A report of an outbreak of toxicity from a novel drug of abuse: ERIC-3.

BACKGROUND: Novel drugs of abuse are becoming more common in the UK, and they represent particular difficulties in management. We present a case series of toxicity due to a novel substance Eric-3. METHODS: This was a retrospective case note review over a 6-month period. Patients were included if their presentation was due to ingestion of Eric-3. Physiological data, symptoms, outcome and destination of the patient from the ED were collected. Postmortem toxicological analysis was obtained for one of the patients who died. RESULTS: 41 attendances were identified from 18 patients. Two patients died and five were admitted to ITU. Heart rate and temperature on arrival tended to be above normal (mean heart rate was 112 bpm, with an SD of 18; mean temperature was 37.45° with an SD of 0.95°). 63.4% of attendances included agitation and 34.1% choreiform movements. α-Methyltryptamine and 3-/4-flouroephedrine were found in the blood of one of the patients who died. CONCLUSIONS: In this outbreak, Eric-3 gave symptoms similar to other stimulants. It may have been a novel substance 3-/4-flouroephedrine. It underlines the need for prospective data collection and information sharing.

Clinical characteristics of cough mixture abusers referred to three substance abuse clinics in Hong Kong: a retrospective study.

OBJECTIVES. Cough mixture is the third most commonly abused substance in patients attending the Prince of Wales Hospital Substance Abuse Clinic. The content of the local cough mixture is not well researched. Paranoid psychosis manifesting as persecutory delusions and derogatory hallucination, as well as mood symptoms, is common in these patients. The natural history and outcome of such psychoses associated with cough mixture abuse are not well known. This study aimed to address these questions. METHODS. This was a retrospective study of cough mixture abuse in Hong Kong. Case records of cough mixture abusers currently receiving treatment at the 3 substance abuse clinics at the Prince of Wales Hospital, Alice Ho Miu Ling Nethersole Hospital, and the North District Hospital were retrieved for data collection. The patients' demographic data, duration and intake pattern of cough mixture, and use of any other drugs were documented. The presenting psychopathology, first urine toxicology results, diagnosis, treatment, number of hospitalizations, and course of the illness were also recorded. RESULTS. A total of 63 patients with the diagnosis of cough mixture abuse were identified in the database; 89% were male. The mean +/- SD age of the patients was 34.4 +/- 6.2 years; 67% were single and 83% were unemployed. The mean +/- SD age of onset of cough mixture abuse was 20 +/- 5 years. Psychiatric symptoms developed a mean +/- SD of 7.6 +/- 6.0 years after onset of abuse. According to the ICD-10 Mental and Behavioural Disorders criteria, the top psychiatric diagnoses were substance-induced psychotic disorder (67%), schizophrenia (19%), depressive disorder (11%), and dysthymia (10%). The most common ingredients in the urine sample at first presentation were promethazine (75%), pseudoephedrine (67%), codeine (60%), ephedrine (57%), zopiclone (17%), and hydrocodone (16%). Additionally, 16% of patients were in the priority follow-up group. The mean +/- SD follow-up period was 6.2 +/- 7.1 years during which there were 3.2 +/- 3.7 episodes of hospitalizations, with a mean +/- SD length of stay in each admission of 25.0 +/- 40.9 days. CONCLUSIONS. Promethazine, ephedrine, pseudoephedrine, codeine, and hydrocodone are the most common ingredients of cough mixture abused in this locality. Psychotic disorders are the most frequent psychiatric diagnosis associated with cough mixture abuse.

[Ephedron dependence--case report]. / Uzaleznienie od efedronu--opis przypadku.

Ephedrone (Methcathinone), a derivative of phenylpropan, (2-(methylamino)-1-phenylpropan-1-one) is synthesised from ephedrine or pseudoephedrine by potassium permanganate oxidation. It has been demonstrated that ephedrone stimulates central nervous system and inhibits dopamine and norepinephrine re-uptake. The authors described the case of a 32-years-old patient, who has been addicted to ephedrone for three years. The case was compared with other articles. Attention was drawn to the growing problem of ephedrone addiction, which is often used as an easier to obtain and cheaper replacement of amphetamine. The risk arising from the intravenous route of ephedrone administration, as well as the potential for manganese poisoning were highlighted. Inconsistency of the existing legislation was also shown, which is prohibiting the use of Catha edulis derivatives and not regulating disposal of substances, which are precursors of psychoactive and addictive ephedrone.

Neurotoxicity following chronic intravenous use of "Russian cocktail".

INTRODUCTION: Recently, neurological abnormalities in methcathinone users have been attributed to manganese. We report similar toxicity in three patients following the use of a mixture similar to methcathinone: potassium permanganate, ephedrine, and aspirin. CASE REPORTS: Three teenagers (15 to 19 years old) presented with extrapyramidal abnormalities and movement disorders following chronic intravenous use of a mixture known as "Russian Cocktail". All three patients had multiple movement disorders. One patient had normal blood manganese concentration (<19 microg/L) and MRI. The other two had elevated blood manganese (2100 microg/L and 3176 microg/L) and MRIs showing bilateral symmetric hyper-intensities on T1-weighted-images in the dentate nucleus, subcortical white substance of cerebellar hemisphere, globus pallidus, and putamen. Abstinence and treatment with EDTA, levodopa, and para-aminosalicylic acid was associated with decreasing blood manganese concentrations and subjective improvement, but no change in objective findings. DISCUSSION: The "Russian Cocktail" likely contains manganese as a result of the oxidation of ephedrine by potassium permanganate in water acidified by acetylsalicylic acid. We believe that manganese with the possible contribution of methcathinone caused the neurological impairments. CONCLUSIONS: Three toxic substances have been made into a mixture administered intravenously, similar to methcathinone. Our patients learned of this mixture, called "Russian Cocktail", from their friends. The toxicity from repeated use of this mixture is one of extrapyramidal abnormalities and movement disorders. Standard therapies were unsuccessful in reversing the clinical toxicity.

Irreversible motor impairment in young addicts--ephedrone, manganism or both?

BACKGROUND: Parkinsonian syndrome related to intravenous use of a "designer" psychostimulant, derived from pseudoephedrine using potassium permanganate as the oxidant, has been observed in drug addicts in Estonia. OBJECTIVE: To describe the symptomatology of four young patients, history of drug administration and chemical analysis of a drug batch. METHODS: Mental and motor function and quality of life were scored and ephedrone was analyzed using electrospray mass spectrometry. Manganese content of the final synthetic mixture was analyzed using Inductively Coupled Plasma-Atomic Emission Spectrometry. RESULTS: None of the four cases scored below the dementia threshold in MMSE, while other ratings (UPDRS, H&Y, PDQ-39) corresponded to disabilities seen in relatively advanced Parkinson's disease. The ephedrone yield of the reaction was approximately 44% and the mixture was found to contain 0.6 g/l of manganese. CONCLUSIONS: The cases were exposed to extreme manganese load. Their symptomatology is probably identical to manganism. The role of ephedrone is presently unknown. Physicians must be aware of early signs of manganism in patients within social risk groups.

Parkinsonism caused by chronic usage of intravenous potassium permanganate.

INTRODUCTION: Chronic overexposure to manganese (Mn) may cause neuronal degeneration. Manganese intoxication is well known to induce parkinsonism. Manganese intoxication may be associated with abnormal magnetic resonance (MR) imaging (abnormal signal hyperintensity in the globus pallidus and substantia nigra on T1-weighted images). CASES: We report an unusual presentation of manganese intoxication due to administration of a combination of acetylsalicylic acid and ephedrine HCl, potassium permanganate, and vinegar melted in tap water and administered parenterally as a psychostimulant substance in 2 cases who developed symptoms resembling parkinsonism. Neurologic examination of both cases revealed disturbances of the extrapyramidal system and a characteristic "cock walk." Tremor was present in the first case, whereas it was lacking in the second one. Cranial MRI showed bilateral symmetric T1-weighted hyperintense patterns in the globus pallidus, probably because of manganese accumulation. Different levels of response to levodopa were reported in the literature; in our cases, there was no response to levodopa. CONCLUSION: Chronic overexposure to manganese may cause an atypical form of parkinsonism associated with increased T1 signal in the basal ganglia on magnetic resonance imaging.

[Adverse reaction of pseudoephedrine]. / Reacción adversa por seudoefedrina.

We present a case of a 7 years old girl who developed an episode of myoclonic movements and tremors after being medicated with a not well quantified amount of a pseudoephedrine/antihistamine combination. We want to highlight the potential toxicity of pseudoephedrine, usually administered as part of cold-syrup preparations which are used for symptomatic treatment of upper respiratory tract cough and congestion associated with the common cold and allergic rhinitis. Although these products are generally considered to be safe either by physicians and parents, we can't underestimate the potential adverse events and toxic effects that can occur when administering these medications.

The use of plasma metanephrine to normetanephrine ratio to determine epinephrine poisoning.

BACKGROUND: Intravenous epinephrine (EPI) is used as a pharmacologic agent to acutely treat patients in cardiac arrest. Unfortunately, there have been several homicide cases where hospitalized patients died due to a purposeful overdose of epinephrine. We measured plasma epinephrine metabolites (metanephrine, MET, and normetanephrine, NMET) to determine if exogenous epinephrine can be distinguished from endogenous epinephrine concentrations in a controlled animal study. METHODS: Rabbits were subjected to three different protocols. In the physiologic stress group (n=8), rabbits were immobilized for 30 min in a restraining tube. In the sub-lethal dose (n=9), 0.01 mg/kg of epinephrine was injected into anesthetized rabbits. In the lethal dose group (n=8), 1.0 mg/kg of epinephrine was administered into anesthetized rabbits. Blood was collected at regular intervals for up to 480 min. The plasma metanephrine and normetanephrine concentrations were measured by liquid chromatography/mass spectrometry and the serum cortisol concentrations by immunoassay. RESULTS: Serum cortisol and plasma metanephrine and normetanephrine concentrations increased in the stressed animals during immobilization demonstrating the endogenous stress model. Following a sub-therapeutic epinephrine dose, plasma metanephrine increased while plasma normetanephrine decreased. The peak plasma metanephrine concentrations were similar to the concentrations observed in the stressed animals; however, the ratio of plasma metanephrine to normetanephrine was significantly different. In the lethal epinephrine dose, both the plasma metanephrine concentrations and ratio of metabolites were significantly greater than those observed in the endogenously stressed animals. CONCLUSIONS: The ratio of plasma metanephrine to normetanephrine is the best marker to determine the presence of exogenous therapeutic and lethal epinephrine administration. However, there were limitations to the study design that could alter these conclusions.

Fatal cold medication intoxication in an infant.

The case history and toxicological findings of an infant fatality involving pseudoephedrine, brompheniramine, and dextromethorphan are presented. Concentrations of brompheniramine and dextromethorphan were measured in both postmortem blood and liver specimens using a gas chromatograph equipped with a nitrogen-phosphorus detector. Brompheniramine and dextromethorphan were 0.40 mg/L and 0.50 mg/L, respectively, in the blood sample and 0.16 mg/kg and 0.57 mg/kg in the liver sample. The concentration of pseudoephedrine in blood and liver specimens was measured using gas chromatography-mass spectrometry and was determined to be 14.4 mg/L in the blood and 16 mg/kg in the liver. Additionally, a baby bottle allegedly administered to the infant was collected as evidence and sent to the Medical Examiner's Office for evaluation. The amounts of total brompheniramine, dextromethorphan, and pseudoephedrine remaining in the baby bottle were 1.4 mg, 9.4 mg, and 40 mg, respectively.

Possible case of mania associated with ma-huang.

Several commercially available weight-loss supplements contain ma-huang, an herb derived from Ephedra sinica. Previous reports have raised awareness that ma-huang supplements may precipitate symptoms consistent with mania in susceptible individuals. A 21-year-old woman required psychiatric hospitalization as a result of acute manic symptoms with psychosis. The emergence of her symptoms coincided with her use of two supplements containing ma-huang. Consumers need to be educated about the potential adverse psychiatric effects of ma-huang in order to make well-informed decisions before using such supplements. A preexisting psychiatric disorder may also increase susceptibility to these adverse effects.

[Fatal poisoning with Letigen]. / Dødsfald med Letigen.

Two cases of fatal caffeine and ephedrine intoxication due to ingestion of an anorectic drug Letigen (200 mg caffeine and 20 mg ephedrine) are reported. A 39-year-old female with a history of prior suicide attempts was found dead in her home by her husband. An empty bottle of Letigen was found. The other case was a 31-year-old female who was found dead in her car which had stopped on the motorway. She had been vomiting in the car. The toxicological analysis revealed fatal ephedrine and caffeine intoxication in both cases. In the first case the manner of death was suicide, the other death remained unresolved. One fatal Letigen intoxication due to suicidal ingestion in Denmark has previously been published.

Suspected caffeine and ephedrine toxicosis resulting from ingestion of an herbal supplement containing guarana and ma huang in dogs: 47 cases (1997-1999).

OBJECTIVE: To describe the clinical signs following ingestion of an herbal supplement containing guarana and ma huang in dogs, estimate minimum dose at which clinical signs of toxicosis and death were reported, and evaluate treatment options. DESIGN: Retrospective study. ANIMALS: 47 dogs with evidence of ingestion of an herbal supplement containing primarily guarana and ma huang. PROCEDURE: Records of dogs that had ingested an herbal supplement containing ma huang and guarana between July 1997 and October 1999 were retrieved from the National Animal Poison Control Center database. Data were retrieved and reviewed regarding signalment, dose ingested, clinical signs, laboratory test results, treatment, and final outcome. Cases were assessed by staff veterinarians as toxicosis or suspected toxicosis on the basis of strength of evidence supporting a diagnosis. RESULTS: Most dogs (80%) developed clinical signs of toxicosis within 8 hours of ingestion, and clinical signs persisted for up to 48 hours. Hyperactivity, tremors, seizures, and behavior changes were reported in 83% of dogs; other signs included vomiting (47%), tachycardia (30%), and hyperthermia (28%). Seventeen percent of the dogs died or were euthanatized. Estimated doses of guarana and ma huang ranged from 4.4 to 296.2 mg/kg (1.98 to 133.2 mg/lb) and 1.3 to 88.9 mg/kg (0.58 to 40.0 mg/lb) of body weight, respectively; minimum dose at which death was reported was 19.1 mg of guarana/kg (8.7 mg/lb) and 5.8 mg of ma huang/kg (2.6 mg/lb). CONCLUSIONS AND CLINICAL RELEVANCE: Accidental ingestion of herbal supplements containing primarily guarana and ma huang in dogs can lead to a potentially lethal condition that may require prompt detoxification and supportive treatment for several days. Most dogs recovered with supportive treatment.

Herbal and alternative medicine.

An extensive range of herbal and dietary supplements is now available, and use of these products by ED patients is fairly common. Emergency physicians should be familiar with some of the products used more frequently for common complaints. Emergency personnel also should be vigilant for toxic syndromes resulting from ingestion of certain of these products and be wary of possible toxicity from any of these supplements owing to their minimal quality control and absence of FDA regulation.