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Alkyl nitrites (“poppers”) are a diverse class of volatile chemical compounds with a varied legal and medical history. Though once commonly prescribed to treat angina, popper use is now almost exclusively recreational. Currently, poppers are widely available and sold legally under labels like “solvent cleaner”, despite marketing suggesting they are meant to be consumed. As a result, there is little incentive for producers to implement robust quality controls to protect users. In this study, nine common popper brands were analyzed using hydrogen-1 and carbon-13 nuclear magnetic resonance spectroscopy to assess the presence of impurities. Physical labels on all nine samples indicated the contents were “pure” isobutyl nitrite, despite contradictory online marketing in several cases. Spectral results showed isobutyl nitrite was present in all popper samples. However, there was evidence that various unlabeled compounds were also present in all samples. The identity and concentration of these contaminants were not clear, but the seemingly ubiquitous presence of impurities and lack of consistency in the tested samples are concerning and may represent a threat to users’ health. We hope the results of this study draw attention to the potential dangers of recreational popper use and the need to reassess how these compounds are regulated.

Alkyl nitrites ("poppers") are a diverse class of volatile chemical compounds with a varied legal and medical history. Though once commonly prescribed to treat angina, popper use is now almost exclusively recreational. Currently, poppers are widely available and sold legally under labels like "solvent cleaner", despite marketing suggesting they are meant to be consumed. As a result, there is little incentive for producers to implement robust quality controls to protect users. In this study, nine common popper brands were analyzed using hydrogen-1 and carbon-13 nuclear magnetic resonance spectroscopy to assess the presence of impurities. Physical labels on all nine samples indicated the contents were "pure" isobutyl nitrite, despite contradictory online marketing in several cases. Spectral results showed isobutyl nitrite was present in all popper samples. However, there was evidence that various unlabeled compounds were also present in all samples. The identity and concentration of these contaminants were not clear, but the seemingly ubiquitous presence of impurities and lack of consistency in the tested samples are concerning and may represent a threat to users' health. We hope the results of this study draw attention to the potential dangers of recreational popper use and the need to reassess how these compounds are regulated. [ABSTRACT FROM AUTHOR]

Methemoglobinemia is a potentially life-threatening condition caused by the formation of methemoglobin, a form of hemoglobin that cannot bind oxygen. While there are some rare congenital causes of methemoglobinemia, most cases are acquired from the effects of specific drugs or environmental exposures. In this retrospective study, we analyzed a large data set of whole blood samples analyzed for methemoglobin at an academic medical center in Midwestern United States that provides both pediatric and adult services. For a 14 year timeframe (May 2009- June 2023), we performed detailed chart analysis of all patients with a methemoglobin concentration of 3.1 % or higher. For an earlier 13 year timeframe (January 1996-April 2009), we performed chart review for all patients with a methemoglobin concentration of 10.0 % or higher. For the 2009–2023 data, dapsone was the most frequent cause of methemoglobinemia (methemoglobin 3.1 % or higher) in both pediatric (73.3 %, 115 clinical encounters, 105 unique patients) and adult (65.3 %, 195 clinical encounters, 190 unique patients) populations. Inhaled nitric oxide as medical therapy was the next most frequent cause in both pediatric (18.1 %) and adult (13.2 %) populations. Causes associated with two or more unique episodes with methemoglobin concentrations of 10.0 % and higher included the following: dapsone (n = 40 episodes), benzocaine (n = 10), recreational use of amyl or isobutyl nitrite (n = 3), suicide attempt with sodium nitrite (n = 3 with 1 fatality; all 3 cases within last 3 years), food contaminated with nitrates (n = 2), and sepsis (n = 2). A total of 18 patients received treatment with methylene blue including 5 cases associated with benzocaine and all of the cases associated with amyl nitrite, isobutyl nitrite, sodium nitrite, and contaminated food. Only 3 patients with dapsone-associated methemoglobinemia received methylene blue, reflecting primary management by dose reduction or discontinuation of drug. Overall, our data reinforce previous studies showing dapsone, inhaled nitric oxide, and nitrites as common agents causing methemoglobinemia in a patient population seen at a medical center. Our data also are consistent with recent epidemiology trends showing increase in suicide attempts using sodium nitrite.

Purpose: To report a case of central retinal vein occlusion in a young patient after the use of amyl nitrate "poppers." Methods: Description of the patient's clinical history, ophthalmic examination, retinal imaging, and treatment. Results: A 38-year-old man presented with a central retinal vein occlusion in his right eye after inhaling amyl nitrite "poppers." There appeared to be a definitive temporal association between poppers use and both the onset of the vein occlusion and the patient's visual scotomata, which recurred immediately after drug use multiple times. Optical coherence tomography displayed cystic macular edema, which was treated with intravitreal bevacizumab. The patient's hypercoagulable laboratory workup was negative. Conclusion: This is the first report of a central retinal vein occlusion associated with poppers inhalation. A high index of suspicion for poppers use should be maintained in young patients who present with retinal vein occlusion, particularly in homosexual patients with a normal laboratory workup that fails to reveal a hypercoagulable etiology. [ABSTRACT FROM AUTHOR]

The article discusses the earliest treatment of angina pectoris, a common condition, particularly among the elderly gentlemen of unseemly lifestyle, in modern medicine. Topics include the first widely used treatment for the alleviation of the pain of angina, effect of nitrate in the diet, and the use of saltpetre in the treatment of angina.

INTRODUCTION: Methemoglobinemia represents an uncommon but potentially serious cause of presentation to the emergency department, resulting in hypoxemia and even death. The symptoms and clinical findings in this condition can be nonspecific and therefore methemoglobinemia can be easily missed if the clinician is not familiar with it. This report presents a case caused by recreational drug use which has rarely been documented previously. CASE REPORT: A 23-year-old male with a history of asthma presents to the emergency department for an episode of syncope after inhalation of amyl nitrite "poppers". He had normal vitals other than tachycardia but was found to have nailbed and perioral cyanosis, a classic but uncommon presentation that is demonstrated in the included clinical image. He was found to have methemoglobinemia caused by his use of amyl nitrite and received supportive care but did not require methylene blue. CONCLUSION: Emergency physicians should familiarize themselves with the classic physical exam findings in methemoglobinemia in order to identify and treat this condition promptly. While this patient had a good outcome with only supportive care and observation, his presentation and the etiology of his condition offer an important teaching point. The possibility of methemoglobinemia after recreational "popper" use should be considered when working up a patient who presents with cyanosis and hypoxemia. [ABSTRACT FROM AUTHOR]

Poppers (nitrite inhalants) are legal, commonly used by men who have sex with men, and associated with HIV acquisition, yet research is lacking on popper use and associated adverse outcomes. People living with HIV (PLWH) in the U.S.-Mexico border region lead binational lives, including accessing care and having sex and drug use partners on both sides of the border, with broad personal and public health implications. Understanding popper use provides crucial information to guide policy and develop targeted interventions for binational PLWH. We examine prevalence and correlates of popper use among HIV-positive Latinos in the border region, an underserved population at risk for poor health outcomes. This cross-sectional study recruited a convenience sample from agencies in San Diego and Tijuana to complete quantitative surveys. Participants (N = 121) were primarily male (82.6%) and gay/bisexual (62%). Lifetime substance use (excluding cannabis) was reported by 72% of participants, and 25.6% reported lifetime popper use. Individuals recruited in the U.S. were significantly more likely to report use of poppers than were participants recruited in Mexico. Our regression model found that identifying as gay/bisexual and having bought, sold, or traded sex for money, drugs, or other goods were independently associated with popper use. Findings shed light on the profile of individuals who use poppers and lay the foundation for further research to understand the context of popper use as it relates to high-risk behavior among PLWH in this region of high transborder mobility. Binational collaborative approaches are needed to improve regional HIV care outcomes and reduce transmission risk. [ABSTRACT FROM AUTHOR]

Objectives: Chemsex refers to the use of sex‐enhancing drugs among men who have sex with men (MSM) in combination with specific sexual and social behaviours. Longitudinal data on this development and the associated health risks are scarce. Methods: Data on all recreational drugs reported in the Swiss HIV Cohort Study (SHCS) from 2007 to 2017 were collected. Drug use was analysed longitudinally for all drug classes. In addition, potential associations between patient characteristics and the consumption of methamphetamine, γ‐hydroxybutric acid/γ‐butyrolactone (GHB/GBL), 3,4‐methylenedioxymethamphetamine (MDMA/XTC), cocaine and amphetamine were analysed. Results: We analysed 166 167 follow‐up entries for 12 527 SHCS participants, including 7101 free text field entries containing information about recreational drugs other than cannabis, cocaine and heroin. Overall, we observed a stable percentage (9.0%) of recreational drug use (excluding cannabis, amyl nitrite and prescription drugs). For MSM, however, there was an increase in overall drug use from 8.8% in 2007 to 13.8% in 2017, with particularly large increases for methamphetamine (from 0.2 to 2.4%; P < 0.001) and GHB/GBL (from 1.0 to 3.4%; P < 0.001). The use of each of the potentially sex‐enhancing drugs methamphetamine, GHB/GBL, cocaine, XTC/MDMA and amphetamine was significantly associated with condomless sex with nonsteady partners, and higher prevalences of depression, syphilis and hepatitis C. Conclusions: The significant increase in the use of chemsex drugs among MSM in the SHCS and the strong association with coinfections and depression highlights the need for harm reduction programmes tailored to MSM. According to our results, improving knowledge about recreational drugs is important for all health care professionals working with people living with HIV. [ABSTRACT FROM AUTHOR]

We report a case of cutaneous sensitization to isobutyl nitrite-containing poppers with subsequent elicitation of dermatitis through airborne exposure by proxy. Keywords: airborne dermatitis; alkyl nitrites; allergic contact dermatitis; amyl nitrite; case report; drugs; irritant contact dermatitis; isobutyl nitrite; isopropyl nitrite; poppers EN airborne dermatitis alkyl nitrites allergic contact dermatitis amyl nitrite case report drugs irritant contact dermatitis isobutyl nitrite isopropyl nitrite poppers 212 214 3 02/25/21 20210301 NES 210301 "Poppers" (alkyl nitrites) are drugs used for recreational (sexual) purposes. Airborne dermatitis, alkyl nitrites, allergic contact dermatitis, amyl nitrite, case report, drugs, irritant contact dermatitis, isobutyl nitrite, poppers, isopropyl nitrite. [Extracted from the article]

The use of stimulant drugs alone or in combination with amyl nitrites (stimulant/nitrites) has been associated with higher rates of risky sexual behavior and predictive of HIV infection among men who have sex with men. However, the temporal pattern of stimulant/nitrite use pre- and post-seroconversion has not been well established. This study assessed changes in stimulant/nitrite use and risky sexual behavior among seroconverting MSM over time. Data were collected in the Baltimore-Washington, DC; Pittsburgh; Chicago; and Los Angeles sites of the Multicenter AIDS Cohort Study (MACS), a longitudinal study of the natural history of HIV infection among MSM. We used propensity scores to select 1044 MSM from 7087 MACS participants composed of 348 seroconverting, 348 seronegative, and 348 seroprevalent participants matched on demographics, recruitment cohort, and study visits. We centered up to four-years of semi-annual data around the seroconversion visit of the seroconverting case within each matched group of participants. Mixed effects regressions estimated the effects of serostatus, recruitment cohort, and time on self-reported stimulant/nitrite use, numbers of male intercourse partners, and numbers of unprotected receptive anal intercourse (URAI) partners. Covariates included demographics, binge drinking, and marijuana use. Seroconverters had the highest odds of stimulant/inhaled nitrite use (AOR 10.3, CI 4.8-22.0), incident rates of intercourse (IRR 1.6, CI 1.3-2.1), and URAI partners (IRR 5.1, CI 3.5-7.3). All participants decreased drug use and sexual risk behavior over time. However, the decreases were largest for seroconverters who nevertheless maintained the highest rates of stimulant/nitrite use and sexual risk. Cohort-related effects were associated with sharp reductions in stimulant/nitrite use and URAI in the early 1990s that rebounded considerably within the first decade of the 2000s. Although all participants decreased risky sexual behavior and stimulant and/or nitrite use over time, seroconverters had the largest decreases. There was no evidence for abrupt or substantial increases in drug use or risky sex post-seroconversion. However, there was substantial variation at the individual level, with the factors underlying this variation not well understood and worth further study. Moreover, stimulant/nitrite use and risky sexual behavior appear to have been strongly influenced by contextual historical and socio-cultural effects. The manner in which contextual factors influence individual behavior is also not well understood and also warrants further study. [ABSTRACT FROM AUTHOR]

Background: Drug use among gay and bisexual men (GBM) is higher than most populations. The use of crystal methamphetamine, erectile dysfunction medication (EDM), and amyl nitrite have been associated with sexual risk behaviour and HIV infection among gay and bisexual men (GBM).Objective: This paper describes an online prospective observational study of licit and illicit drug use among GBM and explores baseline prevalence of drug use in this sample. Capturing these data poses challenges as participants are required to disclose potentially illegal behaviours in a geographically dispersed country. To address this issue, an entirely online and study specific methodology was chosen.Methods: Men living in Australia, aged 16.5 years of age or older, who identified as homosexual or bisexual or had sex with at least one man in the preceding 12 months were eligible to enrol.Results: Between September 2014 and July 2015, a total of 2250 participants completed the baseline questionnaire, of whom, 1710 (76.0%) consented to six-monthly follow-up. The majority (65.7%) were recruited through Facebook targeted advertising. At baseline, over half (50.5%) the men reported the use of any illicit drug in the previous six months, and 28.0% had used party drugs. In the six months prior to enrolment, 12.0% had used crystal methamphetamine, 21.8% had used EDM, and 32.1% had used amyl nitrite. Among the 1710 men enrolled into the cohort, 790 men had used none of these drugs.Conclusion: Ease of entry and minimal research burden on participants helped ensure successful recruitment into this online cohort study. Study outcomes will include the initiation and cessation of drug use, associated risk behaviours, and health consequences, over time. Results will provide insights into the role gay community plays in patterns of drug use among GBM. [ABSTRACT FROM AUTHOR]

• Japan enacted aggressive bans on new psychoactive substances, resulting in supply shortages. • The prohibited drugs included 5-MeO-DIPT and alkyl nitrites that were widely used among men who have sex with men (MSM). • Following the supply shortages, 18% of Japanese men living with HIV (97% MSM) substituted these drugs with methamphetamine. • Those who used substitutes were marked by low socioeconomic status and high sexual risk behavior. • After the supply shortages, methamphetamine use significantly increased by 93%. • Harm reduction interventions are needed to address the increased methamphetamine use. Since 2005, Japan has incrementally banned a range of new psychoactive substances (NPS), including 5-MeO-DIPT (5MO; foxy) and alkyl nitrites (AN; rush, poppers) that have commonly been used among men who have sex with men (MSM). After the largest ban in 2014, these drugs were reported to have disappeared from the domestic market. Given that 5MO/AN/NPS use has been prevalent among men living with HIV in Japan, a population largely comprised of MSM, we sought to characterize changes in their drug use behavior following the supply shortages. Using data from two waves of a nationwide survey of people living with HIV in Japan in 2013 and 2019–20 (n = 1042), we employed multivariable modified Poisson regression to identify correlates of self-reported reactions to the 5MO/AN/NPS shortages and changes in drug use behavior in 2019–20 vs. 2013. Among 391 men (96.7% MSM) surveyed in 2019–20, following the supply shortages, 234 (59.8%) stopped using 5MO/AN/NPS, 52 (13.3%) retained access to the supply, and 117 (29.9%) used substitute drugs: most commonly, methamphetamine (60.7%). Individuals who used substitutes were more likely to report unprotected sex (adjusted relative risk [ARR]=1.67; 95% confidence interval [CI]: 1.13–2.47) as well as low (ARR=2.35; 95% CI: 1.46–3.79) and lower middle (vs. upper middle to high) socioeconomic status (ARR=1.55; 95% CI: 1.00–2.41). The prevalence of past-year methamphetamine use (ARR=1.93; 95% CI: 1.11–3.35) and self-reported uncontrollable drug use (ARR=1.62; 95% CI: 1.07–2.53) were significantly higher in 2019–20 compared to 2013. Following the supply shortages, approximately one-fifth of our participants used methamphetamine as a substitute for 5MO/AN/NPS. Methamphetamine use and perceived uncontrollable drug use also appeared to have increased at the population level after the supply shortages. These findings suggest a potentially harmful substance displacement effect of the aggressive ban. Harm reduction interventions are needed in this population. [ABSTRACT FROM AUTHOR]

[Display omitted] We report herein, a metal-free isoamyl nitrite mediated efficient synthesis of 1,2,4-oxadiazoles by one-pot cycloaddition reaction of aldoximes with nitriles. The structure of the 1,2,4-oxadiazole derivatives was confirmed by studies of spectral analysis. Current methodology provides a novel pathway to access 1,2,4-oxadiazole derivatives. [ABSTRACT FROM AUTHOR]

We report a case of visual alterations after the first use of poppers in a young male patient. A 32-year-old male patient with no past medical history presented with decreased central visual acuity and phosphenes in both eyes. He admitted the use of poppers a day before the symptoms began. Optical coherence tomography showed bilateral disruption of the ellipsoid zone. Poppers' use is increasing in young people and so is the possibility of visual and structural alterations that can persist over time as a result of macular toxicity.

We report a clinical scenario involving a 51-year-old male patient with a history of prediabetes and gastritis who exhibited altered mental status following the consumption of poppers, a supplement containing nitrites, which is used for erectile stimulation. Shortly after the ingestion, the patient experienced convulsions, foaming at the mouth, and subsequently developed altered mental status and severe respiratory distress. The diagnosis of methemoglobinemia was confirmed based on elevated methemoglobin levels on venous blood gas analysis. Notably, the patient's blood had a chocolate-colored appearance upon admission, which is a characteristic finding in methemoglobinemia. Prompt recognition and management, including the administration of methylene blue, led to the resolution of symptoms. This case highlights the potential complications associated with the consumption of poppers and emphasizes the importance of early intervention., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Idries et al.)

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An efficient, one-pot approach has been described for the synthesis of 3,5-disubstituted isoxazoles from substituted aldoximes (mixture of E and Z) and alkynes, using alkyl nitrites under conventional heating conditions. The key nitrile oxide intermediates that are required for the synthesis of isoxazoles are formed by treatment of substituted aldoxime with either tert-butyl nitrite or isoamyl nitrite. The generated nitrile oxides underwent in situ [3+2] dipolar cycloaddition to the substituted alkynes to give 3,5-disubstituted isoxazoles regioselectively in high to excellent yields. The developed synthetic methodology was applied for the synthesis of a previously reported potent hDGAT1 inhibitor. [ABSTRACT FROM AUTHOR]

The abuse of alkyl nitrites is common among adolescents and young adults worldwide. However, the information regarding the effects of alkyl nitrites on the central nervous system and the associated psychological abuse potential is scarce. The abuse potential of 3 representative alkyl nitrites – isobutyl nitrite, isoamyl nitrite, and butyl nitrite – was evaluated in mice using conditioned place preference tests with an unbiased method. The dopamine levels released by synaptosomes extracted from the striatal region were measured using high performance liquid chromatography. Mice treated with the test substances (50 mg/kg, i.p.) exhibited a significantly increased drug-paired place preference. Moreover, greater levels of dopamine were released by striatal region synaptosomes in response to isobutyl nitrite treatment in mice. Thus, our findings suggest that alkyl nitrites could lead to psychological dependence and dopaminergic effects. Furthermore, these results provide scientific evidence to support the regulation of alkyl nitrites as psychoactive substances in the future. [ABSTRACT FROM AUTHOR]

We report a case of visual alterations after the first use of poppers in a young male patient. A 32-year-old male patient with no past medical history presented with decreased central visual acuity and phosphenes in both eyes. He admitted the use of poppers a day before the symptoms began. Optical coherence tomography showed bilateral disruption of the ellipsoid zone. Poppers' use is increasing in young people and so is the possibility of visual and structural alterations that can persist over time as a result of macular toxicity. [ABSTRACT FROM AUTHOR]

The article discusses the acute management of central retinal artery occlusion (CRAO). Topics include the use of inhaled amyl nitrite to remove a presumed embolus by vasodilation, various treatments for CRAO including ocular massage, anterior chamber paracentesis, and intravenous tirofiban, and the role of thrombolysis in the treatment of CRAO.

A series of aromatic and heteroaromatic primary amides were converted directly to carboxylic acids by heating with amyl nitrite in acetic acid. Most conversions proceeded to give reasonable to excellent yields on a range of substrates containing various functional groups. This reagent system is thus applicable for the direct hydrolysis of a range of different primary carboxamides. The reaction with a phenolic aromatic substrate afforded two alternative nitration products as major outcomes, evidencing alternative reaction pathways resulting from the free phenolic OH. [ABSTRACT FROM AUTHOR]