Pharmacologic and Clinical Considerations of Nalmefene, a Long Duration Opioid Antagonist, in Opioid Overdose

Opioid use disorder is a well-established and growing problem in the United States. It is responsible for both psychosocial and physical damage to the affected individuals with a significant mortality rate. Given both the medical and non-medical consequences of this epidemic, it is important to understand the current treatments and approaches to opioid use disorder and acute opioid overdose. Naloxone is a competitive mu-opioid receptor antagonist that is used for the reversal of opioid intoxication. When given intravenously, naloxone has an onset of action of approximately 2 min with a duration of action of 60–90 min. Related to its empirical dosing and short duration of action, frequent monitoring of the patient is required so that the effects of opioid toxicity, namely respiratory depression, do not return to wreak havoc. Nalmefene is a pure opioid antagonist structurally similar to naltrexone that can serve as an alternative antidote for reversing respiratory depression associated with acute opioid overdose. Nalmefene is also known as 6-methylene naltrexone. Its main features of interest are its prolonged duration of action that surpasses most opioids and its ability to serve as an antidote for acute opioid overdose. This can be pivotal in reducing healthcare costs, increasing patient satisfaction, and redistributing the time that healthcare staff spend monitoring opioid overdose patients given naloxone.

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Assessing the Relationships Between COVID-19 Stay-at-Home Orders and Opioid Overdoses in the State of Pennsylvania

Journal of Drug Issues ◽

10.1177/00220426211006362 ◽

2021 ◽

pp. 002204262110063

Author(s):

Brian King ◽

Ruchi Patel ◽

Andrea Rishworth

Keyword(s):

Age Groups ◽

The United States ◽

Opioid Use Disorder ◽

Opioid Overdose ◽

Policy Recommendations ◽

Opioid Use ◽

Fentanyl Analogs ◽

Measure Change ◽

Using Data ◽

At Home

COVID-19 is compounding opioid use disorder throughout the United States. While recent commentaries provide useful policy recommendations, few studies examine the intersection of COVID-19 policy responses and patterns of opioid overdose. We examine opioid overdoses prior to and following the Pennsylvania stay-at-home order implemented on April 1, 2020. Using data from the Pennsylvania Overdose Information Network, we measure change in monthly incidents of opioid-related overdose pre- versus post-April 1, and the significance of change by gender, age, race, drug class, and naloxone doses administered. Findings demonstrate statistically significant increases in overdose incidents among both men and women, White and Black groups, and several age groups, most notably the 30–39 and 40–49 ranges, following April 1. Significant increases were observed for overdoses involving heroin, fentanyl, fentanyl analogs or other synthetic opioids, pharmaceutical opioids, and carfentanil. The study emphasizes the need for opioid use to be addressed alongside efforts to mitigate and manage COVID-19 infection.

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Illicit Opioid Intoxication: Diagnosis and Treatment

Substance Abuse Research and Treatment ◽

10.4137/sart.s7090 ◽

2011 ◽

Vol 5 ◽

pp. SART.S7090

Author(s):

A. Fareed ◽

S. Stout ◽

J. Casarella ◽

S. Vayalapalli ◽

J. Cox ◽

...

Keyword(s):

Signs And Symptoms ◽

The United States ◽

Opioid Overdose ◽

Opioid Use ◽

Heroin Use ◽

Treatment And Prevention ◽

Pain Medications ◽

Opioid Intoxication ◽

Opioid Drugs ◽

Opioid Medications

Opioid intoxications and overdose are associated with high rates of morbidity and mortality. Opioid overdose may occur in the setting of intravenous or intranasal heroin use, illicit use of diverted opioid medications, intentional or accidental misuse of prescription pain medications, or iatrogenic overdose. In this review, we focused on the epidemiology of illict opioid use in the United States and on the mechanism of action of opioid drugs. We also described the signs and symptoms, and diagnoses of intoxication and overdose. Lastly, we updated the reader about the most recent recommendations for treatment and prevention of opioid intoxications and overdose.

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If We Build It, Will They Come? Perspectives on Pharmacy-Based Naloxone Among Family and Friends of People who use Opioids: A Mixed Methods Study

10.21203/rs.3.rs-1167901/v1 ◽

2021 ◽

Author(s):

Susannah Slocum ◽

Jenny E. Ozga ◽

Alexander Y. Walley ◽

Robin A. Pollini ◽

Rebecca Joyce

Keyword(s):

Mixed Methods ◽

Drug Use ◽

Support Groups ◽

Perceived Risk ◽

The United States ◽

Opioid Antagonist ◽

Prescription Opioid ◽

Opioid Overdose ◽

Opioid Use ◽

The Impact

Abstract Background: Expanding access to the opioid antagonist naloxone to reduce overdose mortality is a public health priority in the United States. Naloxone standing orders (NSOs) have been established in many states to increase naloxone dispensing at pharmacies, but increased pharmacy access does not ensure optimal uptake among those likely to witness an overdose. In a prior statewide purchase trial, we documented high levels of naloxone access at Massachusetts pharmacies under a statewide NSO. In this study, we characterize barriers to pharmacy-based naloxone uptake among potential opioid overdose “bystanders” (friends or family of people who use opioids) that may be amenable to intervention.Methods: Eligible bystanders were Massachusetts residents >18 years of age, did not use illicit opioids in the past 30 days, and knew someone who currently uses illicit opioids. We used a sequential mixed methods approach, in which a series of semi-structured qualitative interviews (N=22) were conducted to inform the development of a subsequent quantitative survey (N=260). Results: Most survey participants (77%) reported ever obtaining naloxone but few (21%) attempted to purchase it at a pharmacy. Qualitative participants revealed that barriers to utilizing the NSO included low perceived risk of overdose, which was rooted in misconceptions regarding the risks of prescription opioid misuse, denial about their loved one’s drug use, and drug use stereotypes; inaccurate beliefs about the impact of naloxone on riskier opioid use; and concerns regarding anticipated stigma and confidentiality. Many participants had engaged in mutual support groups, which served as a source of free naloxone for half (50%) of those who had ever obtained naloxone.Conclusions: Despite high levels of pharmacy naloxone access in Massachusetts, few bystanders in our study had attempted to obtain naloxone under the NSO. Low perceived risk of overdose, misinformation, stigma and confidentiality were important barriers to pharmacy naloxone uptake, all of which are amenable to intervention. Support groups provided a setting for addressing stigma and misinformation and provided a discreet and comfortable setting for naloxone access. Where these groups do not exist and for bystanders who do not participate in such groups, pharmacies are well-positioned to fill gaps in naloxone availability.

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Opioid Overdose Education, Prevention, and Management (DRAFT)

10.1093/med/9780190265366.003.0013 ◽

2018 ◽

Cited By ~ 1

Author(s):

Bernd Wollschlaeger

Keyword(s):

The United States ◽

Opioid Use Disorder ◽

Opioid Overdose ◽

Opioid Use ◽

Death Rates ◽

Overdose Prevention ◽

Overdose Death ◽

Good Samaritan ◽

Opioid Deaths ◽

Good Samaritan Laws

In reviewing the elements of opioid overdose education, prevention, and management, this chapter focuses particularly on practical interventions that are available and deserve advocacy; e.g., provision of naloxone to those with opioid use disorder and to possible first responders. It moves from a discussion of the epidemiology of opioid deaths to the more individual topic of patient risk for overdose. Prophylactic interventions in the form of education of the patient’s family and friends, and agreements for treatment with informed consent are described. There follows a discussion of management of the opioid poisoning itself, including use/distribution of naloxone injection. Two figures are included: drug overdose death rates in the United States (2014); a map describing the current states with naloxone or “good Samaritan” laws impacting opioid overdose management. A text box with resources includes directions for initiation of community overdose prevention and intervention schemes.

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NIOSH Responds to the U.S. Drug Overdose Epidemic

NEW SOLUTIONS A Journal of Environmental and Occupational Health Policy ◽

10.1177/10482911211040754 ◽

2021 ◽

pp. 104829112110407

Author(s):

Jamie C. Osborne ◽

L. Casey Chosewood

Keyword(s):

United States ◽

Substance Use ◽

Drug Overdose ◽

Drug Users ◽

Illicit Drugs ◽

Occupational Safety ◽

The United States ◽

Opioid Use Disorder ◽

Opioid Overdose ◽

Opioid Use

The United States is experiencing an evolving and worsening drug overdose epidemic. Although the rate of drug use among workers has remained relatively stable, the risk of overdose and death among drug users has not, as illicit drugs have increased in potency and lethality. The cumulative impacts of COVID-19 and the opioid crisis increase the likelihood of illness and death among workers with opioid use disorder. Workplaces represent a critical point of contact for people living in the United States who are struggling with or recovering from a substance use disorder, and employment is a vital source of recovery “capital.” The benefits of addressing substance use in the workplace, supporting treatment, and employing workers in recovery are evident. The National Institute for Occupational Safety and Health has published research to inform policy and practice toward prevention efforts and has developed accessible resources and toolkits to support workers, employers, and workplaces in combatting the opioid overdose crisis and creating safer, healthier communities.

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Epidemiology of Substance Use Disorders

Substance Use Disorders ◽

10.1093/med/9780190920197.003.0001 ◽

2020 ◽

pp. 3-28

Author(s):

L. Morgan Snell ◽

Andrew J. Barnes ◽

Peter Cunningham

Keyword(s):

The United States ◽

Opioid Use Disorder ◽

Opioid Overdose ◽

Prescription Opioids ◽

Opioid Epidemic ◽

Provider Education ◽

Opioid Use ◽

Prescribing Practices ◽

The Us ◽

Overdose Deaths

Nearly 3 million Americans have a current or previous opioid use disorder, and recent data indicate that 10.2% of US adults have ever misused pain relievers. In 2015, approximately 800,000 individuals used heroin, while 4 million misused prescription opioids. Although use of other drugs such as alcohol and cannabis is more prevalent, opioid use contributes to significant morbidity, mortality, and social and economic costs. While the current US opioid overdose epidemic began with prescription opioids, since 2015, heroin and synthetic opioids (e.g., fentanyl) have driven continued increases in opioid overdose deaths, contributing to a recent decline in overall life expectancy in the United States. Policies to address the opioid epidemic by changing clinical practice include provider education, monitoring prescribing practices, and expanding the clinical workforce necessary to treat opioid use disorders. The opioid epidemic appears to be largely a US phenomenon and a consequence of both structural challenges in the US healthcare system and growing socioeconomic disparities, and thus it will require policies including and beyond delivery system reforms to resolve it.

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0730 Individuals Receiving Methadone For Medication-Assisted Treatment Of Opioid Use Disorder Show Evidence Of Respiratory Depression

SLEEP ◽

10.1093/sleep/zsaa056.726 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A278-A278

Author(s):

M Finlay ◽

M Wilson ◽

J A Erwin ◽

D A Hansen ◽

M E Layton ◽

...

Keyword(s):

Respiratory Depression ◽

Standard Of Care ◽

Nrem Sleep ◽

Opioid Use Disorder ◽

Apnea Hypopnea Index ◽

Opioid Overdose ◽

Opioid Use ◽

Medication Assisted Treatment ◽

Replacement Treatment ◽

Central Apneas

Abstract Introduction A well-established consequence of opiate use is respiratory depression during sleep, with a high prevalence of central sleep apneas. Medication-assisted treatment (MAT) is a widely used therapy for opioid use disorder (OUD) designed to reduce withdrawal symptoms and drug cravings. We investigated the presence of respiratory depression during sleep in patients receiving methadone-based opioid replacement treatment as part of a MAT program for OUD. Methods N=6 individuals (5 females, ages 43.8±12.8y, BMI 27.2±4.1kg/m2), who were within 90 days of methadone initiation, underwent in-laboratory overnight polysomnography (8h TIB, 22:00-06:00). Apneaic and hypopneic events were determined using AASM criteria. Results The average Apnea-Hypopnea Index (AHI) was 16.5±9.0 events/h, with 2 individuals exceeding the threshold of moderate sleep apnea (>15 events/h). 89.5% of the observed apnea-hypopnea events occurred during NREM sleep. Of all events, 57.1±16.3% were central apneas; and of all obstructive, central, and mixed apnea events, 93.0±14.3% were central apneas. Conclusion Individuals with OUD receiving methadone-based MAT may be at risk of respiratory depression during sleep, as evidenced by the frequent occurrence of central sleep apneas. Such risk could be a contributing factor in opioid overdose deaths. Currently, performing respiratory assessments during sleep is not considered standard of care in MAT programs. Our preliminary data suggest that monitoring and treatment of respiratory depression during sleep may be indicated in OUD patients on methadone-based MAT. Support Supported in part by a seed grant from the Washington State University Office of Research Advancement and Partnerships.

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Public perceptions of naloxone use in the outpatient setting

Mental Health Clinician ◽

10.9740/mhc.2019.07.275 ◽

2019 ◽

Vol 9 (4) ◽

pp. 275-279 ◽

Cited By ~ 4

Author(s):

Jordan O. Smith ◽

Scott S. Malinowski ◽

Jordan M. Ballou

Keyword(s):

The United States ◽

Outpatient Setting ◽

Opioid Use Disorder ◽

Public Perceptions ◽

Amazon Mechanical Turk ◽

Opioid Overdose ◽

Opioid Use ◽

Reversal Agent ◽

Electronic Survey ◽

Accidental Overdose

Abstract Introduction Naloxone has become an important component of preventing deaths from opioid overdose. Although studies have confirmed its cost-effectiveness, naloxone is rarely prescribed proactively in case of accidental overdose. The perception still exists that a reversal agent may enable patients with opioid use disorder to continue abusing opioids without fear of death from overdose. This study was designed to determine the general public's knowledge of naloxone and their perceptions about receiving a naloxone prescription with opioid use. Methods Participants were recruited through Amazon Mechanical Turk (MTurk), where a link directed participants to an electronic survey. Participants were included if they were 18 years of age or greater and currently living in the United States. Participants were paid $0.10 USD via Amazon MTurk upon completing the survey. Results Four hundred five participants successfully completed the survey, and 61% were aware that there is a medication available to treat opioid overdose. The majority of participants responded positively to the idea of acquiring naloxone. Responses were evenly split for agreeing and disagreeing with the statement “naloxone is only necessary for people who abuse opioids.” Although 51% of respondents believed that having naloxone available enables people who abuse opioids, 88% agreed that naloxone is beneficial for people who accidentally overdose on opioids. A majority believed that naloxone should be made available upon request to anyone concerned about opioid overdose. Discussion Participants were generally aware of the availability of an opioid reversal agent and responded positively to 3 different methods of acquiring naloxone through their prescriber or pharmacist.

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Relapse rates among veterans on maintenance doses of combination buprenorphine and naloxone for opioid use disorder

Mental Health Clinician ◽

10.9740/mhc.2020.05.080 ◽

2020 ◽

Vol 10 (3) ◽

pp. 80-84

Author(s):

Katie J. Binger ◽

Elayne D. Ansara ◽

Talia M. Miles ◽

Samantha L. Schulte

Keyword(s):

Substance Use ◽

The United States ◽

Opioid Use Disorder ◽

Opioid Overdose ◽

Opioid Use ◽

Significant Difference ◽

Secondary Outcomes ◽

The Difference ◽

Time To Relapse ◽

Recovery Program

Abstract Introduction Opioid use disorder (OUD) can cause significant morbidity and mortality with more than 115 people dying from an opioid overdose daily in the United States. Treatment with buprenorphine/naloxone (BUP/NAL) can be effective; however, there is conflicting evidence on the utility of higher doses in preventing relapse. This study was designed to assess BUP/NAL maintenance doses and the rate of relapse in veterans with OUD. Methods Patients diagnosed with OUD who received a prescription for BUP/NAL through the substance use disorder recovery program were retrospectively evaluated. Patients were categorized into 2 treatment groups: those prescribed ≤16 mg of BUP/NAL daily and those prescribed >16 mg of BUP/NAL daily. The primary outcome was to determine rates of relapse between maintenance doses of BUP/NAL. Secondary outcomes included evaluating the difference in rates of relapse between daily versus take-home dosing, tablets versus films, time to relapse, and use of illicit substances during treatment. Results Patients prescribed >16 mg of BUP/NAL daily had statistically significantly lower rates of relapse compared to patients prescribed ≤16 mg of BUP/NAL daily (P = .0018). Regarding secondary outcomes, there was a statistically significant difference in time to relapse (P = .036) and dosage form (P = .0124). Difference in administration of dose and illicit substance use during treatment were not statistically significant. Discussion This study identified that rate of relapse can be lowered and time to relapse can be lengthened when doses >16 mg of BUP/NAL are prescribed in the veteran population for OUD.

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Opioids

ASAM Handbook of Addiction Medicine ◽

10.1093/med/9780197506172.003.0006 ◽

2020 ◽

pp. 109-148

Author(s):

Darius A. Rastegar

Keyword(s):

Respiratory Depression ◽

Opioid Use Disorder ◽

Opioid Antagonist ◽

Opioid Use ◽

Opioid Agonist ◽

Level Of Consciousness ◽

Long Acting ◽

Self Help Groups ◽

Prescription Pain Relievers

Opioids are a class of drugs that include heroin and prescription pain relievers that produce analgesia and euphoria. More than 2 million Americans have an opioid use disorder. Acute effects include analgesia, respiratory depression, miosis, and euphoria. Overdose is a serious complication of opioid use, characterized by depressed level of consciousness and respiratory depression. It can be treated with naloxone. Withdrawal symptoms include dysphoria, yawning, tearing, diarrhea, cramps, nausea, and piloerection. Buprenorphine, methadone, clonidine, and lofexidine can be used to ameliorate the symptoms of withdrawal. However, supervised withdrawal alone rarely leads to long-term abstinence. There are a number of psychosocial treatments, including self-help groups, outpatient therapy, and residential treatment; the data on their effectiveness are limited. Pharmacotherapy with an opioid agonist (methadone or buprenorphine) is the most effective treatment. Long-acting injectable naltrexone, an opioid antagonist, is also effective, but it is more difficult to initiate.

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