piperidines and Rhabdomyolysis

Rhabdomyolysis (R) is a complex condition involving the rapid dissolution of damaged or injured skeletal muscle. This leads to the direct release of intracellular components, including myoglobin, creatine kinase, aldolase, and lactate dehydrogenase, as well as electrolytes, into the bloodstream and extracellular space. Clinically, R shows a triad of symptoms: myalgia, limb weakness, and myoglobinuria without hematuria, while myoglobin has been recognized as playing a part in the development of acute kidney injury. Coturnism is a relatively rare disease, mostly found in the European countries bordering the Mediterranean Sea, characterized by acute R. It follows the consumption of Coturnix coturnix, a species of quails common in Europe, that have ingested the toxic substances (and especially coniine) present in the herbaceous plant called hemlock (Conium maculatum). Coniine may be lethal at a dose of 150 mg but it has neurotoxic effects at smaller doses, with acute R and acute kidney injury. Freezing and cooking the meat does not inactivate the alkaloids present in the birds' flesh and digestive tract. The clinical course of coturnism includes neurotoxicosis, tremor, vomiting, muscle paralysis, respiratory paralysis/failure, R and acute kidney injury. In appropriate geographical and temporal settings, it should be considered when diagnosing patients with acute R. The genetic, biochemical and epidemiological characteristics of coturnism are not yet fully known, while we wait reliable data from experimental studies.

Topics: Acute Kidney Injury; Alkaloids; Animals; Foodborne Diseases; Humans; Muscle, Skeletal; Piperidines; Plant Poisoning; Quail; Rhabdomyolysis

The aim of this paper is to highlight the symptomatology in three Conium maculatum intoxication incidents, one of which was fatal. A number of studies were reviewed in order to update and summarize the relevant literature on the incidence, sociodemographic variables, method of poisoning, pathophysiology, diagnosis, variables associated with survival and fatality, management, and treatment of C. maculatum intoxication as well as the biosynthesis and biological effects of poison hemlock alkaloids. Results show that hemlock poisoning is relatively rare, although incidence varies in different regions, despite its worldwide distribution. Hemlock poisoning is more common in European and especially Mediterranean countries. The majority of the patients are adult males over 38 years of age. The clinical course of hemlock poisoning includes neurotoxicosis, tremor, vomiting, muscle paralysis, respiratory paralysis/failure, rhabdomyolysis, and acute renal failure. The therapeutic management focuses on absorption reduction, close observation for complications, and supportive therapy (especially for respiration). Acute occurrence is severe and life-threatening, but the survival rate is high if treatment is provided promptly. Recovery is rapid, generally taking only a few days.

Topics: Accidents; Aged; Alkaloids; Animals; Antidotes; Antiemetics; Charcoal; Chromatography, Liquid; Conium; Gas Chromatography-Mass Spectrometry; Gastric Lavage; Humans; Livestock; Male; Molecular Structure; Phytotherapy; Piperidines; Plant Poisoning; Respiratory Paralysis; Rhabdomyolysis; Suicide

Topics: Acute Kidney Injury; Analgesics, Opioid; Humans; Imidazoles; Male; Middle Aged; Patient Acuity; Piperidines; Rhabdomyolysis; Selective Serotonin Reuptake Inhibitors; Sertraline

Recent studies suggested that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, developed for the treatment of chronic lymphocytic leukemia, may prevent NLRP3 inflammasome activation in macrophages, IL-1β secretion and subsequent development of inflammation and organ fibrosis. The role of NLRP3 has been underlined in the various causes of acute kidney injury (AKI), a pathology characterized by high morbimortality and risk of transition toward chronic kidney disease (CKD). We therefore hypothesized that the BTK-inhibitor ibrutinib could be a candidate drug for AKI treatment. Here, we observed in both an AKI model (glycerol-induced rhabdomyolysis) and a model of rapidly progressive kidney fibrosis (unilateral ureteral obstruction), that ibrutinib did not prevent inflammatory cell recruitment in the kidney and fibrosis. Moreover, ibrutinib pre-exposure led to high mortality rate owing to severer rhabdomyolysis and AKI. In vitro, ibrutinib potentiated or had no effect on the secretion of IL-1β by monocytes exposed to uromodulin or myoglobin, two danger-associated molecule patterns proteins involved in the AKI to CKD transition. According to these results, ibrutinib should not be considered a candidate drug for patients developing AKI.

Topics: Acute Kidney Injury; Adenine; Agammaglobulinaemia Tyrosine Kinase; Animals; Antineoplastic Agents; Blood Specimen Collection; Fibrosis; Humans; Kidney; Leukemia, Lymphocytic, Chronic, B-Cell; Leukocytes, Mononuclear; Macrophages; Male; Mice, Inbred C57BL; Mortality; Myoglobin; Pharmaceutical Preparations; Piperidines; Protein Kinase Inhibitors; Rhabdomyolysis

Topics: Anesthetics, Intravenous; Child; Humans; Infusions, Intravenous; Phosphatidate Phosphatase; Piperidines; Propofol; Remifentanil; Rhabdomyolysis

Topics: Acute Kidney Injury; Adult; Antidepressive Agents, Tricyclic; Benzodiazepines; Chromatography, Liquid; Creatinine; Dose-Response Relationship, Drug; Emergency Service, Hospital; Hospitalization; Humans; Male; Piperidines; Rhabdomyolysis; Tandem Mass Spectrometry

Novel psychoactive substances (NPS) are easily accessible and the consumption has increased in recent years. New compounds as well as compounds derived from pharmaceutical research or the patent literature are provided, mostly without any declaration. As a consequence, severe adverse reactions may occur after consumption of unknown doses of these drugs, in particular after mixed intake of different psychoactive substances or co-medication. The toxic effects in such cases are not predictable. We report cases of rhabdomyolysis in patients after consumption of desoxipipradrol in combination with other NPS. Particularly in case of synergistic serotonergic effects a distinct stimulation of 5-HT2A-receptors (or 5-HT1A-receptors) should be considered which may lead to serotonergic syndrome.

Topics: Adolescent; Adult; Designer Drugs; Diagnosis, Differential; Female; Humans; Illicit Drugs; Male; Piperidines; Psychotropic Drugs; Rhabdomyolysis; Serotonin Syndrome; Young Adult

Over the past decade, there has been a sharp increase in the number of newly identified synthetic drugs. These new drugs are often derivatives of previously abused substances but have unpredictable toxicity. One of these drugs is gacyclidine, a derivative of phencyclidine (PCP). Gacyclidine has been studied as a neuroprotective agent in trauma and as a therapy of soman toxicity. There are no previous reports of its use as a drug of abuse.. During a two-month period in the summer of 2013, a series of patients with severe agitation and end-organ injury were identified in an urban academic Emergency Department (ED). A urine drug of abuse screen was performed on all patients, and serum samples were sent for comprehensive toxicology analysis. A total of five patients were identified as having agitation, rhabdomyolysis, and elevated troponin (Table 1). Three of the five patients reported use of methamphetamine, and all five patients had urine drug screens positive for amphetamine. Comprehensive serum analysis identified methamphetamine in three cases, cocaine metabolites in one case, and a potential untargeted match for gacyclidine in all five cases. No other drugs of abuse were identified.. This is the first series of cases describing possible gacyclidine intoxication. The possible source of the gacyclidine is unknown but it may have been an adulterant in methamphetamine as all patients who were questioned reported methamphetamine use. These cases highlight the importance of screening for new drugs of abuse when patients present with atypical or severe symptoms. Gacyclidine has the potential to become a drug of abuse both by itself and in conjunction with other agents and toxicity from gacyclidine can be severe. It is the role of the medical toxicology field to identify new agents such as gacyclidine early and to attempt to educate the community on the dangers of these new drugs of abuse.

Topics: Academic Medical Centers; Adult; Combined Modality Therapy; Cyclohexenes; Designer Drugs; Drug Users; Emergency Service, Hospital; Fatal Outcome; Female; Humans; Illicit Drugs; Male; Middle Aged; Multiple Organ Failure; Neurotoxicity Syndromes; Piperidines; Psychomotor Agitation; Psychotropic Drugs; Rhabdomyolysis; Toxicokinetics; Treatment Outcome; Treatment Refusal

Topics: Cholinesterase Inhibitors; Donepezil; Humans; Indans; Neuroleptic Malignant Syndrome; Piperidines; Rhabdomyolysis

A 13-year-old girl presented with right ventricular failure secondary to Ebstein's malformation (downward displacement of the tricuspid valve leaflets with adherence to the right ventricular muscle and redundancy or dysplasia of the tricuspid valve leaflets). She subsequently required a heart transplant but developed rhabdomyolysis early in the postoperative period and required ventilatory support for more than 3 weeks. A variety of causes were considered, but her condition improved only when cyclosporin was eliminated from the immunosuppression regimen. We believe it is likely that the rhabdomyolysis has been caused by cyclosporin. If so, this has occurred both earlier in the clinical course and at lower serum concentrations than previously described.

Topics: Acute Disease; Adolescent; Anesthetics, Intravenous; Creatinine; Cyclosporine; Female; Heart Transplantation; Humans; Immunosuppressive Agents; Piperidines; Postoperative Complications; Propofol; Remifentanil; Rhabdomyolysis

Topics: Alkaloids; Animals; Female; Foodborne Diseases; Humans; Middle Aged; Piperidines; Quail; Rhabdomyolysis

In the past, hemlock poisoning was only known for its neurotoxic effects; quite recently non-neurological features, consisting of rhabdomyolysis and acute renal failure, have been also described. Here we report our experience with these clinical findings, which we frequently observe in accidental hemlock poisoning. Between 1972 and 1990 we studied 18 patients: 17 of them were poisoned by conline (an alkaloid of Conium maculatim) in Apulia (Italy), and one by cicutoxin (the active principle of water hemlock) in New Mexico (USA). In the non-rapidly-fatal cases we tested myoglobinuria, serum muscle enzymes, and renal function. In the patients with acute renal failure we performed microscopical examination of kidney specimens; immunohistochemistry was carried out to identify myoglobin and actin in tubules. Coniine was detected in urine, serum, or tissues. Neurological features were present in all of our cases: coniine had a curare-like effect on the neuromuscular junction, whereas cicutoxin was convulsant on the central nervous system. In addition rhabdomyolysis was noted in the 17 subjects poisoned by coniine. Acute renal failure was observed in five patients; it was confirmed by histological evidence of tubular necrosis with intratubular deposition of myoglobin and actin released by rhabdomyolysis. Our cases seem to be the first with histopathologically proven acute tubular necrosis in coniine intoxication. In conclusion, in hemlock poisoning neurotoxic manifestations may be accompanied by rhabdomyolysis and acute tubular necrosis; increased awareness of these clinical features is recommended in order to improve the diagnostic and therapeutic procedure.

Topics: Adult; Aged; Alkaloids; Alkynes; Diynes; Fatty Alcohols; Female; Humans; Kidney Tubular Necrosis, Acute; Male; Middle Aged; Nervous System Diseases; Piperidines; Plant Poisoning; Rhabdomyolysis

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Alkaloids; Analgesics; Animals; Birds; Female; Humans; Kidney Tubular Necrosis, Acute; Male; Middle Aged; Piperidines; Rhabdomyolysis; Seasons