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1.
Rev Neurol ; 76(2): 35-40, 2023 01 16.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36631962

RESUMO

INTRODUCTION: Sodium oxybate (SXB) was administered for the first time in 1979 in 16 patients with narcolepsy with cataplexy (NT1) that improved up to 20 months. AIMS: To evaluate the effect of SXB on daytime sleepiness and sleep architecture by video-polysomnography in a sample of 23 NT1 adult patients (13 men, 10 females) treated up to three years. Additional goal was to study the presence of sleep comorbidities. PATIENTS AND METHODS: NT1 patients were diagnosed according to International Classification of Sleep Disorders, third edition. We conducted a longitudinal observational study and a video-polysomnography comparing the sleep parameters of patients treated with an initial nocturnal dose of 4.5 g of SXB after six months (FU-1), one year (FU-2) and three years (FU-3) of uninterrupted treatment. Video-polysomnography parameters were analyzed including apnea-hypopnea and periodic leg movements indexes. RESULTS: Patients were HLA-DQB1*06:02 positive except a familial case. Thirteen patients (56%) discontinued SXB treatment over the three-year of the study. The two-nightly doses has been one of the reason for discontinuing treatment as well as insufficient compliance, mild or severe side effects, comorbidities and pregnancy. We found significant differences at FU-2 in sleep structure with an increased in stage N2 (p < 0.03) and a higher periodic leg movements index (p < 0.01). At FU-3 we found significant differences in sleep structure with an increase in stage N1 (p = 0.03) and in comorbidities (periodic leg movements and apnea-hypopnea indexes). There was not significant change on daytime sleepiness during the study. CONCLUSIONS: SXB was administered in low-medium doses. Two-nightly doses and sleep fragmentation linked to sleep comorbidities at long-term lead to drug withdrawal.


TITLE: Efecto a largo plazo del oxibato de sodio en la somnolencia diurna y en la estructura del sueño en pacientes con narcolepsia de tipo 1.Introducción. El oxibato de sodio (SXB) se utilizó en 1979 en 16 enfermos con narcolepsia-cataplejía (NT1) que mejoraron tras 20 meses de tratamiento. Objetivos. Evaluar el efecto del SXB en la somnolencia diurna y en la estructura del sueño mediante videopolisomnografía en una muestra de 23 enfermos de NT1 (13 hombres y 10 mujeres) tratados durante tres años. Investigamos adicionalmente la presencia de comorbilidad. Pacientes y métodos. Diagnosticamos a los enfermos de acuerdo con la Clasificación Internacional de Trastornos del Sueño, tercera edición. Realizamos un estudio longitudinal, observacional y de videopolisomnografía, comparando los parámetros de sueño y los índices de apnea-hipopnea y de movimientos periódicos de las piernas de los enfermos, tratados con una dosis nocturna inicial de 4,5 g de SXB al cabo de seis meses (C-1), un año (C-2) y tres años (C-3) de tratamiento ininterrumpido. Resultados. Todos los enfermos eran HLA-DQB1*06:02 positivos, excepto un caso familiar. Trece enfermos (56%) interrumpieron el tratamiento debido a las dos tomas nocturnas, así como a la presencia de efectos secundarios, comorbilidad y embarazo. Encontramos diferencias significativas en C-2 en la estructura del sueño con aumento del estadio N2 (p < 0,03) y del índice de movimientos periódicos de las piernas (p < 0,01). En el control C-3 encontramos diferencias significativas en la estructura del sueño con aumento del estadio N1 (p = 0,03), y de los índices de movimientos periódicos de las piernas y de apnea-hipopnea. Conclusiones. El SXB se administró en dos dosis nocturnas, lo que, unido a la fragmentación del sueño y a la aparición de comorbilidades, condujo a la interrupción del tratamiento a largo plazo.


Assuntos
Narcolepsia , Sono , Oxibato de Sódio , Adulto , Feminino , Humanos , Masculino , Apneia/complicações , Seguimentos , Narcolepsia/complicações , Narcolepsia/tratamento farmacológico , Sono/efeitos dos fármacos , Oxibato de Sódio/administração & dosagem , Oxibato de Sódio/efeitos adversos
2.
Clin Transl Sci ; 14(6): 2278-2287, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34121333

RESUMO

American Academy of Sleep Medicine practice parameters designate sodium oxybate (SXB) as a standard of care for cataplexy, excessive daytime sleepiness (EDS), and disrupted night-time sleep in narcolepsy. Recently, a lower-sodium oxybate (LXB) with 92% less sodium than SXB was approved in the United States for the treatment of cataplexy or EDS in patients 7 years of age and older with narcolepsy. Two phase I, open-label, randomized, single-dose crossover pharmacokinetic studies in healthy adults were conducted. Single 4.5-g oral doses of LXB and SXB were administered in a fasted or fed state. In the fasted state at equivalent oxybate doses, LXB, compared with SXB, had a lower maximum plasma concentration (Cmax ; study 1 [total aqueous volume, 240 ml]: 101.8 vs. 135.7 µg/ml; study 2 [60 ml]: 94.6 vs. 123.0 µg/ml), delayed time to Cmax (Tmax ; study 1: 0.75 vs. 0.5 h; study 2: 1.0 vs. 0.5 h), but similar area under the curve (AUC; study 1: AUC0-t , 235.4 vs. 263.9 µg∙h/ml; AUC0-∞ , 236.5 vs. 265.2 µg∙h/ml; study 2: AUC0-t , 241.5 vs. 254.7 µg∙h/ml; AUC0-∞ , 243.1 vs. 256.3 µg∙h/ml). Bioequivalence criteria were met for AUC but not Cmax (both studies). Cmax and AUC were lower under fed than fasted conditions (LXB and SXB); differences between fed versus fasted were smaller for LXB than SXB. These pharmacokinetic differences between LXB and SXB are likely due to the lower sodium content in LXB. Pooled analyses demonstrated that a higher Cmax is associated with a higher incidence of nausea and vomiting.


Assuntos
Anestésicos Intravenosos/farmacocinética , Oxibato de Sódio/farmacocinética , Adulto , Anestésicos Intravenosos/administração & dosagem , Disponibilidade Biológica , Estudos Cross-Over , Feminino , Humanos , Masculino , Narcolepsia/tratamento farmacológico , Oxibato de Sódio/administração & dosagem , Equivalência Terapêutica , Adulto Jovem
3.
AAPS J ; 23(1): 22, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33417072

RESUMO

Gamma-hydroxybutyrate (GHB) is a short-chain fatty acid present endogenously in the brain and used therapeutically for the treatment of narcolepsy, as sodium oxybate, and for alcohol abuse/withdrawal. GHB is better known however as a drug of abuse and is commonly referred to as the "date-rape drug"; current use in popular culture includes recreational "chemsex," due to its properties of euphoria, loss of inhibition, amnesia, and drowsiness. Due to the steep concentration-effect curve for GHB, overdoses occur commonly and symptoms include sedation, respiratory depression, coma, and death. GHB binds to both GHB and GABAB receptors in the brain, with pharmacological/toxicological effects mainly due to GABAB agonist effects. The pharmacokinetics of GHB are complex and include nonlinear absorption, metabolism, tissue uptake, and renal elimination processes. GHB is a substrate for monocarboxylate transporters, including both sodium-dependent transporters (SMCT1, 2; SLC5A8; SLC5A12) and proton-dependent transporters (MCT1-4; SLC16A1, 7, 8, and 3), which represent significant determinants of absorption, renal reabsorption, and brain and tissue uptake. This review will provide current information of the pharmacology, therapeutic effects, and pharmacokinetics/pharmacodynamics of GHB, as well as therapeutic strategies for the treatment of overdoses. Graphical abstract.


Assuntos
Overdose de Drogas/terapia , Hidroxibutiratos/farmacocinética , Oxibato de Sódio/farmacocinética , Abuso Oral de Substâncias/terapia , Alcoolismo/complicações , Alcoolismo/tratamento farmacológico , Animais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Overdose de Drogas/etiologia , Humanos , Hidroxibutiratos/administração & dosagem , Hidroxibutiratos/toxicidade , Taxa de Depuração Metabólica , Narcolepsia/tratamento farmacológico , Oxibato de Sódio/administração & dosagem , Oxibato de Sódio/toxicidade , Abuso Oral de Substâncias/etiologia , Síndrome de Abstinência a Substâncias/tratamento farmacológico
4.
Artigo em Inglês | MEDLINE | ID: mdl-33178485

RESUMO

Patients with essential tremor, vocal tremor, torticollis, myoclonus-dystonia and posthypoxic myoclonus often benefit in a surprisingly rapid and robust manner from ingestion of a modest amount of alcohol (ethanol). Despite considerable investigation, the mechanism of ethanol's ability to produce this effect remains a mystery. In this paper, we review the pharmacology of ethanol and its analogue GHB (or sodium oxybate), summarize the published literature of alcohol-responsive hyperkinetic movement disorders, and demonstrate videos of patients we have treated over the last fifteen years with either an ethanol challenge or with chronic sodium oxybate therapy. We then propose a novel explanation for this phenomenon-namely, that ingestion of modest doses of ethanol (or sodium oxybate) normalizes the aberrant motor networks underling these disorders. We propose that alcohol and its analogues improve clinical symptoms and their physiologic correlate by restoring the normal firing pattern of the major outflow pathways of the cerebellum (the Purkinje cells and deep cerebellar nuclei), We present evidence to support this hypothesis in animal models and in affected patients, and suggest future investigations to test this model.


Assuntos
Adjuvantes Anestésicos/farmacologia , Comportamento Animal/efeitos dos fármacos , Depressores do Sistema Nervoso Central/farmacologia , Núcleos Cerebelares/efeitos dos fármacos , Etanol/farmacologia , Transtornos dos Movimentos/fisiopatologia , Células de Purkinje/efeitos dos fármacos , Oxibato de Sódio/farmacologia , Adjuvantes Anestésicos/administração & dosagem , Bebidas Alcoólicas , Animais , Depressores do Sistema Nervoso Central/administração & dosagem , Núcleos Cerebelares/fisiopatologia , Distúrbios Distônicos/fisiopatologia , Tremor Essencial/fisiopatologia , Etanol/administração & dosagem , Humanos , Hipóxia Encefálica/complicações , Mioclonia/etiologia , Mioclonia/fisiopatologia , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiopatologia , Oxibato de Sódio/administração & dosagem , Torcicolo/fisiopatologia , Distúrbios da Voz/fisiopatologia
5.
Clin Transl Sci ; 13(5): 932-940, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32216084

RESUMO

The pharmacokinetics (PKs) of sodium oxybate (SXB) was evaluated in a subset of participants from a study of SXB treatment in children (aged 7-11 years; n = 11) and adolescents (aged 12-17 years; n = 18) with narcolepsy with cataplexy. PK evaluation was conducted over 2 nights during the period when participants received a stable nightly SXB dose. The SXB dose on night 1 was half of night 2 and was administered in two equally divided doses: dose 1 was administered > 2 hours after the evening meal, and dose 2 was administered ≥ 4 hours after dose 1. Noncompartmental PK analysis demonstrated higher plasma concentrations post-dose 2 vs. post-dose 1, higher than dose-proportional increases in area under the concentration-time curve from 0 to 4 hours (AUC0-4h ) after dose 1, indicating nonlinear clearance, and better correlation between exposure and mg/kg than exposure and gram dose. To confirm the noncompartmental findings, identify factors affecting SXB PK, and compare with prior results in adults, a population PK (PopPK) model was established combining PK data from the current study with prior data from adults (132 healthy volunteers and 13 with narcolepsy). A two-compartment PopPK model with first-order absorption and nonlinear clearance from the central compartment described the data well. PopPK identified weight as the main intrinsic factor and food as the main extrinsic factor affecting SXB PK, and predicts similar PK profiles on a mg/kg basis across ages. These results, along with previously reported efficacy and safety outcomes, support weight-based SXB dose initiation in pediatric patients.


Assuntos
Peso Corporal , Cataplexia/tratamento farmacológico , Cálculos da Dosagem de Medicamento , Narcolepsia/tratamento farmacológico , Oxibato de Sódio/farmacocinética , Administração Oral , Adolescente , Área Sob a Curva , Cataplexia/sangue , Cataplexia/complicações , Criança , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Modelos Biológicos , Narcolepsia/sangue , Narcolepsia/complicações , Oxibato de Sódio/administração & dosagem
6.
Clin Ter ; 170(1): e44-e45, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31850483

RESUMO

Drug-facilitated sexual assaults (DFSA) currently represent overwhelming issue in its multidisciplinary approach. They occur when alcohol or drugs are used to compromise an individual's ability to consent to a sexual act. These substances facilitate a perpetrator to commit sexual assault because they inhibit a person's ability to resist and can prevent them from remembering the assault. If on the one hand alcohol remains the most commonly used drug in crimes of sexual assault, on the other hand drugs being used by perpetrators in crimes of sexual assault include, but are not limited to, Rohypnol (but also other benzodiazepines can be used), GHB (Gamma Hydroxybutyric Acid), GBL (Gamma-Butyrolactone), ketamine and others. The authors briefly examine the main issues of GHB-facilitated sexual assault in forensic investigation, drawing the attention of the whole scientific community to the importance of a correct assessment of each GHB-FSA, even when it is only suspected and by providing some practical advices.


Assuntos
Vítimas de Crime/psicologia , Vítimas de Crime/estatística & dados numéricos , Drogas Ilícitas , Delitos Sexuais/estatística & dados numéricos , Oxibato de Sódio/administração & dosagem , Adulto , Feminino , Humanos , Masculino
7.
Expert Opin Drug Saf ; 19(2): 159-166, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31876433

RESUMO

Introduction: Sodium oxybate (SMO) has been approved in Italy and in Austria for the treatment of alcohol use disorder (AUD). This study describes the cumulative postmarketing and clinical safety experience with SMO in AUD.Areas covered: Safety data for SMO at approved posology in AUD were identified from: (i) the clinical trial registries of the US National Institutes of Health (NIH) and the European Medicines Agency (EMA), (ii) reports from the biomedical literature and (iii) available pharmacovigilance safety information from the EMA.Expert opinion: Safety data from 3 recent large randomized clinical studies (520 participants) and 43 earlier clinical studies (2547 participants) showed that SMO has a good safety profile in AUD patients. The safety profile was confirmed by pharmacovigilance data resulting from 299 013 patients exposed to SMO in Austria and Italy. Main adverse events were transitory dizziness and vertigo. Serious adverse events were rare. No death attributable to SMO has been reported. Risks of abuse or dependence are low in patients without psychiatric comorbidities or poly-drug use. The adverse events of SMO are transitory and do not require discontinuation of treatment. SMO abuse or dependence are extremely rare in patients without psychiatric comorbidities or poly-drug use.


Assuntos
Alcoolismo/tratamento farmacológico , Oxibato de Sódio/administração & dosagem , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Oxibato de Sódio/efeitos adversos
9.
Sleep Med ; 62: 29-31, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31526967
10.
J Forensic Sci ; 64(1): 302-303, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29783276

RESUMO

Somnophilia, the desire to have sex with an unconscious, sleeping, or comatose person who is unable to respond, is a sexual paraphilia that is seldom reported. The underlying desire is often overshadowed by the act of sexual violation and when using GHB or GBL to induce unconsciousness, as in the case presented here, the victim might not even be able to recall, for certain, that they have been sexually violated. A case study is offered of a somnophile who adulterated drinks to render young men unconscious, so he could rape them in that state, before progressing to administering drugs anally on the pretext of applying lubrication to the anus to facilitate sexual intercourse. The offender's fetishistic compulsion to have sex with unconscious men propelled him to experiment with the means by which he surreptitiously administered drugs to his victims in order to deepen their comatose state.


Assuntos
Coma/induzido quimicamente , Hipnóticos e Sedativos/administração & dosagem , Transtornos Parafílicos/psicologia , Estupro , 4-Butirolactona/administração & dosagem , 4-Butirolactona/intoxicação , Overdose de Drogas , Homicídio , Humanos , Hipnóticos e Sedativos/intoxicação , Masculino , Oxibato de Sódio/administração & dosagem , Oxibato de Sódio/intoxicação
11.
Sleep Med Rev ; 43: 23-36, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30503715

RESUMO

Excessive daytime sleepiness (EDS) and cataplexy are common symptoms of narcolepsy, a sleep disorder associated with the loss of hypocretin/orexin (Hcrt) neurons. Although only a few drugs have received regulatory approval for narcolepsy to date, treatment involves diverse medications that affect multiple biochemical targets and neural circuits. Clinical trials have demonstrated efficacy for the following classes of drugs as narcolepsy treatments: alerting medications (amphetamine, methylphenidate, modafinil/armodafinil, solriamfetol [JZP-110]), antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors), sodium oxybate, and the H3-receptor inverse agonist/antagonist pitolisant. Enhanced catecholamine availability and regulation of locus coeruleus (LC) norepinephrine (NE) neuron activity is likely central to the therapeutic activity of most of these compounds. LC NE neurons are integral to sleep/wake regulation and muscle tone; reduced excitatory input to the LC due to compromise of Hcrt/orexin neurons (likely due to autoimmune factors) results in LC NE dysregulation and contributes to narcolepsy/cataplexy symptoms. Agents that increase catecholamines and/or LC activity may mitigate EDS and cataplexy by elevating NE regulation of GABAergic inputs from the amygdala. Consequently, novel medications and treatment strategies aimed at preserving and/or modulating Hcrt/orexin-LC circuit integrity are warranted in narcolepsy/cataplexy.


Assuntos
Cataplexia/tratamento farmacológico , Tratamento Farmacológico/métodos , Imunogenética , Narcolepsia/tratamento farmacológico , Neurobiologia , Adjuvantes Anestésicos/administração & dosagem , Antidepressivos/administração & dosagem , Antidepressivos Tricíclicos/administração & dosagem , Cataplexia/metabolismo , Estimulantes do Sistema Nervoso Central/administração & dosagem , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Modafinila/administração & dosagem , Narcolepsia/metabolismo , Oxibato de Sódio/administração & dosagem
13.
Hum Psychopharmacol ; 33(6): e2679, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30426556

RESUMO

OBJECTIVE: Gamma-hydroxybutyrate (GHB) is an endogenous GHB-/GABA-B receptor agonist and a narcolepsy treatment. However, GHB is also abused for its prohedonic effects. On a neuronal level, it was shown that GHB increases regional cerebral blood flow in limbic areas such as the right anterior insula (rAI) and the anterior cingulate cortex (ACC). We aimed to further explore the association between the subjective and neuronal signatures of GHB. METHOD: We assessed subjective effects and resting-state functional connectivity (rsFC) of an rAI- and an ACC-seed in 19 healthy male subjects after GHB (35 mg/kg p.o.) using a placebo-controlled, double-blind, randomized, cross-over functional magnet resonance imaging design. RESULTS: GHB increased subjective ratings for euphoria (p < 0.001) and sexual arousal (p < 0.01). Moreover, GHB increased rAI-rsFC to the right thalamus and the superior frontal gyrus and decreased ACC-rsFC to the bilateral paracentral lobule (all p < 0.05, cluster corrected). Moreover, GHB-induced euphoria was associated with rAI-rsFC to the superior frontal gyrus (p < 0.05, uncorrected). CONCLUSIONS: GHB induces prohedonic effects such as euphoria and sexual arousal and in parallel modulates limbic rsFC with areas linked to regulation of mood, cognitive control, and sexual experience. These results further elucidate the drug's effects in neuropsychiatric disorders and as drug of abuse.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Conectoma/métodos , Euforia/efeitos dos fármacos , Agonistas dos Receptores de GABA-B/farmacologia , Libido/efeitos dos fármacos , Sistema Límbico/efeitos dos fármacos , Oxibato de Sódio/farmacologia , Adulto , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiologia , Estudos Cross-Over , Método Duplo-Cego , Agonistas dos Receptores de GABA-B/administração & dosagem , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/fisiologia , Humanos , Sistema Límbico/diagnóstico por imagem , Sistema Límbico/fisiologia , Imageamento por Ressonância Magnética , Masculino , Oxibato de Sódio/administração & dosagem , Adulto Jovem
14.
Forensic Sci Int ; 292: 50-60, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30292936

RESUMO

Drug-facilitated sexual assault (DFSA) is a sexual act in which the victim is unable to give or rescind consent due to intoxication with alcohol and/or drugs that have been self-administered (opportunistic DFSA) or covertly administered by the perpetrator (predatory DFSA). The drugs that are most commonly associated with DFSA are flunitrazepam and gamma-hydroxybutyric acid (GHB). They cause sedation and amnesia, are readily dissolved in beverages and are rapidly eliminated from the system. However, drugs such as amphetamine and cocaine, which are central nervous system (CNS) stimulants, have also been encountered in DFSA cases. This paper critically evaluates trend data from cohort studies, identifying drugs that have been detected in DFSA cases and reports on the differences in drugs used between opportunistic and predatory DFSA. This is the first time that a critical multifactorial review of drugs used in DFSA has been conducted. The pharmacology of each identified group of drugs is presented, showing why these compounds are of interest and used in the perpetration of DFSA. Furthermore, the pharmacology and mechanisms of action are described to explain how the drugs cause their effects. It is also apparent from this study that if meaningful data is to be exchanged between law enforcement agencies then it is necessary to agree on protocols for the collection of evidence and the drugs for which analysis should be performed and indeed on the analytical methods used.


Assuntos
Vítimas de Crime , Delitos Sexuais , Detecção do Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Barbitúricos/administração & dosagem , Barbitúricos/efeitos adversos , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Cannabis/efeitos adversos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Cocaína/administração & dosagem , Cocaína/efeitos adversos , Relação Dose-Resposta a Droga , Toxicologia Forense , Meia-Vida , Antagonistas dos Receptores Histamínicos/administração & dosagem , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Oxibato de Sódio/administração & dosagem , Oxibato de Sódio/efeitos adversos
15.
Psychopharmacology (Berl) ; 235(11): 3223-3232, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30232528

RESUMO

RATIONALE: Gamma-hydroxybutyrate acid (GHB), a GABAB receptor agonist approved for treatment of narcolepsy, impairs driving ability, but little is known about doses and plasma concentrations associated with impairment and time course of recovery. OBJECTIVE: To assess effects of oral GHB (Xyrem®) upon driving as measured by a driving simulator, and to determine plasma concentrations associated with impairment and the time course of recovery. METHODS: Randomized, double-blind, two-arm crossover study, during which 16 participants received GHB 50 mg/kg orally or placebo. GHB blood samples were collected prior to and at 1, 3, and 6 h post dosing. Driving simulator sessions occurred immediately after blood sampling. RESULTS: Plasma GHB was not detectable at baseline or 6 h post dosing. Median GHB concentrations at 1 and 3 h were 83.1 mg/L (range 54-110) and 24.4 mg/L (range 7.2-49.7), respectively. Compared to placebo, at 1 h post GHB dosing, significant differences were seen for the life-threatening outcome collisions (p < 0.001) and off-road accidents (p = 0.018). Although driving was not faster, there was significantly more weaving and erratic driving with GHB as measured by speed deviation (p = 0.002) and lane position deviation (p = 0.004). No significant impairment regarding driving outcomes was found in the GHB group at 3 and 6 h post dose. CONCLUSION: GHB in doses used to treat narcolepsy resulted in severe driving impairment at 1 h post dosing. After 3 to 6 h, there was full recovery indicating that safe driving is expected the next morning after bedtime therapeutic GHB use in the absence of other substances.


Assuntos
Adjuvantes Anestésicos/administração & dosagem , Condução de Veículo/psicologia , Simulação por Computador , Dirigir sob a Influência/psicologia , Oxibato de Sódio/administração & dosagem , Adjuvantes Anestésicos/efeitos adversos , Adjuvantes Anestésicos/sangue , Administração Oral , Adulto , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Narcolepsia/sangue , Narcolepsia/tratamento farmacológico , Oxibato de Sódio/efeitos adversos , Oxibato de Sódio/sangue
16.
Tidsskr Nor Laegeforen ; 138(13)2018 09 04.
Artigo em Inglês, Norueguês | MEDLINE | ID: mdl-30180500

RESUMO

BAKGRUNN: Formålet med undersøkelsen var å kartlegge forekomsten av rusmiddelbruk under sex (chemsex) blant et utvalg av mannlige pasienter ved Olafiaklinikken i Oslo, en poliklinikk for seksuelt overførbare infeksjoner. Vi ønsket også å se hvilke variabler innen psykisk helse, seksuelt overførbare infeksjoner og seksualatferd som var assosiert med chemsex for menn som har sex med menn og menn som har sex med kvinner. MATERIALE OG METODE: Studien var anonym og spørreskjemabasert blant mannlige pasienter ved poliklinikken i perioden 1.7.2016-20.10.2016. RESULTATER: Svarprosenten var 96 (1 050 fikk utdelt skjema, 1 013 ble inkludert). Av disse rapporterte 144 (14 %) bruk av chemsex i løpet av det siste året - 87 (17 %) menn som har sex med menn og 57 (12 %) menn som har sex med kvinner. Av de som hadde hatt chemsex, oppga flere menn som har sex med menn hivinfeksjon, at de hadde hatt syfilis, over ti sexpartnere og hadde deltatt på sexfest det siste året. Flere menn som har sex med kvinner oppga psykiske plager. FORTOLKNING: Det bør utredes nærmere hvordan helsevesenet best kan møte chemsexbrukernes behov. Spesielt er det viktig med informasjon om skadereduksjonstiltak og støtte til de som ønsker å slutte eller redusere bruken av chemsex.


Assuntos
Drogas Desenhadas , Drogas Ilícitas , Comportamento Sexual , Adolescente , Adulto , Bissexualidade , Cocaína/administração & dosagem , Infecções por HIV/epidemiologia , Hepatite C/epidemiologia , Heterossexualidade , Homossexualidade Masculina , Humanos , Ketamina/administração & dosagem , Masculino , Saúde Mental , Metanfetamina/administração & dosagem , Metanfetamina/análogos & derivados , Pessoa de Meia-Idade , Noruega/epidemiologia , Refugiados , Parceiros Sexuais , Minorias Sexuais e de Gênero , Doenças Bacterianas Sexualmente Transmissíveis/epidemiologia , Fatores Socioeconômicos , Oxibato de Sódio/administração & dosagem , Inquéritos e Questionários , Sexo sem Proteção , Adulto Jovem
17.
Sleep Med ; 50: 175-180, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30075393

RESUMO

OBJECTIVE: Cross-sectional studies show a lower health-related quality of life (HRQoL) in individuals with narcolepsy. We aimed to describe changes in HRQoL after two years of multidisciplinary follow-up in a cohort of mainly post-H1N1 vaccination narcolepsy type-1 (NT1) patients in Norway. METHODS: Prospective-cohort study. Narcolepsy diagnosis was based on the International Classification of Sleep Disorders (third edition). Psychiatric comorbidity was assessed using the Achenbach System of Empirically Based Assessment (ASEBA). HRQoL was evaluated with the Pediatric Quality of Life Inventory (PedsQL™ Generic Core Scales 4.0) at baseline and follow-up. Mean follow-up time was 20.7 (2.7) months. RESULTS: Thirty one patients (18 females) with NT1, mean age 14.6 (SD = 4.8) years answered questionnaires at baseline and follow-up. On a group level, the PedsQL Total Health Summary score significantly improved by a mean of 5.9 (95%CI = 0.4, 11.9), p = 0.038; this was mainly driven by improvements in the Physical Health Summary score by 9.8 (3.0, 16.5) points, p = 0.006 and the School Functioning Scale score by 7.5 (1.0, 13.9) points p = 0.025. The Total ASEBA score was correlated with PedsQL Total Health Summary score at baseline, but not with changes in HRQoL. Sodium oxybate (Xyrem®) treatment at follow up was positively associated with changes in PedsQL Total Health Summary score, after adjusting for age and gender, p = 0.027. CONCLUSION: HRQoL in NT1 patients improved after two years of follow-up. The use of sodium oxybate (Xyrem®) at follow-up was associated with increases in HRQoL. Psychiatric comorbidity was correlated with HRQoL at baseline but did not predict changes in HRQoL at follow-up.


Assuntos
Influenza Humana/complicações , Narcolepsia/psicologia , Vacinação/efeitos adversos , Adjuvantes Anestésicos/uso terapêutico , Adolescente , Criança , Comorbidade , Estudos Transversais , Feminino , Humanos , Programas de Imunização/métodos , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/epidemiologia , Masculino , Narcolepsia/classificação , Narcolepsia/tratamento farmacológico , Narcolepsia/fisiopatologia , Noruega/epidemiologia , Estudos Prospectivos , Qualidade de Vida/psicologia , Índice de Gravidade de Doença , Oxibato de Sódio/administração & dosagem , Oxibato de Sódio/uso terapêutico , Vacinação/estatística & dados numéricos , Adulto Jovem
18.
Sleep Med ; 47: 1-6, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29880141

RESUMO

BACKGROUND: Currently, cardiovascular measurements in children affected with type 1 narcolepsy (NT1) have never been investigated, and neither have their modulation by the administration of sodium oxybate (SO). METHODS: Twelve drug-naïve NT1 children (four males, eight females) with a mean age of 11 ± 3.16 years underwent a nocturnal polysomnography, at baseline and during the first night of SO administration. Data were contrasted with those recorded in 23 age-matched healthy controls. Heart rate variability (HRV) analysis was performed by analyzing the electrocardiogram signal for automatic detection of R waves with a computer program calculating a series of standard time-domain measures and obtaining spectral parameters, by means of a Fast-Fourier Transform. RESULTS: In sleep stages N2 and N3, NT1 children showed increased power in the low-frequency (LF) and very-LF (VLF) ranges, when compared to controls. In addition, HRV (as measured by time domain parameters) during all sleep stages tended to be slightly higher in patients when compared to controls. Treatment with SO did not change significantly any parameter, but an overall trend to mildly decreased HRV that reached a significant value only during R sleep. CONCLUSIONS: HRV during all sleep stages tended to be slightly higher in young patients when compared to controls, confirming the presence of a slight sympathovagal system imbalance even in NT1 children. SO tends to decrease these values especially during REM sleep and in that regard, further studies supporting these preliminary findings and considering the long-term effects of SO on heart rate parameters are warranted.


Assuntos
Adjuvantes Anestésicos/administração & dosagem , Frequência Cardíaca/fisiologia , Narcolepsia/tratamento farmacológico , Oxibato de Sódio/administração & dosagem , Criança , Eletrocardiografia/métodos , Feminino , Humanos , Masculino , Polissonografia/métodos , Fases do Sono/fisiologia
19.
Int J STD AIDS ; 29(2): 128-134, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28691863

RESUMO

Reports of sexualised drug taking (chemsex) have increased significantly in recent years. There is currently limited intelligence on chemsex outside of London. An anonymous survey was promoted via several sources including voluntary services and a sexual health clinic in order to establish the risks associated with chemsex, and how support services can best be tailored to meet the needs of those in Greater Manchester, UK. Quantitative and qualitative data were collected on demographics, drug use, sexual practices and barriers and facilitators to accessing support. Fifty-two men who have sex with men completed the online survey. Thirty-nine (75%) were HIV-positive and 11 (21%) were hepatitis C virus (HCV) positive, all of whom were HIV/HCV co-infected. The most commonly used drugs were mephedrone (81%) and gamma hydroxybutyrate/gamma butyrolactone (79%). Nineteen (37%) reported ever injecting drugs. High-risk sexual practices were reported by respondents. Barriers to accessing support included a fear of being recognised. Findings demonstrate those engaging in chemsex are participating in a number of high-risk sexual practices, taking substances with significant risks and administering these substances in potentially high-risk ways. Results demonstrate the need for promotion of existing services, with key areas to target where chemsex sessions are most commonly arranged. Results may be useful in other metropolitan cities, both for commissioning and tailoring of chemsex support services.


Assuntos
4-Butirolactona/administração & dosagem , Infecções por HIV/epidemiologia , Hepatite C/epidemiologia , Homossexualidade Masculina/psicologia , Internet , Metanfetamina/análogos & derivados , Comportamento Sexual/efeitos dos fármacos , Oxibato de Sódio/administração & dosagem , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , 4-Butirolactona/efeitos adversos , Adulto , Coinfecção/epidemiologia , Infecções por HIV/diagnóstico , Redução do Dano , Humanos , Londres/epidemiologia , Masculino , Metanfetamina/administração & dosagem , Metanfetamina/efeitos adversos , Pessoa de Meia-Idade , Assunção de Riscos , Parceiros Sexuais , Oxibato de Sódio/efeitos adversos , Inquéritos e Questionários , Sexo sem Proteção , Adulto Jovem
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