10 mg of MTX daily for one month instead of the once-toxicity symptoms. The serum level of MTX was requested, and treatment with folinic acid was initiated until the patient improved with the discontinuation of MTX. DISCUSSION: There is limited literature about the lack the total cumulative dose, duration of intake, or serum level of MTX. All this information was provided in this case report, but drug-drug interactions were not reviewed, although aspirin and pantoprazole were identified as having interactions with methotrexate in this patient. Minimum total cumulative dose identification may help assess the toxicity risk in such patients. CONCLUSION: Low-dose MTX chronic toxicity still needs further information to guide the patient's risk of toxicity and when to initiate treatment. Safety-practical measures should be implemented to prevent such administration errors.
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Calcium channel blocker poisoning is one of the most common poisonings encountered which presents with life-threatening complications. However, there is no unified approach for treating these patients in the existing literature. This study aimed to assess the effects of different treatment modalities used in calcium channel blocker poisoning, as reported by previous studies. The primary outcomes studied were mortality and hemodynamic parameters after treatment. The secondary outcomes were the length of hospital stay, length of intensive care unit stay, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. A thorough literature search was performed through Ovid, PubMed, Cochrane Library, and Google Scholar from January 2014 to December 31, 2022, to identify all studies analyzing the effects of the treatment of calcium channel blocker poisoning on the desired outcomes. Two reviewers reviewed 607 published articles from January 2014 to December 2022 to identify studies analyzing the effects of the treatment of calcium channel blocker poisoning on desired outcomes. In this review, 18 case reports, one case series, and one cohort study were included. Most patients were treated with an injection of calcium gluconate or calcium chloride. The use of calcium along with dopamine and norepinephrine was found to have lower mortality rates. A few patients were also treated with injection atropine for bradycardia. High-dose insulin therapy was used in 14 patients, of whom two did not survive. In the cohort study, 66 calcium channel blocker toxicity patients were included. These patients were treated with high-dose insulin therapy. A total of 11 patients with calcium channel blocker toxicity succumbed. Although it was found to be associated with improved hemodynamic parameters and lower mortality, side effects such as hypokalemia and hypoglycemia were noted. Intravenous lipid emulsion therapy (administered to eight patients), extracorporeal life support (used in three patients with refractory shock or cardiac arrest), injection glucagon, methylene blue, albumin infusion, and terlipressin were associated with a lower mortality rate as well as improvement in hemodynamic parameters. None of the case reports provided any information on end-organ damage on long-term follow-up.
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In 2021, there were over 100,000 drug overdose deaths in the United States (US). Death rates have increased faster among women than men, particularly among Black and Indigenous people. Although drug overdose is a leading cause of pregnancy-associated deaths, birthing people are rarely emphasized in discussions of overdose and research and services remain limited. Data show increases in drug use and deaths among women of child-bearing age, with risks continuing in the postpartum period. Harms experienced by birthing people who use drugs occur in the context of broader inequities in maternal morbidity and mortality that lead to disparate reproductive health outcomes. Shared structural antecedents (e.g. intersecting sexism and racism, stigma, and punitive policies) underlie overlapping epidemics of overdose and maternal morbidity and mortality. Here we discuss the unique challenges placed on birthing people who use drugs and make recommendations on how to mitigate harms by improving access to and delivery of quality care and addressing unjust policies and practices. We highlight the need for integrated health services, clearer guidelines rooted in equity, and the need for changes to policy and practice that support rather than punish. To better serve individuals and families impacted by substance use, we need multilevel solutions that advance gender equity and racial justice to reshape and/or dismantle the systems that undergird oppression.
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Mainstays of opioid overdose prevention include medications for opioid use disorder (e.g., methadone or buprenorphine) and naloxone distribution. Inadequate access to buprenorphine limits its uptake, especially in communities of color, and people with opioid use disorders encounter multiple barriers to obtaining necessary medications including insurance, transportation, and consistent availability of telephones. UMass Memorial Medical Center and our community partners sought to alleviate these barriers to treatment through the deployment of a mobile addiction service, called the Road to Care. Using this approach, multidisciplinary and interprofessional providers deliver holistic addiction care by centering our patients' needs with respect to scheduling, location, and convenience. This program also extends access to buprenorphine and naloxone among people experiencing homelessness. Additional systemic and individualized barriers encountered are identified, as well as potential solutions for future mobile addiction service utilization. Over a two-year period, we have cared for 1,121 individuals who have accessed our mobile addiction service in over 4,567 encounters. We prescribed buprenorphine/naloxone (Suboxone®) to 330 individuals (29.4% of all patients). We have distributed nearly 250 naloxone kits directly on-site or and more than 300 kits via prescriptions to local pharmacies. To date, 74 naloxone rescue attempts have been reported back to us. We have demonstrated that a community-based mobile addiction service, anchored within a major medical center, can provide high-volume and high-quality overdose prevention services that facilitate engagement with additional treatment. Our experience is described as a case study below.
Subject(s)
Buprenorphine , Drug Overdose , Opioid-Related Disorders , Humans , Community Health Services , Naloxone/therapeutic use , Buprenorphine, Naloxone Drug Combination/therapeutic use , Opioid-Related Disorders/prevention & control , Opioid-Related Disorders/drug therapy , Buprenorphine/therapeutic use , Drug Overdose/drug therapy , Drug Overdose/prevention & controlABSTRACT
Our study aimed to test the potential of Citrus oils in protecting against paracetamol (PAR)-induced hepatotoxicity. The essential oils of Pineapple sweet orange (OO), Murcott mandarin (MO), Red grapefruit (GO), and Oval kumquat (KO) were investigated using gas chromatography coupled with mass spectrometry (GC/MS). Twenty-seven compounds were identified, with monoterpene hydrocarbons being abundant class. d-Limonene had the highest percentage (92.98 %, 92.82 %, 89.75 %, and 94.46 % in OO, MO, GO, and KO, respectively). Hierarchical cluster analysis (HCA) and principal components analysis (PCA) revealed that octanal, linalool, germacrene D, and d-limonene were the principal discriminatory metabolites that segregated the samples into three distinct clusters. Inâ vitro antioxidant capacities were ranged from 1.2-12.27, 1.79-5.91, and 235.05-585.28â µM Trolox eq/mg oil for 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic (ABTS), ferric-reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC), respectively. Inâ vivo, citrus oils exhibited a significant reduction in alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and nitric oxide (NO). Additionally, there was an increase in glutathione reductase (GSH), and the liver architecture was nearly normal. Molecular docking revealed that d-limonene exhibited a good inhibitory interaction with cytochrome P450 (CYP450) isoforms 1A2, 3A4, and 2E1, with binding energies of -6.17, -4.51, and -5.61â kcal/mol, respectively.
Subject(s)
Chemical and Drug Induced Liver Injury , Citrus , Oils, Volatile , Oils, Volatile/chemistry , Citrus/chemistry , Antioxidants/chemistry , Acetaminophen , Limonene , Herb-Drug Interactions , Molecular Docking SimulationABSTRACT
Background Despite abundant sunlight exposure, vitamin D deficiency remains a major challenge in Saudi Arabia. Meanwhile, the widespread use of vitamin D supplements has prompted concerns about toxicity, which although rare, can have severe health consequences. Objective The objective of this cross-sectional study was to analyze the prevalence and associated factors of iatrogenic vitamin D toxicity among the Saudi population of vitamin D users due to overcorrection. Methods An online questionnaire was used to collect data from 1,677 participants across all regions of Saudi Arabia. The questionnaire included responses on the prescription, duration of vitamin D intake, dosage, frequency, history of vitamin D toxicity, symptom onset, and duration. Results One thousand six hundred and seventy-seven responses were included across all regions of Saudi Arabia. A majority of participants were female (66.7%) and around half were aged 18-25 years. A history of vitamin D use was reported by 63.8% of participants, and 48% were still using vitamin D supplements. Most participants (79.3%) consulted a physician, and 84.8% had taken a vitamin D test before using the supplement. Commonly reported motives for taking vitamin D included vitamin D deficiency (72.1%), lack of sun exposure (26.1%), and hair loss (20.6%). Symptoms of overdose were reported by 6.6% of participants, with 3.3% having an overdose and 2.1% experiencing both overdose and symptoms. Conclusion This study showed that although a large portion of the Saudi population is taking vitamin D supplements, the prevalence of vitamin D toxicity is relatively low. However, this prevalence should not be ignored, and further research is needed to understand the factors contributing to vitamin D toxicity in order to minimize its occurrence.
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BACKGROUND: Leucovorin (folinic acid) is a commonly used antidote for severe toxicity with low-dose methotrexate, but its optimum dose is unclear, varying from 15 to 25 mg every 6-h. METHODS: Open-label RCT included patients with severe low-dose (≤ 50 mg/week) methotrexate toxicity defined as WBC ≤ 2 × 10^9/L or platelet ≤ 50 × 10^9/L and randomized them to receive either usual (15 mg) or high-dose (25 mg) intravenous leucovorin given every 6-h. Primary outcome was mortality at 30-days and secondary outcomes were hematological recovery and mucositis recovery. TRIAL REGISTRATION NUMBER: CTRI/2019/09/021152. RESULTS: Thirty-eight patients were included, most with underlying RA who had inadvertently overdosed MTX (taken daily instead of weekly). At randomization, the median white blood and platelet count were 0.8 × 10^9/L and 23.5 × 10^9/L. 19 patients each were randomized to receive either usual or high-dose leucovorin. Number (%) of deaths over 30-days was 8 (42) and 9 (47) in usual and high-dose leucovorin groups (Odds ratio 1.2, 95% CI 0.3 to 4.5, p = 0.74). On Kaplan-Meier, there was no significant difference in survival between the groups (hazard ratio 1.1, 95% CI 0.4 to 2.9, p = 0.84). On multivariable cox-regression, serum albumin was the only predictor of survival (hazard ratio 0.3, 95% CI 0.1 to 0.9, p = 0.02). There was no significant difference in hematological or mucositis recovery between the two groups. CONCLUSION: There was no significant difference in survival or time-to hematological recovery between the two doses of leucovorin. Severe low-dose methotrexate toxicity carried a significant mortality.
Subject(s)
Methotrexate , Mucositis , Humans , Leucovorin/therapeutic use , Methotrexate/therapeutic use , Mucositis/chemically induced , Mucositis/drug therapy , Blood PlateletsABSTRACT
Depression is a common mental disorder that seriously affects the quality of life and leads to an increasing global suicide rate. Macro, micro, and trace elements are the main components that maintain normal physiological functions of the brain. Depression is manifested in abnormal brain functions, which are considered to be tightly related to the imbalance of elements. Elements associated with depression include glucose, fatty acids, amino acids, and mineral elements such as lithium, zinc, magnesium, copper, iron, and selenium. To explore the relationship between these elements and depression, the main literature in the last decade was mainly searched and summarized on PubMed, Google Scholar, Scopus, Web of Science, and other electronic databases with the keywords "depression, sugar, fat, protein, lithium, zinc, magnesium, copper, iron, and selenium". These elements aggravate or alleviate depression by regulating a series of physiological processes, including the transmission of neural signals, inflammation, oxidative stress, neurogenesis, and synaptic plasticity, which thus affect the expression or activity of physiological components such as neurotransmitters, neurotrophic factors, receptors, cytokines, and ion-binding proteins in the body. For example, excessive fat intake can lead to depression, with possible mechanisms including inflammation, increased oxidative stress, reduced synaptic plasticity, and decreased expression of 5-Hydroxytryptamine (5-HT), Brain Derived Neurotrophic Factor (BDNF), Postsynaptic density protein 95(PSD-95), etc. Supplementing mineral elements, such as selenium, zinc, magnesium, or lithium as a psychotropic medication is mostly used as an auxiliary method to improve depression with other antidepressants. In general, appropriate nutritional elements are essential to treat depression and prevent the risk of depression.
Subject(s)
Selenium , Trace Elements , Humans , Copper , Selenium/therapeutic use , Magnesium , Depression/drug therapy , Lithium , Quality of Life , Trace Elements/therapeutic use , Trace Elements/metabolism , Zinc/therapeutic use , Zinc/metabolism , Iron/metabolism , InflammationABSTRACT
BACKGROUND: People with Opioid Use Disorder (PWOUD) represent an underserved and marginalized population for whom treatment gaps exist. Low-barrier programs like mobile care units and street outreach programs have yielded increased access to buprenorphine and social services, however, OUD pertinent co-occurring behavioral health and medical conditions are frequently left unaddressed. A novel, tailored, comprehensive care delivery model may reduce disparities and improve access to care across a range of pathologies in this historically difficult to reach population and enhance efforts to provide universal treatment access in a harm reduction setting. METHODS: Descriptive data were collected and analyzed regarding patient demographics, retention in treatment and services rendered at a new, wrap-around, low-barrier buprenorphine clinic established at an existing harm reduction site in New Mexico between August 1, 2020, and August 31, 2021. RESULTS: 203 people used any service at the newly implemented program, 137 of whom specifically obtained medical and/or behavioral health care services including prescriptions for buprenorphine at least once from the physician onsite. Thirty-seven unique medical and psychiatric conditions were treated, representing a total of 565 separate encounters. The most common service utilized was buprenorphine treatment for opioid use disorder (81%), followed by treatment for post-traumatic stress disorder (62%), anxiety (44.5%) and depression (40.9%). Retention in buprenorphine treatment was 31.2% at 6 months. CONCLUSIONS: An innovative, multidisciplinary, buprenorphine-centric care model, which targets a wide range of OUD pertinent pathologies while employing a harm reduction approach, can enhance utilization of these services among an underserved PWOUD population in a manner which moves our health system toward universal OUD treatment access thereby potentially reducing overdose and existing disparities.
Subject(s)
Buprenorphine , Opioid-Related Disorders , Humans , Analgesics, Opioid/therapeutic use , Opiate Substitution Treatment , Opioid-Related Disorders/therapy , Opioid-Related Disorders/drug therapy , Buprenorphine/therapeutic use , Delivery of Health CareABSTRACT
PURPOSE: About 11.4 million individuals admitted to misusing an opioid in the past year. The purpose of this study was to determine if nurses' definitions of pain management differed by location, and to assess the challenges treating patients with pain management concerns. This study fills a gap by comparing quantitative and qualitative feedback from nurses on pain management concerns in their practice location. METHODS: Data were collected using an electronic survey emailed to licensed nurses across the United States. The mixed methods survey used multiple choice, select all that apply, and open-ended responses to gather data on nurses' perceptions of pain management. One hundred and eighty nurses completed the survey and were included in the study. Sixty-six percent practiced in an urban hospital. FINDINGS: Rural and urban nurses defined pain management as nonopioids and opioids. Seventy-one percent of urban nurses defined pain management as physical therapy compared to only 61% of rural nurses. Similarly, 62% of urban nurses identified homeopathic medicines and treatments as pain management techniques compared to 52% of rural nurses. From the qualitative data, 32% of rural nurses stated that patients with pain management concerns only want pain medications compared to 14% of urban nurses. CONCLUSIONS: Nurses have a critical position in and valuable perspective on the opioid epidemic. Rural communities are relatively disadvantaged in combatting the opioid epidemic. The finding that rural residents only want pain medication instead of alternative pain management options further challenges the country's rural health care workforce.
Subject(s)
Nurses , Rural Population , Humans , United States , Pain/drug therapy , Analgesics, Opioid/therapeutic use , Surveys and QuestionnairesABSTRACT
Background and Objectives: CDC data indicate that the U.S. is experiencing a sustained epidemic of drug-related mortality, with such deaths exceeding a record 100,000 in 2021, up 47% from 2019. Opioids, especially the synthetic opioid fentanyl, account for approximately 75% of this mortality. This study evaluates a proposed Consciousness-Based® approach that may possibly help reduce trends in drug-related fatalities by mitigating what WHO refers to as an "epidemic of stress" in society that helps fuel drug misuse and other negative public health trends. This approach involves providing support in public and private sector public health initiatives for individual and group practice of a subjective, evidence-based meditation procedure suitable for those of all educational, cultural, and religious backgrounds: the Transcendental Meditation® (TM®) technique and its advanced aspect, the TM-Sidhi® program. Materials and Methods: Segmented-trend regression analysis of monthly CDC data on U.S. drug-related fatality rates (dfr) from a prospective social experiment (2002-2016) was used to replicate and extend prior peer-reviewed research. Results: As hypothesized, (1) practice of the TM and TM-Sidhi program by a group of theoretically predicted size (â1% of the U.S. population) was associated with a statistically and practically significant reduction in dfr trend during the five-year "demonstration period" of the quasi-experiment; and (2) monthly dfr trend subsequently increased during the five-year follow-up period when the group fell below the required size (both p's < 0.0001). The estimated total percent decrease in dfr during the demonstration period was 35.5%, calculated relative to the baseline mean. This decline was followed by total dfr increases of 11.8% and 47.4% relative to the demonstration-period mean during the two phases of the follow-up period. Conclusion: Existing evidence warrants implementation and further evaluation of this approach in U.S. public health initiatives.
Subject(s)
Group Practice , Meditation , HumansABSTRACT
Multivitamins are commonly used by the general population, often without medical prescription. The purpose of this report is to inform on the daily vitamin D supply provided by multivitamins containing vitamin D that are commercialized online by Amazon in Western and Southern Europe. We surveyed multivitamins aimed at adults using the following marketplaces: amazon.es®, amazon.de®, amazon.it®, and amazon.fr®. We identified 199 vitamin D3-containing multivitamins sold by Amazon marketplaces: 77 from amazon.es®, 73 from amazon.de®, 33 from amazon.it®, and 16 from amazon.fr®. No multivitamin contained vitamin D2. The daily vitamin D3 supply ranged from 16 to 2000 IU: it was less than 400 IU daily in 108 (54%), 400−800 IU daily in 53 (27%), and more than 800 IU daily in the remaining 38 (19%) products. The vitamin D3 supply of products sold by amazon.it® was on average higher (p < 0.05) than that of products sold by amazon.de®, amazon.fr®, and amazon.es®. In conclusion, the vitamin D supply of multivitamins sold by Amazon may be insufficient, marginally sufficient, or adequate for subjects at high risk of hypovitaminosis D such as subjects 65 years or more of age, pregnant (or lactating) women, or patients on drug treatment or with an underlying disease, where a vitamin D supplementation is advocated.
Subject(s)
Vitamin D Deficiency , Vitamin D , Adult , Pregnancy , Humans , Female , Lactation , Vitamins/therapeutic use , Cholecalciferol/therapeutic use , Vitamin D Deficiency/prevention & control , Vitamin D Deficiency/drug therapy , Europe , Dietary SupplementsABSTRACT
RATIONALE: Hyperthermia induced by psychomotor stimulants may cause leakage of the blood-brain barrier, vasogenic edema, and lethality in extreme cases. Current treatments such as whole-body cooling are only symptomatic and a clear need to develop pharmacological interventions exists. Dantrolene sodium, a peripheral muscle relaxant used in the treatment of malignant hyperthermia, has been proposed as potentially effective to treat MDMA-hyperthermia in emergency rooms. However, debate around its efficacy for this indication persists. OBJECTIVES: To investigate dantrolene as a treatment for illicit hyperthermia induced by psychomotor stimulant drugs, we examined how Ryanodex®, a concentrated formulation of dantrolene sodium produced by Eagle Pharmaceuticals, influences 3,4-methylenedioxymethamphetamine (MDMA)- and methamphetamine (METH)-induced hyperthermia in awake freely moving rats. We injected rats with moderate doses of MDMA (9 mg/kg) and METH (9 mg/kg) and administered Ryanodex® intravenously (6 mg/kg) after the development of robust hyperthermia (>2.5 °C) mimicking clinical acute intoxication. We conducted simultaneous temperature recordings in the brain, temporal muscle, and skin to determine the basic mechanisms underlying temperature responses. To assess the efficacy of dantrolene in attenuating severe hyperthermia, we administered MDMA to rats maintained in a warm ambient environment (29 °C), conditions which produce robust brain and body hyperthermia (>40 °C) and lethality. RESULTS: Dantrolene failed to attenuate MDMA- and METH-induced hyperthermia, though locomotor activity was significantly reduced. All animals maintained at warm ambient temperatures that received dantrolene during severe drug-induced hyperthermia died within or soon after the recording session. CONCLUSIONS: Our results suggest that dantrolene sodium formulations are not mechanistically suited to treat MDMA- and METH-induced hyperthermia.
Subject(s)
Hyperthermia, Induced , Methamphetamine , N-Methyl-3,4-methylenedioxyamphetamine , Rats , Animals , Dantrolene/pharmacology , Body Temperature , BrainABSTRACT
Paracetamol overdose is common in developed countries but less than 10% involve large ingestions exceeding 30 g or 500 mg/kg. High dose acetylcysteine (NAC) has been proposed in patients taking large paracetamol overdoses based on reports of hepatotoxicity despite early initiation of NAC treatment with the commonly used 300 mg/kg intravenous acetylcysteine regimen. The evidence from cohorts of patients treated with the standard NAC regimen after large paracetamol overdoses shows that it is effective in most patients. A small study in patients with paracetamol overdoses of 40 g or more and paracetamol concentrations above the 300 mg/L nomogram line showed that modification of the standard NAC regimen to provide a total of 400-500 mg/kg NAC over 21-22 h may reduce the risk of hepatotoxicity (peak ALT > 1000 IU/L) but the impact on development of hepatic failure, liver transplantation and mortality with this approach is presently unknown. Better risk stratification of patients taking paracetamol overdose may allow higher dose NAC and adjunctive treatments such as CYP2E1 inhibition and extracorporeal removal of paracetamol to be targeted to those patients at the highest risk of hepatotoxicity after a large paracetamol overdose.
Subject(s)
Analgesics, Non-Narcotic , Chemical and Drug Induced Liver Injury , Drug Overdose , Drug-Related Side Effects and Adverse Reactions , Humans , Acetaminophen , Analgesics, Non-Narcotic/therapeutic use , Acetylcysteine/therapeutic use , Drug Overdose/drug therapy , Retrospective StudiesABSTRACT
Paracetamol poisoning continues to be a worldwide problem and, despite the availability of an effective antidote, acetylcysteine (NAC), the optimal way to use this antidote, particularly following very large doses of paracetamol, has not been established. Recent case series have shown an increased toxicity from high doses of paracetamol, even in those receiving prompt NAC therapy, particularly in patients above the 300 mg/L nomogram treatment line. Clinical trial evidence supporting shorter NAC dosing now allows the possibility for intensifying treatment without the risk of very high rates of ADRs. New biomarkers also show the possibility of early identification of patients at risk of liver injury who might also benefit from increased intensity treatment. This article discusses these data and proposes a logical therapy for increasing NAC dosing which now requires clinical trial testing.
Subject(s)
Analgesics, Non-Narcotic , Chemical and Drug Induced Liver Injury , Drug Overdose , Drug-Related Side Effects and Adverse Reactions , Humans , Acetylcysteine/therapeutic use , Acetaminophen , Antidotes/therapeutic use , Drug Overdose/drug therapyABSTRACT
Nevada, like the rest of the United States, is undergoing substantial challenges with opioid misuse and overdose deaths, further exacerbated by the COVID-19 pandemic. While much of the attention around opioid overdose prevention is centered on treatment and recovery, it is important to understand the factors that influence initiation of use, and the function opioids play in people's everyday lives. We conducted qualitative semi-structured individual interviews using purposive and snowball sampling among 35 people across Nevada with a current or prior history of illegal opioid or nonmedical opioid use. Our study aimed to understand why people start to use drugs, why they continue to use, what motivates them to continue to use or to seek treatment, and why individuals maintain recovery or return to use. We found five significant themes as perceived by the participants: that trauma is a risk factor for drug misuse; that the function of opioids in everyday life is a source of temporary relief but highly disruptive in the longer term; that recovery is most often a complicated and nonlinear process; that there are many barriers to accessing services that are both logistical and psychosocial; and that compassion, hope, and having a sense of purpose are crucial to the recovery process. The experiences of the study participants portray opioid use as a rational choice to escape the emotional ramifications of trauma. However, due to the physiological dependence and physical risk of opioids, drug policies that criminalize addiction, societal stigma, and the barriers to timely access of harm reduction, treatment, and recovery services, opioid users often become trapped in a distressing and dangerous cycle. Lastly, respondents indicated that hope, value, belonging, and purpose are powerful factors in cultivating intrinsic motivation for making positive changes and fostering resilience in the recovery process. Opioid misuse services should help meet basic needs and incorporate holistic approaches to recovery that acknowledge past trauma and the complexity of the recovery process.