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Expert Opinion on Drug Metabolism &... 2023Paracetamol is one of the most used medicines worldwide and is the most common important poisoning in high-income countries. In overdose, paracetamol causes... (Review)
Review
INTRODUCTION
Paracetamol is one of the most used medicines worldwide and is the most common important poisoning in high-income countries. In overdose, paracetamol causes dose-dependent hepatotoxicity. Acetylcysteine is an effective antidote, however despite its use hepatotoxicity and many deaths still occur.
AREAS COVERED
This review summarizes paracetamol overdose and toxicity (including mechanisms, risk factors, risk assessment, and treatment). In addition, we summarize the epidemiology of paracetamol overdose worldwide. A literature search on PubMed for poisoning epidemiology and mortality from 1 January 2017 to 26 October 2022 was performed to estimate rates of paracetamol overdose, liver injury, and deaths worldwide.
EXPERT OPINION
Paracetamol is widely available and yet is substantially more toxic than other analgesics available without prescription. Where data were available, we estimate that paracetamol is involved in 6% of poisonings, 56% of severe acute liver injury and acute liver failure, and 7% of drug-induced liver injury. These estimates are limited by lack of available data from many countries, particularly in Asia, South America, and Africa. Harm reduction from paracetamol is possible through better identification of high-risk overdoses, and better treatment regimens. Large overdoses and those involving modified-release paracetamol are high-risk and can be targeted through legislative change.
Topics: Humans; Acetaminophen; Drug Overdose; Acetylcysteine; Chemical and Drug Induced Liver Injury; Cost of Illness
PubMed: 37436926
DOI: 10.1080/17425255.2023.2223959 -
Pharmacology & Therapeutics May 2022Overdose deaths are often viewed as the leading edge of the opioid epidemic which has gripped the United States over the past two decades (Skolnick, 2018a). This... (Review)
Review
Overdose deaths are often viewed as the leading edge of the opioid epidemic which has gripped the United States over the past two decades (Skolnick, 2018a). This emphasis is perhaps unsurprising because opioid overdose is both the number-one cause of death for individuals between 25 and 64 years old (Dezfulian et al., 2021) and a significant contributor to the decline in average lifespan (Dowell et al., 2017). Exacerbated by the COVID 19 pandemic, it was estimated there were 93,400 drug overdose deaths in the United States during the 12 months ending December 2020, with more than 69,000 (that is, >74%) of these fatalities attributed to opioid overdose (Ahmad et al., 2021). However, the focus on mortality statistics (Ahmad et al., 2021; Shover et al., 2020) tends to obscure the broader medical impact of nonfatal opioid overdose. Analyses of multiple databases indicate that for each opioid-induced fatality, there are between 6.4 and 8.4 non-fatal overdoses, exacting a significant burden on both the individual and society. Over the past 7-8 years, there has been an alarming increase in the misuse of synthetic opioids ("synthetics"), primarily fentanyl and related piperidine-based analogs. Within the past 2-3 years, a structurally unrelated class of high potency synthetics, benzimidazoles exemplified by etonitazene and isotonitazene ("iso"), have also appeared in illicit drug markets (Thompson, 2020; Ujvary et al. 2021). In 2020, it was estimated that over 80% of fatal opioid overdoses in the United States now involve synthetics (Ahmad et al., 2021). The unique physicochemical and pharmacological properties of synthetics described in this review are responsible for both the morbidity and mortality associated with their misuse as well as their widespread availability. This dramatic increase in the misuse of synthetics is often referred to as the "3rd wave" (Pardo et al., 2019; Volkow and Blanco, 2020) of the opioid epidemic. Among the consequences resulting from misuse of these potent opioids is the need for higher doses of the competitive antagonist, naloxone, to reverse an overdose. The development of more effective reversal agents such as those described in this review is an essential component of a tripartite strategy (Volkow and Collins, 2017) to reduce the biopsychosocial impact of opioid misuse in the "synthetic era".
Topics: Adult; Analgesics, Opioid; Drug Overdose; Humans; Middle Aged; Naloxone; Opiate Overdose; United States; COVID-19 Drug Treatment
PubMed: 34637841
DOI: 10.1016/j.pharmthera.2021.108019 -
Drug and Alcohol Dependence Jan 2021The United States (U.S.) is experiencing an ongoing opioid crisis. Economic burden estimates that describe the impact of the crisis are needed when considering federal...
BACKGROUND
The United States (U.S.) is experiencing an ongoing opioid crisis. Economic burden estimates that describe the impact of the crisis are needed when considering federal and state resources devoted to addressing overdoses. In this study, we estimate the societal costs for opioid use disorder and fatal overdose from all opioids in 2017.
METHODS
We estimated costs of fatal overdose from all opioids and opioid use disorder based on the incidence of overdose deaths and the prevalence of past-year opioid use disorder for 2017. Incidence of fatal opioid overdose was obtained from the National Vital Statistics System; prevalence of past-year opioid use disorder was estimated from the National Survey of Drug Use and Health. Costs were estimated for health care, criminal justice and lost productivity. Costs for the reduced quality of life for opioid use disorder and life lost due to fatal opioid overdose were valued using U.S. Department of Health and Human Services guidelines for valuing reductions in morbidity and mortality.
RESULTS
Costs for opioid use disorder and fatal opioid overdose in 2017 were estimated to be $1.02 trillion. The majority of the economic burden is due to reduced quality of life from opioid use disorder and the value of life lost due to fatal opioid overdose.
CONCLUSIONS
These estimates can assist decision makers in understanding the magnitude of opioid use disorder and fatal overdose. Knowing the magnitude and distribution of the economic burden can inform public policy, clinical practice, research, and prevention and response activities.
Topics: Analgesics, Opioid; Cost of Illness; Criminal Law; Delivery of Health Care; Drug Overdose; Humans; Opiate Overdose; Opioid Epidemic; Opioid-Related Disorders; Prevalence; Quality of Life; United States
PubMed: 33121867
DOI: 10.1016/j.drugalcdep.2020.108350 -
Clinical Toxicology (Philadelphia, Pa.) Mar 2023Illicit opioids, consisting largely of fentanyl, novel synthetic opioids, and adulterants, are the primary cause of drug overdose fatality in the United States....
INTRODUCTION
Illicit opioids, consisting largely of fentanyl, novel synthetic opioids, and adulterants, are the primary cause of drug overdose fatality in the United States. Xylazine, an alpha-2 adrenergic agonist and veterinary tranquilizer, is being increasingly detected among decedents following illicit opioid overdose. Clinical outcomes in non-fatal overdose involving xylazine are unexplored. Therefore, among emergency department patients with illicit opioid overdose, we evaluated clinical outcome differences for patients with and without xylazine exposures.
METHODS
This multicenter, prospective cohort study enrolled adult patients with opioid overdose who presented to one of nine United States emergency departments between 21 September 2020, and 17 August 2021. Patients with opioid overdose were screened and included if they tested positive for an illicit opioid (heroin, fentanyl, fentanyl analog, or novel synthetic opioid) or xylazine. Patient serum was analyzed liquid chromatography quadrupole time-of-flight mass spectroscopy to detect current illicit opioids, novel synthetic opioids, xylazine and adulterants. Overdose severity surrogate outcomes were: (a) cardiac arrest requiring cardiopulmonary resuscitation (primary); and (b) coma within 4 h of arrival (secondary).
RESULTS
Three hundred and twenty-one patients met inclusion criteria: 90 tested positive for xylazine and 231 were negative. The primary outcome occurred in 37 patients, and the secondary outcome occurred in 111 patients. Using multivariable regression analysis, patients positive for xylazine had significantly lower adjusted odds of cardiac arrest (adjusted OR 0.30, 95% CI 0.10-0.92) and coma (adjusted OR 0.52, 95% CI 0.29-0.94).
CONCLUSIONS
In this large multicenter cohort, cardiac arrest and coma in emergency department patients with illicit opioid overdose were significantly less severe in those testing positive for xylazine.
Topics: Adult; Humans; United States; Analgesics, Opioid; Xylazine; Opiate Overdose; Prospective Studies; Coma; Fentanyl; Drug Overdose; Emergency Service, Hospital
PubMed: 37014353
DOI: 10.1080/15563650.2022.2159427 -
American Journal of Kidney Diseases :... Jun 2022Poisoning is a common problem in the United States. Acid-base disturbances, electrolyte derangements, or acute kidney injury result from severe poisoning from toxic... (Review)
Review
Poisoning is a common problem in the United States. Acid-base disturbances, electrolyte derangements, or acute kidney injury result from severe poisoning from toxic alcohols, salicylates, metformin, and acetaminophen. Lithium is highly sensitive to small changes in kidney function. These poisonings and drug overdoses often require the nephrologist's expertise in diagnosis and treatment, which may require correction of acidosis, administration of selective enzyme inhibitors, or timely hemodialysis. The clinical and laboratory abnormalities associated with the poisonings and drug overdoses can develop rapidly and lead to severe cellular dysfunction and death. Understanding the pathophysiology of the disturbances and their clinical and laboratory findings is essential for the nephrologist to rapidly recognize the poisonings and establish an effective treatment plan. This installment of AJKD's Core Curriculum in Nephrology presents illustrative cases of individual poisonings and drug overdoses and summarizes up to date information on their prevalence, clinical and laboratory findings, pathophysiology, diagnosis, and treatment.
Topics: Acidosis; Curriculum; Drug Overdose; Humans; Metformin; Nephrologists; Poisoning
PubMed: 34895948
DOI: 10.1053/j.ajkd.2021.06.030 -
American Journal of Public Health Aug 2022Xylazine is a nonopioid veterinary anesthetic and sedative that is increasingly detected in the illicit drug supply in the United States. Data indicate a striking...
Xylazine is a nonopioid veterinary anesthetic and sedative that is increasingly detected in the illicit drug supply in the United States. Data indicate a striking prevalence of xylazine among opioid-involved overdose deaths. The emergence of xylazine in the illicit drug supply poses many unknowns and potential risks for people who use drugs. The public health system needs to respond by increasing testing to determine the prevalence of xylazine, identifying its potential toxicity at various exposure levels, and taking mitigating action to prevent harms. Currently, there is little testing capable of identifying xylazine in drug supplies, which limits the possibility of public health intervention, implementation of harm reduction strategies, or development of novel treatment strategies. (. 2022;112(8):1212-1216. https://doi.org/10.2105/AJPH.2022.306881).
Topics: Analgesics, Opioid; Drug Overdose; Harm Reduction; Humans; Illicit Drugs; Opiate Overdose; Public Health; United States; Xylazine
PubMed: 35830662
DOI: 10.2105/AJPH.2022.306881 -
American Journal of Public Health Sep 2023
Topics: Humans; Harm Reduction; Drug Overdose; Social Justice
PubMed: 37556788
DOI: 10.2105/AJPH.2023.307379 -
American Family Physician Feb 2024Poisoning is the leading cause of injury-related morbidity and mortality in the United States. The highest rates of exposure to poisons occur in children five years and...
Poisoning is the leading cause of injury-related morbidity and mortality in the United States. The highest rates of exposure to poisons occur in children five years and younger, but opioid overdoses in young adults account for most deaths from poisonings in recent years. Intentional or accidental medication poisoning should be considered when evaluating patients with mental status changes, vital sign abnormalities, seizures, and gastrointestinal or cardiovascular problems. For all poisoned patients, a comprehensive history and physical examination are needed. Knowledge of toxidromes may help identify the cause in unknown ingestions; however, their usefulness may be limited when multiple toxins are ingested. Electrocardiography is indicated in patients reporting chest pain and dyspnea and in overdoses of beta blockers, tricyclic antidepressants, and antidysrhythmics. Measurement of electrolyte, serum creatinine, and serum bicarbonate levels and calculation of the anion gap may be helpful based on the clinical presentation. Treatment of a patient with acute poisoning is based on resuscitation and stabilization with a focus on airway, breathing, and circulation. When poisoning is suspected, the Poison Control provides health care workers and the public with access to a specialist 24 hours a day.
Topics: Child; Young Adult; Humans; United States; Drug-Related Side Effects and Adverse Reactions; Drug Overdose; Poisoning
PubMed: 38393798
DOI: No ID Found -
Substance Abuse 2022Opioid overdose is a preventable injury leading to high morbidity and premature mortality in communities across the United States. Overdoses take place where people use...
BACKGROUND
Opioid overdose is a preventable injury leading to high morbidity and premature mortality in communities across the United States. Overdoses take place where people use drugs, including commercial and public locations like community pharmacies, and necessitate swift detection and response to avoid harm and, even more seriously, death. The presence of emergency and safety protocols improves occupational health and safety for all in the workplace. The aim of this study was to assess the prevalence of experience with on-site pharmacy overdose and to explore pharmacist and site characteristics associated with having a known protocol for responding to on-site overdose emergencies.
UNLABELLED
: An anonymous, online survey about naloxone provision and opioid safety was delivered by email, through professional pharmacy associations and continuing education attendance lists, to 3,100 pharmacists in Massachusetts and Rhode Island between October 2017 and January 2018. Survey items gauged socio-demographics, practice site characteristics, safer opioid dispensing and naloxone provision. Summary statistics and bivariate analyses were conducted to describe characteristics associated with items pertaining to on-site overdose policy awareness.
UNLABELLED
: Of the 357 respondents (11.5% response rate), 154 (5.0%) answered the questions of interest: 17.5% reported having at least one suspected overdose on-site at their practice location, while 42.9% reported that they were knowledgeable about and could locate at their practice location an on-site overdose protocol detailing how to respond to an overdose. Pharmacists who were knowledgeable about protocols were also more likely to offer naloxone to patients ( = 0.02) and did not practice at a chain pharmacy ( = 0.01).
UNLABELLED
: Community pharmacies that stock and distribute naloxone are key parts of community efforts to address the opioid crisis. Pharmacies and other healthcare settings should develop and implement on-site overdose response protocols and cultivate a norm of naloxone provision to patients.
Topics: Analgesics, Opioid; Drug Overdose; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pharmacies; Pharmacists; Pharmacy; United States
PubMed: 32186478
DOI: 10.1080/08897077.2020.1736236 -
The Medical Journal of Australia May 2023
Topics: Humans; Drug Overdose; Nonprescription Drugs; Analgesics, Opioid
PubMed: 37041656
DOI: 10.5694/mja2.51927