In 2016 and 2017 an outbreak of the Zika virus</span><span style="font-family:""> </span><span style="font-family:Verdana;">in new locales shocked populations</span&...In 2016 and 2017 an outbreak of the Zika virus</span><span style="font-family:""> </span><span style="font-family:Verdana;">in new locales shocked populations</span><span style="font-family:""> </span><span style="font-family:Verdana;">into awareness of the disease and of its imputed ability to cause serious fetal abnormalities, particularly microcephaly. There was a major reduction in travel by people of child-bearing age. But the temporary regression in </span><span style="font-family:Verdana;">the </span><span style="font-family:Verdana;">spread, and preoccupation with COVID-19, seem to have overshadowed concern about Zika virus. In order to investigate this phenomenon, we conducted an online survey of 157 high-school students from four schools in different parts of the United States regarding their knowledge, practices, and attitudes about Zika virus. The mean age of the respondents was 16.4 </span><span style="font-family:""><span style="font-family:Verdana;">±</span><span style="font-family:Verdana;"> 1.1 years, 55% were girls, and 60% attended public (rather than private) schools. Most students (70%) had taken no steps to prevent Zika, but said they would tell their parents or a physician if they were exposed. They relied primarily on school and the internet (76% and 72%, respectively) as trusted sources of information about the virus. The majority (73%) said they would spend some time to learn more about Zika;girls exhibited more concern than did boys. Half (50%) of respondents knew the signs and symptoms of Zika, but only 20% knew all the ways Zika could be transmitted and 31% why Zika prevention was crucial for pregnant women and their partners. The results of this study suggest that comprehensive national preventive healthcare educational programs are needed.展开更多
There is accumulating evidence that the subfamily of large-conductance potassium (“big”, “BK”) channels are involved in diverse, and perhaps coordinated, protective or counteractive responses to local or generaliz...There is accumulating evidence that the subfamily of large-conductance potassium (“big”, “BK”) channels are involved in diverse, and perhaps coordinated, protective or counteractive responses to local or generalized ischemia and hypoxia. Although widely distributed, the physiological differences among BK channels which results from posttranslational modification (alternative splicing) and co-assembly with auxiliary modulatory subunits (<em>β</em><sub>1-4</sub> and <em>γ</em><sub>1-4</sub>), bestows localized differences in subunit composition, distribution, 2<sup>nd</sup>-messenger coupling, and pharmacologic properties. Due to the ubiquitous nature of BK channels and the multiplicity of subtypes, they have many potential therapeutic applications in the maintenance of oxygen homeostasis, cerebro- and cardio-protection, and stimulation of respiration in response to drug-induced respiratory depression. BK channels may also offer other potentially broad and underrecognized promising targets for novel pharmaceutical development.展开更多
<span style="font-family:Verdana;"><strong>Introduction:</strong></span><span><span><span style="font-family:""><span style="font-family:Verda...<span style="font-family:Verdana;"><strong>Introduction:</strong></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> The inflammatory mechanisms of COVID-19 suggest that corticosteroids may be beneficial, but their benefits must outweigh their potential risks. The RECOVERY trial results suggest that dexamethasone 6 mg/day </span><span style="font-family:Verdana;">(but not other steroids) may confer mortality benefits on ventilated COVID-19 </span><span style="font-family:Verdana;">patients.</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">Methods:</span></b></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> This is a narrative review of the literature about the use of ciclesonide and dexamethasone for COVID-19 patients. Literature is being created rapidly and this review is offered as a state-of-the-science narration.</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">Results:</span></b></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> The SARS-CoV-2 virus is an RNA virus whose RNA is transcribed via open reading frames, making its elimination difficult. Coronaviruses have evolved multiple strategies for proteolytic activation of the spike;viral replication occurs entirely in the cytoplasm. In this connection, the RNA-cleaving endoribonuclease (NSP-15 also known as EndoU) may play a key role by facilitating viral double-stranded RNA recognition by the host’s macrophages. </span><span style="font-family:Verdana;">Furthermore, the virus is able to undergo RNA recombination rapidly,</span><span style="font-family:Verdana;"> enabling it to evade host immunity and develop drug resistance. Cicleson展开更多
Initially thought to be an opioid receptor subtype, Sigma-1 receptors (S1R) are now known to be unique proteins that have chaperone-like properties. As such, they play critical roles in cellular signaling, homeostasis...Initially thought to be an opioid receptor subtype, Sigma-1 receptors (S1R) are now known to be unique proteins that have chaperone-like properties. As such, they play critical roles in cellular signaling, homeostasis, and cell survival. These roles offer significant insight for understanding homeostasis of normal physiologic processes, and the pathophysiologic consequences of disruption of normal function. Because of the broad nature of chaperone action, S1R agonists and antagonists represent potential drug discovery goals for the pharmacotherapeutic treatment of a variety of disorders that result from dysfunctional proteins. The present study summarizes the S1R as a pharmacologic chaperone crucial for protein folding and cellular homeostasis. Through literature review and thermodynamic analysis, it explores how S1R stabilizes target proteins, influencing neuroprotection and potential drug therapies. The binding of chaperones to target proteins is thermodynamically favorable, offering insights into treating diseases linked to protein misfolding.展开更多
Benzodiazepines and other benzodiazepine receptor agonists, such as the “Z” drugs, are widely prescribed medications mainly used for treating anxiety and seizures, and for inducing sedation. Unfortunately, despite t...Benzodiazepines and other benzodiazepine receptor agonists, such as the “Z” drugs, are widely prescribed medications mainly used for treating anxiety and seizures, and for inducing sedation. Unfortunately, despite their popularity, benzodiazepine prescribing often exceeds recommendations and the consequences can be severe. On September 23, 2020, the United States FDA announced a new requirement for a Boxed Warning for benzodiazepines prescribing. Along with this announcement, the FDA stated that relevant information regarding the initiation, continuation, and discontinuation of benzodiazepines is lacking. Here, we describe initial pilot studies intended to investigate the questions 1) can animal models be developed that demonstrate benzodiazepine physical dependence and/or withdrawal symptoms, and 2) determine whether translocator protein (TSPO) plays a role in benzodiazepine dependence and/or withdrawal processes. The former was demonstrated, methodological limitations prevented the latter.展开更多
Polysubstance (combinations of substances) abuse and overdose deaths now surpass mono-substance abuse and overdose deaths. Several international and governmental organizations such as the WHO (World Health Organizatio...Polysubstance (combinations of substances) abuse and overdose deaths now surpass mono-substance abuse and overdose deaths. Several international and governmental organizations such as the WHO (World Health Organization), CDC (Centers for Disease Control and Prevention), several of the Institutes of the NIH (National Institutes of Health), Regulators, and Enforcement Agencies, among others, track and provide a valuable source of statistical information about drug (prescription and illicit) (mis)use and overdose. The information is disseminated free to stakeholders and the general public for use. Although the numeric presentations of the data are helpful and adequate for professionals, the non-expert and the visual learner often find visual representation more clear and more compelling. With this in mind, the aim of this study was to present polysubstance use and overdose using visual maps of the available data. This article considers the opioids.展开更多
Recent publications reveal the disturbing information that a minor edit to an algorithm being used for designing legitimate drug candidates redirected the program in a way that resulted in the surprising design of nov...Recent publications reveal the disturbing information that a minor edit to an algorithm being used for designing legitimate drug candidates redirected the program in a way that resulted in the surprising design of novel chemical warfare agent candidates. Although this outcome was not the result of nefarious intent, and appropriate chemical defense authorities were notified, the potential implications of some misapplication of a drug-design algorithm for nefarious purposes are clear. This Commentary summarizes how otherwise benign Artificial Intelligence (AI) algorithms used for drug discovery can be easily reversed to design novel chemical warfare agents for which no effective antidote will be available, or perhaps even envisioned.展开更多
Abuse of drug substances and resultant overdose deaths are no longer very straightforward—viz., attributable to a single chemical entity of known purity. The reality is that most overdose deaths involve polysubstance...Abuse of drug substances and resultant overdose deaths are no longer very straightforward—viz., attributable to a single chemical entity of known purity. The reality is that most overdose deaths involve polysubstance use (i.e., the use of combinations of substances). Further, the combinations are often of unknown purity, and even of unknown composition. Overdose deaths are at all-time highs. The depressing statistics are monitored and reported by several international and governmental organizations such as the WHO (World Health Organization), CDC (Centers for Disease Control and Prevention), several Institutes of the NIH (National Institutes of Health), Regulators, and Enforcement Agencies (e.g., DEA). The information is disseminated for free for review and use. But it is our observation that although numeric presentation is helpful and adequate for professionals, the non-expert and the visual learner often find a visual representation clearer and compelling. With this in mind, we present the “gestalt” of polysubstance use and overdose using available maps of the data. The previous article in the series considered the opioids. This one considers amphetamines and cocaine, and places the rise in opioid-associated overdose deaths in the context of other abused drugs.展开更多
On September 23, 2020, in order “To address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated ...On September 23, 2020, in order “To address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines”. With this announcement, the FDA proclaimed that much more needs to be known about the initiation, continuation, and discontinuation of these widely-used drugs. Unfortunately, relevant information is lacking, since for many years, there has been a notable sparsity in the funding and conduct of basic and clinical research on these drugs. In order to begin to fill the void, it is valuable to (re)examine animal models. We here describe a model of conditioned place-preference (CPP) for rats and for the first time, to our knowledge, show that the representative benzodiazepine alprazolam induces positive place-preference in male rats.展开更多
The rise in “vaping”-associated deaths in the United States raises serious concerns. A justification for some level of risk is that e-cigarettes might pro</span><span style="font-family:Verdana;"&...The rise in “vaping”-associated deaths in the United States raises serious concerns. A justification for some level of risk is that e-cigarettes might pro</span><span style="font-family:Verdana;">vide a </span></span><span style="font-family:Verdana;">“</span><span style="font-family:Verdana;">reverse-gateway” from smoking traditional cigarettes to a less-harmful</span><span style="font-family:Verdana;"> alternative. But are users actually smokers? We developed an electronic on-line survey to gather data regarding e-cigarette usage in a target study population of pharmacy students. The survey was created using Google Forms to collect the responses anonymously. We surveyed medical-savvy healthcare students about their e-cigarette use, and whether or not their healthcare providers were aware of their e-cigarette use. Although nearly one-fourth of a convenience sampling of 134 pharmacy-student respondents (23.9%) reported using e-cigarettes, only 2.0% reported prior regular cigarette use, 28% used cartridges containing nicotine and only 11.2% had tried and wanted to quit. The majority (64.1%) reported that their healthcare providers did not ask about such use, and respondents did not volunteer this information. The results of this pilot survey reveal a significant e-cigarette use among health-aware pharmacy students, and they do not support the notion that the respondents do so to quit smoking. The observation that most of the students’ healthcare providers did not inquire about their e-cigarette use, coupled with the finding that users did not volunteer their vaping behavior</span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> suggests that the information should be included when getting a medical history. Further research is needed to determine what behavioral factors may play a role in this type of decision-making among student healthcare professionals.展开更多
Polysubstance Abuse (PSA) greatly complicates an attempt to implicate a single drug as sole cause of an overdose death. Since PSA now occurs in the majority of cases of drug overdoses, many or most overdose deaths are...Polysubstance Abuse (PSA) greatly complicates an attempt to implicate a single drug as sole cause of an overdose death. Since PSA now occurs in the majority of cases of drug overdoses, many or most overdose deaths are polysubstance overdose deaths. And since many of the substances involved in a polysubstance Overdose Death (POD) are Central Nervous System (CNS) depressants, many of which can cause overdose death themselves, or synergistically with opioids, it is somewhat puzzling that prescription opioids have been singled out as the cause of these deaths—without reference to PSA. This is particularly puzzling in light of the fact that the issues of PSA and POD have been recognized and discussed in the literature since at least the 1960’s and before. We therefore here consider the question: are we facing an “opioid” crisis or, instead, a “polysubstance crisis”? And we wonder if the issue has been over-simplified, to the detriment of the individuals affected, and to society more broadly. There is a need for an “agnostic” respiratory stimulant that can reverse polysubstance-induced respiratory depression.展开更多
<span lang="EN-US" style="white-space:normal;font-family:Verdana;">The benzodiazepines were introduced into medical practice during the 1960s. At the time, they represented a safer alternativ...<span lang="EN-US" style="white-space:normal;font-family:Verdana;">The benzodiazepines were introduced into medical practice during the 1960s. At the time, they represented a safer alternative to extant therapies used for anxiety, such as the barbiturates. However, on September 23, 2020, the United States FDA indicated that more is needed to be known about the initiation, continuation, and discontinuation of </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">the </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">us</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">e of</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;"> these widely-used drugs with publication of the announcement </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">“</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">to address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines.</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">”</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;"> Because for many years</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">, </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">there has been a sparsity </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">of </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">research on these drugs, relevant information is unfortunately lacking at this critical time. It is therefore valuable to (re)establish animal models and begin to collect relevant data. We here use a model of conditioned place</span><span lang="EN-US" style="white-space:normal;" "=""> </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">preference (CPP) </span><span lang="EN-U展开更多
<span style="font-family:Verdana;">The </span><span style="font-family:Verdana;">“</span><span style="font-family:Verdana;">opioid crisis</span><sp...<span style="font-family:Verdana;">The </span><span style="font-family:Verdana;">“</span><span style="font-family:Verdana;">opioid crisis</span><span style="font-family:Verdana;">”</span><span style="font-family:""><span style="font-family:Verdana;"> has had a tremendous impact not only on its victims, but also on the practice of medicine, pain patients, and society in general. Unfortunately, efforts to “stem the tide” have not been successful at reducing overdose deaths. Counterbalancing the many ardent efforts to eliminate overdose deaths (such as the current widespread availability and use of opioid-receptor antagonists such as naloxone) is influx of the illicit fentanoids (</span><i><span style="font-family:Verdana;">i.e</span></i><span style="font-family:Verdana;">., fentanyl and analogs). In addition to their high-potency, the fentanoids differ in surprising ways from more “traditional” opioids such as morphine and heroin. This uniqueness contributes to a reduced effectiveness of opioid receptor antagonists in the treatment of opioid overdose. Further greatly complicating overdose treatment is polysubstance abuse (e.g., an opioid plus a benzodiaze</span><span style="font-family:Verdana;">pine). The non-opioid in the combination is not responsive to an opio</span><span style="font-family:Verdana;">id-recep</span></span><span style="font-family:Verdana;">- </span><span style="font-family:""><span style="font-family:Verdana;">tor antagonist, which imparts additional challenges. Thus, the new reality in</span><span style="font-family:Verdana;">troduces complications that negatively impact efforts to reverse </span></span><span style="font-family:Verdana;">“</span><span style="font-family:Verdana;">opioid</span><span style="font-family:Verdana;">”</span><span style="font-family:""><span style="font-family:Verdana;"> overdose. New approaches to improve outcomes in individuals who experience </span><span style="font-family:Verdana;">respiratory depression due to fentanoid-induced or polysubstance-i展开更多
文摘In 2016 and 2017 an outbreak of the Zika virus</span><span style="font-family:""> </span><span style="font-family:Verdana;">in new locales shocked populations</span><span style="font-family:""> </span><span style="font-family:Verdana;">into awareness of the disease and of its imputed ability to cause serious fetal abnormalities, particularly microcephaly. There was a major reduction in travel by people of child-bearing age. But the temporary regression in </span><span style="font-family:Verdana;">the </span><span style="font-family:Verdana;">spread, and preoccupation with COVID-19, seem to have overshadowed concern about Zika virus. In order to investigate this phenomenon, we conducted an online survey of 157 high-school students from four schools in different parts of the United States regarding their knowledge, practices, and attitudes about Zika virus. The mean age of the respondents was 16.4 </span><span style="font-family:""><span style="font-family:Verdana;">±</span><span style="font-family:Verdana;"> 1.1 years, 55% were girls, and 60% attended public (rather than private) schools. Most students (70%) had taken no steps to prevent Zika, but said they would tell their parents or a physician if they were exposed. They relied primarily on school and the internet (76% and 72%, respectively) as trusted sources of information about the virus. The majority (73%) said they would spend some time to learn more about Zika;girls exhibited more concern than did boys. Half (50%) of respondents knew the signs and symptoms of Zika, but only 20% knew all the ways Zika could be transmitted and 31% why Zika prevention was crucial for pregnant women and their partners. The results of this study suggest that comprehensive national preventive healthcare educational programs are needed.
文摘There is accumulating evidence that the subfamily of large-conductance potassium (“big”, “BK”) channels are involved in diverse, and perhaps coordinated, protective or counteractive responses to local or generalized ischemia and hypoxia. Although widely distributed, the physiological differences among BK channels which results from posttranslational modification (alternative splicing) and co-assembly with auxiliary modulatory subunits (<em>β</em><sub>1-4</sub> and <em>γ</em><sub>1-4</sub>), bestows localized differences in subunit composition, distribution, 2<sup>nd</sup>-messenger coupling, and pharmacologic properties. Due to the ubiquitous nature of BK channels and the multiplicity of subtypes, they have many potential therapeutic applications in the maintenance of oxygen homeostasis, cerebro- and cardio-protection, and stimulation of respiration in response to drug-induced respiratory depression. BK channels may also offer other potentially broad and underrecognized promising targets for novel pharmaceutical development.
文摘<span style="font-family:Verdana;"><strong>Introduction:</strong></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> The inflammatory mechanisms of COVID-19 suggest that corticosteroids may be beneficial, but their benefits must outweigh their potential risks. The RECOVERY trial results suggest that dexamethasone 6 mg/day </span><span style="font-family:Verdana;">(but not other steroids) may confer mortality benefits on ventilated COVID-19 </span><span style="font-family:Verdana;">patients.</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">Methods:</span></b></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> This is a narrative review of the literature about the use of ciclesonide and dexamethasone for COVID-19 patients. Literature is being created rapidly and this review is offered as a state-of-the-science narration.</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">Results:</span></b></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> The SARS-CoV-2 virus is an RNA virus whose RNA is transcribed via open reading frames, making its elimination difficult. Coronaviruses have evolved multiple strategies for proteolytic activation of the spike;viral replication occurs entirely in the cytoplasm. In this connection, the RNA-cleaving endoribonuclease (NSP-15 also known as EndoU) may play a key role by facilitating viral double-stranded RNA recognition by the host’s macrophages. </span><span style="font-family:Verdana;">Furthermore, the virus is able to undergo RNA recombination rapidly,</span><span style="font-family:Verdana;"> enabling it to evade host immunity and develop drug resistance. Cicleson
文摘Initially thought to be an opioid receptor subtype, Sigma-1 receptors (S1R) are now known to be unique proteins that have chaperone-like properties. As such, they play critical roles in cellular signaling, homeostasis, and cell survival. These roles offer significant insight for understanding homeostasis of normal physiologic processes, and the pathophysiologic consequences of disruption of normal function. Because of the broad nature of chaperone action, S1R agonists and antagonists represent potential drug discovery goals for the pharmacotherapeutic treatment of a variety of disorders that result from dysfunctional proteins. The present study summarizes the S1R as a pharmacologic chaperone crucial for protein folding and cellular homeostasis. Through literature review and thermodynamic analysis, it explores how S1R stabilizes target proteins, influencing neuroprotection and potential drug therapies. The binding of chaperones to target proteins is thermodynamically favorable, offering insights into treating diseases linked to protein misfolding.
文摘Benzodiazepines and other benzodiazepine receptor agonists, such as the “Z” drugs, are widely prescribed medications mainly used for treating anxiety and seizures, and for inducing sedation. Unfortunately, despite their popularity, benzodiazepine prescribing often exceeds recommendations and the consequences can be severe. On September 23, 2020, the United States FDA announced a new requirement for a Boxed Warning for benzodiazepines prescribing. Along with this announcement, the FDA stated that relevant information regarding the initiation, continuation, and discontinuation of benzodiazepines is lacking. Here, we describe initial pilot studies intended to investigate the questions 1) can animal models be developed that demonstrate benzodiazepine physical dependence and/or withdrawal symptoms, and 2) determine whether translocator protein (TSPO) plays a role in benzodiazepine dependence and/or withdrawal processes. The former was demonstrated, methodological limitations prevented the latter.
文摘Polysubstance (combinations of substances) abuse and overdose deaths now surpass mono-substance abuse and overdose deaths. Several international and governmental organizations such as the WHO (World Health Organization), CDC (Centers for Disease Control and Prevention), several of the Institutes of the NIH (National Institutes of Health), Regulators, and Enforcement Agencies, among others, track and provide a valuable source of statistical information about drug (prescription and illicit) (mis)use and overdose. The information is disseminated free to stakeholders and the general public for use. Although the numeric presentations of the data are helpful and adequate for professionals, the non-expert and the visual learner often find visual representation more clear and more compelling. With this in mind, the aim of this study was to present polysubstance use and overdose using visual maps of the available data. This article considers the opioids.
文摘Recent publications reveal the disturbing information that a minor edit to an algorithm being used for designing legitimate drug candidates redirected the program in a way that resulted in the surprising design of novel chemical warfare agent candidates. Although this outcome was not the result of nefarious intent, and appropriate chemical defense authorities were notified, the potential implications of some misapplication of a drug-design algorithm for nefarious purposes are clear. This Commentary summarizes how otherwise benign Artificial Intelligence (AI) algorithms used for drug discovery can be easily reversed to design novel chemical warfare agents for which no effective antidote will be available, or perhaps even envisioned.
文摘Abuse of drug substances and resultant overdose deaths are no longer very straightforward—viz., attributable to a single chemical entity of known purity. The reality is that most overdose deaths involve polysubstance use (i.e., the use of combinations of substances). Further, the combinations are often of unknown purity, and even of unknown composition. Overdose deaths are at all-time highs. The depressing statistics are monitored and reported by several international and governmental organizations such as the WHO (World Health Organization), CDC (Centers for Disease Control and Prevention), several Institutes of the NIH (National Institutes of Health), Regulators, and Enforcement Agencies (e.g., DEA). The information is disseminated for free for review and use. But it is our observation that although numeric presentation is helpful and adequate for professionals, the non-expert and the visual learner often find a visual representation clearer and compelling. With this in mind, we present the “gestalt” of polysubstance use and overdose using available maps of the data. The previous article in the series considered the opioids. This one considers amphetamines and cocaine, and places the rise in opioid-associated overdose deaths in the context of other abused drugs.
文摘On September 23, 2020, in order “To address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines”. With this announcement, the FDA proclaimed that much more needs to be known about the initiation, continuation, and discontinuation of these widely-used drugs. Unfortunately, relevant information is lacking, since for many years, there has been a notable sparsity in the funding and conduct of basic and clinical research on these drugs. In order to begin to fill the void, it is valuable to (re)examine animal models. We here describe a model of conditioned place-preference (CPP) for rats and for the first time, to our knowledge, show that the representative benzodiazepine alprazolam induces positive place-preference in male rats.
文摘The rise in “vaping”-associated deaths in the United States raises serious concerns. A justification for some level of risk is that e-cigarettes might pro</span><span style="font-family:Verdana;">vide a </span></span><span style="font-family:Verdana;">“</span><span style="font-family:Verdana;">reverse-gateway” from smoking traditional cigarettes to a less-harmful</span><span style="font-family:Verdana;"> alternative. But are users actually smokers? We developed an electronic on-line survey to gather data regarding e-cigarette usage in a target study population of pharmacy students. The survey was created using Google Forms to collect the responses anonymously. We surveyed medical-savvy healthcare students about their e-cigarette use, and whether or not their healthcare providers were aware of their e-cigarette use. Although nearly one-fourth of a convenience sampling of 134 pharmacy-student respondents (23.9%) reported using e-cigarettes, only 2.0% reported prior regular cigarette use, 28% used cartridges containing nicotine and only 11.2% had tried and wanted to quit. The majority (64.1%) reported that their healthcare providers did not ask about such use, and respondents did not volunteer this information. The results of this pilot survey reveal a significant e-cigarette use among health-aware pharmacy students, and they do not support the notion that the respondents do so to quit smoking. The observation that most of the students’ healthcare providers did not inquire about their e-cigarette use, coupled with the finding that users did not volunteer their vaping behavior</span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> suggests that the information should be included when getting a medical history. Further research is needed to determine what behavioral factors may play a role in this type of decision-making among student healthcare professionals.
文摘Polysubstance Abuse (PSA) greatly complicates an attempt to implicate a single drug as sole cause of an overdose death. Since PSA now occurs in the majority of cases of drug overdoses, many or most overdose deaths are polysubstance overdose deaths. And since many of the substances involved in a polysubstance Overdose Death (POD) are Central Nervous System (CNS) depressants, many of which can cause overdose death themselves, or synergistically with opioids, it is somewhat puzzling that prescription opioids have been singled out as the cause of these deaths—without reference to PSA. This is particularly puzzling in light of the fact that the issues of PSA and POD have been recognized and discussed in the literature since at least the 1960’s and before. We therefore here consider the question: are we facing an “opioid” crisis or, instead, a “polysubstance crisis”? And we wonder if the issue has been over-simplified, to the detriment of the individuals affected, and to society more broadly. There is a need for an “agnostic” respiratory stimulant that can reverse polysubstance-induced respiratory depression.
文摘<span lang="EN-US" style="white-space:normal;font-family:Verdana;">The benzodiazepines were introduced into medical practice during the 1960s. At the time, they represented a safer alternative to extant therapies used for anxiety, such as the barbiturates. However, on September 23, 2020, the United States FDA indicated that more is needed to be known about the initiation, continuation, and discontinuation of </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">the </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">us</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">e of</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;"> these widely-used drugs with publication of the announcement </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">“</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">to address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines.</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">”</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;"> Because for many years</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">, </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">there has been a sparsity </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">of </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">research on these drugs, relevant information is unfortunately lacking at this critical time. It is therefore valuable to (re)establish animal models and begin to collect relevant data. We here use a model of conditioned place</span><span lang="EN-US" style="white-space:normal;" "=""> </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">preference (CPP) </span><span lang="EN-U
文摘<span style="font-family:Verdana;">The </span><span style="font-family:Verdana;">“</span><span style="font-family:Verdana;">opioid crisis</span><span style="font-family:Verdana;">”</span><span style="font-family:""><span style="font-family:Verdana;"> has had a tremendous impact not only on its victims, but also on the practice of medicine, pain patients, and society in general. Unfortunately, efforts to “stem the tide” have not been successful at reducing overdose deaths. Counterbalancing the many ardent efforts to eliminate overdose deaths (such as the current widespread availability and use of opioid-receptor antagonists such as naloxone) is influx of the illicit fentanoids (</span><i><span style="font-family:Verdana;">i.e</span></i><span style="font-family:Verdana;">., fentanyl and analogs). In addition to their high-potency, the fentanoids differ in surprising ways from more “traditional” opioids such as morphine and heroin. This uniqueness contributes to a reduced effectiveness of opioid receptor antagonists in the treatment of opioid overdose. Further greatly complicating overdose treatment is polysubstance abuse (e.g., an opioid plus a benzodiaze</span><span style="font-family:Verdana;">pine). The non-opioid in the combination is not responsive to an opio</span><span style="font-family:Verdana;">id-recep</span></span><span style="font-family:Verdana;">- </span><span style="font-family:""><span style="font-family:Verdana;">tor antagonist, which imparts additional challenges. Thus, the new reality in</span><span style="font-family:Verdana;">troduces complications that negatively impact efforts to reverse </span></span><span style="font-family:Verdana;">“</span><span style="font-family:Verdana;">opioid</span><span style="font-family:Verdana;">”</span><span style="font-family:""><span style="font-family:Verdana;"> overdose. New approaches to improve outcomes in individuals who experience </span><span style="font-family:Verdana;">respiratory depression due to fentanoid-induced or polysubstance-i
