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Poppers: Legal highs with questionable contents? A case series of poppers maculopathy
Abstract
Background:
Poppers are volatile alkyl nitrite compounds that are inhaled to enhance sexual experience and for their psychoactive effects. A less well-known side effect is foveal maculopathy, which has emerged following changes in their chemical composition. It is unclear if certain individuals are more susceptible to retinal damage or if there is a relationship between pattern of inhalation and brands used.
Methods:
A case series of 12 patients presenting to Sussex Eye Hospital, Brighton, with poppers-related visual impairment. Follow-up data were available in 10 cases, at a median time interval of 5 months (range 0-31 months). Eight samples of poppers were analysed using proton nuclear magnetic resonance spectroscopy.
Results:
Patients presented with disrupted central vision occurring soon after inhalation. All demonstrated disruption of the inner segment/outer segment junction on spectral domain optical coherence tomography. Six of the brands implicated in causing visual symptoms contained isopropyl nitrite, while Jungle Juice Plus varieties, used without side effects in one case, contained amyl nitrite, 2-methyl butyl nitrite and isobutyl alcohol. In general, symptomatic resolution, alongside partial, if not full, recovery of foveal architecture was observed following abstention.
Discussion:
On the basis of the products tested here, it seems that isopropyl nitrite is toxic to the fovea and can cause significant visual disturbance. The production of poppers is unregulated and their popularity is concerning, particularly given their exemption from the Psychoactive Substances Act 2016, which might suggest that they are harmless chemicals.
... Though the original popper, amyl nitrite, was deemed safe enough to be deregulated and was available over-the-counter as recently as 1969, increasing recreational usage prompted tighter legal controls to limit its availability [4]. As a result, recreational popper use has shifted toward other chemical species in the alkyl nitrite family [4,8,9]. In recent decades, there have been several bans on specific alkyl nitrite compounds in the US and Psychoactives 2024, 3 401 elsewhere; however, popper manufacturers have routinely circumvented legal regulation by altering the chemical structure of the alkyl nitrite species they produce [5,[10][11][12]. ...
... However, with poppers, this issue may be concealed by the pseudo-legal status of this drug class. While regulation has limited the availability of some older alkyl nitrite species, novel compounds, like isobutyl nitrite, remain legal and are widely sold as solvents, cleaners, or room odorizers [7,8,28,29]. This labeling scheme may help producers avoid oversight from the Food and Drug Administration, and despite public FDA consumer updates regarding risks and threats, their packaging and status in popular culture make it clear they are meant to be inhaled [8,29]. ...
... While regulation has limited the availability of some older alkyl nitrite species, novel compounds, like isobutyl nitrite, remain legal and are widely sold as solvents, cleaners, or room odorizers [7,8,28,29]. This labeling scheme may help producers avoid oversight from the Food and Drug Administration, and despite public FDA consumer updates regarding risks and threats, their packaging and status in popular culture make it clear they are meant to be inhaled [8,29]. Further, the legacy of the amyl nitrite as a high-purity prescription drug with a relatively favorable safety profile may now be inappropriately assumed for all poppers [19,20]. ...
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.
... Popper maculopathy is a bilateral maculopathy caused by inhalation of poppers, which are volatile alkyl nitrite compounds used recreationally for their psychoactive effects [10]. OCT findings in the acute phase include disruption of the subfoveal EZ/IZ layers with varying levels of subfoveal elevation on OCT [10]. ...
... Popper maculopathy is a bilateral maculopathy caused by inhalation of poppers, which are volatile alkyl nitrite compounds used recreationally for their psychoactive effects [10]. OCT findings in the acute phase include disruption of the subfoveal EZ/IZ layers with varying levels of subfoveal elevation on OCT [10]. Symptoms and signs recover completely within a few weeks in the majority of cases; however, there may be persistence of symptoms in a small number of cases [10]. ...
... OCT findings in the acute phase include disruption of the subfoveal EZ/IZ layers with varying levels of subfoveal elevation on OCT [10]. Symptoms and signs recover completely within a few weeks in the majority of cases; however, there may be persistence of symptoms in a small number of cases [10]. There was no history of popper abuse in our case, and there was no visual recovery. ...
A 44-year-old male presented with unilateral sudden onset reduced visual acuity. The optical coherence tomography (OCT) scan demonstrated submacular fluid with thickening and hyper-reflectivity of the outer retinal layers, together with subfoveal retinal pigment epithelial hyper-reflectivity corresponding to a small area of foveal interdigitation zone/ellipsoid zone (IZ/EZ) loss in the detached retina. An OCT 4 months later showed resolution of the submacular fluid, but the IZ/EZ loss persisted with thinning of the outer nuclear layer, resulting in a poor visual outcome. The clinical findings most likely represent a case of unilateral acute idiopathic maculopathy; however, the OCT features and poor visual outcome are not typical. Differential diagnoses include acute solar maculopathy, central serous chorioretinopathy, poppers maculopathy, whiplash maculopathy, and acute retinal pigment epitheliitis.
... Nonetheless, this discordance may point to a cumulative effect. Although some cases have been reported after one isolated exposure, 9,28 in most cases patients have consumed poppers for several years. Indeed, Davies et al. found a dose-related effect. ...
... Several different brands are most commonly involved. A recent article by Rewbury et al. offers a list of eight products, 28 all with flamboyant names, such as "Jungle juice", "Hard on", "Berlin XXX" or "Liquid gold". Most of them contain a fifty-fifty mix of Isopropyl nitrite and isopropyl alcohol, although other alcohols and nitrites are also present. ...
... In the Rewbury et al. series, in three out of twelve cases of those using poppers for 20 years visual loss took place when the subject switched to a new brand. 28 Sega et al. published a case in which, despite continuous use, visual symptoms disappeared after the subject was able to identify which brands induced the visual symptoms. 31 A synergetic effect with other drugs has also been suggested. ...
Aim
To review the available literature on poppers maculopathy (PM).
Material and methods
Sixty-four patients (60 with bilateral and 4 with unilateral involvement), for a total of 124 eyes were reported in PubMed, Google Scholar and Embase. Patterns were analyzed according to country, age, gender, sexual orientation, HIV status, consumption habits, visual acuity at presentation (VAP), final visual acuity (VAF) and optical coherence tomography (OCT).
Results
Most cases (110 eyes) of PM were reported in European countries and affected middle-aged men (only 8 eyes from female users). The median age was 38.7 years (SD = 10.5 years). Final visual acuity (Median = 0.8; Interquartile range: 0.67–1) was higher than visual acuity at presentation (Median = 0.67; Interquartile range: 0.4–0.8). Many articles lack data on sexual orientation and HIV status as this is considered very personal information. One third of the eyes (40 eyes) developed PM after a single exposure. No significant differences were found between eyes that developed PM after a single exposure and those which developed the condition after several exposures. The most commonly reported pattern was an interruption of the ellipsoid line (68 eyes).
Conclusion
PM is more prevalent in Europe or European ophthalmologists are more likely to diagnose PM. PM usually affects middle-aged men given that this condition generally appears with chronic exposure to poppers. VAF was higher than VAP, suggesting that this toxicity is in part reversible. Information about HIV status was not provided in most recent articles, thus it is not possible to make inferences about the possible implication of HIV drugs as cofactors for the development of this retinal toxicity.
... A "poppereket" évtizedek óta használják, de csak az elmúlt években figyeltek fel látáskárosító, maculopathiát okozó hatásukra [37][38][39][40]. Hátterében a diagnosztika jelentős fejlődése (például az optikaikoherencia-tomográfia [OCT] megjelenése) mellett a szerek összetételében bekövetkező változásokat feltételezik. ...
... Hátterében a diagnosztika jelentős fejlődése (például az optikaikoherencia-tomográfia [OCT] megjelenése) mellett a szerek összetételében bekövetkező változásokat feltételezik. 2006-ban az izobutil-nitrit karcinogénné nyilvánítását követően többen látásromlást jeleztek azok közül, akik az izobutil-nitritszármazékokat az izopropil-nitrit-származékokra cserélték [37,38]. A használók hasonló panaszokat (a centrális látás károsodása, homályos látás, szikralátás, fényérzékenység) említettek. ...
... A tünetek gyorsan (néhány óra-nap múlva) jelentkeztek, rendszeres, de akár egyszeri használatot követően is előfordultak. A vizsgálatok során a látásélesség enyhe vagy mérsékelt csökkenését, OCT-val a subfoveolaris régióban a retina külső/belső szegment találkozásának szakadását, foveolaris hipo-, hiperreflektivitást, oftalmoszkópiával finom sárga lerakódásokat észleltek a foveolában [38][39][40]. Az elváltozások általában mindkét szemet érintették, de féloldaliakat is leírtak. Hui és kollégái a rendszeres használóknál súlyosabb léziókat tapasztaltak [39]. ...
Összefoglaló. A methaemoglobinaemia az oxigén szállítására képtelen methemoglobin szintjének kóros emelkedését jelenti a vérben, ami jelentős szöveti oxigénhiányt okozhat, súlyos, akár életveszélyes tünetekhez vezethet. Methaemoglobinaemiát számos, oxidáló hatású exogén anyag idézhet elő, ezek közé tartoznak a partidrogként használt alkil-nitritek, az ún. "popperek" is. A "poppereket" korábban "alacsony rizikójú" drogként tartották számon, azonban számos esetet közöltek, amikor súlyos, időnként fatális kimenetelű methaemoglobinaemiát okoztak. A folyadékok gőzének belélegzése euforizáló, szexuálisvágy-fokozó és simaizom-lazító hatású, ezért a "popperek" igen népszerűek a homo- és biszexuális férfiak körében, de fiatal felnőttek és tinédzserek is használják. A folyadékok szájon át való fogyasztása különösen veszélyes. A szerzők két esetet ismertetnek, amelyekben a "popperek" használatát követően methaemoglobinaemia alakult ki. Mindkét betegnél, a jó általános állapot mellett, centrális és perifériás cyanosis tüneteit észlelték. Az alkalmazás módja (inhaláció/lenyelés), a methaemoglobinaemia súlyossága (16,4% és 57%) és a terápia eltérő volt a két betegnél. Az első beteg oxigén adása és tüneti kezelés mellett gyógyult, a másodiknál antidotum (metilénkék) adására is szükség volt. Mindketten panaszmentesen távoztak a kórházból. A szerzők célja az volt, hogy felhívják a figyelmet az illékony alkil-nitrit-származékok által okozott methaemoglobinaemiára, annak felismerésére, kezelésére, és bemutassák azok kevésbé ismert szövődményeit is. Orv Hetil. 2021; 162(8): 306-313. Summary. Methemoglobinemia means the abnormally elevated level of methemoglobin in the blood, which is incapable of oxygen transport, accordingly it can cause significant tissue hypoxia, leading to severe or even life-threatening clinical symptoms. Several exogen oxidative agents can induce methemoglobinemia, including alkyl-nitrites which are also used as party drugs, the so-called 'poppers'. The 'poppers' were previously considered 'low-risk' drugs, however, several cases have been published when they caused severe, sometimes fatal methemoglobinemia. Inhaling vapours from liquids has euphoric, smooth-muscle relaxing and aphrodisiac effects, therefore 'poppers' are extremely popular among gay and bisexual men but also used by young adults and teenagers. Oral consumption of the fluids is particularly dangerous. The authors present two cases when methemoglobinemia developed after 'poppers' usage. Both patients were in good general condition and symptoms of central and peripheral cyanosis were detected. The method of application (inhalation/ ingestion), the severity of methemoglobinemia (16,4% and 57%) and the treatment were different in the two patients. The first patient recovered with inhalation of oxygen and symptomatic treatment; the second patient required administration of antidote (methylene blue). Both patients left the hospital without complaints. The authors' aim was to attract attention to methemoglobinemia caused by volatile alkyl-nitrites, its recognition, treatment and to present their lesser-known complications. Orv Hetil. 2021; 12(8): 306-313.
... 3 The pathogenesis remains unclear; however, it is believed to be the result of the toxic effects of nitric oxide. 2,4,5 Our patient developed symptoms soon after using poppers for the first time. Diagnostics showed typical changes that entirely resolved after abstinence and reoccurred after using certain types of poppers. ...
... This is comparable to some other case reports. 4,5 To the best of our knowledge, we are the first to report a case where, surprisingly, the symptoms and function improved entirely after switching from butyl nitrite, isobutyl nitrite, or isopropyl nitrite to amyl nitrite or pentyl nitritebased poppers, alhough the patient continued to use them several times per week. This is supported by a case series of Rewbury et al. ...
... where symptoms were linked to certain popper brands, and it was suggested that chemically different poppers differ in their toxic effect. 5 We speculate that the steric properties of the alkyl group might influence the binding affinity of poppers to a currently unknown binding site within a cone photoreceptor, resulting in differing toxicity of various alkyl nitrites. ...
... The term poppers appeared in the 1960s when the capsules of amyl nitrite were cracked or "popped" to release the chemical, and since then, it is common among gay population, and nowadays it is becoming popular among young people as a recreational drug that can increase sexual desire and cause euphoria and vasodilation, and it is the fourth common drug in the frequency of usage after marijuana, cocaine, and ecstasy. [1,2] We report a case of visual alterations after the first use of this drug in a young male patient. ...
... Few studies have described a small but yet significant proportion of poppers users that complain of visual symptoms, even after first use. [1][2][3][4] Symptoms described are blurred vision on central visual field; scotoma and phosphenes that can persist for hours and even days; and subtle foveal changes such as yellow deposits on fundus evaluation. [2,3] On funduscopy, the presence of bilateral yellow dots at the fovea may indicate correlation with the findings on OCT. ...
... [1][2][3][4] Symptoms described are blurred vision on central visual field; scotoma and phosphenes that can persist for hours and even days; and subtle foveal changes such as yellow deposits on fundus evaluation. [2,3] On funduscopy, the presence of bilateral yellow dots at the fovea may indicate correlation with the findings on OCT. [5] Reports have shown a macular disruption in the EZ (hyper-or hyporeflectivity) visualized on OCT that can vary among patients and that can persist or resolve after abstinence of the drug and that are independent of the time of exposition, [2,5,6] suggesting the involvement of the outer retina instead of retinal pigment epithelium or retinal circulation. ...
... Le mécanisme physiopathologique de l'atteinte maculaire n'est pas connu. L'atteinte spécifique de la fovéa suggère un mécanisme photo-induit que pourrait aggraver la libération aiguë et massive de NO (le NO étant un modulateur physiologique du métabolisme et de la fonction des photorécepteurs) [7]. La fréquence de ces lésions n'est pas connue. ...
... Il existe vraisemblablement une susceptibilité individuelle. Par ailleurs, la description de cas survenant après un changement de marque chez des consommateurs habituels évoque des différences de toxicité entre les poppers [7]. ...
... Il n'existe pas de traitement spécifique, et la prise en charge repose avant tout sur l'arrêt de la consommation de poppers [7]. Toutefois, leur poursuite ne provoque pas [7]. ...
... To date, the exact mechanism of popper toxicity remains unknown. One thought is that alkyl nitrites cause upregulation of nitric oxide, which may increase photoreceptor photosensitivity [1,4,5].This mechanism is corroborated by the fact that both nitrite toxicity and photic damage result in a maculopathy characterized by focal ellipsoid zone disruption or loss on SD-OCT [9]. ...
... Previous reports in the literature have documented spontaneous resolution of symptoms and imaging findings over time. Patients had better visual recovery if they abstained from the drug once symptoms began, or if they were taking the drug infrequently or for the first time [4,9]. Pahlitzsch et al. [10] described one patient who demonstrated near resolution of the maculopathy following 6 months of oral lutein supplementation. ...
... 39,40 Additionally, reports of popper-induced maculopathy have been reported. 41,42 Healthier options to decrease pain or improve pleasure during RAI are needed. Understanding an individual's issues with insertion may provide an opportunity for health education and prevention. ...
Background
Receptive anal intercourse (RAI) is commonly practiced among individuals of all sexual orientations. However, negative stigmatization by society and health care professionals leads to the underreporting or this practice.
Aim
We sought to assess and describe the subjective role of the prostate as a pleasure center in participants with diverse RAI experiences. The secondary aim was to describe nonprostatic areas within the anorectal region that produce erotic sensation and/or pain.
Methods
The exploratory sequential multimethod study design included focus groups and semistructured interviews with 30 individuals with prostates who had engaged in RAI. We used graphic elicitation of natal male anatomy to enhance visualization and assess participant perspectives.
Outcomes
The main outcome of interest was the identification of anatomic locations of erogenous sensation and pain during RAI.
Results
Among the participants (median age 38, range 24–77 years), most participants (90%) identified as cisgender male. Three major themes emerged within the motivations for RAI, including (1) deriving intrinsic pleasure, (2) providing both pleasure for a partner and a way to improve intimacy/connection, and (3) an inability to be the insertive partner due to physical or mental challenges. The data suggest that the anorectal region produces a variety of erogenous sensations which participants find pleasurable. Overall, 2 major areas of erogenous sensation occur along the anterior rectal wall and within the anus. Within the context of RAI, 2 distinct categories of pain emerged, including pain with insertion and pain at other times.
Clinical Implications
Understanding where erogenous sensation originates for each individual may predict sexual functioning after various surgical interventions. Timing and location of pain may aid in further characterizing anodyspareunia.
Strengths and Limitations
Our study utilized a sequential design (from focus groups to interviews) with diverse RAI experiences, especially regarding age, geographic location, and prostate pathology. We included individuals of diverse gender identities, but too few to evaluate these groups independently from cisgender men.
Conclusion
People with prostates experience pleasure in multiple areas during RAI. Contrary to some lay literature, the prostate region is not the subjective pleasure center for all individuals. Timing and location of pain during RAI may inform areas for intervention. Providing a language for pleasure and pain during RAI may improve communication between not only sexual partners but also clinicians and patients.
... In the 1970's, "poppers," or alkyl nitrites, became a popular drug of choice for many LGBTQ+ party-goers. Though originally developed as a symptom reducer for angina in the mid-19th century (Stolberg, n.d.), after a little more than a century of use the drug was forced to find a new market once glycerine tablets became the preferred form of treatment (Rewbury et al., 2017). ...
National attention began to focus on Northern Saskatchewan after 6 young,
Indigenous women, ages 10 to 14, died by suicide in in October 2016. Data collected in
Saskatchewan in 2017 has been made public, and it states that nearly 500 suicides have
been completed by First Nations people in the province since 2005. While governmental
bodies have made repeated pledges to work with these First Nations communities to solve the suicide crisis, no provincial or federal suicide prevention strategies have been enacted, and poor data collection methods further inhibit the ability to implement effective measures. Beginning with a theoretical discussion on Durkheim’s conceptualization of suicide, I will highlight the importance of social variables that should be viewed as enabling forces for suicidal behaviour. This will lead into a discussion on colonialism as a social determinant of mental health, as oppressive practices present in Canada’s history—such as The Indian Act, the reserve system, and a legacy of residential schools—have had considerable, negative consequences on the mental health of Indigenous people. However, symbolic healing through the act of cultural reclamation has been cited as a promising solution. Using the narrative of one individual’s story of symbolic healing as an entry point for inquiry, I will tie this healing process into a larger commentary on its potential to be applied as a preventive suicide measure for First Nations youth. The paper will conclude with a discussion on the current, biologically reductionist therapeutic responses being employed by the Saskatchewan government which should be viewed as an enabling force that perpetuates suicide rates in Northern Saskatchewan communities. It is necessary for the implementation of new mental health procedures that incorporate not only holistic worldviews into psychiatric practices, but also culturally relevant and trauma-informed approaches that are based in Indigenous knowledge and self-determination.
... In most cases, this was either not asked, disclosed or documented. It is also noteworthy that not all poppers contain the 'ingredients' listed on the bottle 53 and as such it is difficult to identify the compound being sold. ...
Objective:
The aim of this systematic review and meta-analysis was to provide an overview of reported cases of poppers maculopathy and a statistical analysis of the clinical presentations, anatomical changes and treatment and follow-up of the rare disease.
Methods:
A systematic search of CINAHL, Embase and PubMed databases was conducted, including a search of the grey literature. Data were pooled to provide a summary of the clinical characteristics and outcomes of poppers maculopathy. Studies were critically appraised using the Joanna Briggs Institute or the Authority, Accuracy, Coverage, Objectivity, Date, Significance checklists.
Results:
Of the 493 articles obtained, 32 were included, consisting of 113 participants with a mean age of 40.2. Most patients were male with bilateral maculopathy and presented with either vision loss or a visual disturbance. Cessation of popper use was the most common form of management prescribed. The mean VA at baseline was 0.22 (logMAR units). For those followed-up, the mean VA significantly improved from 0.24 to 0.11 (Z = -5.800, p = <0.001). Bilateral yellow foveal spots were viewed on fundoscopy in 53 patients, and a sub-foveal disturbance of the ellipsoid layer was reported on spectral domain optical coherence tomography in 89 patients. By 6 months, SD-OCT anatomical changes mostly improved or resolved.
Conclusion:
Recreational users of poppers who develop maculopathy generally present with vision loss or a visual disturbance secondary to foveal disruption. Patients have a good visual prognosis, with cessation of poppers potentially having a role in improved outcomes. With the high prevalence of use among gay and bisexual men, awareness of related maculopathy and presenting symptoms by clinicians is important to mitigate side effects.
... If swallowed poppers can cause cyanosis followed by death due to too much methemoglobin because the hemoglobin can no longer transport the amount of oxygen required by the tissues which is a condition referred to as acquired Methemoglobinemia. Because of the wide usage of these nitrite esters especially isopropyl nitrite for recreational consumption coupled with side effects arising from their use a comparative study of Diabetes blood vs. normal blood appears warranted [7][8][9][10][11][12][13][14][15][16][17][18]. ...
The effect of isopropyl nitrite on human Type 2 Diabetes blood was undertaken using non diabetics blood as the control group. The differences in patient characteristics such as the mean ages and weights of the two groups were not statistically significant (P>0.05), and the ratios of non-smokers to smokers were similar meaning that the two groups were well matched. These studies revealed that diabetics erythrocytes with a mean HbA1C value ± SEM of 11.4 ± 0.27% were oxidized at a significantly greater rate than that of the control blood (P<0.05). The isopropyl nitrite mean oxidation time ± SEM of diabetics blood was 1.5 ± 0.05 min (n = 20). For the nondiabetics blood a mean HbA1C ± SEM value of 5.5 ± 0.08% was obtained with a mean oxidation time ± SEM of the non-diabetics blood of 4.6 ± 0.13 min (n=20). These studies demonstrate that Diabetes blood has an enhanced susceptibility of oxidation into methemoglobin by isopropyl nitrite compared to its respective control group, i.e., the normal blood. This finding could be attributed to the fact that isopropyl nitrite is a nitrite ester which contains a saturated three hydrocarbon chain similar to other analogous nitrite esters (ethyl nitrite, butyl nitrite, pentyl nitrite and hexyl nitrite) which also contain saturated hydrocarbon chains that previously showed a statistically significant increased oxidation time for diabetics blood (P<0.05) [1-6]. Thus this study confirms that the difference in the number of methylene molecules has no impact on the rate of oxidation on either diabetics blood or nondiabetics blood (P>0.05). These findings also imply that the increased susceptibility to isopropyl nitrite induced oxidation reaction in diabetics blood is a direct function of the amount of HbA1C present in the blood, i.e., a clear inverse relation appears to exist between the amount of HbA1C present and the oxidation time
... became popular among men who have sex with men, frequently perceived as harmless by consumers and often sold stating other uses. 1 The most commonly detected aromatic nitrites are amyl, butyl, isobutyl or isopropyl nitrite, but compositions vary. 2,3 Intoxications caused by inhalation and oral ingestion have been reported comprehensively, but intravenous administration has not been described before. 4,5 ...
Background:
Poppers are nitrite-containing liquids, which are inhaled for their aphrodisiac and hallucinogenic effects. Despite some cases of severe poisonings, poppers are often perceived as harmless by consumers. Inhalation and ingestion of poppers are well known, but, according to our literature review, intravenous abuse has not been reported before.
Case presentation:
A 34-year-old man injected poppers intravenously for recreational purposes. He then suffered from dyspnoea and general discomfort. Upon arrival of emergency medical services, the patient was dyspnoeic with blue-grey skin colour and oxygen saturation was 82% on ambient air. Non-invasive ventilation was necessary, and he was transferred to the intensive care unit. Toluidine blue was administered because of a methaemoglobinaemia of 40% and methaemoglobin levels dropped to 0.4%. He was discharged home after a 24-hour observation. We additionally analysed the contents of the poppers bottle: isopropyl nitrite, isopropanol and acetone were detected. Possible complications and the treatment regarding intravenous administration of poppers are discussed.
Conclusion:
We present the first published case of intravenous poppers abuse. Our patient suffered from methaemoglobinaemia and was rapidly discharged after treatment with toluidine blue. No specific treatment regarding the contents of the poppers bottle, apart from isopropyl nitrite, was necessary.
Purpose
To describe imaging features of Macular Telangiectasia Type 2 (MacTel) eyes experiencing ellipsoid zone (EZ) recovery.
Methods
MacTel patients with EZ-recovery were identified from the Natural History and Observational Registry Study and underwent retinal imaging including optical coherence tomography (OCT) and fundus photography. Eyes were graded according to the classification system by Gass and Blodi, the EZ-loss area was measured and OCT parameters were assessed by two independent readers. Parameters were analysed for their presence prior to EZ-recovery.
Results
Twenty-four eyes of 21 patients (12 female, 57.12%; mean age 68 ± 8.54 years) were included in this study and followed for 21.25 ± 12.79 months. At baseline, mean EZ-loss area was 0.036 ± 0.028 mm ² and 0.01 ± 0.013 mm ² at follow-up (p<0.001). A persisting external limiting membrane overlaying the EZ-loss was detected in 16 cases (66%) and hyperreflective changes in the outer retina were present in 18 cases (75%). Best corrected visual acuity was 0.23 (20/32) ± 0.33 logMar at baseline and 0.34 (20/40) ± 0.34 logMar at follow up (p=0.3).
Conclusion
Distinct OCT features precede ellipsoid zone recovery in MacTel and warrant further studies investigating implications for patient care and clinical trial interpretation.
The illicit drug trade generates billions of dollars in revenue per year, much of which comes from wholesale and retail sales late in the supply chain. Yet, the methods retailers and low-level wholesalers use to launder this revenue remain poorly understood. Using in-depth interviews with illicit drug entrepreneurs in the United States and the United Kingdom, this article analyses laundering strategies among such market actors. Our findings indicate that a significant proportion of their illicit proceeds are disposed of through relatively small-scale 'everyday' cash transactions (< $1,000) that are effectively untraceable. For those generating more substantial revenues, a variety of accessible and uncomplicated laundering strategies are employed, such as reporting such revenues as taxable income, using proxies to launder funds, and using revenues as investment capital within small-scale legal enterprise. Ultimately, we identify uncomplicated , yet largely effective, methods of laundering criminal proceeds among our sample of low-to medium-level illicit drug sellers. Though the sums at an individual level are relatively trivial, the 'mass of minor offences' of this nature likely accounts for a significant share of laundered drug revenues in Western consumer drug markets.
A man in his 60s with no relevant previous medical history presented to an urban, major trauma centre by ambulance after being found with a head injury in a nightclub. The paramedics reported he was hypoxic, hypotensive and tachycardic with altered mental status. At the emergency department, he had oxygen saturations of 85% despite high-flow oxygen and was hypotensive at 88/43mmHg. We were concerned the patient was haemorrhaging given the lack of response to oxygen therapy and their hypotension. However, an arterial blood gas (ABG) established a diagnosis of methemoglobinaemia. Methylthioninium chloride was promptly administered, and the patient’s condition improved. He later reported using recreational drugs, including alkyl nitrites (‘poppers’). He was monitored until his fraction of methaemoglobin returned to normal baseline levels with serial ABGs. He was discharged 24 hours later. It was suspected that his use of alkyl nitrites was the most likely cause of methaemoglobinaemia.
When inhaled, poppers products (alkyl nitrites) relax smooth muscle tissue and produce a pleasant "rush." As such, they are used by some gay, bisexual, and other men who have sex with men (sexual minority men), including during anal intercourse. In 2013, Health Canada cracked down on poppers sales by introducing threats of fines and imprisonment and seizing poppers in stores and at the border. While no new legislation was introduced, Health Canada takes the position that poppers fall within the definition of a "drug" under the Food and Drugs Act because they "modify organic function" in humans. This crackdown has not prevented poppers use and has added harms related to an illicit and unregulated drug supply. In an effort to reduce harms and advance more equitable and public health-centred approaches to poppers drug policy, we discuss how a series of anticipated outcomes (accessibility, equity, consumer safety, commercial feasibility, and stigma) relate to the following alternative approaches to regulation: (1) poppers as a prescription medicine; (2) poppers as a non-prescription drug (likely accessible 'over-the-counter'); (3) poppers as a consumer product rather than just a medicine; and (4) ending the crackdown without legislative changes. To improve health equity and reduce harms among sexual minority men in a way that is politically and commercially feasible, we recommend the last approach-ending the crackdown without legislative changes-including ceasing the confiscation of poppers products in stores and at the border.
This study will provide a thorough review of systemic (and select intravitreal) medications, along with illicit drugs that are capable of causing various patterns of retinal toxicity. The diagnosis is established by taking a thorough medication and drug history, and then by pattern recognition of the clinical retinal changes and multimodal imaging features. Examples of all of these types of toxicity will be thoroughly reviewed, including agents that cause retinal pigment epithelial disruption (hydroxychloroquine, thioridazine, pentosan polysulfate sodium, dideoxyinosine), retinal vascular occlusion (quinine, oral contraceptives), cystoid macular edema/retinal edema (nicotinic acid, sulfa-containing medications, taxels, glitazones), crystalline deposition (tamoxifen, canthaxanthin, methoxyflurane), uveitis, miscellaneous, and subjective visual symptoms (digoxin, sildenafil). The impact of newer chemotherapeutics and immunotherapeutics (tyrosine kinase inhibitor, mitogen-activated protein kinase kinase, checkpoint, anaplastic lymphoma kinase, extracellular signal-regulated kinase inhibitors, and others), will also be thoroughly reviewed. The mechanism of action will be explored in detail when known. When applicable, preventive measures will be discussed, and treatment will be reviewed. Illicit drugs (cannabinoids, cocaine, heroin, methamphetamine, alkyl nitrite), will also be reviewed in terms of the potential impact on retinal function.
Background
Poppers (alkyl nitrites) are vasodilators used by many gay, bisexual, and other men who have sex with men (GBMSM) to relieve pain, enhance pleasure, and facilitate penetration during sex. In 2013, the Canadian government cracked down on the sale of poppers products, however prevalence of poppers use among GBMSM in Canada remains high. Poppers have been studied by medical researchers since the 1980s, yet qualitative and community-based research to inform federal policy, remains somewhat less common.
Methods
We conducted a critical interpretive synthesis (CIS) to better understand poppers health literature using the medical model of health as a point of reference. Analysis was performed using inductive and deductive methods including reflexive note-taking, mind-mapping, and close coding. 153 publications were identified to inform this review of which 5 were chosen for coding based on a purposive sampling framework.
Results
Our findings are unified within a theoretical construct we term responsibility. Responsibility is a construct we use to describe the bias we identified in health sciences literature regarding poppers use that tends to exaggerate the necessity for poppers cessation, and devalue both the benefits of poppers use and the perspectives and experiences of people who use poppers. The emphasis on individual behavior change within the literature appears to be motivated less by objective measures or assessments of health risks and outcomes, and more by harmful stereotypes that position gay men and people who use drugs as inherently irresponsible.
Conclusion
We conclude by discussing how these findings have important implications for the review of current policy on poppers sales in Canada which remains influenced by a literature base prejudiced by factors such as homophobia, heteronormativity, and drug stigma, and recommend areas for future work.
A wide range of ocular diseases can present with serous subretinal fluid in the macula and therefore clinically mimic central serous chorioretinopathy (CSC). In this manuscript, we categorise the diseases and conditions that are part of the differential diagnosis into 12 main pathogenic subgroups: neovascular diseases, vitelliform lesions, inflammatory diseases, ocular tumours, haematological malignancies, paraneoplastic syndromes, genetic diseases, ocular developmental anomalies, medication-related conditions and toxicity-related diseases, rhegmatogenous retinal detachment and tractional retinal detachment, retinal vascular diseases, and miscellaneous diseases. In addition, we describe 2 new clinical pictures associated with macular subretinal fluid accumulation, namely serous maculopathy with absence of retinal pigment epithelium (SMARPE) and serous maculopathy due to aspecific choroidopathy (SMACH). Differentiating between these various diseases and CSC can be challenging, and obtaining the correct diagnosis can have immediate therapeutic and prognostic consequences. Here, we describe the key differential diagnostic features of each disease within this clinical spectrum, including representative case examples. Moreover, we discuss the pathogenesis of each disease in order to facilitate the differentiation from typical CSC.
Toxic retinopathies are most frequently induced by external stimulants (e.g. nicotine, poppers, methanol) and are less frequently undesired side effects of systemic drugs (e.g. hydroxychloroquine, ethambutol, MEK, ERK, FLT3 or checkpoint inhibitors, didanosine, pentosan polysulfate sodium) or intravitreally applied drugs. The clinical symptoms of undesired side effects of drugs are often similar to retinal diseases from other causes, which interferes with the recognition of the undesired side effects of drugs. Clinical findings, pathophysiological mechanisms and if advisable strategies for screening are discussed. The focus is on the presentation of confirmed undesirable side effects with established associations for medications which have long been approved. For novel medications, in addition potential but not proven associations are presented to facilitate the recognition of additional cases with side effects for these medications.
In recent years, the range of combined narcotic drugs has widened. New chemical modifications have emerged, including so-called designer drugs, whose action on the body and in particular on the state of vision is increasingly difficult to determine. While the problem of drug abuse is growing drastically, timely detection of a possible toxic damage to the eye induced by drugs and reliable diagnosis differentiating such damage from other etiologies becomes a topical practical issue. The paper presents a clinical case of poppers maculopathy (poppers being a slang name of aromatic volatile alkyl nitrite compounds). Ophthalmological manifestations and differential diagnostic criteria of the damage are described. The mechanisms of action and possible treatment methods are discussed.
This book is intended as a guide to help the clinician determine where a visual problem is a drug-induced ocular side effect. We continually review spontaneous case reports from the National Registry of Drug-Induced Ocular Side Effects, the World Health Organization, the Food and Drug Administration, and the world literature. We have attempted to classify a suspected adverse event with our impression to causality (i.e. certain, probable, unlikely, conditional/unclassified). This chapter discusses cardiac, vascular, and renal drugs including drugs used to treat migraine, antianginal drugs, antiarrythmic drugs, antihypertensive drugs, bronchodilators, diuretics, osmotics, peripheral vasodilators, and vasopressors.
Purpose:
To determine the extent of remnant cone structure within early foveal ellipsoid zone (EZ) lesions in macular telangiectasia type 2 longitudinally using both confocal and split detector adaptive optics scanning light ophthalmoscopy (AOSLO).
Methods:
Spectral domain optical coherence tomography (SDOCT), confocal and split detector AOSLO were acquired from seven patients (10 eyes) with small (early) EZ lesions on SDOCT secondary to macular telangiectasia type 2 at baseline, 6 months, and 12 months. The presence of cone structure on AOSLO in areas of EZ loss as well as cones at 1° eccentricity, and their change over time were quantified.
Results:
By split detector AOSLO, remnant cone structure was identified within and on the borders of all foveal EZ lesions. Within the extent of these lesions, cone spacing ranged from 4.97 to 9.95 µm at baseline, 5.30 to 6.10 µm at 6 months, and 4.99 to 7.12 µm at 12 months. Four eyes with significantly smaller EZ lesions showed evidence of recovery of EZ reflectivity on SDOCT B-scans. Remnant cone structure was identified in some areas where EZ reflectivity recovered at the following time point. Eyes that showed recovery of EZ reflectivity had a continuous external limiting membrane.
Conclusions:
Remnant cone structure can persist within small SDOCT-defined EZ lesions, which can wax and wane in appearance over time. AOSLO can help to inform the interpretation of SDOCT imaging.
Translational relevance:
The absence of EZ in early macular telangiectasia type 2 and other retinal conditions needs careful interpretation because it does not always indicate an absence of underlying cone structure. The integrity of the external limiting membrane may better predict the presence of remnant cone structure and recovery of EZ reflectivity.
Background
Poppers (i.e., alkyl nitrites) are commonly used during sex by gay, bisexual, and other men who have sex with men (sexual minority men). Poppers act as vasodilators when inhaled, resulting in a sensation some users refer to as a ‘head rush’, while also relaxing smooth muscles and facilitating penetration during anal sex. In 2013, Health Canada initiated a crackdown on poppers products. The current study aims to examine the experiences and perspectives of young sexual minority men who use poppers in the context of the federal crackdown.
Methods
We draw on 50 semi-structured, in-depth interviews collected from 2018 to 2019 in Vancouver with sexual minority men ages 15–30. We used a combination of both inductive and deductive techniques during data analysis to identify several key themes.
Results
Participants’ discussions reflected positive effects of poppers use relating to sexual pleasure and bodily control. Participants used poppers to enhance pleasure, reduce pain and injury (e.g., from tears in anal tissue), and improve their capacity to “let go” and enjoy sex. Conversely, some participants described a loss of control resulting from poppers use, including experiences of dependency on poppers for sexual pleasure. Poppers were also discussed as linked to participants’ personal identities as sexual minority men. In the context of the federal crackdown, uncertainty about the health effects of poppers use was high, while knowledge to safely and comfortably procure poppers in Canada was, at times, low.
Conclusion
Poppers play an important role in the experience of sexual pleasure and the ability to reduce harms during anal sex. Unfortunately, the current crackdown restricts access to a safe and regulated supply while creating uncertainty and confusion about poppers use. We call on the federal government to bring the voices of sexual minority men to the forefront in the revisiting of the federal crackdown on poppers in Canada.
Purpose:
To assess whether near infrared autofluorescence (NIR-AF) imaging is a useful imaging modality in the diagnosis of handheld laser retinal injuries.
Design:
Retrospective observational case series.
Methods:
12 patients identified to have handheld laser retinal injuries were included at two academic centers. Patients underwent ophthalmic assessment and retinal imaging including fundus photography, optical coherence tomography (OCT), conventional blue autofluorescence (B-AF) and NIR-AF imaging.
Results:
In all cases, lesions consistent with retinal laser injury were detected by NIR-AF imaging. The lesions showed a characteristic appearance with central hyperfluorescence and surrounding hypofluorescence although the number and extent of lesions varied between patients. Findings using other imaging modalities were variable: on color fundus photography these included localized pigmentary changes and on OCT imaging an ellipsoid zone interruption or outer nuclear layer changes. Only subtle changes were evident on B-AF imaging. Other macular conditions, such as poppers retinopathy or solar maculopathy, which may have similar findings on OCT imaging as laser damage, can be differentiated using NIR-AF imaging.
Conclusion:
An increased incidence of retinal injuries secondary to handheld lasers has been reported in recent years. We show that the diagnosis and full extent of retinal laser injuries is best demonstrated by NIR-AF, as other modalities give variable results. We propose that NIR-AF should be included when investigating patients suspected of macular injury secondary to exposure to handheld lasers.
We analysed poppers collected from drug amnesty bins and bought from festivals over two time periods spanning the classification of isobutyl nitrite as a Schedule 2 carcinogenic substance in Category 2, Regulation 5 of the Dangerous substances and Preparations (Safety) Regulations 2006
Background
Poppers are a recreational substance of abuse belonging to the alkyl nitrite family of compounds. In the United Kingdom, where they are legal to purchase but illegal to sell for human consumption, 10% of the general population have tried them. They are considered low risk to physical and mental health. Two recent case series from France demonstrated foveal pathology in individuals associated with poppers use.MethodA case series of seven patients presenting to four hospitals in the United Kingdom with visual impairment and maculopathy associated with inhalation of poppers.ResultsAll patients experienced visual symptoms associated with poppers use. The majority had impaired visual acuity, central scotomata, distortion, or phosphenes. Clinical signs on fundoscopy ranged from normal foveal appearance to yellow, dome-shaped lesions at the foveola. Spectral domain optical coherence tomography (SD-OCT) showed varying degrees of disruption of the presumed inner segment/outer segment (IS/OS) junction.DiscussionAlthough poppers have been in use for several decades, in 2007, following legislative changes, there was a change in the most commonly used compound from isobutyl nitrite to isopropyl nitrite. There were no reports of 'poppers maculopathy' before this. Poppers maculopathy may be missed if patients are not directly questioned about their use. The disruption or loss of the presumed IS/OS junction on SD-OCT are a characteristic feature. Further study of maculopathy in poppers users is now needed. Raising public awareness of the ocular risks associated with their use may be necessary.Eye advance online publication, 19 October 2012; doi:10.1038/eye.2012.191.
Eye is the official journal of the Royal College of Ophthalmologists. It aims to provide the practising ophthalmologist with information on the latest clinical and laboratory-based research.
To describe foveal damage in habitual use of poppers, a popular recreational drug.
Retrospective observational case series. Six patients with bilateral vision loss after chronic popper inhalation were seen in 4 university-based ophthalmology departments. Symptoms, medical history, ophthalmic examination, and functional and morphological tests are described.
All patients experienced progressive bilateral vision loss, with central photopsia in 2 cases. Initial visual acuities ranged from 20/50 to 20/25. In all patients, a bilateral yellow foveal spot was present that, by optical coherence tomography, was associated with disruption of the outer segments of foveal cones. Functional and anatomical damage was restricted to the fovea. The poppers involved were identified as isopropyl nitrite in 3 cases. Four patients showed anatomical and/or functional improvement over several months after discontinuing popper inhalation.
Repeated inhalation of poppers may be associated with prolonged bilateral vision loss due to the disruption of foveal cone outer segments. Retinal damage may progressively improve following drug discontinuation.
Background:
"Poppers" is a slang term for a group of alkyl nitrites that are used as recreational drugs. Their inhalative intoxication leads to muscle relaxation, analgesia, and euphoria. Maculopathy is a rare but serious side-effect.
Patients/methods:
Clinical, imaging, and electrophysiological findings of seven patients with maculopathy after consumption of poppers were presented.
Results:
All seven patients were male with a median age of 35 years (range 28-45 years), the median duration of periodical poppers use until the onset of symptoms was 9.8 years (one day to 25 years). Five of seven patients were HIV-positive, one patient was negative, and the HIV-status of one patient was unknown. Median average of visual acuity at presentation was 20/30 in each eye. In all patients, optical coherence tomography (OCT) showed pathognomonic alterations of the outer foveal retina. One patient showed an almost complete restitution of the maculopathy six months after cessation of drug use and following the oral intake of Lutein. Imaging alterations returned to normal and visual acuity recovered from 20/50 and 20/30 (right and left eye, respectively) to 20/20 on both eyes. Follow up of two other cases showed no relevant functional decline or improvement.
Discussion:
Toxic maculopathy due to the consumption of poppers is an important differential diagnosis in acute visual loss without clinico-morphological correlate. Optical coherence tomography is the only reliable diagnostic tool in these cases. Complete recovery of visual function and macular morphology is rare, even after cessation of drug abuse. Oral lutein therapy may have a beneficial effect.
Eye is the official journal of the Royal College of Ophthalmologists. It aims to provide the practising ophthalmologist with information on the latest clinical and laboratory-based research.
Amyl nitrite poppers' are recreational drugs, which are a potent source of nitric oxide. The use of poppers' can cause psychoactive stimulation, reduced blood pressure, tachycardia and involuntary muscle relaxation. Their use is becoming increasingly common around the world, including approximately 60% of Australia's male homosexual community. We report the first case of popper'-induced vision loss in Australasia. [Krilis M, Thompson J, Lusthaus J, Atik A, Jankelowitz S. 'Popper'-induced vision loss. Drug Alcohol Rev 2013;32:333-334]
In the light-adapted vertebrate retina, nitric oxide (NO) modulates synaptic transmission between photoreceptors and second-order neurons. Although NO is believed to be a mediator of adaptation, its effect on photoreceptors in situ is not known yet. Therefore, we studied rod and cone activities in rat eyes in situ, using the electroretinogram (ERG). Rod and cone ERGs were functionally isolated by intravitreal 20mM glutamate, which suppressed the activity of all retinal cells except rods and cones for about 90min. The addition of NO-donor, SNAP, to the glutamate solution decreased the amplitude of the rod single-flash ERG by approximately 40%, compared to the amplitude of the rod ERG isolated by glutamate alone, but it increased the amplitude of the isolated, intense paired-flash cone ERG by approximately 40%. An excess of the NO-scavenger, CPTIO, had no significant effect on either rod or cone ERGs. A broad-spectrum NO-synthase inhibitor, L-NAME, increased the amplitude of the rod ERG by approximately 50%, but had no significant effect on the cone ERG. We suggest that NO directly modulates the light-evoked activity of rod and cone photoreceptors in situ, but in opposite ways.
The effects of sublingual nitroglycerin and inhaled amyl nitrite on the arteriolar and venous beds of the forearm were studied in 11 normal subjects. Forearm blood flow was measured with a strain-gauge plethysmograph, and venous tone was determined both by an acute occlusion technic, and by several equilibration technics. Nitroglycerin reduced systemic arterial pressure, elevated forearm blood flow, lowered forearm vascular resistance and decreased venous tone. Amyl nitrite diminished arterial pressure, elevated forearm blood flow, markedly decreased forearm vascular resistance, but in contrast to nitroglycerin augmented venous tone strikingly. This venoconstriction was abolished or diminished when adrenergic activity was impeded by administration of either guanethidine or reserpine.
Nitric oxide synthase (NOS), the enzyme that catalyzes the formation of nitric oxide from L-arginine, exists in three major isoforms, neuronal, endothelial, and immunologic. Neuronal and endothelial isoforms are constitutively expressed, and require calcium for activation. Both of these isoforms can be induced (i.e., new protein synthesis occurs) under appropriate conditions. The immunologic isoform is not constitutively expressed, and requires induction usually by immunologic activation; calcium is not necessary for its activation. Neuronal and immunologic NOS have been detected in the retina. Neuronal NOS may be responsible for producing nitric oxide in photoreceptors and bipolar cells. Nitric oxide stimulates guanylate cyclase of photoreceptor rod cells and increases calcium channel currents. In the retina of cats, NOS inhibition impairs phototransduction as assessed by the electroretinogram. Inducible nitric oxide synthase, found in Müller cells and in retinal pigment epithelium, may be involved in normal phagocytosis of the retinal outer segment, in infectious and ischemic processes, and in the pathogenesis of diabetic retinopathy. Nitric oxide contributes to basal tone in the retinal circulation. To date, findings are conflicting with respect to its role in retinal autoregulation. During glucose and oxygen deprivation, nitric oxide may increase blood flow and prevent platelet aggregation, but it may also mediate the toxic effects of excitatory amino acid release. This reactive, short-lived gas is involved in diverse processes within the retina, and its significance continues to be actively studied.
The oxygenated carotenoids zeaxanthin and lutein, found in the macular area of the retina, may offer protection against or repair of oxidative damage associated with the degenerative diseases of aging. Since both superoxide and nitrogen monoxide, which react to form peroxynitrite, are found in the retina, we studied the reaction of peroxynitrite with zeaxanthin in liposomes. Zeaxanthin was easily incorporated into liposomes constructed from the fully saturated lipid L-alpha-dimyristoyl-phosphatidylcholine (C14:0) and from egg lecithin, and its absorbance spectrum in liposomes strongly resembles in shape and amplitude that of zeaxanthin dissolved in methanol. The reaction between peroxynitrite and zeaxanthin is first-order in both substrates. The pH profile indicates that the reaction with zeaxanthin involves peroxynitrous acid and not the conjugate anion. We hypothesize that zeaxanthin plays a major role in protection of macular tissue from oxidative damage.
Commonly referred to as "poppers," inhaled nitrites have a long history of abuse. Poppers are rapid-onset, short-acting potent vasodilators that produce a rush characterized by warm sensations and feelings of dizziness. Poppers sometimes are used to facilitate anal intercourse because of their actions on the anal sphincter. Epidemiologically, the frequent use of nitrites by men who have sex with men has led some experts to implicate these chemicals in the pathogenesis of Kaposi's sarcoma and acquired immunodeficiency syndrome. Controlled clinical trials to examine this potential correlation have not been conducted, and the use of nitrites simply may be a marker for other high-risk behaviors such as unprotected sex. Although regulated in the United States, many nitrite compounds and isomers are sold at various venues including bars, bookstores, and over the Internet. Adverse effects associated with these products vary from mild allergic reactions to life-threatening methemoglobinemia. The potential for drug-drug interactions and a propensity toward unsafe sex also exist. Clinicians should be familiar with the populations most likely to abuse these agents and with the clinical effects and management guidelines for acute ingestions.
Nitroglycerine has been used clinically in the treatment of angina for 130 years, yet important details on the mechanism of action, biotransformation, and the associated phenomenon of nitrate tolerance remain unanswered. The biological activity of organic nitrates can be said to be nitric oxide mimetic, leading to recent, exciting progress in realizing the therapeutic potential of nitrates. Unequivocally, nitroglycerine and most other organic nitrates, including NO-NSAIDs, do not behave as NO donors in the most fundamental action: in vitro activation of sGC to produce cGMP. The question as to whether the biological activity of nitrates results primarily or exclusively from NO donation will not be satisfactorily answered until the location, the apparatus, and the mechanism of reduction of nitrates to NO are defined. Similarly, the therapeutic potential of nitrates will not be unlocked until this knowledge is attained. Aspects of the therapeutic and biological activity of nitrates are reviewed in the context of the chemistry of nitrates and the elusive efficient 3e- reduction required to generate NO.
To report retinal alterations after Isobutyl nitrite (popper) inhalation.
Case Report.
A 30-year-old man presented a sudden visual decrease following the use of Isobutyl nitrite (popper) while he was at a discotheque. His visual acuity (VA) was 20/50 in the right eye (RE) and 20/63 in the left eye (LE). Ophthalmoscopy revealed symmetric alteration of the foveal reflex with a small yellowish-white spot in the foveal area, much more evident in the RE. Fluorescein angiography and OCT were normal. Visual field showed a mild reduction of central differential light sensitivity. A progressive recovery was noted and at one month's follow-up VA was 20/25 in OU with very faint yellowish-white spots.
The inhalation of drugs as "popper" may cause a visual loss by unclear mechanisms.
Flupirtine has been shown to function as a neuroprotectant and is presently used in man to treat a number of conditions. The aim of this study was to investigate the specific antioxidant properties of flupirtine in relation to oxidant-induced damage to retinal photoreceptors. Initial in vitro studies on brain membranes showed that flupirtine was approximately 20 times more potent than trolox (vitamin E analogue) and 8 times more potent than metipranolol at attenuating lipid peroxidation caused by the nitric oxide donor, sodium nitroprusside (SNP). Subsequent immunohistochemical studies revealed that following an intraocular injection of SNP, retinal photoreceptors are the only retinal cell types that appear to be clearly affected. This was supported by electroretinogram (ERG) recordings which showed both the a- and b-wave amplitudes to be significantly reduced. Western blotting techniques showed that SNP caused a significant decrease in photoreceptor-specific markers (RET-P1, rhodopsin kinase), an increase in cleaved caspase-3, Bcl-2, and cleaved PARP proteins that are associated with apoptosis and no change in the ganglion cell specific marker, neurofilament (NF-L). This was supported by RT-PCR data where rhodopsin (photoreceptor specific) mRNA was reduced while Thy-1 and NF-L (ganglion cell specific) mRNAs were unaffected. In addition SNP caused an elevation of glial cell response mRNAs primarily associated with Müller cells (GFAP, CNTF, bFGF) as well as caspase-3 and Bcl-2. Importantly, when flupirtine was co-injected, the effects to the retina caused by SNP on retinal proteins and mRNAs were in most cases significantly blunted. The conclusion reached from this study is that flupirtine is a powerful antioxidant and when injected into the eye with SNP attenuates the detrimental influence of SNP to retinal photoreceptors. Since oxidative stress has been implicated in retinal diseases like age-related macular degeneration (AMD) this study provides "proof of principle" for the idea that flupirtine may help individuals suffering from such retinal diseases.
To detect and quantify current risk factors for HIV seroconversion among gay men seeking repeat tests at sexual health clinics.
Unmatched case control study conducted in London, Brighton and Manchester, UK.
75 cases (recent HIV positive test following a negative test within the past 2 years) and 157 controls (recent HIV negative test following a previous negative test within the past 2 years) completed a computer-assisted self interview focused on sexual behaviour and lifestyle between HIV tests.
Cases and controls were similar in socio-demographics, years since commencing sex with men, lifetime number of HIV tests, reasons for seeking their previous HIV tests and the interval between last HIV tests (mean = 10.5 months). Risk factors between tests included unprotected receptive anal intercourse (URAI) with partners not believed to be HIV negative (adjusted odds ratio (AOR) and 95% confidence interval 4.1, 1.8 to 9.3), where increased risk was associated with concomitant use of nitrite inhalants, receiving ejaculate and increasing numbers of partners. Independent risk was also detected for unprotected insertive anal intercourse (UIAI) with more than one man (AOR 2.7, 1.3 to 5.5) and use of nitrite inhalants (AOR 2.4, 1.1 to 5.2).
HIV serodiscordant unprotected anal intercourse remains the primary context for HIV transmission among gay men, with increased risk associated with being the receptive partner, receiving ejaculate and use of nitrite inhalants. Although the HIV transmission risk of URAI is widely acknowledged, this study highlights the risk of UIAI and that nitrite inhalants may be an important facilitator of transmission when HIV exposure occurs.
Making it Count, Briefing sheet 7-Poppers
- R Pebody
Drug Misuse Declared: Findings from the 2010/11 British Crime Survey England and Wales. Home Office
- K Smith
- J Flatley
Advisory Council on the Misuse of Drugs, The Home Office
- L Iversen