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Alharbi S, Aldubayan MA, Alhowail AH, Almogbel YS, Emara AM. Co-abuse of amphetamine and alcohol harms kidney and liver. Sci Rep 2024; 14:23400. [PMID: 39379507 PMCID: PMC11461853 DOI: 10.1038/s41598-024-74459-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Accepted: 09/26/2024] [Indexed: 10/10/2024] Open
Abstract
The prevalence of alcohol use disorder was found 75% higher among amphetamine dependent patients. Alcohol and amphetamine alone have nephrotoxicity and hepatoxicity. But, the degree of risk with coabuse of alcohol and amphetamine is unknown. The objective of this study was to assess toxic effects of amphetamine-alcohol co-abuse on the liver and kidney. he present study was a cross-sectional study conducted et al. Amal Hospital for Mental Health, Qassim region, KSA and include one hundred participants. Seventy-five participants were patients hospitalized for the treatment of abuse, and twenty-five participants, were healthy voluntaries, have no history of abuse. An experienced psychiatrist conducted patient interviews and assessed the patients using the DSM-5 criteria. The data from healthy participants were considered as a control. The abuse group was paired with the control group by age and lifestyle. Participants were split into: Group I: Control group (n = 25); Group II: Amphetamine (AMP) abuser group (n = 25); Group III: Alcohol abuser group (n = 25) and Group IV: Combined drug abuser group (AMP and alcohol) (n = 25). The socio-demographic data was collected. Complete medical examination, Body Mass Index and samples of blood and urine were collected from all participants for analytical tests; determination of alcohol and AMP levels, kidney functions and liver functions. The mean BMI values in groups II, III, and IV showed no significant change from the control group. The serum level of albumin and alkaline phosphatase showed significant decrease in all abuser groups. While, alanine transaminase (ALT), Aspartate transaminase (AST) and osteopontin levels showed significant increase in all abuser groups. Fasting blood sugar values showed significant increase in alcohol abusers. On the other hand, it revealed no significant change in AMP and combined groups. The mean values of urea showed no significant change in AMP and alcohol abusers and significant increase in combined drug abuser group. The serum creatinine and all abuser groups showed significant increase in Cystatin C. The alteration in the most of studied biochemical parameters were more than two folds in combined group compared with that of AMP or alcohol groups. Study reveals synergistic liver and kidney toxicity. Amphetamine-alcohol co-abuse significantly heightens kidney and liver toxicity.
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Affiliation(s)
- Sharifah Alharbi
- Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Al Qassim, 51452, Buraydah, Saudi Arabia
| | - Maha A Aldubayan
- Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Al Qassim, 51452, Buraydah, Saudi Arabia
| | - Ahmad H Alhowail
- Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Al Qassim, 51452, Buraydah, Saudi Arabia
| | - Yasser S Almogbel
- Department of Pharmacy Practice, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia
| | - Ashraf M Emara
- Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Al Qassim, 51452, Buraydah, Saudi Arabia.
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Abstract
Substance use disorders (SUDs) are often associated with alcohol use disorders (AUDs) and psychiatric comorbidities. In addition, they are often subjected to polytherapy. For these reasons SUDs patients are at greater risk of developing liver disease. In this concise review, liver damage from amphetamines, cannabinoids, cocaine and opioids is analyzed and the need to identify a possible associated alcohol use disorder is also suggested. Early identification of liver fibrosis is required in SUDs patients. Fibrosis is the most significant predictor of both prognosis and long-term survival. Its identification helps to promote the abstention from substances and alcohol. Active use of heroin, cocaine and synthetic substances is an absolute contraindication for liver transplantation. In cases of remission and adherence to a significant care path, the patient is re-evaluated. An addiction specialist should be present within the transplant team. If this is not present, a close collaboration with an addiction unit is mandatory.
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Affiliation(s)
- Gianni Testino
- Unit of Addiction and Hepatology, Alcohological Regional Centre, ASL3 c/o San Martino Hospital, Genoa, Italy -
| | - Patrizia Balbinot
- Unit of Addiction and Hepatology, Alcohological Regional Centre, ASL3 c/o San Martino Hospital, Genoa, Italy
| | - Rinaldo Pellicano
- Unit of Gastroenterology, Molinette Hospital, Città della Salute e della Scienza, Turin, Italy
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Nicol JJE, Yarema MC, Jones GR, Martz W, Purssell RA, MacDonald JC, Wishart I, Durigon M, Tzemis D, Buxton JA. Deaths from exposure to paramethoxymethamphetamine in Alberta and British Columbia, Canada: a case series. CMAJ Open 2015; 3:E83-90. [PMID: 25844375 PMCID: PMC4382046 DOI: 10.9778/cmajo.20140070] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Paramethoxymethamphetamine (PMMA) is a ring-substituted amphetamine similar in structure to 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"), but substantially more toxic. We describe the clinical features of fatal exposures in the provinces of Alberta and British Columbia, Canada. METHODS We conducted a retrospective case series on deaths in Alberta and BC between June 2011 and April 2012 for which forensic toxicologic analysis was positive for PMMA and the drug was implicated as the primary toxic agent. Data collected included patient demographics, exposure history, clinical features, investigations, therapy provided and postmortem toxicologic findings. RESULTS A total of 27 PMMA-associated deaths (20 in Alberta, 7 in BC) were reported in the 11-month period. The median age was 24 (range 14-52) years, and 22 (81%) were male. Ten patients were pronounced dead at the scene, and 17 died in hospital. The median time from exposure to death was 17 (range 5-264) hours. The median first-recorded vital signs (and ranges) were: heart rate 160 (86-201) beats/min, blood pressure 89/43 (69/30-162/83) mm Hg, respiratory rate 40 (26-48) breaths/min, oxygen saturation 81% (68%-100%) and temperature 39.4°C (34-43.8°C). Sixteen of the 17 people who died in hospital presented with clinical features consistent with serotonin syndrome. End-organ dysfunction included hepatic (30%) and acute kidney injury (85%), rhabdomyolysis (54%), coagulopathy (61%) and cardiac ischemia (15%). Other drugs identified on toxicologic analysis were MDMA (n = 27), cocaine or its metabolite benzoylecgonine (n = 14) and methamphetamine (n = 12). INTERPRETATION Exposure to PMMA was characterized by multiorgan dysfunction and serotonin syndrome, followed by cardiovascular collapse. In addition to PMMA, multiple synthetic amphetamines were present on toxicologic analysis. When evaluating patients suspected of exposure to sympathomimetic drugs of abuse, clinicians must anticipate multiple clinical effects from the increased release of dopamine, serotonin, norepinephrine and other neurotransmitters.
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Affiliation(s)
| | - Mark C Yarema
- Department of Emergency Medicine, University of Calgary, Calgary, Alta. ; Poison and Drug Information Service, Alberta Health Services, Calgary, Alta
| | | | | | - Roy A Purssell
- British Columbia Drug and Poison Information Centre, Vancouver, BC ; Department of Emergency Medicine, University of British Columbia, Vancouver, BC
| | - Judy C MacDonald
- Population, Public and Aboriginal Health, Alberta Health Services - Calgary Zone, Calgary, Alta. ; Department of Community Health Sciences, University of Calgary, Calgary, Alta
| | - Ian Wishart
- Department of Emergency Medicine, University of Calgary, Calgary, Alta
| | - Monica Durigon
- Environmental Health Services, British Columbia Centre for Disease Control, Vancouver, BC ; Canadian Field Epidemiology Program, Public Health Agency of Canada, Ottawa, Ont
| | - Despina Tzemis
- British Columbia Centre for Disease Control, Vancouver, BC
| | - Jane A Buxton
- School of Population and Public Health, University of British Columbia, Vancouver, BC ; British Columbia Centre for Disease Control, Vancouver, BC
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Luciano RL, Perazella MA. Nephrotoxic effects of designer drugs: synthetic is not better! Nat Rev Nephrol 2014; 10:314-24. [PMID: 24662435 DOI: 10.1038/nrneph.2014.44] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Designer drugs are synthetic, psychoactive substances with similar structures and activity to existing scheduled drugs or controlled chemical compounds. The use of these drugs is not generally considered illegal and they cannot be detected using standard toxicology tests--essentially they are considered to be 'legal highs'. Over the past several years, increasing numbers of designer drugs have become available. These drugs are classified as amphetamine derivatives, phenylpiperazine derivatives, synthetic cathinones, synthetic cannabinoids, phencyclidine derivatives and synthetic opioids. Although euphoria is the desired effect, neuropsychiatric and cardiac manifestations are frequently observed in individuals using these drugs at high doses or using drugs that are contaminated with other substances. Some designer drugs are also associated with adverse renal effects, including acute kidney injury from pigment nephropathy, acute tubular necrosis, obstructive nephropathy and hyponatraemia. The misuse of these drugs should be recognized and clinicians made aware of the potential for acute nephrotoxicity as the health burden of these compounds increases.
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Affiliation(s)
- Randy L Luciano
- Department of Internal Medicine, Section of Nephrology, Yale University School of Medicine, BB 114, 330 Cedar Street, New Haven, CT 06520-8029, USA
| | - Mark A Perazella
- Department of Internal Medicine, Section of Nephrology, Yale University School of Medicine, BB 114, 330 Cedar Street, New Haven, CT 06520-8029, USA
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Severe chronic hepatitis secondary to prolonged use of ecstasy and cocaine. Clin Res Hepatol Gastroenterol 2013; 37:e109-13. [PMID: 23910059 DOI: 10.1016/j.clinre.2013.06.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2013] [Accepted: 06/18/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Severe acute hepatotoxicity is a well known complication following the ingestion of ecstasy (3,4-methylenedioxymethamphetamine [MDMA] ecstasy). Hepatic dysfunction has also been reported after acute cocaine intoxication. However, chronic hepatitis after prolonged use of ecstasy and/or cocaine has rarely been reported. METHODS We report the case of a 27-year-old woman hospitalized with edema, ascites and severe liver failure (prothrombin rate 33%), following the use of ecstasy and cocaine over the previous 9 months. Clinical, biological, radiological and pathology findings were recorded at admission and over 8 years' follow-up. RESULTS Liver biopsy showed architectural distortion caused by bridging fibrosis, proliferation of cholangioles, and lesions of active interface hepatitis. Other causes of acute and chronic liver disease were excluded. Magnetic resonance imaging showed marked liver fibrosis. After withdrawal of both substances clinical examination and liver function tests progressively normalized. Long-term monitoring with magnetic resonance imaging showed progressive regression of fibrosis. CONCLUSION Use of ecstasy and cocaine may cause chronic hepatitis leading to marked liver fibrosis, which may regress after withdrawal of both substances.
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Vajro P, Maddaluno S, Veropalumbo C. Persistent hypertransaminasemia in asymptomatic children: A stepwise approach. World J Gastroenterol 2013; 19:2740-2751. [PMID: 23687411 PMCID: PMC3653148 DOI: 10.3748/wjg.v19.i18.2740] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2012] [Revised: 12/20/2012] [Accepted: 01/19/2013] [Indexed: 02/06/2023] Open
Abstract
We aimed to examine the major causes of isolated chronic hypertransaminasemia in asymptomatic children and develop a comprehensive diagnostic flow diagram. A MEDLINE search inclusive of publications throughout August 2012 was performed. We found only a small number of publications that had comprehensively investigated this topic. Consequently, it was difficult to construct a diagnostic flowchart similar to those already available for adults. In children, a “retesting panel” prescription, including gamma-glutamyl transpeptidase and creatine kinase in addition to aminotransferases, is considered a reasonable approach for proficiently confirming the persistence of the abnormality, ruling out cholestatic hepatopathies and myopathies, and guiding the subsequent diagnostic steps. If re-evaluation of physical and historical findings suggests specific etiologies, then these should be evaluated in the initial enzyme retesting panel. A simple multi-step diagnostic algorithm incorporating a large number of possible pediatric scenarios, in addition to the few common to adults, is available. Accurately classifying a child with asymptomatic persistent hypertransaminasemia may be a difficult task, but the results are critical for preventing the progression of an underlying, possibly occult, condition later in childhood or during transition. Given the high benefit/cost ratio of preventing hepatic deterioration, no effort should be spared in diagnosing and properly treating each case of persistent hypertransaminasemia in pediatric patients.
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Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, Bastos MDL. Toxicity of amphetamines: an update. Arch Toxicol 2012; 86:1167-1231. [PMID: 22392347 DOI: 10.1007/s00204-012-0815-5] [Citation(s) in RCA: 267] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2012] [Accepted: 02/02/2012] [Indexed: 01/06/2023]
Abstract
Amphetamines represent a class of psychotropic compounds, widely abused for their stimulant, euphoric, anorectic, and, in some cases, emphathogenic, entactogenic, and hallucinogenic properties. These compounds derive from the β-phenylethylamine core structure and are kinetically and dynamically characterized by easily crossing the blood-brain barrier, to resist brain biotransformation and to release monoamine neurotransmitters from nerve endings. Although amphetamines are widely acknowledged as synthetic drugs, of which amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are well-known examples, humans have used natural amphetamines for several millenniums, through the consumption of amphetamines produced in plants, namely cathinone (khat), obtained from the plant Catha edulis and ephedrine, obtained from various plants in the genus Ephedra. More recently, a wave of new amphetamines has emerged in the market, mainly constituted of cathinone derivatives, including mephedrone, methylone, methedrone, and buthylone, among others. Although intoxications by amphetamines continue to be common causes of emergency department and hospital admissions, it is frequent to find the sophism that amphetamine derivatives, namely those appearing more recently, are relatively safe. However, human intoxications by these drugs are increasingly being reported, with similar patterns compared to those previously seen with classical amphetamines. That is not surprising, considering the similar structures and mechanisms of action among the different amphetamines, conferring similar toxicokinetic and toxicological profiles to these compounds. The aim of the present review is to give an insight into the pharmacokinetics, general mechanisms of biological and toxicological actions, and the main target organs for the toxicity of amphetamines. Although there is still scarce knowledge from novel amphetamines to draw mechanistic insights, the long-studied classical amphetamines-amphetamine itself, as well as methamphetamine and MDMA, provide plenty of data that may be useful to predict toxicological outcome to improvident abusers and are for that reason the main focus of this review.
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Affiliation(s)
- Márcia Carvalho
- REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Portugal
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Daul AM, Beuhler MC. Niacin toxicity resulting from urine drug test evasion. J Emerg Med 2010; 41:e65-8. [PMID: 20138459 DOI: 10.1016/j.jemermed.2009.11.029] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2009] [Accepted: 11/15/2009] [Indexed: 10/19/2022]
Abstract
BACKGROUND Niacin, a well-established agent for treating dyslipidemia, has been promoted on the Internet as a method for passing urine drug screening, although there are no data to support its use for this purpose. In a handful of cases, this practice has resulted in serious niacin toxicity. OBJECTIVES The aim of this article is to describe a unique clinical presentation of niacin toxicity. CASE REPORT A 23-year-old previously healthy man presented to an Emergency Department with altered mental status, fever, acute renal failure, microangiopathic hemolytic anemia, thrombocytopenia, and coagulopathy. It was revealed that he had taken approximately 22.5 g of sustained-release niacin over the preceding 48 h in an attempt to pass a pre-employment urine drug screen. After a complicated hospital course that included mechanical ventilation for respiratory failure and hemodialysis for acute renal failure, the patient made a full recovery and was discharged 10 days after his initial presentation. CONCLUSION After a massive niacin overdose, the young man in this case presented with a complex clinical picture that mimicked concurrent thrombotic thrombocytopenic purpura and disseminated intravascular coagulation. Although this patient was fortunate to make a full recovery, the case highlights the potential for multi-system toxicity with niacin overdose, and the potential for harm posed by medical misinformation on the Internet.
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Affiliation(s)
- Anne M Daul
- Department of Emergency Medicine, Carolinas Medical Center, Charlotte, North Carolina 28203, USA
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9
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Kasman LM, London LL, London SD, Pilgrim MJ. A mouse model linking viral hepatitis and salivary gland dysfunction. Oral Dis 2009; 15:587-95. [PMID: 19656314 DOI: 10.1111/j.1601-0825.2009.01600.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
OBJECTIVE Viral hepatitis is known to cause xerostomia in humans, but this has not been reported in an animal model. We report a severe, acute, highly reproducible saliva deficiency occurring in BALB/c mice as a result of experimental viral hepatitis. MATERIALS AND METHODS BALB/c mice, splenectomized or carrying genetic mutations to detect immunological contributions to the saliva deficiency syndrome, were infected intraperitoneally with a non-lethal dose of murine cytomegalovirus. Pilocarpine-stimulated saliva volumes were determined between 0 and 15 days after infection. Salivary gland, liver, spleen, and sera were analyzed for the presence of virus, cytokines, inflammatory infiltrates, and tissue damage. RESULTS Saliva deficiency was detectable 2 days after cytomegalovirus infection, peaked at 88% below normal by day 7, and resolved partially in all mice by 15 days postinfection as sialoadenitis increased. Neither salivary gland viral titers, sialoadenitis, splenectomy, nor systemic inflammatory markers correlated with hyposalivation severity. Elevated liver enzymes did correlate with hyposalivation, and mice genetically resistant to murine cytomegalovirus-induced hepatitis were significantly protected. CONCLUSIONS Murine cytomegalovirus-induced salivary gland dysfunction is biphasic, with an acute hepatitis-associated phase and a later sialoadenitis-associated phase. Acute murine cytomegalovirus infection of BALB/c mice may provide a model for investigation of hepatitis-associated xerostomia.
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Affiliation(s)
- L M Kasman
- Department of Microbiology and Immunology, Medical University of South Carolina, BSB-201, PO Box 250504, 173 Ashley Ave, Charleston, SC 29403, USA.
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Upreti VV, Eddington ND, Moon KH, Song BJ, Lee IJ. Drug interaction between ethanol and 3,4-methylenedioxymethamphetamine ("ecstasy"). Toxicol Lett 2009; 188:167-72. [PMID: 19446252 PMCID: PMC3596109 DOI: 10.1016/j.toxlet.2009.03.023] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2008] [Revised: 03/24/2009] [Accepted: 03/25/2009] [Indexed: 01/02/2023]
Abstract
Alcohol (ethanol) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are frequently co-abused, but recent findings indicate a harmful drug interaction between these two agents. In our previous study, we showed that MDMA exposure inhibits the activity of the acetaldehyde (ACH) metabolizing enzyme, aldehyde dehydrogenase2 (ALDH2). Based on this finding, we hypothesized that the co-administration of MDMA and ethanol would reduce the metabolism of ACH and result in increased accumulation of ACH. Rats were treated with MDMA or vehicle and then administered a single dose of ethanol. Liver ALDH2 activity decreased by 35% in the MDMA-treated rats compared to control rats. The peak concentration and the area under the concentration versus time curve of plasma ACH were 31% and 59% higher, respectively, in the MDMA-ethanol group compared to the ethanol-only group. In addition, the MDMA-ethanol group had 80% higher plasma transaminase levels than the ethanol-only group, indicating greater hepatocellular damage. Our results not only support a drug interaction between MDMA and ethanol but a novel underlying mechanism for the interaction.
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Affiliation(s)
- Vijay V. Upreti
- Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA
| | - Natalie D. Eddington
- Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA
| | - Kwan-Hoon Moon
- Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-9410, USA
| | - Byoung-Joon Song
- Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-9410, USA
| | - Insong J. Lee
- Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA
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Abstract
INTRODUCTION Methamphetamine has been recognized as a common cause of acute toxic hepatitis in adults with clinical and histologic features indistinguishable from acute viral hepatitis. Clinical presentation of methamphetamine hepatotoxicity ranges from mild acute hepatitis with prompt recovery to fulminant hepatic failure. The pathophysiology of this hepatotoxicity is not well elucidated. Prenatal exposure to methamphetamine has been linked to intrauterine growth retardation and variety of withdrawal symptoms. Neonatal cholestasis is rare but serious problem that indicates hepatobiliary dysfunction and has several categories of etiologies. These include infectious, metabolic, endocrine, toxic, structural, familial, and autoimmune disorders. Cholestatic hepatitis is a recognized complication of exposure to some drugs including carbamazepine and trimethoprim-sulfamethoxazole. CASE A 35-week preterm, appropriate for gestational age, white girl was born to a 39-year-old mother who had no prenatal care. The mother's urine drug screen revealed methamphetamine. The baby passed pale meconium and her subsequent stools were hypo-pigmented. A detailed work up was done and was unremarkable except for hepatobiliary scintigraphy, with no activity noted in the small bowel on delayed imaging. An operative cholangiogram and liver biopsy were performed. The cholangiogram revealed patent bile ducts. Liver biopsy was consistent with acute viral or toxic hepatitis. Gradual drop of bilirubin was noted. With negative extensive work up for other etiology, known hepatotoxicity of methamphetamine, early onset of cholestasis that improved without specific therapy, it is strongly suspected that prenatal exposure to methamphetamine is the most likely culprit in this patient. DISCUSSION This is the first recorded case of neonatal cholestasis related to prenatal exposure to methamphetamine. Methamphetamine is considered the fastest-growing illicit drug in United States. Hence, prenatal exposure to methamphetamine is expected to rise. Healthcare providers should become aware of the possibility of methamphetamine effect on the fetal liver. Raising awareness of the expectant mothers through the healthcare profession may reduce the risk of this condition.
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Devlin RJ, Henry JA. Clinical review: Major consequences of illicit drug consumption. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2008; 12:202. [PMID: 18279535 PMCID: PMC2374627 DOI: 10.1186/cc6166] [Citation(s) in RCA: 118] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Because illicit drugs are now widely consumed, every doctor needs to know their acute medical consequences and complications. Here, we review the problems associated with the different drugs from a systems-based viewpoint. Apart from the respiratory depressant effect of opioids, crack cocaine is the most common cause of respiratory complications, mainly linked with its mode of use, with airway burns, pneumothorax, pneumomediastinum, and lung syndromes being well-recognised sequelae. Because of its marked cardiovascular effects, cocaine is also a major cause of coronary syndromes and myocardial infarction. Amphetamines may produce similar effects less commonly. Hyperthermia may occur with cocaine toxicity or with 3,4-methylenedioxymethamphetamine (MDMA) due to exertion or from serotonin syndrome. Cerebral haemorrhage may result from the use of amphetamines or cocaine. Hallucinations may follow consumption of LSD, amphetamines, or cocaine. MDMA is a major cause of acute severe hyponatraemia and also has been linked with hepatic syndromes. Collapse, convulsions, or coma may be caused in different circumstances by opioids, MDMA, or gamma hydroxybutyrate and may be aggravated by other sedatives, especially alcohol and benzodiazepines. Recognition of these acute complications is urgent, and treatment must be based on an understanding of the likely underlying problem as well as on basic principles of supportive care.
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Affiliation(s)
- Robert J Devlin
- Guy's and St Thomas' NHS Foundation Trust, Lambeth Palace Road, London SE1 7EH, UK
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Hall AP, Henry JA. Acute toxic effects of ‘Ecstasy’ (MDMA) and related compounds: overview of pathophysiology and clinical management. Br J Anaesth 2006; 96:678-85. [PMID: 16595612 DOI: 10.1093/bja/ael078] [Citation(s) in RCA: 171] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Since the late 1980s 'Ecstasy' (3,4-methylenedioxymethamphetamine, MDMA) has become established as a popular recreational drug in western Europe. The UK National Criminal Intelligence Service estimates that 0.5-2 million tablets are consumed weekly in Britain. It has been reported that 4.5% of young adults (15-34 yr) in the UK have used MDMA in the previous 12 months. Clinically important toxic effects have been reported, including fatalities. While the phenomenon of hyperpyrexia and multi-organ failure is now relatively well known, other serious effects have become apparent more recently. Patients with acute MDMA toxicity may present to doctors working in Anaesthesia, Intensive Care and Emergency Medicine. A broad knowledge of these pathologies and their treatment is necessary for anyone working in an acute medical speciality. An overview of MDMA pharmacology and acute toxicity will be given followed by a plan for clinical management.
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Affiliation(s)
- A P Hall
- Department of Anaesthesia and Intensive Care Medicine, University Hospitals of Leicester NHS Trust, Leicester Royal Infirmary, Leicester LE1 5WW, UK.
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14
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Smets G, Bronselaer K, De Munnynck K, De Feyter K, Van de Voorde W, Sabbe M. Amphetamine toxicity in the emergency department. Eur J Emerg Med 2005; 12:193-7. [PMID: 16034267 DOI: 10.1097/00063110-200508000-00010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
XTC and other amphetamines are considered to be safe by the majority of partying young people who are unaware of (or unwilling to know about) the acute and chronic toxicity of these substances, and these drugs are widespread, illicit stimulants. In this article, we describe four cases of severe acute toxicity due to recreational use of amphetamines 3,4-methylene-dioxymethamphetamine, 3,4-methylenedioxyethylamphetamine, 3,4-methylenedioxyamphetamine, 4-methylthioamphetamine or p-methoxyamphetamine, with emphasis on the presenting symptoms and acute treatment in the emergency department.
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Affiliation(s)
- Gert Smets
- Department of Emergency Medicine, University Hospitals of Leuven, Belgium
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Malicević Z, Ninković M, Vasiljević I, Selaković V, Jovanović M. [Biochemical, pharmacological and toxic effects of n-metil 3,4-methylenedioxyamphetamine--"ecstasy"]. VOJNOSANIT PREGL 2005; 62:467-75. [PMID: 16047861 DOI: 10.2298/vsp0506467m] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
<zakljucak> Navedeni podaci ukazuju da ?ekstazi? nije, kako se to posebno medju omladinom smatra, laka, bezopasna i zabavna droga. Obilje nezeljenih psihickih, neuroloskih, hepatickih, bubreznih, kardiovaskularnih i drugih toksicnih efekata pokazuje samo da oni nisu dobro procenjeni, a najopasnije je sto se desavaju pri upotrebi uobicajenih prosecnih doza ove droge. Uzivaoci u vecini slucajeva prelaze preko nezeljenih efekata MDMA i veoma lako se vracaju omiljenoj piluli, ali vremenom nezeljeni efekti postaju naglaseniji. U pokusaju da savladaju depresivnost, anksioznost i bezrazlozni zamor uzivaoci "ekstazija" obicno posezu za alkoholom ili drugim tezim narkoticima, cime posle privremenog "poboljsanja" stanje postaje jos teze, a put u tesku narkomaniju postaje sasvim izvestan. Usled nepoznavanja stvarne toksicnosti "ekstazija" zdravstveni radnici svih profila moraju uloziti napor i javnost upoznati sa stvarnim cinjenicama, posebno mlade koji iz neznanja i pomodarstva koriste "ekstazi".
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Affiliation(s)
- Zivorad Malicević
- Vojnomedicinska akademija, Institut za medicinska istrazivanja, Beograd, Srbija i Crna Gora
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White FV, Dehner LP. Viral diseases of the liver in children: diagnostic and differential diagnostic considerations. Pediatr Dev Pathol 2004; 7:552-67. [PMID: 15630523 DOI: 10.1007/s10024-004-8101-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2004] [Accepted: 09/01/2004] [Indexed: 01/04/2023]
Abstract
This review summarizes the general histologic features of acute and chronic hepatitides and highlights those morphologic findings that may suggest or be diagnostic of a specific agent or etiology. The main epidemiologic, clinical, and pathologic features of the hepatotropic viruses are discussed, with an emphasis on pediatric studies and the differential diagnosis of hepatitis in childhood.
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Affiliation(s)
- Frances V White
- Department of Pathology and Immunology, Lauren V. Ackerman Laboratory of Surgical Pathology,St. Louis Children's Hospital at the Washington University Medical Center, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
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Abstract
Side effects in the short term Recreational use of Ecstasy (3,4-methylenedioxymethamphetamine or MDMA), a synthetic drug, has considerably increased over the last decade. Since its appearance it is associated with the rave culture, but its use has spread to other social settings. The drug produces euphoria and empathy, but can lead to side effects, notably acute, potentially lethal, toxicity (malignant hyperthermia and/or hepatitis). Neurotoxicity in the long-term Moreover, MDMA has been shown to induce long-term deleterious effects and provoke neurotoxic affecting the serotoninergic system. However, the psychopathological consequences of such neurotoxicity are still controversial, particularly since many ecstasy consumers are multi-drug users. A complex pharmacological profile The mechanism of action of MDMA involves various neurobiological systems (serotonin, dopamine, noradrenalin), that may all interact.
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Affiliation(s)
- Julie Salzmann
- Laboratoire de neuropsychopharmacologie des addictions, Université René-Descartes, Paris (75)
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Au WL, Lim TCC, Seow DCC, Koh PL, Loh NK, Lim MSF, Tan IK, Yee WC. Serial diffusion-weighted magnetic resonance imaging in adult-onset citrullinaemia. J Neurol Sci 2003; 209:101-4. [PMID: 12686410 DOI: 10.1016/s0022-510x(02)00439-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
A 25-year-old Chinese man presented with a 2-year history of recurrent coma. His plasma ammonia level was extremely elevated, with raised citrulline level and absence of argininosuccinic acid. Adult-onset citrullinaemia, a condition rarely reported outside the Japanese population, was diagnosed. Serial magnetic resonance (MR) imaging, including diffusion-weighted (DW) studies, showed initial involvement of the insula cortex and cingulate gyrus, changing to a pattern of multiple small lesions in the depths of the cortical sulci. This changing pattern of lesions over time on DW MR imaging has not previously been described in adult-onset citrullinaemia.
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Affiliation(s)
- Wing Lok Au
- Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng 308433, Singapore.
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Núñez O, Bañares R, Barrio J, Menchén L, Diego AD, Salinero E, Clemente G. [Variability of the clinical expression of Ecstasy-induced hepatotoxicity]. GASTROENTEROLOGIA Y HEPATOLOGIA 2002; 25:497-500. [PMID: 12361531 DOI: 10.1016/s0210-5705(02)70299-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
3,4-methylenedioxymethamphetamine (MDMA) is an amphetamine derivative, known as ecstasy. Because of its euphoric effects, the use of this substance as a drug of abuse is becoming increasingly widespread. The development of hyperthermia, disseminated intravascular coagulation, rhabdomyolysis, acute renal failure, cardiac arrhythmia and neurotoxicity have been described in association with the use of this drug. Moreover, in the last few years, cases of liver involvement, associated or not with the above-mentioned entities, have been described, ranging from mild acute hepatitis to fulminant hepatic failure and death. We present four cases of ecstasy-induced hepatotoxicity. Outcome was favorable in three patients while the fourth required liver transplantation. Consequently, ecstasy ingestion should be ruled out as a cause of acute non-viral hepat
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Affiliation(s)
- O Núñez
- Servicio de Aparato Digestivo, Sección de Hepatología, Hospital Universitario Gregorio Maranon, Madrid, Spain
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Gowing LR, Henry-Edwards SM, Irvine RJ, Ali RL. The health effects of ecstasy: a literature review. Drug Alcohol Rev 2002; 21:53-63. [PMID: 12189005 DOI: 10.1080/09595230220119363] [Citation(s) in RCA: 93] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is the third most used illicit drug, after cannabis and amphetamines. There has been considerable interest in the adverse effects of use, with particular attention given to a small number of deaths related to ecstasy use, and the neurotoxic effects of MDMA. This paper reviews case reports of adverse effects attributed to ecstasy use, and the findings of animal and human studies, so as to identify the health effects of ecstasy use, and factors contributing to their occurrence. The incidence of serious acute adverse events related to ecstasy is low. It is the unpredictability of those adverse events and the risk of mortality and substantial morbidity that makes the health consequences of ecstasy significant. Hyperthermia and hyponatraemia are the most significant acute adverse effects, and can occur even when MDMA is the only drug used. Ecstasy users should be aware of the importance of controlling body temperature and fluid intake, early signs of adverse effects, and the need to seek medical assistance promptly. Neurotoxicity is potentially the most significant long-term effect of ecstasy. The clinical implications of neurotoxicity are uncertain at this time, but short-term memory impairment may be significant.
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Affiliation(s)
- Linda R Gowing
- Evidence-Based Practice Unit, Drug and Alcohol Services Council, University of Adelaide, Parkside, South Australia, Australia
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Abstract
This article reviews the history, pharmacology, and adverse events associated with the use of 3,4-methylenendioxymethamphetamine (MDMA), commonly known as Ecstasy. Past research describing the neurotoxic effects of MDMA in animals, current research on the neurotoxic effects of MDMA in humans, and the attendant changes in psychologic functioning will be highlighted in this review. Finally, the limitations of human research on the effects of MDMA and suggestions for future MDMA research will be discussed.
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Affiliation(s)
- G O'Leary
- Harvard Medical School, Alcohol and Drug Abuse Treatment Program, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA.
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Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 6-2001. A 17-year-old girl with marked jaundice and weight loss. N Engl J Med 2001; 344:591-9. [PMID: 11207356 DOI: 10.1056/nejm200102223440808] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Fineschi V, Centini F, Mazzeo E, Turillazzi E. Adam (MDMA) and Eve (MDEA) misuse: an immunohistochemical study on three fatal cases. Forensic Sci Int 1999; 104:65-74. [PMID: 10533279 DOI: 10.1016/s0379-0738(99)00095-x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Three fatal cases of MDMA/MDEA misuse have been examined. These referred to white males between 19 and 20 years of age, in which post-mortem toxicology showed the presence of MDMA (in one case), MDEA (in one case) and both (in one case). The clinical data were analysed and the histopathological findings were studied following immunohistochemical investigations. A complete immunohistochemical study has made it possible to demonstrate rhabdomyolysis and myoglobinuria with alterations of the organs typical of a DIC. Clinical, histopathological and toxicological data suggest that severe or fatal complications following ecstasy ingestion could be related to idiosyncratic response.
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Affiliation(s)
- V Fineschi
- Unit of Legal Medicine, University of Bari, Italy.
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Delaforge M, Jaouen M, Bouille G. Inhibitory metabolite complex formation of methylenedioxymethamphetamine with rat and human cytochrome P450. Particular involvement of CYP 2D. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 1999; 7:153-158. [PMID: 21781921 DOI: 10.1016/s1382-6689(99)00007-1] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/1998] [Revised: 01/27/1999] [Accepted: 02/01/1999] [Indexed: 05/31/2023]
Abstract
Methylenedioxymethamphetamine (MDMA or ecstasy) is a common recreational drug used at rave parties. Unfortunately, MDMA may have neurological effects and in some cases causes hepatotoxicity. MDMA binds to cytochrome P450 in rat and human hepatic microsomal preparations. Upon metabolic transformation of either the methylenedioxy or the methylamino function, it forms an inhibitory P450-metabolite complex. This inhibitory complex is formed predominantly with the P450 2D isozymes. This complex formation may account for the clinical toxicity observed upon ingestion of MDMA, particularly with other compounds normally metabolized by P450 2D6.
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Affiliation(s)
- M Delaforge
- C.E.A Saclay, DSV/DRM/SPI, Bât. 136, 99191, Gif sur Yvette, Cedex, France; Université René Descartes, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CNRS URA 400, 45 rue des Saints-Pères, 75270, Paris, Cedex 06, France
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Hamilton J, Balint P, Field M, Sturrock RD. A concealed cause of recurrent renal failure in a patient with juvenile chronic arthritis. Ann Rheum Dis 1999; 58:396-8. [PMID: 10381481 PMCID: PMC1752909 DOI: 10.1136/ard.58.7.396] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Affiliation(s)
- J Hamilton
- Centre for Rheumatic Diseases, University Department of Medicine, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER
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Jones AL, Simpson KJ. Review article: mechanisms and management of hepatotoxicity in ecstasy (MDMA) and amphetamine intoxications. Aliment Pharmacol Ther 1999; 13:129-33. [PMID: 10102941 DOI: 10.1046/j.1365-2036.1999.00454.x] [Citation(s) in RCA: 102] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The social use of ecstasy (methylenedioxymethampheta-mine, MDMA) and amphetamines is widespread in the UK and Europe, and they are popularly considered as 'safe'. However, deaths have occurred and hepatotoxicity has featured in many cases of intoxication with amphetamine or its methylenedioxy analogues such as ecstasy. Recreational use of these drugs presents an important but often concealed cause of hepatitis or acute liver failure, particularly in young people. The patterns of liver damage and multiple putative mechanisms of injury are discussed. Recognition of the aetiological agent requires a high index of suspicion. Optimum management of the resultant liver damage, including the controversial role of liver transplantation for fulminant hepatic failure, is also discussed.
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Affiliation(s)
- A L Jones
- Guy's and St Thomas' Hospital NHS Trust, Medical Toxicology Unit, London, UK
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Andreu V, Mas A, Bruguera M, Salmerón JM, Moreno V, Nogué S, Rodés J. Ecstasy: a common cause of severe acute hepatotoxicity. J Hepatol 1998; 29:394-7. [PMID: 9764985 DOI: 10.1016/s0168-8278(98)80056-1] [Citation(s) in RCA: 107] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
BACKGROUND/AIMS Ecstasy is a synthetic amphetamine recently identified as a possible cause of acute liver injury. This drug is consumed by young people and has a marked effect on improving sociability. The extent of ecstasy-associated severe hepatic damage is unknown to date. METHODS The clinical histories of 62 patients with acute liver failure admitted to the Intensive Care Liver Unit between January 1994 and December 1996 were reviewed to assess the frequency, the epidemiological, clinical and histological characteristics and the outcome of ecstasy-induced severe hepatitis. RESULTS Over this period of time, five patients (8%) were admitted because of ecstasy-induced acute liver failure, representing 31% of the cases with drug hepatotoxicity. Ecstasy was the second most common cause of liver injury in patients under the age of 25 years, being 20% in this subset of patients and 36% after ruling out the cases of viral etiology. All the patients had severe liver disease of acute onset, with jaundice, high peak of serum transaminases activity, hypoglycemia and low prothrombin activity, but no hepatic encephalopathy. Full recovery was observed in all cases from 3 to 12 months. CONCLUSIONS Ecstasy is responsible for a relatively high number of cases of acute liver failure in young people. Therefore, the use of this drug should be investigated in all patients with severe hepatitis of unclear origin. Efforts must be made to advise young people of the risks of ecstasy consumption.
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Affiliation(s)
- V Andreu
- Liver Unit, Hospital Clínic i Provincial, Barcelona, Spain
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