Cocaine-Induced Toxic Leukoencephalopathy: A Case Report.

Cocaine is a widely abused controlled substance. Cocaine use is associated with a myriad of side effects and a sequelae of consequences secondary to its harmful nature and potential adulterants, the most recently described and less known sequelae being leukoencephalopathy. In our case, we describe a 58-year-old male who presented to the ED with agitation and acute stroke-like symptoms with reported rapid onset. Cocaine induced toxic leukoencephalopathy is a diagnosis of exclusion, thus other etiologies of disease were ruled out in a full neurological and infectious workup; most importantly consisting of extensive brain imaging, alluding to the diagnosis of acute cocaine induced toxic leukoencephalopathy in an individual with a confirmed history of cocaine and cannabinoid abuse. Although there is no targeted therapy for the condition to our knowledge, we utilized a supportive approach to treatment in contrast to other reported treatment modalities which included the use of steroids, plasma exchange, and intravenous immunoglobulin. Furthermore, we describe the clinical evaluation and treatment throughout the patient's hospital course with his eventual marked improvement from initial presentation.

Acute Pancreatitis Secondary to Cocaine Intoxication: A Case Series.

Gallstones, alcohol use, hypertriglyceridemia, and hypercalcemia have been considered the most common causes of acute pancreatitis; however, about 20% of the cases remain idiopathic since no definite cause can be established. It has been noticed that there is a small number of patients who have presented to the hospital with a diagnosis of acute pancreatitis who have concurrently been using cocaine yet have no recent alcohol use and no gallstones. The purpose of this series of case reports is to review the evidence behind the association between cocaine and pancreatitis. In most of the cases, the etiology of acute pancreatitis is usually straightforward. However, when faced with a patient who has acute pancreatitis but lacks the common causes such as alcoholism, gallstones, normal triglyceride levels, and no evidence of malignancy, it seems reasonable to consider drugs as a potential cause for pancreatitis.

Cocaine-Induced Toxic Leukoencephalopathy: A Case Report.

We present a case here where a 57-year-old South Asian male with disturbed mental status developed multifocal leukoencephalopathy, which we believe was caused by cocaine usage. Cocaine was detected in the urine toxicological sample. Non-acute CT head, with a follow-up brain MRI demonstrating hyperintensity of the T2 FLAIR signal corresponding to diffusion restriction throughout the whole supratentorial white matter, involving semiovale and subcortical U fibres in the occipital lobes as well as posterior frontal and parietal centrum. It was less likely that the patient had posterior reversible encephalopathy syndrome (PRES), which can potentially manifest similarly in a clinical and imaging context because there was no abrupt rise of blood pressure at presentation or during the patient's stay. Extensive examinations were conducted to exclude additional factors that may contribute to the patient's appearance, including autoimmune, vasculitis, and infectious diseases. Levamisole, a significant chemical that is frequently used to increase the volume of cocaine samples and has been linked to neuronal damage, should be examined in individuals who use cocaine and exhibit these kinds of clinical symptoms. The patient was prescribed 250 mg of methylprednisolone twice daily for five days after it was determined that cocaine-induced neuronal toxicity was the cause of his symptoms. Although no improvement was seen right away, over the course of the next few days, he did exhibit a gradual, albeit slight, improvement in his mental status while residing in the nursing home. It is crucial to comprehend the possible connection between cocaine usage, a commonly abused drug, and people exhibiting similar clinical symptoms. To have a better understanding of the pathophysiology and possible treatment approach, more research is necessary as there is now no recommended therapy regimen.

A Case of Cocaine Toxicity From Body Stuffing.

Here, we report a case of body stuffing leading to severe cocaine toxicity. Medical management and supportive care are usually the best course of action in cases of body stuffing, as seen in our case. While surgery is rarely indicated, surgical consultation should occur early to ensure prompt intervention if obstruction or perforation occurs.

Acute Cocaine Intoxication: An Approach to Severe Hepatic and Renal Dysfunctions.

Cocaine is a highly addictive substance. Its poisoning can lead to potentially fatal multi-organ dysfunction. We report a case of cocaine overdose with severe multi-organ dysfunction. A healthy 51-year-old man was admitted to the emergency room due to behaviour changes and seizure after inhaling crack. Multiple dysfunctions were developed, with emphasis on liver and kidney dysfunction, due to their severity. The patient had marked hepatic cytolysis with a peak on the third day with alanine aminotransferase (ALT) and aspartate aminotransferase (AST): 7941 and 4453 IU/L, respectively with mild coagulopathy and hyperbilirubinemia. Underwent empirical treatment with acetylcysteine ​​with good clinical response. Also developed anuric AKIN3 acute kidney injury secondary to rhabdomyolysis, requiring treatment with intermittent haemodialysis. The approach to a case with severe multiorgan dysfunction is described, with special emphasis on the use of acetylcysteine. The good evolution of the patient can corroborate the use of this drug as a potential modifier of prognosis.

Catecholamine Mega Storm Triggered by Cocaine Use and Thyrotoxicosis Crisis.

Takotsubo cardiomyopathy (TCM) is a well-recognized non-ischemic complication of physical and emotional stressors leading to heart dysfunction. Both thyroid storm and cocaine have been implicated with TCM to varying degrees. We present the case of a 26-year-old male with Graves' disease and cocaine abuse who was hospitalized with thyroid storm resulting in takotsubo cardiomyopathy and cardiogenic shock. The patient had a long and complicated hospital course, requiring advanced therapies including extracorporeal membrane oxygenation and other medical and mechanical circulatory support therapies. With treatment for thyroid storm using antithyroid medications and steroids, the patient eventually had complete recovery of his left ventricular function and was ultimately weaned from pressors, inotropes and mechanical support.

Posterior Reversible Encephalopathy Syndrome With Hemorrhagic Conversion in a Patient With Active Polysubstance Abuse: A Case Report and Review of Literature.

Posterior reversible encephalopathy syndrome (PRES) is a neurovascular sequence noted in patients with preeclampsia/eclampsia, solid-organ/bone marrow transplantation, and malignant hypertension. The mechanism in which PRES occurs has not yet been determined. It has been hypothesized that it may be related to endothelial cell dysfunction or injury leading to the compromise of the blood-brain barrier. The clinical presentations vary but are similar to symptoms of increased intracranial pressure, such as headache, visual changes, focal neurological deficits, seizures, and altered mental status. Although the pathology suggests reversibility, that is not always the case in which severe ischemic damage has occurred. We present a patient who came to the emergency room with a history of substance abuse and tested positive on a urinary toxicology screen for methamphetamine and cocaine. In the US, polysubstance use has been more prevalent in recent years. Furthermore, literature has highlighted the additive effects on one's blood pressure when such drugs are combined. Our patient presented with altered mental status, hypertension, and pinpoint pupils. Over the course of her stay, the patient's mentation slowly improved and was able to follow commands intermittently. We believe that this is the first documented case of polysubstance abuse in correlation to PRES. We hypothesize that the mechanism of PRES resulted from the multiplicative effect of several illicit drugs known to cause transient hypertensive episodes and their ability to disrupt the structural proteins imperative for the blood-brain barrier.

Effects of alcohol on metabolism and toxicity of cocaine in rats.

As most cocaine users drink alcohol, it is interesting to understand how a non-lethal dose of alcohol affects the metabolism and toxicity of cocaine. In this study, we examined the correlation between dose-dependent toxicity and the metabolism/pharmacokinetic (PK) profile of cocaine with or without alcohol (ethanol, 1 g/kg) co-administration in rats. The cocaine toxicity in rats with or without alcohol co-administration is characterized by not only the commonly used LD50, but also the average times for the appearance of convulsion and death as well as total toxicity level (TTL) in the blood. All these data have consistently demonstrated that co-administration of alcohol increased cocaine toxicity, and that the alcohol-enhanced toxicity of cocaine is mainly attributed to the observed two additional metabolites (cocaethylene and norcocaethylene - products of chemical reactions of cocaine with alcohol catalyzed by metabolic enzymes carboxylesterase-1 and liver microsomal cytochrome P450 3A4) that are more toxic than cocaine itself. So, evaluation of the substance TTL should account for the blood levels of not only cocaine itself, but also its all toxic metabolites. In addition, for rats died of a lethal dose of cocaine (60 or 100 mg/kg) combined with 1 g/kg alcohol, we also determined the TTL at the time of death, demonstrating that death would occur once the TTL reached a threshold (~16 µM).

Intravenous Lipid Emulsion for the Treatment of Perioperative Cocaine Intoxication.

Symptomatic cocaine intoxication in the preoperative period is a potentially life-threatening condition, especially before emergent surgery. The anesthesiologist is faced with a dilemma where the patient is deemed unsafe for induction of general anesthesia but also in need of immediate surgical intervention. Cocaine is a local anesthetic and, as such, has been proposed to respond to lipid emulsion treatment as other local anesthetics would. We present a case supporting this statement and review the relevant published literature on the topic.

Evaluation of Cocaine Effect on Endogenous Metabolites of HepG2 Cells Using Targeted Metabolomics.

Cocaine toxicity has been a subject of study because cocaine is one of the most common and potent drugs of abuse. In the current study the effect of cocaine on human liver cancer cell line (HepG2) was assessed. Cocaine toxicity (IC50) on HepG2 cells was experimentally calculated using an XTT assay at 2.428 mM. The metabolic profile of HepG2 cells was further evaluated to investigate the cytotoxic activity of cocaine at 2 mM at three different time points. Cell medium and intracellular material samples were analyzed with a validated HILIC-MS/MS method for targeted metabolomics on an ACQUITY Amide column in gradient mode with detection on a triple quadrupole mass spectrometer in multiple reaction monitoring. About 106 hydrophilic metabolites from different metabolic pathways were monitored. Multivariate analysis clearly separated the studied groups (cocaine-treated and control samples) and revealed potential biomarkers in the extracellular and intracellular samples. A predominant effect of cocaine administration on alanine, aspartate, and glutamate metabolic pathway was observed. Moreover, taurine and hypotaurine metabolism were found to be affected in cocaine-treated cells. Targeted metabolomics managed to reveal metabolic changes upon cocaine administration, however deciphering the exact cocaine cytotoxic mechanism is still challenging.

Cocaine Body Packing: A New Record.

We present a case of a 39-year-old man who was brought in by ambulance to the ED after ingesting 103 packets of cocaine prior to return to the United Kingdom (UK) from Holland. He presented with a persistent sinus tachycardia and mild abdominal pain but no evidence of peritonitis on examination. Contrast-enhanced CT showed widespread distribution of packets from the stomach to the sigmoid colon. He was taken to theater for emergency laparotomy and retrieval of the packets, which was done successfully without the need of any bowel resection. He was then discharged to police custody following a 10-day admission. This is the highest number of cocaine packets reported in the UK literature. This case report discusses the importance of a multidisciplinary approach in safely managing body packers who also present with signs of cocaine toxicity.

Reengineering of Albumin-Fused Cocaine Hydrolase CocH1 (TV-1380) to Prolong Its Biological Half-Life.

Therapeutic treatment of cocaine toxicity or addiction is a grand medical challenge. As a promising therapeutic strategy for treatment of cocaine toxicity and addiction to develop a highly efficient cocaine hydrolase (CocH) capable of accelerating cocaine metabolism to produce physiologically/biologically inactive metabolites, our previously designed A199S/S287G/A328W/Y332G mutant of human butyrylcholinesterase (BChE), known as cocaine hydrolase-1 (CocH1), possesses the desirably high catalytic activity against cocaine. The C-terminus of CocH1, truncated after amino acid #529, was fused to human serum albumin (HSA) to extend the biological half-life. The C-terminal HSA-fused CocH1 (CocH1-HSA), known as Albu-CocH1, Albu-CocH, AlbuBChE, Albu-BChE, or TV-1380 in literature, has shown favorable preclinical and clinical profiles. However, the actual therapeutic value of TV-1380 for cocaine addiction treatment is still limited by the short half-life. In this study, we designed and tested a new type of HSA-fused CocH1 proteins, i.e., N-terminal HSA-fused CocH1, with or without a linker between the HSA and CocH1 domains. It has been demonstrated that the catalytic activity of these new fusion proteins against cocaine is similar to that of TV-1380. However, HSA-CocH1 (without a linker) has a significantly longer biological half-life (t1/2 = 14 ± 2 h) compared to the corresponding C-terminal HSA-fused CocH1, i.e., CocH1-HSA (TV-1380 with t1/2 = 5-8 h), in rats. Further, the N-terminal HSA-fused CocH1 proteins with a linker have further prolonged biological half-lives: t1/2 = 17 ± 2 h for both HSA-EAAAK-CocH1 and HSA-PAPAP-CocH1, and t1/2 = 18 ± 3 h for HSA-(PAPAP)2-CocH1. These N-terminal HSA-fused CocH1 proteins may serve as more promising protein drug candidates for cocaine addiction treatment.

In vivo characterization of toxicity of norcocaethylene and norcocaine identified as the most toxic cocaine metabolites in male mice.

BACKGROUND: Majority of cocaine users also consume alcohol, and concurrent use of cocaine and alcohol produces cocaethylene, norcocaine, norcocaethylene, and other non-toxic metabolites. It is essential to know their relative toxicity for development of a truly effective therapeutics for cocaine toxicity treatment. METHODS: Drug (norcocaethylene or norcocaine)-induced acute toxicity was characterized by the occurrence (and the timing) of prostration, seizure, and death after intraperitoneal administration of the drug (n = 15) using the same strain (Swiss Webster) of male mice reported in previous study by Hearn et al. to determine LD50 of cocaine and cocaethylene. In addition, drug (cocaine, cocaethylene, norcocaine, or norcocaethylene)-induced hyperactivity was determined by locomotor activity testing (n = 8). RESULTS: According to the animal data, norcocaethylene (LD50=∼39.4 mg/kg) and norcocaine (LD50=∼49.7 mg/kg) are the most toxic metabolites, but they do not induce significant hyperactivity. In addition, the relative toxicity of drugs correlates with the time to the occurrence of prostration/seizure/death after the drug administration. CONCLUSIONS: The relative toxicity of these toxic drugs can be ranked in this order: norcocaethylene > norcocaine > cocaethylene > cocaine. The data suggest that norcocaethylene, norcocaine, and cocaethylene are all significant contributors to acute toxicity of cocaine in concurrent use of cocaine and alcohol. Hence, future therapeutic development for cocaine toxicity treatment must account for detoxification of these more toxic metabolites. In addition, the relative toxicity of different drugs correlates with the average time to the occurrence of death, seizure, or prostration after the drug administration with a same dose close to their LD50 values.

Benzimidazolone-based selective σ2 receptor ligands: Synthesis and pharmacological evaluation.

Sigma receptors (σRs) are considered to be a significant and valid target for developing new medications to address several diseases. Their potential involvement in numerous central nervous system disorders, neuropathic pain, addiction, and cancer has been extensively reported. In particular, the σ2R has been identified as potential target for the development of pharmaceutical agents intended to treat the negative effects associated with drugs of abuse. As a continuation of our previous efforts to develop new selective σ2R ligands, a series of benzimidazolone derivatives were designed, synthesized, and characterized. The newly synthesized ligands were evaluated through in vitro radioligand binding assays to determine their affinity and selectivity towards both σ1 and σ2 receptors. Several derivatives displayed high affinity for the σ2R (Ki = 0.66-68.5 nM) and varied from preferring to selective, compared to σ1R (σ1/σ2 = 5.8-1139). Among them, compound 1-{4-[4-(4-fluorophenyl)piperazin-1-yl]butyl}-3-propyl-1,3-dihydrobenzimidazol-2-one dihydrochloride (14) displayed the ability to produce a dose-dependent reduction in the convulsive effects of cocaine in a rodent model after injecting 10 mg/kg (i.p.). These preliminary results support the use of selective σ2R ligands in the development of useful pharmacological tools or potential pharmacotherapies for cocaine toxicity.

Effectiveness of a Cocaine Hydrolase for Cocaine Toxicity Treatment in Male and Female Rats.

Development of a truly effective medication for treatment of cocaine abuse has been a grand challenge. There is no FDA-approved therapeutic agent specific for cocaine addiction or overdose. An enzyme therapy using an efficient cocaine-metabolizing enzyme could be a promising treatment strategy for cocaine overdose and addiction. One of our previously designed cocaine hydrolases (CocHs), known as CocH1, was fused with human serum albumin (HSA) to prolong the biological half-life. The fusion protein CocH1-HSA is an investigational new drug (IND) approved by the FDA for clinical trials in cocaine addiction treatment, but not in cocaine overdose/toxicity treatment. In the present study, we aimed to evaluate the pharmacokinetic profile of CocH1-HSA and its effectiveness for cocaine toxicity treatment in male and female rats and demonstrate the clinical potential. The data demonstrate that enzyme CocH1-HSA has very similar pharmacokinetic profile in male and female rats. For both male and female rats, the enzyme can rapidly eliminate cocaine even if the cocaine dose is as high as 180 mg/kg (LD100). Based on the animal data, whenever the enzyme is given to a living subject, the remaining cocaine in the body will be converted rapidly to physiologically inactive metabolites and, thus, reverse the cocaine toxicity and help the subject to recover. So, an enzyme therapy using CocH1-HSA can effectively treat cocaine toxicity and prevent the subject from further damage by cocaine. The data obtained clearly demonstrate the promising clinical potential of CocH1-HSA in cocaine overdose treatment for both genders.

Multi-System Complications after Intravenous Cocaine Abuse.

BACKGROUND: Use and abuse of cocaine are associated with numerous adverse effects, independent of the route of administration. More severe conditions of poisoning, however, are observed after cocaine intravenous administration. AIM: We present a case of severe poisoning after violent intravenous injection of cocaine, but with a good outcome. CASE PRESENTATION: Cocaine was intravenously (i.v.) administered in 16-years old female patient as a homicide attempt. Shortly after that, patient experienced series of generalised tonic-clonic seizures, was highly febrile (40°C), somnolent, agitated, presenting with tachycardia, tachypnea and with increased blood pressure 150/90 mmHg. Neurologic status, lumbar puncture and computerised tomography (CT) of the brain were without remarks. Electroencephalogram (EEG) was characterised with signs of diffuse encephalopathy, and acid-base analyses resulted in metabolic acidosis. Urine screening revealed the presence of cocaine and benzodiazepines. The patient presented with signs of the hepatic lesion, acute renal insufficiency (ARI), and increased D-dimers resulting from activated fibrinolysis. The patient was discharged in stable general condition after being hospitalised for 23 days. CONCLUSION: Intravenous abuse of cocaine results in overdose and serous multi-system complications requiring multidisciplinary diagnostic and intensive therapeutic approach.

Self-reported cocaine use is not associated with elevations in high-sensitivity troponin I.

OBJECTIVE: High-sensitivity troponin (hsTn) assays detect 10 times lower concentrations of cardiac troponin than conventional assays. We examined the effects of self-reported cocaine use to determine whether those with acute cocaine use being evaluated for ACS are more likely to have elevated hsTnI than those nonusers being evaluated for ACS. METHODS: We conducted a sub-analysis of a prospective cohort of ED patients evaluated for acute coronary syndrome. Recent cocaine use was determined by structured patient interviews. High-sensitivity troponin (Abbott) and conventional troponin I (Abbott, cTnI) were measured on samples drawn at presentation. Urine toxicology screen for cocaine metabolite was obtained at the discretion of treating clinicians. RESULTS: Of 1862 patients enrolled, 444 reported prior cocaine use and 99 reported cocaine use within the preceding month. Median hsTn in patients with last cocaine use within 24 h, 2-7 days, 1 week-1 month, >1 month, and no prior cocaine use were: 9 (IQR: 3-17) ng/L, 6 (IQR: 3-24.3) ng/L, 6 (IQR: 3-89.5) ng/L, 3 (IQR: 3-18.5) ng/L and 3 (IQR: 3-17) ng/L, respectively. Urine toxicology assays (UTox) for cocaine were performed in 640 (34.4%) patients. The median hsTn for those who were UTox+, UTox - and those without a UTox were: 9 ng/L (IQR: 3-48.5), 9 ng/L (IQR: 3-40) and 3 ng/L (IQR: 3-12), respectively. There were no differences in the prevalence of new troponin elevations (hsTn >99th percentile but cTnI <99th percentile) in those with recent cocaine use compared to those without recent cocaine use. CONCLUSIONS: In this first investigation of hsTn in patients with self-reported recent cocaine use, we have determined that hsTn does not lead to an increase in the prevalence of troponin elevation in cocaine users.

Atraumatic splenic rupture and ileal volvulus following cocaine abuse.

We present the case of a 38-year-old male with an atraumatic splenic rupture, hemoperitoneum, and ileal volvulus following acute cocaine intoxication. Computed tomography showed a "whirl sign", a subcapsular splenic hematoma with suspected peripheral laceration, and diffuse hemoperitoneum. At laparotomy, the spleen was confirmed to be the source of bleeding and was removed. A nonreducible volvulus was found at the distal ileum, and this segment of small bowel was removed. The patient had an uneventful postoperative recovery.

Extracorporeal membrane oxygenation for profound cardiogenic shock due to cocaine toxicity.

Cocaine toxicity can result in myocardial infarction from coronary vasospasm. The current treatment algorithm includes intravenous and/or intracoronary vasodilator administration with an expectantly quick resolution of symptoms and signs of ischemia. However, in situations in which myocardial injury persists, the optimal management is uncertain. We present a case in which extracorporeal membrane oxygenation effectively stabilized a patient with ongoing hemodynamic instability who experienced repeated episodes of myocardial injury and ventricular tachyarrhythmias due to cocaine toxicity. .

Foreign material in the gastrointestinal tract: cocaine packets.

Smuggling drugs by swallowing or inserting into a body cavity is not only a serious and growing international crime, but can also lead to lethal medical complications. The most common cause of death in 'body packers', people transporting drugs by ingesting a packet into the gastrointestinal tract, is acute drug toxicity from a ruptured packet. However, more than 30 years after the initial report of body packing, there is still no definitive treatment protocol for the management of this patient group. The treatment strategy is determined according to the particular condition of the patient and the clinical experience of the treatment center. Surgical intervention is also less common now, due to both the use of improved packaging materials among smugglers and a shift towards a more conservative medical approach. Herein, we report a case of toxicity from ingested packets of cocaine that leaked and, despite surgery, resulted in exitus of the patient.