Acute interstitial nephritis associated with ingestion of Achyranthes japonica extract: a case report.

BACKGROUND: The Japanese chaff flower, Achyranthes japonica, is used as complementary medicine to control degenerative arthritis. Although commonly used in South Korea, there has been no report of side effects. We report the first case of acute interstitial nephritis (AIN) that occurred in a woman who ingested A. japonica extract for 4 months. CASE PRESENTATION: A 56-year-old Korean woman was admitted for deterioration of renal function. She had general weakness and nausea for 1 month. Her initial blood urea nitrogen and serum creatinine levels were 26.3 mg/dL and 3.2 mg/dL, respectively. She acknowledged ingesting A. japonica extract for the past 4 months. Renal histology demonstrated AIN represented by immune cell infiltration into the interstitium, tubulitis, and tubular atrophy, but the glomeruli were intact. A. japonica was discontinued immediately and conservative management was started. Renal function was nearly restored to the baseline level without medication after 13 months. CONCLUSION: This is a rare case report of AIN associated with a pure A. japonica extract. In the case of unknown etiology of AIN, physicians should ask about the use of herbal medicines, nutraceuticals, and traditional folk medicines including A. japonica.

Unusual Presentation of Kratom Overdose With Rhabdomyolysis, Transient Hearing Loss, and Heart Failure.

Kratom mainly grows in Southeast Asia. It is widely used for pain management and opioid withdrawal, which is available online for cheaper prices. Alkaloids extracted from kratom such as mitragynine and 7-hydroxy mitragynine exhibit analgesic properties by acting through µ receptors. Commonly reported side effects of kratom include hypertension, tachycardia, agitation, dry mouth, hallucinations, cognitive and behavioral impairment, cardiotoxicity, renal failure, cholestasis, seizures, respiratory depression, coma, and sudden cardiac death from cardiac arrest. Rhabdomyolysis is a less commonly reported lethal effect of kratom. Limited information is available in the literature. In this article, we present a case of a 45-year-old female who is overdosed with kratom and presented with lethargy, confusion, transient hearing loss, and right lower extremity swelling and pain associated with weakness who was found to have elevated creatinine phosphokinase. She was diagnosed with rhabdomyolysis, compartment syndrome, multiorgan dysfunction including acute kidney injury, liver dysfunction, and cardiomyopathy. She underwent emergent fasciotomy and required hemodialysis. Her renal and liver function subsequently improved. We described the case and discussed pharmacology and adverse effects of kratom toxicity with a proposed mechanism and management. We conclude that it is essential for emergency physicians, internists, intensivists, cardiologists, and nephrologists to be aware of these rare manifestations of kratom and consider a multidisciplinary approach.

Near-fatal poisoning after ricin injection.

OBJECTIVE: To report a near-fatal poisoning after intentional injection of ricin from a castor bean (Ricinus communis) extract. CASE REPORT: A 21 year-old man self-injected ∼3 mL of a castor bean extract intramuscularly and subcutaneously in the left antecubital fossa. Upon admission to our ED (1 h post-exposure; day 1, D1) he was awake and alert, but complained of mild local pain and showed slight local edema and erythema. He evolved to refractory shock (∼24 h post-exposure) that required the administration of a large volume of fluids and high doses of norepinephrine and vasopressin, mainly from D2 to D4. During this period, he developed clinical and laboratory features compatible with systemic inflammatory response syndrome, multiple organ dysfunction, capillary leak syndrome, rhabdomyolysis, necrotizing fasciitis and possible compartment syndrome. The patient underwent forearm fasciotomy on D4 and there was progressive improvement of the hemodynamic status from D7 onwards. Wound management involved several debridements, broad-spectrum antibiotics and two skin grafts. Major laboratory findings within 12 days post-exposure revealed hypoalbuminemia, proteinuria, thrombocytopenia, leukocytosis and increases in cytokines (IL-6, IL-10 and TNF-α), troponin and creatine kinase. Ricin A-chain (ELISA) was detected in serum up to D3 (peak at 24 h post-exposure), with ∼79% being excreted in the urine within 64 h post-exposure. Ricinine was detected in serum and urine by LC-MS up to D5. A ricin A-chain concentration of 246 µg/mL was found in the seed extract, corresponding to the injection of ∼738 µg of ricin A-chain (∼10.5 µg/kg). The patient was discharged on D71, with limited range of motion and function of the left forearm and hand. CONCLUSION: Ricin injection resulted in a near-fatal poisoning that evolved with septic shock-like syndrome, multiple organ dysfunction and necrotizing fasciitis, all of which were successfully treated with supportive care.

A comparative analysis of kratom exposure cases in Thailand and the United States from 2010-2017.

Background: Interest in the Southeast Asian natural remedy kratom has increased in Western countries recently, along with increasing concern over its potential toxic effects.Objective: To describe and compare demographics, common co-exposure substances, clinical effects, treatments, and medical outcomes of kratom "abuse" exposures in the United States (US) and Thailand.Methods: This is a retrospective analysis of kratom "abuse" exposures, defined as use when attempting to gain a psychotropic effect, reported to the National Poison Data System (NPDS) in the US and the Ramathibodi Poison Center (RPC) in Thailand from 2010 to 2017. Multivariate analysis identified risk factors for severe medical outcomes, defined as both ICU admissions and death.Results: Nine-hundred-twenty-eight cases were included (760 from NPDS and 168 from RPC). A greater proportion of cases involved co-exposures in Thailand (64.8% versus 37.4%; odds ratio [OR] = 3.10, 95% confidence interval [CI] = 2.15-4.47, p < .01). Both countries had a similar prevalence of opioid and benzodiazepine co-ingestions, but the US had more co-ingestions with other sedatives (4.6% versus 0%, OR = 0, 95% CI = 0-0.47, p < .01). Common clinical effects included tachycardia (30.4%), agitation/irritability (26.2%), and drowsiness/lethargy (21.1%). Six deaths occurred, including one single-substance exposure in the US, three multiple-substance exposures in the US, and two multiple-substance exposures in Thailand. Severe medical outcomes were reported more frequently in the US (OR = 18.82, 95% CI = 5.85-60.56, p < .01).Conclusions: Despite lower frequencies of co-ingestants overall, US kratom abuse exposures yielded greater clinical severity. This disparity may be attributable to differences in the products labeled "kratom," greater sedative co-exposures in the US, and/or differences in population genetics or use patterns.

Role of anthraquinones in Cassia occidentalis induced hepato-myo-encephalopathy.

ETHNOPHARMACOLOGICAL RELEVANCE: The different plant parts of Cassia occidentalis Linn, (CO) such as root, leaves, seeds and pods have traditionally been used in multifarious medicines for the treatment of dysentery, diarrhea, constipation, fever, eczema, cancer and venereal diseases. MATERIALS AND METHODS: A systematic search of literature has been done in books and scientific databases like Science Direct, Pubmed, Google Scholar and Scopus etc. These sources were used to compile, analyze and review the information regarding the phytochemistry, toxicology and mechanism of toxicity of CO. The various references on this subject are cited in our review ranging from 1956 to 2019. RESULTS: Unintentional exposure of CO causes serious pathological condition in children, known as hepato-myo-encephalopathy (HME). The toxicity after CO consumption is associated with the presence of anthraquinones (AQs), a class of secondary plant metabolites. These AQs at high concentrations are known to cause detrimental effects on essential vital organs such as liver, kidney, spleen, brain, muscle and reproductive organs. The animal studies in rodent models as well as clinical investigations have clearly revealed that CO toxicity is associated with enhanced hepatotoxicity serum markers (ALT, AST, and LDH) and presence of necrotic lesions in liver. Furthermore, CO also causes vacuolization in muscle tissue and increases the level of CPK which is a prominent muscle damage marker. Apart from these target organs, CO consumption also causes neuronal damage via disturbing the levels of different proteins such as (GFAP and b-tubulin III). The mechanistic studies show that AQs present in CO have the potential to disturb the cellular homeostasis via binding to DNA, increasing the production ROS and showing inhibitory effects on essential enzymes etc. Therefore, AQs have been observed to be the primary culprit agents contributing to the toxicity of CO in children and animals. CONCLUSION: Despite its therapeutic potential, CO consumption can be detrimental if consumed in high amounts. A thorough analysis of literature reveals that AQs are the primary factors contributing to toxicity of CO seeds. Exposure to CO seeds causes HME, which is a serious life threatening condition for the malnourished children from lower strata. Multiple mechanisms are involved in the CO induced HME in patients. Lack of appropriate diagnostic measures and a poor understanding of the CO toxicity mechanism in humans and animals complicate the clinical management of CO poisoning subjects. Therefore, development of point of care diagnostic kits shall help in early diagnosis & suitable management of CO poisoning.

Death from Poppy Tea Consumption.

The historical practice of brewing poppy tea for its opioid-like effects is reoccurring with modern-day substance users. We present four postmortem cases with toxicology results that serve as case studies for the potential hazards of poppy tea ingestion. There is limited information regarding the risks of this practice due to the variability of the morphine content of the opium exuded from the plant. While internet tea recipes offer guidance, differences in poppy cultivation, washing, and infusing time are some of the reasons why the beverage may contain inconsistent and clinically significant alkaloid concentrations for each preparation. Variability in opioid tolerance along with additional drugs taken will impact the overall degree of toxicity experienced from the opiates in the tea. Advancements in the genetic modification of the poppy plant could greatly alter the ratio of alkaloids seen in biological fluids and will be highly dependent on the source of the poppy product. The blood concentrations of free morphine and free codeine in cases 1-3 where the toxicity from the tea was considered the primary cause of death were 0.94 and 0.11 mg/L, 0.62 and 0.034 mg/L, and 0.16 and 0.010 mg/L, respectively. The urine concentrations of morphine and codeine were 13 and 0.94 mg/L in case 1 and 16 and 1.6 mg/L in case 2, respectively. The opium alkaloids thebaine and laudanosine were identified qualitatively by our routine organic base/neutral drug detection procedure.

Raising antibodies against epoxyscillirosidine, the toxic principle contained in Moraea pallida Bak. (Iridaceae), in rabbits.

Moraea pallida Bak. (yellow tulp) poisoning is the most important plant cardiac glycoside toxicosis in South Africa. The toxic principle, a bufadienolide, is 1α, 2α-epoxyscillirosidine. The aim was to investigate the potential to develop a vaccine against epoxyscillirosidine. Epoxyscillirosidine, proscillaridin and bufalin, were successfully conjugated to hen ovalbumin (OVA), bovine serum albumin (BSA) and keyhole limpet haemocyanin (KLH). There was a low immune response following vaccination of adult male New Zealand White rabbits with epoxyscillirosidine-OVA (n = 3) and OVA (n = 3) using Freund's adjuvant in Trial (T) 1. The immune response improved significantly in T2 following doubling of the dose to 0.8 mg/rabbit and changing the adjuvant to Montanide. In T3, the rabbits (n = 15), allocated into 5 equal groups, vaccinated with proscillaridin-BSA, bufalin-BSA, epoxyscillirosidine-KLH, epoxyscillirosidine-BSA and BSA respectively, using Montanide adjuvant, developed antibodies against the administered immunogens, with epoxyscillirosidine-KLH inducing the highest immune response. Proscillaridin and bufalin antibodies cross-reacted with epoxyscillirosidine in an enzyme linked immunosorbent assay. The conjugation methodology will be adjusted in the future to target optimal conjugation efficiency. Additional vaccination will be conducted in search of neutralizing antibodies against the yellow tulp toxin. The cross-reactivity of proscillaridin and bufalin antibodies with epoxyscillirosidine could be studied in future to explore the potential to prevent yellow tulp poisoning.

Pattern of Poisoning in a Tertiary Care Center with Special Reference to Odollam Poisoning.

INTRODUCTION: Suicide is a major public health challenge in Kerala. Majority of adult poisoning is intentional. Most of those who attempt 'deliberate self harm' are young adults and many a time the reason is trivial. OBJECTIVES: To find out the pattern of poisoning, prognostic factors in different type of poisoning, precipitating factors for deliberate self harm and to suggest preventive measures. METHODOLOGY: This was a prospective observational study conducted among patients admitted with history of poisoning in a tertiary care centre in Kerala. Detailed history, physical examination, relevant lab investigations were done in all the patients. Psychiatric assessment and counselling was done in all survivors. RESULTS: A total of 195 patients were included in this study-109 males and 86 females. The intention of poisoning was suicidal in 98.82% of cases. The mortality rate was 13.33%. Common poisons consumed were odollam, drugs, pesticides and rodenticides. Majority of deaths were due to organophosphorous compounds (42.31%) followed by odollam (38.46%). The common precipitating factors were family problems, personal stressors and marital discord in both sexes. Psychiatric assessment showed adjustment disorder as the commonest problem followed by impulsive act. CONCLUSION: The common poisons ingested are organophosphorous compounds, drugs and odollam. Organophosphorous and odollam carries higher mortality. Pesticide regulation, use of less toxic pesticides in agriculture, early management and quick referral to well equipped hospitals will help in reducing mortality. Suicide prevention programmes like psychosocial support and counselling, raising public awareness about deliberate self harm and alcohol de-addiction programmes will help in reducing the incidence of deliberate self harm.

Rapid identification of Aconitum plants based on loop-mediated isothermal amplification assay.

OBJECTIVE: Aconitum plants (Ranunculaceae) exhibit toxicity, and accidental ingestion of the plants has been reported in Japan. Identifying the cause of poisoning is important for emergency medical treatment, and a rapid and simple detection technique is required for the identification of poisoning cause. In the present study, we developed a rapid and simple method for detecting Aconitum plant DNA using a loop-mediated isothermal amplification (LAMP) assay. RESULTS: Specific LAMP primers for Aconitum plants were designed based on the trnL-trnF intergenic spacer region. Using the LAMP primers, the LAMP assay included an initiation reaction of 10 min followed by amplification for 20 min at the isothermal reaction temperature of 65 °C. The LAMP reaction was demonstrated to be specific and highly sensitive to Aconitum plants, given that the assay can be used for 1 pg of purified DNA. Using raw extracted DNA as template, the entire detection procedure from DNA extraction to final detection required only 30 min. Moreover, the protocol identified samples containing approximately 5 mg of Aconitum plants cooked and digested with artificial gastric juice. The currently proposed protocol exhibits good potential as a screening method of Aconitum plant poisoning for emergency medical care.

Cleistanthus collinus poisoning affects mitochondrial respiration and induces oxidative stress in the rat kidney.

Cleistanthus collinus is a poisonous shrub used for deliberate self-harm in rural areas of South India and intake of boiled decoction of leaves is a common method of self-harm. Distal renal tubular acidosis (dRTA) is an important clinical symptom observed in C. collinus poisoning, and renal V-ATPases may be potential targets of damage. However, a lack of understanding of molecular mediators involved hampers medical management, which is mainly supportive. We hypothesized that C. collinus poisoning induces renal oxidative stress; probably by inducing mitochondrial uncoupling, which compromises V-ATPase activity to ultimately produce dRTA. This was tested by exposing renal BBMV, kidney cells in culture, and Wistar rats to C. collinus poisoning. Exposure to C. collinus aqueous extract resulted in significant elevations in the lipid peroxidation marker, conjugated dienes, in cell culture and in vivo. A significant decrease in mitochondrial respiratory control ratio was observed in kidneys from C. collinus-treated animals suggesting that mitochondrial oxidative phosphorylation is uncoupled. This was accompanied by significant increase in ADP levels and a decrease in proton pump activity. Thus, these results demonstrate that C. collinus poisoning induces oxidative stress which influences proton pump activity, probably due to feedback inhibition by elevated ADP levels because of mitochondrial dysfunction in the rat kidney.

Cade oil poisoning: about a case.

Throughout Morocco, cade oil is used in folk medicine for many purposes, in particular for atopic dermatosis. It is also used as a wormer. Cade oil poisoning of newborns and infants thus often has an iatrogenic origin, resulting especially from the ingestion of a significant amount or from a prolonged and extensive cutaneous application. Thus, this oil, used for therapeutic purposes, is responsible for a non-negligible number of cases of poisoning, some fatal. We report a case of poisoning after cutaneous application of cade oil in a 2-month-old infant. The outcome was fatal. This report calls attention to the real possibility of this event and emphasizes the interest of preventing it by promoting information to families in Morocco.

Syrian rue seeds interacted with acacia tree bark in an herbal stew resulted in N,N-dimethyltryptamine poisoning.

Introduction: Illicit substance use is an increasing problem all over the world, especially in adolescents and young adults. It is a challenge to make a definitive diagnosis of a specific substance in a poisoning case without toxicology laboratory confirmation. We confirmed the presence of N,N-dimethyltryptamine (DMT) by liquid chromatograph tandem mass spectrometer (LC/MS/MS) in biologic samples from two patients who presented with signs and symptoms consistent with sympathomimetic toxicity following the consumption of an herbal stew. Case: Two patients consumed an herbal stew together developed DMT poisoning from the interaction between Syrian rue seeds containing alkaloids with monoamine oxidase inhibitor (MAOI) activity and Acacia tree bark containing DMT. Patients' blood and spot urine was analyzed by LC/MS/MS which revealed the presence of DMT (case 1 urine: 1206 ng/mL, serum: 25 ng/mL; case 2 urine: 478 ng/mL, serum: undetectable) and harmaline (case 1 urine: 1564 ng/mL, serum: 3.3 ng/mL; case 2 urine: 1230 ng/mL, serum: undetectable). Discussion: The diagnosis of DMT poisoning is confirmed by the presence of DMT and harmaline in patients' serum and urine. Case 1 exhibited more severe signs and symptoms (e.g., altered consciousness, rhabdomyolysis, and elevated liver enzyme) than case 2. This may be explained by the presence of psychoactive DMT levels in the blood of case 1 whereas DMT was undetected in the blood of case 2. Conclusions: Consumption of an herbal stew composed of Syrian rue seeds and Acacia tree bark may be equivalent to taking a combination of DMT and MAOI, which may precipitate a sympathomimetic syndrome. Physicians should be aware that unusual clinical presentations may be the result of drug-drug interactions from a mixed herbal preparation.

Kratom exposures reported to United States poison control centers: 2011-2017.

Context: Kratom, or Mitragyna speciosa, is a plant indigenous to Southeast Asia that has gained national attention in the United States for its increased use in the self-management of opioid withdrawal and pain, as well as for concerns about its safety. Methods: This study analyzes exposures to kratom reported to poison control centers (PCCs) in the United States during 2011-2017 from the National Poison Data System (NPDS). Discussion: From 2011 through 2017, 1807 kratom exposures were reported to United States PCCs. Almost two-thirds (65.0%) of these exposures occurred during 2016-2017. Most exposures occurred among adults ≥20 years (88.9%), males (70.8%), at a residence (86.1%), and were intentional (74.3%). Among first-ranked kratom exposures, 31.8% resulted in admission to a health care facility (HCF) and 51.9% in a serious medical outcome. Multiple-substance exposures were associated with greater odds of admission to a HCF (OR: 2.80; 95% CI: 2.21-3.55) and a serious medical outcome (OR: 2.25; 95% CI: 1.77-2.85) compared with single-substance exposures. There were 11 deaths associated with kratom exposure, including two that occurred after exposure to kratom only. Among kratom-only exposures, 86.1% resulted in one or more clinical effects. The most common clinical effects were agitation/irritability (22.9%) and tachycardia (21.4%). There were seven neonatal exposures, including five experiencing withdrawal. Conclusions: Kratom is associated with a variety of serious medical outcomes, especially when used with other substances. More research is needed to define the human response to kratom. Increased regulation of kratom products would help guarantee product quality and safety. Individuals who choose to use kratom should be educated about its potential risks, including the dangers of using it in combination with other substances.

Cleistanthus collinus poisoning: a case report of intentional poisoning.

We report a case of 50-year-old male patient from tribal area in South Indian state of Telangana, who ingested the liquid extract from crushed leaves of the plant, cleistanthus collinius with the intention of self-harm. Immediate gastric lavage and activated charcoal administration was done and the patient was subsequently admitted into an acute medical care unit. During first 24 hours of monitoring, the patient was clinically stable. There was mild normal anion gap metabolic acidosis and hypokalaemia on arterial blood gas (ABG) and was corrected accordingly. On second day of admission he developed acute onset shortness of breath. Chest auscultation revealed extensive bilateral coarse crackles. Chest X-ray was suggestive of acute respiratory distress syndrome (ARDS). The patient had to be intubated. Continuous renal replacement therapy (CRRT) was initiated in view of worsening metabolic acidosis and unstable haemodynamics. In spite of appropriate intensive care measures, the patient succumbed to illness. Immediate gastric lavage and activated charcoal administration was done and the patient was subsequently admitted into an acute medical care unit. During first 24 hours of monitoring, the patient was clinically stable. There was mild normal anion gap metabolic acidosis and hypokalaemia on ABG and was corrected accordingly. On second day of admission, he developed acute onset shortness of breath. Chest auscultation revealed extensive bilateral coarse crackles. Chest X-ray was suggestive of ARDS. The patient had to be intubated on day 2. CRRT was initiated in view of worsening metabolic acidosis and unstable haemodynamics. In spite of appropriate intensive care measures, the patient gradually deteriorated, had cardiac arrest and passed away on day 5 of his hospital stay.

Colchicine Extract Suicidal Lethal Poisoning Confirmation Using High-Resolution Accurate Mass Spectrometry: A Case Study.

A case of suspected acute and lethal intoxication caused by colchicine has been reported. The woman was hospitalized after her suspicion of suicidal poisoning by a rare autumn crocus (Colchicum autumnale). Suspected colchicine poisoning was confirmed using a novel UHPLC method with a modern reversed-phase stationary phase with a sub 2-micron superficial porous particle size combined with a QTOF mass spectrometer. Sample preparation procedure included the addition of propiverine as internal standard, protein precipitation using methanol and solid phase extraction. High-resolution MS only and targeted MS/MS modes are reported for the qualitative analysis and screening of other potential drugs of abuse in blood samples. All Ion MS mode was used for quantitative determination of colchicine afterward. The concentration of colchicine in the blood sample was approximately 41 ng/mL, and more than 200 µg/mL of the plant extract used for the suicide.

Concentrations of various forms of vitamin B6 in ginkgo seed poisoning.

A 2-year-old girl required medical attention for a sudden onset of repetitive tonic-clonic convulsions after ingesting 20-30 ginkgo seeds. Concentrations of the major forms of circulating vitamin B6, pyridoxal-5'-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid, as well as the known ginkgo seed toxin 4'-O-methylpyridoxine (MPN) were measured in the serum and cerebrospinal fluid (CSF). PLP is an active form of vitamin B6 and necessary for γ-aminobutyric acid (GABA) production. High MPN concentrations were observed in both the serum and CSF. As the PLP to PL ratio was markedly decreased in serum and CSF examinations, we suspected the ratio to be important in GABA production. This case report provides novel information on the metabolism of vitamin B6 in humans as a result of ginkgo seed poisoning.

Lethal Injection of a Castor Bean Extract: Ricinine Quantification as a Marker for Ricin Exposure Using a Validated LC-MS/MS Method.

Ricin is a highly toxic agent derived from the castor bean plant (Ricinus communis). Poisoning occurs commonly by oral ingestion of the beans. Injection of ricin is believed to be more lethal. Ricin is a large glycosylated protein difficult to detect in clinical samples. Instead, ricinine, a small alkaloid found in the same beans, is used as surrogate marker for ricin exposure. We describe a simple LC-MS/MS method for the detection of ricinine in serum, blood and urine, validated according to EMA guidelines and successfully applied to patient samples of a suicidal death after injection of a castor bean extract. A 26-year-old man self-presented to the emergency department with severe abdominal cramps and nausea after injection of a castor bean extract. Due to rapid deterioration of his hemodynamic function despite early aggressive fluid resuscitation, he was transferred to ICU. Abdominal cramps worsened and a fulminant diarrhea developed, resulting in hypovolemic shock and cardiorespiratory collapse. Despite full supportive therapy, the patient died approximately 10 hours after injection due to multiple organ failure. Ricinine was quantified by LC-MS/MS after LLE with diethyl ether using ricinine-D3 as internal standard. Six hours after injection, ricinine concentrations in serum and blood were 16.5 and 12.9 ng/mL, respectively, which decreased to 12.4 and 10.6 ng/mL, 4 hours later. The urinary concentration was 81.1 ng/mL 7 hours after injection, which amply exceeded the levels previously reported in similar cases with lethal outcome. Concentrations of ricinine, compatible with a lethal exposure to castor beans, were detected in serum, blood and urine. Ricinine was also found in bile and liver tissue.

Bizarre and scary ECG in yew leaves poisoning: Report of successful treatment.

Yew leaves poisoning is a rare life-threatening intoxication, whose diagnosis can be difficult. Initial symptoms are nausea, vomiting, abdominal pain, dizziness, tachycardia, muscle weakness, confusion, beginning within 1 hr from ingestion and followed by bradycardia, ventricular arrhythmias, ventricular fibrillation, severe hypotension, and death. Taxine-derived alkaloids are responsible for the toxicity of the yew leaves, blocking sodium and calcium channels, and causing conduction abnormalities. Because of lack of a specific antidote and limited efficacy of common antiarrhythmic drugs, prompt diagnosis, detoxification measures, and immediate hemodynamic support (also with transvenous cardiac stimulation) are essential.

The medicinal chemistry and neuropharmacology of kratom: A preliminary discussion of a promising medicinal plant and analysis of its potential for abuse.

The leaves of Mitragyna speciosa (commonly known as kratom), a tree endogenous to parts of Southeast Asia, have been used traditionally for their stimulant, mood-elevating, and analgesic effects and have recently attracted significant attention due to increased use in Western cultures as an alternative medicine. The plant's active alkaloid constituents, mitragynine and 7-hydroxymitragynine, have been shown to modulate opioid receptors, acting as partial agonists at mu-opioid receptors and competitive antagonists at kappa- and delta-opioid receptors. Furthermore, both alkaloids are G protein-biased agonists of the mu-opioid receptor and therefore, may induce less respiratory depression than classical opioid agonists. The Mitragyna alkaloids also appear to exert diverse activities at other brain receptors (including adrenergic, serotonergic, and dopaminergic receptors), which may explain the complex pharmacological profile of raw kratom extracts, although characterization of effects at these other targets remains extremely limited. Through allometric scaling, doses of pure mitragynine and 7-hydroxymitragynine used in animal studies can be related to single doses of raw kratom plant commonly consumed by humans, permitting preliminary interpretation of expected behavioral and physiological effects in man based on this preclinical data and comparison to both anecdotal human experience and multiple epidemiological surveys. Kratom exposure alone has not been causally associated with human fatalities to date. However, further research is needed to clarify the complex mechanism of action of the Mitragyna alkaloids and unlock their full therapeutic potential. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.'