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1.
Int J Mol Sci ; 21(21)2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33142953

RESUMO

New psychoactive substances are being used as drugs and appear to be quite popular nowadays. Thanks to their specific properties, these drugs create inimitable experiences for intoxicated people. Synthetic cathinones are the most common compounds in these new drugs. Among them, α-pyrrolidopentadione (α-PVP), or "Flakka" (street name), is one of the most famous cathinone-designed drugs. Similar to other synthetic cathinone drugs, α-PVP can effectively inhibit norepinephrine and dopamine transmitters. The adverse reactions of α-PVP mainly include mania, tachycardia, and hallucinations. An increasing number of people are being admitted to emergency wards due to the consequences of their use. This work mainly summarizes the history, synthesis, pharmacology, toxicology, structure-activity relationship, metabolism, clinical process and health risks, poisoning and death, forensic toxicology, and legal status of α-PVP. We hope this review will help bring more attention to the exploration of this substance in order to raise awareness of its negative impacts on humans.


Assuntos
Alcaloides/envenenamento , Estimulantes do Sistema Nervoso Central/envenenamento , Drogas Ilícitas/envenenamento , Pentanonas/envenenamento , Psicotrópicos/envenenamento , Pirrolidinas/envenenamento , Transtornos Relacionados ao Uso de Substâncias/etiologia , Humanos , Relação Estrutura-Atividade , Transtornos Relacionados ao Uso de Substâncias/patologia
2.
Forensic Sci Med Pathol ; 16(3): 493-497, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32219708

RESUMO

We describe the sudden death of a middle-aged man while having a sauna under the influence of α-pyrrolidinovalerophenone (α-PVP) (PM blood concentration: 0.8 mg/L), amphetamine (0.34 mg/L), and other drugs (buprenorphine, benzodiazepines), and engaging in solitary sexual activities. The drugs' effects on the cardio-circulatory system and on body thermoregulation combined with the high temperatures are likely to have been central mechanisms leading to death. The high levels of adrenaline triggered by sexual arousal and the respiratory depression caused by buprenorphine, in association with benzodiazepines, may have also contributed to his death. This previously unreported type of accidental autoerotic death illustrates the risk of using amphetamine-like sympathomimetic drugs (e.g. cathinone derivates) in hot environments such as a sauna, and during sexual activities therein.


Assuntos
Anfetamina/envenenamento , Drogas Desenhadas/envenenamento , Masturbação , Pirrolidinas/envenenamento , Banho a Vapor/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/complicações , Anfetamina/sangue , Benzodiazepinas/sangue , Buprenorfina/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Pirrolidinas/sangue , Insuficiência Respiratória
3.
Leg Med (Tokyo) ; 42: 101626, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31751796

RESUMO

INTRODUCTION: Cathinones are currently the second largest and the second most frequently seized group of new psychoactive substances (NPS). One of the most recent synthetic cathinones that has appeared on the 'legal highs' market is alpha-pyrrolidinoisohexanophenone (α-PiHP). CASE HISTORY: An 18-year-old man was found dead in an apartment. The autopsy materials were collected for toxicological analyses. METHODS: The quantitative analyses were carried out by LC-MS/MS. RESULTS: α-PiHP was detected and quantified in all post-mortem materials except the hair. The determined concentrations of the compound in the blood, urine and bile were 69 ng/mL, 2072 ng/mL, and 341 ng/mL respectively. The concentrations of α-PiHP in solid tissues were in the range of 7-478 ng/g. 4-Chloromethcathinone (4-CMC), N-ethylhexedrone, benzoylecgonine and 3,4-methylenedioxymethamphetamine (MDMA) were also detected in some materials. DISCUSSION: No cases presenting concentrations of α-PiHP in biological materials have been reported so far. Due to the similarity of structures and the reported dosages, an attempt to compare the concentrations of α-PVP and α-PHP has been made. In the described case, functional death through intoxication of α-PiHP was accepted as the final cause of death. The other detected substances did not contribute to death due to their very likely distant administration. CONCLUSION: α-PiHP is another new synthetic cathinone that is a danger to the life of users. The described fatal intoxication case presents the concentrations of α-PiHP in post-mortem materials. This data could be valuable for further interpretation of other results from toxicological analyses in cases where the use of α-PiHP is suspected.


Assuntos
Medicina Legal , Pirrolidinas/envenenamento , Adolescente , Cromatografia Líquida/métodos , Humanos , Masculino , Pirrolidinas/análise , Espectrometria de Massas em Tandem/métodos
4.
Leg Med (Tokyo) ; 35: 44-49, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30268690

RESUMO

We report a case of intoxication with a mixture of three synthetic cannabinoids and a synthetic cathinone, which have been disclosed by a highly sensitive progressing technology. A man was found dead, and his forensic autopsy was performed at our department. After further examinations of his specimens, EAM-2201 and α-PVP have been newly found in his lung. The concentrations of EAM-2201 have not been reported yet in any authentic human specimens although its existence (not quantified) in blood was reported in 2015. Therefore, a sensitive quantitation method of these compounds in blood and solid tissues has been devised using the sensitive instrument. The limits of detection of these compounds were in the range of 3-10 pg/ml with their quantification range of 10-1000 pg/ml in blood. The femoral vein blood levels of EAM-2201 and AB-PINACA were 56.6 ±â€¯4.2 and 12.6 ±â€¯0.1 pg/ml, respectively, and AB-FUBINACA could be detected but not quantifiable in the blood specimens; α-PVP could not be detected. The standard addition method was employed for the quantification of these compounds in the lung, liver and kidney specimens. The lung levels of EAM-2201, AB-PINACA, AB-FUBINACA and α-PVP were 348 ±â€¯34, 355 ±â€¯30, 124 ±â€¯12 and 59.0 ±â€¯7.4 pg/g, respectively. In conclusion, in this study, the concentrations of EAM-2201 in authentic human specimens including blood and solid tissues and those of AB-PINACA and AB-FUBINACA in solid tissue specimens were quantified for the first time to our knowledge.


Assuntos
Alcaloides/envenenamento , Canabinoides/envenenamento , Indazóis/envenenamento , Indóis/envenenamento , Naftalenos/envenenamento , Pentanonas/envenenamento , Pirrolidinas/envenenamento , Valina/análogos & derivados , Alcaloides/sangue , Alcaloides/metabolismo , Autopsia , Canabinoides/sangue , Canabinoides/metabolismo , Medicina Legal , Humanos , Indazóis/sangue , Indazóis/metabolismo , Indóis/sangue , Indóis/metabolismo , Rim/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , Masculino , Naftalenos/sangue , Naftalenos/metabolismo , Pentanonas/sangue , Pentanonas/metabolismo , Pirrolidinas/sangue , Pirrolidinas/metabolismo , Distribuição Tecidual , Valina/sangue , Valina/metabolismo , Valina/envenenamento
5.
J Med Toxicol ; 14(4): 265-271, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29923027

RESUMO

INTRODUCTION: Many new psychoactive substances (NPS) introduced as recreational drugs have been associated with severe intoxication and death. METHODS: Blood and/or urine samples were collected from intoxicated patients treated at Swedish hospitals that participated in the STRIDA project, a nationawide effort to address the growing problem of NPS. In patients undergoing evaluation for drug overdose, α-PBP was identified using liquid chromatography-mass spectrometry. Demographic and clinical data were collected during Poisons Information Centre consultations and retrieved from medical records. RESULTS: From April 2013 to November 2015, 43 patients tested positive for α-PBP. However, α-PBP was never specifically mentioned during consultation but only confirmed analytically. The α-PBP concentrations ranged 2.0-13,200 ng/mL in urine and 2.0-440 ng/mL in serum. The patients were aged 19-57 (mean 34) years, 81% were men, and 73% were known drug addicts. All cases except 1 also involved other NPS and/or classical drugs. MDPV, α-PVP, and other pyrovalerone analogues were the most common other NPS (31 cases; 72%). CNS depressants were detected in 28 cases (65%), with benzodiazepines (16 cases) being most frequent. Main clinical characteristics were agitation/anxiety (59%), tachycardia (54%), and hypertension (37%), and 14 patients (33%) required monitoring in the intensive care unit of which 8 were graded as severe intoxications. No fatalities were reported. CONCLUSION: Patients with intoxication from α-PBP resembled those by NPS cathinones MDPV and α-PVP. As patients never specifically declared α-PBP intake and poly-drug intoxication was common, they may have been unaware of the actual substance taken.


Assuntos
Drogas Desenhadas/envenenamento , Overdose de Drogas/epidemiologia , Pentanonas/envenenamento , Pirrolidinas/envenenamento , Adulto , Ansiedade/induzido quimicamente , Ansiedade/epidemiologia , Ansiedade/psicologia , Depressores do Sistema Nervoso Central/envenenamento , Cromatografia Líquida de Alta Pressão , Demografia , Overdose de Drogas/terapia , Usuários de Drogas/estatística & dados numéricos , Feminino , Humanos , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Agitação Psicomotora/epidemiologia , Agitação Psicomotora/psicologia , Estudos Retrospectivos , Suécia/epidemiologia , Taquicardia/induzido quimicamente , Taquicardia/epidemiologia , Adulto Jovem
6.
Clin Toxicol (Phila) ; 56(4): 256-263, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28895757

RESUMO

CONTEXT: An increasing number of new psychoactive substances (NPS) of different chemical classes have become available through marketing and sale over the Internet. This report from the Swedish STRIDA project presents the prevalence, laboratory results, and clinical features in intoxications involving 11 stimulant pyrovalerone NPS derivatives over a 5-year period. STUDY DESIGN: Case series of consecutive patients with admitted or suspected intake of NPS presenting to Swedish hospitals for emergency treatment from January 2011 to March 2016. PATIENTS AND METHOD: Blood and urine samples were collected from intoxicated patients presenting to hospitals all over Sweden. Analyses of NPS and other drugs of abuse were performed by immunochemical and liquid chromatography-mass spectrometry multi-component methods. Clinical data were collected during consultation with the Swedish Poisons Information Centre (PIC), and retrieved from medical records. The study involved analytically confirmed cases with 11 pyrovalerone drugs. RESULTS: During the study period, 114 intoxications were detected that involved any of 11 new pyrovalerone drugs. In addition to these new pyrovalerone derivatives, 3,4-methylenedioxypyrovalerone (MDPV) was detected in 17 of the cases and α-pyrrolidinovalerophenone (α-PVP) in 45 cases. Identification was made according to forensic standards and comprised the following substances: 4F-α-PVP, α-PHP, PV8, 4Me-PPP, α-PBP, 4F-PV8, α-PPP, MDPHP, α-PVT, 4Cl-α-PVP, and 4F-α-PHP. The three most frequently detected drugs were α-PBP, MDPHP, and 4F-α-PVP. The age range of patients was 16-66 (median 30) years and 84% were males. The substance concentrations in urine and serum were highly variable, ranging from 1 ng/mL to 300 µg/mL. Poly-drug use was common with only 8 of 114 cases (7%) involving one pyrovalerone drug. The additional substances comprised other NPS and classical psychoactive drugs. The patients showed a variety of clinical signs; agitation, delirium, hallucinations, excessive motor activity, seizures, tachycardia, hypertension, and/or hyperthermia. CONCLUSIONS: In analytically confirmed NPS-related intoxications, 11 new pyrovalerone derivatives in addition to MDPV and α-PVP were found. The clinical features were consistent with a sympathomimetic toxidrome, but the urine and serum concentrations were highly variable. The results demonstrated that many novel pyrovalerone stimulants were introduced on the recreational NPS drugs market. Analytical investigations were necessary to obtain this information.


Assuntos
Benzodioxóis/envenenamento , Estimulantes do Sistema Nervoso Central/envenenamento , Pirrolidinas/envenenamento , Adolescente , Adulto , Idoso , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Suécia/epidemiologia , Adulto Jovem , Catinona Sintética
7.
Intern Med J ; 47(1): 109-111, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28076917

RESUMO

Methylenedioxypyrovalerone (MDPV) is a synthetic, cathinone-derivative, central nervous system stimulant taken to produce a cocaine- or methamphetamine-like high. Physical manifestations include tachycardia, hypertension, arrhythmias, hyperthermia, sweating, rhabdomyolysis, hyperkalaemia, disseminated intravascular coagulation, oliguria and seizures. We report a patient who presented with severe metabolic acidosis, multi-organ dysfunction, rhabdomyolysis, hyperkalaemia and seizures. This case highlights that even though a urine drug screen for routine psychostimulant drugs is negative, clinicians need to be vigilant about the adverse effects of MDPV as a possible cause of multi-organ dysfunction. Substances such as this can only be detected by special tests, such as gas/liquid chromatography mass spectrometry. This is the first reported case of MDPV toxicity successfully treated in Australia to the best of our knowledge.


Assuntos
Benzodioxóis/envenenamento , Estimulantes do Sistema Nervoso Central/envenenamento , Drogas Desenhadas/envenenamento , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Insuficiência de Múltiplos Órgãos/terapia , Pirrolidinas/envenenamento , Adulto , Alcaloides/agonistas , Austrália , Febre/induzido quimicamente , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Terapia de Substituição Renal , Rabdomiólise/induzido quimicamente , Catinona Sintética
8.
J Forensic Sci ; 62(2): 553-556, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28028802

RESUMO

This study presents the fatal case of a young man who was admitted to the ICAU due to sudden cardiac arrest. An interview revealed that the patient had taken some unspecified crystals. From the moment of admission, his condition deteriorated dramatically as a result of increasing circulatory insufficiency. After a few hours, sudden cardiac arrest occurred again and the patient was pronounced dead. In the course of a medicolegal autopsy, samples of biological material were preserved for toxicology tests and histopathological examination. The analysis of samples using the LC-MS/MS technique revealed the presence of α-PVP in the following concentrations: blood-174 ng/mL, urine-401 ng/mL, brain-292 ng/g, liver-190 ng/g, kidney-122 ng/g, gastric contents-606 ng/g. The study also presents findings from the parallel histopathological examination. Based on these findings, cardiac arrest secondary to intoxication with alpha-PVP was determined as the direct cause of the patient's death.


Assuntos
Alcaloides/envenenamento , Drogas Desenhadas/envenenamento , Psicotrópicos/envenenamento , Pirrolidinas/envenenamento , Adulto , Alcaloides/análise , Química Encefálica , Cromatografia Líquida , Drogas Desenhadas/análise , Conteúdo Gastrointestinal/química , Parada Cardíaca/induzido quimicamente , Humanos , Rim/química , Fígado/química , Masculino , Psicotrópicos/análise , Pirrolidinas/análise , Espectrometria de Massas em Tandem
10.
Clin Toxicol (Phila) ; 54(7): 568-75, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27412885

RESUMO

CONTEXT: An increasing number of new psychoactive substances (NPS) of different chemical classes have become available through marketing and sale over the Internet. This report from the Swedish STRIDA project presents the prevalence, laboratory results, and clinical features in a series of intoxications involving the stimulant NPS α-pyrrolidinovalerophenone (α-PVP), a potent dopamine re-uptake inhibitor, over a 4-year period. STUDY DESIGN: Observational case series of consecutive patients with admitted or suspected intake of NPS presenting to hospitals in Sweden from 2012 to 2015. PATIENTS AND METHODS: In the STRIDA project, blood and urine samples are collected from intoxicated patients with admitted or suspected intake of NPS or unknown drugs presenting to hospitals over the country. Analysis of NPS is performed by mass spectrometry multicomponent methods. Clinical data are collected when caregivers consult the Swedish Poisons Information Centre (PIC), and retrieved from medical records. The severity of poisoning is graded retrospectively using the Poisoning Severity Score (PSS). The inclusion criteria for this study included absence of other stimulants than α-PVP. RESULTS: During the 4-year study period, 23 intoxications were originally coded as "α-PVP related" out of a total 3743 NPS-related inquiries (0.6%) at the PIC. The present study covered 42 analytically confirmed cases in which α-PVP was the only stimulant detected. The age range of patients was 20-58 (median 32) years, of which 79% were males. The α-PVP concentration in serum was 4.0-606 (median 64; n = 42) ng/mL and 2.0-41,294 (median 1782; n = 25) ng/mL in urine. There was no statistically significant association between the serum α-PVP concentration and urinary α-PVP/creatinine ratio in 25 cases, where both sets of data were available. In 14/42 (33%) cases, α-PVP was the only psychoactive substance identified. In the remaining cases, additional substances comprised opioids, benzodiazepines, and ethanol. The main clinical manifestations were tachycardia (80%), agitation (70%), hypertension (33%), hallucinations (20%), and delirium (18%). Classification of poisoning severity yielded 25 (60%) moderate (PSS 2), 7 (17%) severe (PSS 3), and 2 fatal cases (PSS 4). CONCLUSIONS: In analytically confirmed α-PVP intoxication cases involving no other stimulant drugs, the urine and serum concentrations showed high variability. The clinical features were consistent with a severe sympathomimetic toxidrome. The results further demonstrated that α-PVP prevailed as a drug of abuse after being classified as a narcotic substance, and despite a high incidence of severe poisonings and fatalities. However, the low prevalence of α-PVP cases registered at the PIC suggested that many were unaware of the actual substance they had taken.


Assuntos
Estimulantes do Sistema Nervoso Central/envenenamento , Drogas Ilícitas/envenenamento , Pirrolidinas/envenenamento , Adulto , Analgésicos Opioides/sangue , Analgésicos Opioides/envenenamento , Analgésicos Opioides/urina , Benzodiazepinas/sangue , Benzodiazepinas/envenenamento , Benzodiazepinas/urina , Estimulantes do Sistema Nervoso Central/sangue , Estimulantes do Sistema Nervoso Central/urina , Creatinina/urina , Delírio/induzido quimicamente , Delírio/diagnóstico , Inibidores da Captação de Dopamina/sangue , Inibidores da Captação de Dopamina/envenenamento , Inibidores da Captação de Dopamina/urina , Etanol/sangue , Etanol/envenenamento , Etanol/urina , Feminino , Alucinações/induzido quimicamente , Alucinações/diagnóstico , Hospitalização , Humanos , Hipertensão/induzido quimicamente , Hipertensão/diagnóstico , Drogas Ilícitas/sangue , Drogas Ilícitas/urina , Masculino , Pessoa de Meia-Idade , Prevalência , Agitação Psicomotora/diagnóstico , Agitação Psicomotora/etiologia , Pirrolidinas/sangue , Pirrolidinas/urina , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/etiologia , Suécia , Taquicardia/induzido quimicamente , Taquicardia/diagnóstico , Adulto Jovem
11.
Clin Toxicol (Phila) ; 54(7): 563-7, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27227375

RESUMO

CONTEXT: α-Pyrrolidinovalerophenone (α-PVP) is a synthetic cathinone that has been abused in recent years. The clinical presentation of acute α-PVP poisoning has not been well characterized. OBJECTIVE: To elucidate the clinical features of acute α-PVP poisoning. MATERIALS AND METHODS: This retrospective case series included eight subjects that visited our hospital emergency department (ED) between March 2012 and November 2014 and had analytically confirmed blood α-PVP levels. Data related to subject demographics, clinical history, laboratory findings, blood drug levels, and outcome were collected. RESULTS: The median age of the eight study subjects was 27 (range; 21-63) years, and six were male. Drug preparations had been administered by rectal insertion (three subjects) or inhalation (five subjects). The time between drug exposure and presentation at the ED was 8.5 (1-24) h and blood α-PVP concentrations ranged from 1.0 to 52.5 ng/ml. Although psychiatric and neurological findings were reported before arrival at the ED in 5/8 and 7/8 subjects, respectively, these were only observed in 1/8 and 2/8 subjects, respectively, at the ED. Symptoms of high body temperature (3/8), tachycardia (5/8), hypertension (3/8), acid-base balance disorder (5/8), coagulopathy (4/6), blood creatinine phosphokinase >190 U/l (6/8), and a blood lactate level > 1.7 mmol/l (5/7) were observed. All subjects survived and were discharged. CONCLUSIONS: This retrospective case series showed that after acute exposure to α-PVP, transient neuropsychiatric findings were accompanied by more persistent sympathomimetic physical findings, disorders of acid-base balance and blood coagulation, high blood creatinine phosphokinase, and hyperlactacidemia.


Assuntos
Pirrolidinas/envenenamento , Detecção do Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Equilíbrio Ácido-Base , Adulto , Coagulação Sanguínea/efeitos dos fármacos , Creatina Quinase/sangue , Feminino , Humanos , Hiperlactatemia/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Substâncias/etiologia , Adulto Jovem
13.
Forensic Sci Int ; 265: 160-5, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26930452

RESUMO

This is a case report of a fatal intoxication in Cyprus related to 3,4-methylenedioxypyrovalerone (MDPV) and 2-(methylamino)-1-phenylpentan-1-one (pentedrone) intake combined with antipsychotic and antidepressant substances. A 42- year old man with a history of serious psychiatric illness was found unresponsive in his bed. Seized materials were also found close to his body. The forensic autopsy reported myocardial infarction due to multidrug intoxication. Toxicology screening in blood and urine was applied. Biological specimens were analysed by enzyme immunoassay procedure and GC/MS. MDPV, pentedrone and etizolam detected and quantitated in blood and urine. Other drugs quantitated in blood were also olanzapine, mirtazapine, and ephedrine. This was the first fatal case reported in Cyprus associated with new psychoactive substances. Additionally, this was the first case reported to Early Warning System of the European Monitoring Center of Drugs and Drug Abuse (EMCDDA), related to multidrug intoxication, attributed to the consumption of cathinones, designer benzodiazepines, and other drugs.


Assuntos
Intoxicação/diagnóstico , Adulto , Antidepressivos/sangue , Antidepressivos/envenenamento , Antipsicóticos/sangue , Antipsicóticos/envenenamento , Benzodioxóis/sangue , Benzodioxóis/envenenamento , Chipre , Evolução Fatal , Toxicologia Forense , Humanos , Masculino , Metilaminas/sangue , Metilaminas/envenenamento , Pentanonas/sangue , Pentanonas/envenenamento , Intoxicação/sangue , Pirrolidinas/sangue , Pirrolidinas/envenenamento , Catinona Sintética
14.
Forensic Sci Int ; 259: e14-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26775198

RESUMO

α-Pyrrolidinovalerophenone (α-PVP) is a synthetic cathinone belonging to the group of "second generation" pyrrolidinophenones that becomes more and more popular as a designer psychostimulant. Here we provide toxicological analytical support for a severe poisoning with α-PVP. Serum and urine samples that were sent to our laboratory were subjected to a general unknown screening procedure. The procedure includes immunoassay-based screening of drugs of abuse in serum and systematic toxicological analysis of urine and serum after neutral and basic liquid-liquid extraction followed by gas chromatography-mass spectrometry (GC-MS). Whereas the immunoassay delivered negative results, analyzing the urine sample by GC-MS in full scan mode disclosed the presence of α-PVP and its metabolites α-(2″-oxo-pyrrolidino)valerophenone (2″-oxo-α-PVP) and 1-phenyl-2-(pyrrolidin-1-yl)pentan-1-ol (OH-α-PVP). In the acetylated urine sample we found additionally N,N-bis-dealkyl-PVP. In serum, α-PVP could be detected after solid phase extraction and a concentration of 29ng/mL was determined. Other forensic relevant substances were not detected. The presented data can explain the psychotic symptoms and behavioural pattern of the subject after abuse of α-PVP, leading to a clinical condition similar to excited delirium syndrome.


Assuntos
Delírio/induzido quimicamente , Drogas Desenhadas/análise , Cromatografia Gasosa-Espectrometria de Massas , Pirrolidinas/sangue , Pirrolidinas/urina , Doença Aguda , Adulto , Delírio/sangue , Delírio/urina , Humanos , Masculino , Pirrolidinas/envenenamento
15.
Neurocrit Care ; 24(3): 454-8, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26666544

RESUMO

BACKGROUND: "Bath salts" or synthetic cathinone toxicity remains a potentially deadly clinical condition. We report a delayed leukoencephalopathy with persistent minimally conscious state. METHODS: Case report. RESULTS: A 36-year-old man presents with delayed encephalopathy, dysautonomia, fulminant hepatic failure, and renal failure from severe rhabdomyolysis after consuming bath salts. MRI showed diffusion restriction in the splenium of the corpus callosum and subcortical white matter. CONCLUSIONS: The combination of acute leukoencephalopathy, rhabdomyolysis and fulminant hepatic failure may point to bath salt inhalation and should be known to neurointensivists.


Assuntos
Alcaloides/envenenamento , Benzodioxóis/envenenamento , Cosméticos/envenenamento , Leucoencefalopatias/induzido quimicamente , Falência Hepática/induzido quimicamente , Estado Vegetativo Persistente/induzido quimicamente , Pirrolidinas/envenenamento , Insuficiência Renal/induzido quimicamente , Adulto , Humanos , Masculino , Rabdomiólise/induzido quimicamente , Catinona Sintética
16.
Clin Toxicol (Phila) ; 53(9): 865-73, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26462932

RESUMO

CONTEXT: In the recent years, there have been an increasing number of new psychoactive substances (NPS) available through marketing and sale on the Internet. The stimulant 3,4-methylenedioxypyrovalerone (MDPV) is a potent dopamine reuptake inhibitor, which can cause serious intoxications requiring intensive care and even fatality. This report from the STRIDA project presents the prevalence, laboratory results, and clinical features in a series of intoxications involving MDPV over a 5-year period. STUDY DESIGN: Observational case series of consecutive patients with admitted or suspected intake of NPS presented at hospitals in Sweden from 2010 to 2014. PATIENTS AND METHODS: Blood and/or urine samples were collected from intoxicated patients with admitted or suspected intake of NPS presenting at hospitals over the country. Analysis of NPS was performed by a liquid chromatography-tandem mass spectrometry multicomponent method. Clinical data were collected when caregivers consulted the Swedish Poisons Information Centre and also retrieved from medical records. The severity of poisoning was graded retrospectively using the poisoning severity score. RESULTS: During the 5-year study period, the number of MDPV-related inquiries to the Poisons Information Centre was 662 out of a total ∼4500 suspected NPS-related inquiries (∼15%), and 201 analytically confirmed MDPV intoxications were enrolled in the study. The study period covered the period when the use of MDPV in Sweden was at its peak and also the decline to an almost zero level. The age range of patients was 18-68 (mean 36, median 35) years, and 71% were males. The MDPV concentrations in serum ranged between 1.0 ng/mL and 1509 ng/mL (mean 63.6, median 20) and between 1.0 ng/mL and 81 000 ng/mL (mean 3880, median 1160) in urine. The urinary values were also creatinine corrected for variation in urine dilution, and the MDPV/creatinine ratio ranged between 0.10 ng/mmol and 2480 ng/mmol (mean 247, median 92.6). There was a statistically significant association between the serum MDPV concentration and the urinary MDPV/creatinine ratio, for 118 cases where both data were available (r = 0.764; p < 0.0001, Spearman's rank correlation). In 30 (15%) cases, MDPV was the single psychoactive substance identified in the serum or urine specimens. In the other 171 cases, other psychoactive substances were detected together with MDPV. The additional substances (n = 61) comprised of both conventional drugs of abuse, other NPS (n = 39), pharmaceuticals, and ethanol. The cathinone-derivative alpha-pyrrolidinovalerophenone (α-PVP) was the most frequent other NPS, and was detected in 58 (29%) cases, followed by methylone in 14 (7%) cases. The main clinical manifestations reported in patients testing positive for MDPV included agitation, tachycardia (≥100/min), and hypertension (systolic blood pressure ≥140 mmHg), which were observed in 130 (67%), 106 (56%), and 65 (34%) cases, respectively. Other symptoms included hallucinations (n = 31, 16%), delirium (n = 29, 15%), hyperthermia (>39°C/102.4°F; n = 18, 10%), and rhabdomyolysis (n = 16, 8%). In MDPV intoxications with serum levels >100 ng/mL, the cases were graded as more severe and hyperthermia was less common. CONCLUSIONS: In a large number of analytically confirmed MDPV intoxications from mostly polydrug users, the urine and serum MDPV concentrations showed a high variability. The clinical features were consistent with a severe sympathomimetic toxidrome. The results also demonstrated that MDPV prevailed as a drug of abuse for a long time, after its classification as a narcotic substance and despite a high incidence of severe poisonings.


Assuntos
Benzodioxóis/envenenamento , Inibidores da Captação de Dopamina/envenenamento , Psicotrópicos/envenenamento , Pirrolidinas/envenenamento , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Adulto , Idoso , Benzodioxóis/sangue , Benzodioxóis/urina , Biomarcadores/sangue , Biomarcadores/urina , Cromatografia Líquida , Inibidores da Captação de Dopamina/sangue , Inibidores da Captação de Dopamina/urina , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Centros de Controle de Intoxicações , Valor Preditivo dos Testes , Prevalência , Psicotrópicos/sangue , Psicotrópicos/urina , Pirrolidinas/sangue , Pirrolidinas/urina , Estudos Retrospectivos , Índice de Gravidade de Doença , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Suécia/epidemiologia , Espectrometria de Massas em Tandem , Fatores de Tempo , Adulto Jovem , Catinona Sintética
17.
Int J Legal Med ; 129(4): 741-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25833171

RESUMO

In this study, we sought to determine what impact the banning of 3, 4- methylenedioxypyrovalerone (MDPV) had on the incidence of MDPV-positive findings and on user profiles in driving under the influence of drugs (DUID) and postmortem (PM) investigations in Finland. All MDPV-positive cases and a selection of corresponding court cases between 2009 and 2012 were examined. The median serum concentration of MDPV in DUID cases was 0.030 mg/L and in PM blood 0.12 mg/L. The number of MDPV-positive cases decreased both in DUID and PM investigations after the drug was banned. The decrease in the mean monthly numbers of MDPV-positive DUID cases was 51.1%. In court cases, MDPV was rarely mentioned until banned and frequently mentioned thereafter. Of the convicted, 37% were without a fixed abode, 98% had other charges besides that of DUID, and 13% appeared in the study material more than once. In MDPV-positive PM cases, the proportion of suicides was very high (24%). Research on new psychoactive substances is required not only to support banning decisions but more importantly to be able to provide a scientific assessment of the risks of these new substances to the public and potential users.


Assuntos
Benzodioxóis/sangue , Drogas Desenhadas/análise , Dirigir sob a Influência/legislação & jurisprudência , Drogas Ilícitas/legislação & jurisprudência , Psicotrópicos/sangue , Pirrolidinas/sangue , Adulto , Benzodioxóis/efeitos adversos , Benzodioxóis/envenenamento , Drogas Desenhadas/efeitos adversos , Feminino , Finlândia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Psicotrópicos/efeitos adversos , Psicotrópicos/envenenamento , Pirrolidinas/efeitos adversos , Pirrolidinas/envenenamento , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Suicídio/estatística & dados numéricos , Adulto Jovem , Catinona Sintética
18.
J Anal Toxicol ; 39(4): 324-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25737339

RESUMO

We report a fatal case of combined α-pyrrolidinovalerophenone (α-PVP) and 2-(methylamino)-1-phenylpentan-1-one (pentedrone) poisoning. A 28-year-old man was taken to hospital in asystole. Despite resuscitation efforts over 30 min, he died. The forensic autopsy showed pulmonary edema and moderately advanced atherosclerotic lesions of the arteries. Microscopic observation revealed chronic changes in the heart. Confirmation of the presence of pentedrone, α-PVP, and its metabolite 1-phenyl-2-(pyrrolidin-1-yl)pentan-1-ol (OH-α-PVP) in tissues and fluids were achieved using gas chromatography-mass spectrometry analysis after liquid-liquid extraction. A quantitative validated liquid chromatography-mass spectrometry method was used to determine the concentrations of the above designer drugs in postmortem samples. Pentedrone, α-PVP, and OH-α-PVP concentrations were 8,794, 901 and 185 ng/mL in whole blood, respectively; 100,044, 2,610 and 2,264 ng/g in the liver, respectively; 22,102, 462 and 294 ng/g in the kidney, respectively; 13,248, 120 and 91 ng/g in the brain, respectively and 500,534, 4,190 and 47 ng/g in the stomach contents, respectively. This is the first known reported death attributed to the combined use of α-PVP and pentedrone. Additionally, this article is the first to report the distribution of pentedrone in postmortem human samples.


Assuntos
Drogas Desenhadas/envenenamento , Metilaminas/envenenamento , Pentanonas/envenenamento , Pirrolidinas/envenenamento , Adulto , Cromatografia Líquida , Drogas Desenhadas/administração & dosagem , Sinergismo Farmacológico , Evolução Fatal , Humanos , Rim/metabolismo , Extração Líquido-Líquido , Fígado/metabolismo , Masculino , Espectrometria de Massas , Metilaminas/administração & dosagem , Pentanonas/administração & dosagem , Intoxicação/sangue , Intoxicação/etiologia , Pirrolidinas/administração & dosagem , Distribuição Tecidual
19.
J Med Toxicol ; 11(2): 185-94, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25468313

RESUMO

The objective of this study was to characterize the acute clinical effects, laboratory findings, complications, and disposition of patients presenting to the hospital after abusing synthetic cathinone. We conducted a retrospective multicenter case series of patients with synthetic cathinone abuse by searching for the terms bath salts, MDPV, methylenedioxypyrovalerone, mephedrone, methcathinone, methylone, methedrone, and cathinone within the "agent" field of a national clinical toxicology database (ToxIC). The medical records of these patients were obtained and abstracted by investigators at each study site. Patients with confirmatory testing that identified a synthetic cathinone in either blood or urine were included in the series. Patients who had either an undetectable synthetic cathinone test or no confirmatory testing were excluded. A data abstraction sheet was used to obtain information on each patient. We entered data into an Excel spreadsheet and calculated descriptive statistics. We identified 23 patients with confirmed synthetic cathinone exposure--all were positive for methylenedioxyprovalerone (MDPV). Eighty-three percent were male and 74 % had recreational intent. The most common reported clinical effects were tachycardia (74 %), agitation (65 %), and sympathomimetic syndrome (65 %). Acidosis was the most common laboratory abnormality (43 %). Seventy-eight percent of patients were treated with benzodiazepines and 30 % were intubated. Ninety-six percent of patients were hospitalized and 87 % were admitted to the ICU. The majority (61 %) of patients was discharged home but 30 % required inpatient psychiatric care. There was one death in our series. The majority of patients presenting to the hospital after abusing MDPV have severe sympathomimetic findings requiring hospitalization. A number of these patients require inpatient psychiatric care after their acute presentation.


Assuntos
Alcaloides/envenenamento , Benzodioxóis/envenenamento , Pirrolidinas/envenenamento , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adolescente , Adulto , Fatores Etários , Diagnóstico Duplo (Psiquiatria) , Feminino , Humanos , Hipnóticos e Sedativos/uso terapêutico , Drogas Ilícitas , Lorazepam/uso terapêutico , Masculino , Pessoa de Meia-Idade , Agitação Psicomotora/psicologia , Sistema de Registros , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Resultado do Tratamento , Adulto Jovem , Catinona Sintética
20.
J Forensic Sci ; 60(1): 95-101, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25421110

RESUMO

Knowledge concerning the distribution of methadone in postmortem human tissue and the effect of postmortem redistribution on methadone is today limited making the choice of a suitable substitute for femoral blood difficult when this is not available. Cardiac blood, femoral blood, muscle, and brain tissue concentrations of the enantiomers of methadone and its metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium were recorded for 155 postmortem cases. Brain and muscle tissue concentrations exceeded the femoral blood concentrations with a median fold of 2.3 and 1.6, respectively, but both had a better correlation than cardiac blood to femoral blood concentrations. The Kruskal-Wallis test showed a significant dependency on time and body mass index for some of the matrix ratios over femoral blood. We conclude brain or muscle tissue may constitute a better alternative for measurement of methadone than cardiac blood for situations in which femoral blood is not available, despite concentrations in both matrices being systematically higher.


Assuntos
Metadona/análise , Entorpecentes/análise , Mudanças Depois da Morte , Pirrolidinas/análise , Adulto , Idoso , Índice de Massa Corporal , Química Encefálica , Feminino , Toxicologia Forense , Humanos , Masculino , Metadona/farmacocinética , Metadona/envenenamento , Pessoa de Meia-Idade , Músculo Esquelético/química , Entorpecentes/farmacocinética , Entorpecentes/envenenamento , Pirrolidinas/farmacocinética , Pirrolidinas/envenenamento , Adulto Jovem
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