Emergence of new psychoactive substance 2-fluorodeschloroketamine: Toxicology and urinary analysis in a cluster of patients exposed to ketamine and multiple analogues.

New psychoactive substances (NPS) emerge continually, amongst which is a growing class of ketamine analogues with an arylcyclohexylamine backbone. Recently we reported a poisoning outbreak associated with 2-oxo-PCE (deschloro-N-ethyl-ketamine). The present report describes the emergence of another ketamine analogue, 2-fluorodeschloroketamine (2F-DCK). The compound was first detected in a patient's urine, its identity confirmed by accurate mass analysis and comparison with reference standard. Four putative metabolites were identified, including nor-2F-DCK, dehydronor-2F-DCK (major metabolite) and two hydroxylated derivatives of nor-2F-DCK. Between January and July 2019, 20 cases of analytically confirmed 2F-DCK exposure were encountered. In 19 out of 20 cases, at least one more ketamine-type drug was detected concurrently with 2F-DCK, including ketamine (90%), deschloroketamine (DCK, 50%), 2-oxo-PCE (45%) and tiletamine (10%). In particular, six of the cases showed the presence of 4 ketamine-type drugs in the same urine sample. The clinical effects observed in patients exposed to 2F-DCK are predominantly neurological (impaired consciousness, agitation, abnormal behaviour) and cardiovascular (hypertension, tachycardia); five patients had loss of consciousness or convulsion. Management was mainly supportive; all patients recovered uneventfully. This is the first clinical case series involving 2F-DCK and frontline medical personnel are urged to be aware of this rapidly expanding class of NPS, in particular the co-ingestion of multiple ketamine analogues.

Cluster of acute poisonings associated with an emerging ketamine analogue, 2-oxo-PCE.

Ketamine and phencyclidine are well-known drugs of abuse of the arylcyclohexylamine class, the backbone of which is used for the synthesis of new psychoactive substances (NPS). In October 2017, a cluster of acute intoxications was encountered where patients presented with ketamine-like toxidrome. Upon initial toxicology screening, however, neither ketamine nor other causative agents were detected in the patients' urine. Instead, an unidentified substance was consistently detected. Further investigations using gas- and liquid-chromatography mass spectrometry led to the identification of an arylcyclohexylamine analogue, 2-oxo-PCE. The present study reports the analytical and toxicological profile of this emerging NPS. Chart review found, in total, 56 cases of 2-oxo-PCE associated acute poisoning between October and November 2017. Laboratory analysis confirmed the presence of 2-oxo-PCE in the urine of all patients; nasal swab samples from three patients revealed the lone presence of 2-oxo-PCE. Urine bedside immunoassay for ketamine was found not to cross-react with 2-oxo-PCE. In 55% of the cases, other drugs of abuse were detected on toxicology analysis; whilst in the remainder, 2-oxo-PCE was used alone. The main clinical symptoms associated with sole 2-oxo-PCE use include impaired consciousness (84%), confusion (60%), abnormal behaviour (44%), hypertension (80%) and tachycardia (40%). Convulsion (16%) was also observed relatively frequently. Management was mainly supportive, whilst three patients required intensive care. All patients recovered uneventfully. In conclusion, frontline clinical and laboratory personnel should be highly vigilant in the lookout for 2-oxo-PCE, a dangerous emerging arylcyclohexylamine analogue.

Evaluation of three rapid oral fluid test devices on the screening of multiple drugs of abuse including ketamine.

Rapid oral fluid testing (ROFT) devices have been extensively evaluated for their ability to detect common drugs of abuse; however, the performance of such devices on simultaneous screening for ketamine has been scarcely investigated. The present study evaluated three ROFT devices (DrugWipe® 6S, Ora-Check® and SalivaScreen®) on the detection of ketamine, opiates, methamphetamine, cannabis, cocaine and MDMA. A liquid chromatography tandem mass spectrometry (LCMS) assay was firstly established and validated for confirmation analysis of the six types of drugs and/or their metabolites. In the field test, the three ROFT devices were tested on subjects recruited from substance abuse clinics/rehabilitation centre. Oral fluid was also collected using Quantisal® for confirmation analysis. A total of 549 samples were collected in the study. LCMS analysis on 491 samples revealed the following drugs: codeine (55%), morphine (49%), heroin (40%), methamphetamine (35%), THC (8%), ketamine (4%) and cocaine (2%). No MDMA-positive cases were observed. Results showed that the overall specificity and accuracy were satisfactory and met the DRUID standard of >80% for all 3 devices. Ora-Check® had poor sensitivities (ketamine 36%, methamphetamine 63%, opiates 53%, cocaine 60%, THC 0%). DrugWipe® 6S showed good sensitivities in the methamphetamine (83%) and opiates (93%) tests but performed relatively poorly for ketamine (41%), cocaine (43%) and THC (22%). SalivaScreen® also demonstrated good sensitivities in the methamphetamine (83%) and opiates (100%) tests, and had the highest sensitivity for ketamine (76%) and cocaine (71%); however, it failed to detect any of the 28 THC-positive cases. The test completion rate (proportion of tests completed with quality control passed) were: 52% (Ora-Check®), 78% (SalivaScreen®) and 99% (DrugWipe® 6S).

Corticosteroid adulteration in proprietary Chinese medicines: a recurring problem.

OBJECTIVES: To investigate adulteration of proprietary Chinese medicines with corticosteroids in Hong Kong. DESIGN: Case series with cross-sectional analysis. SETTING: A tertiary clinical toxicology laboratory in Hong Kong. PATIENTS: All patients using proprietary Chinese medicines adulterated with corticosteroids and referred to the authors' centre from 1 January 2008 to 31 December 2012. MAIN OUTCOME MEASURES: Patients' demographic data, clinical presentation, medical history, drug history, laboratory investigations, and analytical findings of the proprietary Chinese medicines were analysed. RESULTS: The records of 61 patients who consumed corticosteroid-adulterated proprietary Chinese medicines were reviewed. The most common corticosteroid implicated was dexamethasone. Co-adulterants such as non-steroidal anti-inflammatory drugs and histamine H1-receptor antagonists were detected in the proprietary Chinese medicine specimens. Among the patients, seven (11.5%) required intensive care, two (3.3%) died within 30 days of presentation, and 38 (62.3%) had one or more complications that were potentially attributable to exogenous corticosteroids. Of 22 (36.1%) patients who had provocative adrenal function testing performed, 17 (77.3% of those tested) had adrenal insufficiency. CONCLUSION: The present case series is the largest series of patients taking proprietary Chinese medicines adulterated with corticosteroids. Patients taking these illicit products are at risk of severe adverse effects, including potentially fatal complications. Adrenal insufficiency was very common in this series of patients. Assessment of adrenal function in these patients, however, has been inadequate and routine rather than discretionary testing of adrenal function is indicated in this group of patients. The continuing emergence of proprietary Chinese medicines adulterated with western medication indicates a persistent threat to public health.

Surveillance of emerging drugs of abuse in Hong Kong: validation of an analytical tool.

OBJECTIVE: To validate a locally developed chromatography-based method to monitor emerging drugs of abuse whilst performing regular drug testing in abusers. DESIGN: Cross-sectional study. SETTING: Eleven regional hospitals, seven social service units, and a tertiary level clinical toxicology laboratory in Hong Kong. PARTICIPANTS: A total of 972 drug abusers and high-risk individuals were recruited from acute, rehabilitation, and high-risk settings between 1 November 2011 and 31 July 2013. A subset of the participants was of South Asian ethnicity. In total, 2000 urine or hair specimens were collected. MAIN OUTCOME MEASURES: Proof of concept that surveillance of emerging drugs of abuse can be performed whilst conducting routine drug of abuse testing in patients. RESULTS: The method was successfully applied to 2000 samples with three emerging drugs of abuse detected in five samples: PMMA (paramethoxymethamphetamine), TFMPP [1-(3-trifluoromethylphenyl)piperazine], and methcathinone. The method also detected conventional drugs of abuse, with codeine, methadone, heroin, methamphetamine, and ketamine being the most frequently detected drugs. Other findings included the observation that South Asians had significantly higher rates of using opiates such as heroin, methadone, and codeine; and that ketamine and cocaine had significantly higher detection rates in acute subjects compared with the rehabilitation population. CONCLUSIONS: This locally developed analytical method is a valid tool for simultaneous surveillance of emerging drugs of abuse and routine drug monitoring of patients at minimal additional cost and effort. Continued, proactive surveillance and early identification of emerging drugs will facilitate prompt clinical, social, and legislative management.

Generalised involuntary limb twitching after ingestion of Mesobuthus martensii Karsch (Quanxie) powder.

Mesobuthus martensii Karsch, commonly known as the Chinese scorpion or Manchurian scorpion, has been used in traditional Chinese medicine as Quanxie to treat chronic pain, tetanus, tremors, convulsion, and paralysis for more than a thousand years. We report a case of poisoning after ingestion of a teaspoon of Quanxie powder. The patient presented with chest pain, dizziness, diaphoresis, generalised involuntary limb twitching, and hypertonia around 15 minutes post-ingestion. The patient recovered uneventfully after supportive management. Intravenous diazepam appeared to be effective in alleviating limb twitching. Failure to accurately measure the dose and to boil before consumption may have contributed to his clinical toxicities.

Simultaneous detection of 93 conventional and emerging drugs of abuse and their metabolites in urine by UHPLC-MS/MS.

Novel psychoactive substances (NPS) are becoming increasingly popular worldwide in recent years, some of which have been reported to cause considerable harm and even fatalities. Currently, simultaneous screening for a comprehensive panel of conventional and novel drugs of abuse is not widely available in most clinical laboratories. The aim of this study was to establish a chromatography/mass spectrometry-based analytical system for the simultaneous detection of conventional drugs of abuse and NPS in urine. Sample preparation entails enzyme digestion and solid phase extraction; analytes were then detected by liquid-chromatography tandem mass spectrometry (LC-MS/MS) with multiple reaction monitoring. Forty-seven conventional drugs (28 parent drugs, 19 metabolites) and 46 NPS analytes (44 parent drugs, two metabolites) are covered by the established method, which has been validated according to international guidelines. The method was then applied to 964 urine samples collected from drug abusers and the results revealed the presence of two NPS - TFMPP and methcathinone - as well as conventional drugs of abuse. To conclude, an LC-MS/MS method has been established that allows the simultaneous detection of over 90 conventional as well as novel psychoactive substances and metabolites in urine samples. The method was successfully applied to authentic specimens revealing the presence of conventional as well as novel drugs of abuse in the local population.

Recipes and general herbal formulae in books: causes of herbal poisoning.

Traditional Chinese medicine is commonly used locally, not only for disease treatment but also for improving health. Many people prepare soups containing herbs or herbal decoctions according to recipes and general herbal formulae commonly available in books, magazines, and newspapers without consulting Chinese medicine practitioners. However, such practice can be dangerous. We report five cases of poisoning from 2007 to 2012 occurring as a result of inappropriate use of herbs in recipes or general herbal formulae acquired from books. Aconite poisoning due to overdose or inadequate processing accounted for three cases. The other two cases involved the use of herbs containing Strychnos alkaloids and Sophora alkaloids. These cases demonstrated that inappropriate use of Chinese medicine can result in major morbidity, and herbal formulae and recipes containing herbs available in general publications are not always safe.

Budd-Chiari syndrome secondary to toxic pyrrolizidine alkaloid exposure.

In this report, we describe a case of pyrrolizidine alkaloid-related Budd-Chiari syndrome in Hong Kong. A 10-month-old boy presented with ascites, right pleural effusion, and hepatomegaly after consumption of herbal drinks for 3 months. His clinical (including imaging) features were compatible with Budd-Chiari syndrome. Budd-Chiari syndrome is a rare disease entity in paediatric patients. In our case, extensive workup performed to look for the underlying cause of Budd-Chiari syndrome was unrevealing, except for toxic pyrrolizidine alkaloid exposure in his herbal drinks.

Mad honey poisoning mimicking acute myocardial infarction.

We report a case of acute poisoning in a 48-year-old man who presented with chest pain, abdominal pain, dizziness, sweatiness, blurred vision, and severe hypotension after ingestion of honey. His electrocardiogram showed sinus bradycardia and transient ST elevation. He made a good recovery after treatment with atropine and close monitoring. Grayanotoxin was detected in his urine and the honey he ingested, which confirmed a diagnosis of mad honey poisoning. This is a condition prevalent in the Black Sea region around Turkey but rarely seen locally. Although mad honey poisoning is life-threatening, early use of atropine is life-saving. Such poisoning may present with ST elevation in the electrocardiogram and symptoms mimicking acute myocardial infarction. It is therefore essential for clinicians to recognise this unusual form of poisoning and avoid the disastrous use of thrombolytic therapy.

Chinese herbal medicine-induced anticholinergic poisoning in Hong Kong.

OBJECTIVE: To study the epidemiology, causes, and clinical course of Chinese herbal medicine-induced anticholinergic poisoning in Hong Kong. DESIGN: Case series. SETTING: Hong Kong. PATIENTS: All case histories of Chinese herbal medicine-induced anticholinergic poisoning (with laboratory confirmation) recorded by the Hong Kong Poison Information Centre over a 93-month period were accessed for analysis. RESULTS: During the relevant period, 22 clusters of Chinese herbal medicine-induced anticholinergic poisoning involving 32 patients were retrieved. The commonest clinical features were mydriasis (n=32, 100%) and confusion (n=24, 75%). No gastro-intestinal decontamination was performed. None of these patients underwent intubation, defibrillation, cardioversion, pacing, fluid resuscitation, inotropic support or dialysis. Of the 32 patients, 17 (53%) were treated with physostigmine because of confusion, three of whom had previously received intravenous benzodiazepines. No patient could be effectively treated with benzodiazepines alone. There was no mortality, and all the patients were discharged within 3 days. None of them re-attended the emergency department within 1 week of discharge. The commonest cause was the substitution of flos campsis (Campsis grandiflora) by the flower of the Datura species (7 clusters [32%] in 10 patients). CONCLUSION: Mydriasis and confusion were the commonest clinical features of Chinese herbal medicine-induced anticholinergic poisoning in Hong Kong. Physostigmine was frequently used in the treatment; benzodiazepines appeared ineffective. The commonest cause was the substitution of flos campsis (Campsis grandiflora) by the flower of the Datura species.

Adulteration of herbal antidiabetic products with undeclared pharmaceuticals: a case series in Hong Kong.

AIMS: The current study aims to examine the problem of adulteration of herbal antidiabetic products with undeclared pharmaceuticals, including both registered and banned drugs. METHODS: All cases involving use of adulterated herbal antidiabetic products referred to a tertiary centre for clinical toxicology analysis from 2005 to 2010 inclusive were retrospectively reviewed. The patients' demographic characteristics, clinical presentations, medical history, drug history and the analytical findings of the herbal antidiabetic products were studied. RESULTS: A total of 27 cases involving use of 29 adulterated herbal antidiabetic products were identified. Seventeen of the patients (63%) had clinical toxicities associated with the illicit products. Hypoglycaemia was the most common adverse effect, followed by lactic acidosis. Analysis of the 29 illicit herbal antidiabetic products revealed eight undeclared registered or banned oral antidiabetic agents, namely glibenclamide (n= 22), phenformin (n= 18), metformin (n= 6), rosiglitazone (n= 6), gliclazide (n= 2), glimepiride (n= 2), nateglinide (n= 1) and repaglinide (n= 1). Non-antidiabetic drugs were also detected in some products. Up to four adulterants were detected within the same product. CONCLUSIONS: Adulteration of herbal antidiabetic products with undeclared pharmaceuticals is a significant yet under-recognized problem. Patients taking these illicit products could be at risk of potentially fatal adverse effects. It is important to educate the public to avoid taking pCMs of dubious source. Effective regulatory measures should be put in place to address the problem.

Case series on a diversity of illicit weight-reducing agents: from the well known to the unexpected.

AIMS: To provide an overview of illicit weight-reducing agents found in over-the-counter slimming products ingested by poisoned patients. METHODS: The clinical details and analytical findings of slimming products involved in poisoning cases between 2004 and 2009 were reviewed. RESULTS: Sixty-six (including one fatal) poisoning cases were encountered. Eighty-one products were analysed and found to contain undeclared prescription weight-loss drugs, drug analogues, banned drugs, drugs used for an inappropriate indication or animal thyroid tissue, with up to six illicit agents within the same product. Many products were readily available from shops or the Internet. CONCLUSIONS: A rich diversity of illicit, potentially harmful weight-reducing agents was found in over-the-counter slimming products.

Psychosis associated with usage of herbal slimming products adulterated with sibutramine: a case series.

CONTEXT: Sibutramine, or its structurally related analogs, is often found as an adulterant in proprietary herbal slimming products in Hong Kong. A few solitary case reports of sibutramine-associated psychosis have been published since 2000. As the only tertiary referral center for clinical toxicology analysis in Hong Kong, we noticed that psychosis was an unusually common feature in patients taking "herbal slimming products" adulterated with sibutramine or its structurally related analogs over the past 5 years. OBJECTIVE: To examine the association between psychosis and the use of sibutramine-adulterated herbal products, in an attempt to elucidate this possible adverse drug reaction. METHODS: This retrospective study reviewed all cases hospitalized with psychotic symptoms confirmed to have used herbal slimming products adulterated with sibutramine, or its analogs, between January 2004 and October 2009. The cases' clinical features, outcome, drug history, and analytical findings of the offending slimming products were studied. Results. Among the 16 confirmed cases, 15 (94%) were female; the median age was 19 years (range: 15-47). Auditory hallucination was documented in 10 (63%), visual hallucination in 6 (38%), persecutory ideas in 6 (38%), delusions in 4 (25%), and suicidal ideation in 2 (13%). For 20 "herbal" slimming products analyzed, 16 were found to have been adulterated with sibutramine, 2 with N-desmethyl-sibutramine, and 1 with N-bisdesmethyl-sibutramine. Other concomitant adulterants were also found and included phenolphthalein in 9, fenfluramine, mazindol, animal thyroid tissue in 2, hydrochlorothiazide and spironolactone in 1. Eight patients disclosed the source of the products: four through the Internet, one obtained over-the-counter locally, with three acquired outside Hong Kong. CONCLUSION: Slimming products claimed "herbal" in origin could often be adulterated with sibutramine and other Western medications. We observed an association between the use of these products and psychotic features. Further studies are warranted to study whether these adverse events are an uncommon adverse drug reaction of sibutramine.

Outbreak of hypoglycaemia: sexual enhancement products containing oral hypoglycaemic agent.

OBJECTIVES: To describe a cluster of Hong Kong subjects with hypoglycaemia, after they had taken various non-prescription sildenafil products containing glibenclamide. DESIGN: Retrospective study. SETTING: A tertiary referral centre for clinical toxicology analysis in Hong Kong. PATIENTS: All men referred to the laboratory for investigation of suspected drug-induced hypoglycaemia from December 2007 to September 2008. MAIN OUTCOME MEASURES: The characteristics of these patients, including their clinical presentations, outcomes, drug history, urine toxicology analysis results, and in some instances, analysis results of unused products. RESULTS: A total of 144 male patients were referred for suspected drug-induced hypoglycaemia. Sildenafil and glibenclamide, or their metabolites, were detected in the urine specimens of 68 (47%) patients, none of whom had been prescribed either drug by a registered medical practitioner. Among these subjects, 24 (35%) denied any use of sexual enhancement products despite repeated questioning. Eight patients had repeated exposure resulting in re-admission. The sources of these sexual enhancement products included pharmacies in Mainland China, friends, local pharmacies, peddlers, or were unknown. Three patients died, one remains in a vegetative state and one suffered cognitive impairment; the remaining 63 recovered fully. Twenty-five unused sexual enhancement products of seven different kinds were recovered for analysis. The median (range) of sildenafil and glibenclamide per unit dose was 64 (0.05-198) mg and 70 (0-158) mg, respectively. CONCLUSION: These illegal products pose a severe and continued threat to society and therefore deserve widespread vigilance, so that such products can be eradicated at their source.

Grayanotoxin poisoning from Rhododendron simsii in an infant.

We report a case of severe poisoning in a 57-day-old infant who presented with vomiting, convulsions, and shock after ingesting a bottle of milk containing a decoction of Rhododendron simsii. The grandmother collected this toxic plant from a cultivated area, believing it was good for the airways. Grayanotoxin was detected in both the urine and plant specimens. The infant made a good recovery after requiring ventilatory support for 2 days. Rhododendron is a common gardening shrub in Hong Kong. Some Rhododendron species are poisonous and contain grayanotoxin. Intentional or accidental ingestion of toxic plants can be severe or even life-threatening. It is therefore essential that clinicians be familiar with local toxic plant species.

Hazards posed by a banned drug--phenformin is still hanging around.

The Hospital Authority Toxicology Reference Laboratory confirmed six cases of phenformin use, with or without complications, from July 2005 to November 2006. Two of the patients presented with potentially fatal phenformin-induced lactic acidosis. Phenformin was found (or suspected to be) adulterating Chinese proprietary medicine in five of the six cases. We report these six cases to highlight the underrecognised hazards posed by phenformin, a banned drug in Hong Kong.

Bromadiolone toxicokinetics: diagnosis and treatment implications.

INTRODUCTION: Ingestion of bromadiolone can lead to prolonged and life-threatening coagulopathy. Traditional treatment of bromadiolone intoxication relies on the coagulation profile. Currently, there is scanty information on bromadiolone elimination kinetics and half-life. CASE REPORT: We report a case of bromadiolone poisoning in a 40-year old female who, by history, ingested four 42.5-gram bags of rat poison (0.005% bromadiolone), equivalent to 8.5 mg bromadiolone (0.17 mg/kg body weight), four days prior to admission. On admission, her prothrombin time was 92.0 seconds, international normalized ratio was 5.7, and activated partial thromboplastin time was 50.2 seconds with no bleeding on clinical examination. The first plasma bromadiolone level (5 days post-ingestion) was 92 ng/mL. Serial measurement of plasma bromadiolone levels confirmed the diagnosis and demonstrated that bromadiolone obeys the elimination kinetic of a two-compartment model with a rapid, fairly steep decline phase (half-life 3.5 days) followed by a slower termination phase (half-life 24 days). Plasma bromadiolone level of less than 10 ng/mL in our patient was associated with a consistently normal coagulation profile without vitamin K1 therapy. CONCLUSIONS: There is a lack of information on the toxicodynamics and toxicokinetics of bromadiolone in humans; further studies are needed before the plasma bromadiolone level can serve as one of the logical and safe therapeutic endpoints for vitamin K1 therapy.

Analogues of erectile dysfunction drugs: an under-recognised threat.

OBJECTIVES: To investigate the problem of drug analogue adulteration in male erectile dysfunction health products. DESIGN: Survey of over-the-counter male erectile dysfunction health products available in convenience stores and pharmacies in Hong Kong. SETTING: Tertiary referral centre for clinical toxicology analysis in Hong Kong. MAIN OUTCOME MEASURES: The pattern and extent of adulteration of male erectile dysfunction health products with sildenafil, tadalafil, and vardenafil as well as their structurally modified analogues. RESULTS: Of 26 products studied, one (4%) was found to contain undeclared sildenafil, while 14 (54%) contained drug analogues of different kinds. The latter included acetildenafil, hydroxyacetildenafil, hydroxyhomosildenafil, and piperidenafil. The first three were analogues of sildenafil and the last was an analogue of vardenafil. One young patient presented with ataxia after taking an acetildenafil-containing product. CONCLUSIONS: The positive rate of concealed drug analogues in male erectile dysfunction health products is alarmingly high. Such analogues are difficult to detect by ordinary laboratory methods, and might be used in an attempt to evade regulatory inspection. Without going through the stringent drug testing process, the adverse effects of these chemicals remain largely unknown and unpredictable. Effective surveillance system and control measures are needed urgently. The medical profession and the public should be alerted to this under-recognised threat.