Altered mental status and end organ damage associated with the use of gacyclidine: a case series.

INTRODUCTION: 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. CASE REPORTS: 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. DISCUSSION: 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.

Pharmacotherapy of critical asthma syndrome: current and emerging therapies.

The critical asthma syndrome (CAS) encompasses the most severe, persistent, refractory asthma patients for the clinician to manage. Personalized pharmacotherapy is necessary to prevent the next acute severe asthma exacerbation, not just the control of symptoms. The 2007 National Asthma Education and Prevention Program Expert Panel 3 provides guidelines for the treatment of uncontrolled asthma. The patient's response to recommended pharmacotherapy is highly variable which risks poor asthma control leading to frequent exacerbations that can deteriorate into CAS. Controlling asthma symptoms and preventing acute exacerbations may be two separate clinical activities with their own unique demands. Clinicians must be prepared to use the entire spectrum of asthma medications available but must concurrently be aware of potential drug toxicities some of which can paradoxically worsen asthma control. Medications normally prescribed for COPD can potentially be useful in the CAS patient, particularly those with asthma-COPD overlap syndrome. Immunomodulation with drugs like omalizumab in IgE-mediated asthma syndromes is one important approach. New and emerging drugs address unique aspects of airway inflammation and biology but at a significant financial cost. The pharmacology and toxicities of the agents that may be used in the treatment of CAS to control asthma symptoms and prevent severe exacerbations are reviewed.

An 11-year review of bupropion insufflation exposures in adults reported to the California Poison Control System.

BACKGROUND: Seizures of both immediate and delayed onset after ingestion of bupropion SR and bupropion XL formulations are well documented, but are less well characterized after insufflation. Bupropion is crushed and insufflated to experience a high similar to that from amphetamines and cocaine. We sought to characterize the abuse of bupropion via insufflation in cases reported to the California Poison Control System (CPCS) and the incidence of seizures. METHODS: An 11-year (2002-2012) retrospective observational case series of insufflated bupropion exposures evaluated in a health care facility (HCF) were reviewed after searching our database for all bupropion insufflation exposures. Patients with coingestants, multiple exposure routes, or age less than 18 were excluded. Data included age, gender, estimated bupropion dose, occurrence of pre-HCF seizures, symptoms and vital signs reported to the CPCS, treatments, and adverse events that occurred until time of discharge. RESULTS: 74 cases were identified (1 excluded due to age, 5 excluded due to additional oral ingestion of bupropion, and 1 excluded due to being unable to follow). A total of 67 cases met inclusion criteria. The median age was 36 (range, 18-65) years. The total dose of bupropion insufflated was reported in 52 pts; median dose of 1500 (range, 100-9000) mg. Eighteen cases (27%) involved staggered or chronic exposures. Of the 67 patients, 20 (30%) experienced a seizure prior to arrival at the HCF. Of these, 19 patients (95%) presented with tachycardia. None of these patients had a second seizure in the emergency department. There were no major medical outcomes and no deaths. Of the 67 patients, 9 patients received benzodiazepines and 6 patients received single-dose activated charcoal. CONCLUSION: The abuse of bupropion by crushing and insufflating through the nose is uncommon (67/2270 or 3.0%) compared with that by oral bupropion exposures reported to CPCS. Seizures are common but are self-limited. Delayed seizures (more than 8 h after exposure) appear to be rare. Tachycardia is present in almost all patients who have seizures.

Alternative drugs of abuse.

The incidence of drug abuse with alternative agents is increasing. The term "alternative drugs of abuse" is a catch-all term for abused chemicals that do not fit into one of the classic categories of drugs of abuse. The most common age group abusing these agents range from 17 to 25 years old and are often associated with group settings. Due to their diverse pharmacological nature, legislative efforts to classify these chemicals as a schedule I drug have lagged behind the development of new alternative agents. The potential reason for abuse of these agents is their hallucinogenic, dissociative, stimulant, anti-muscarinic, or sedative properties. Some of these drugs are easily obtainable such as Datura stramonium (Jimson Weed) or Lophophora williamsii (Peyote) because they are natural plants indigenous to certain regions. The diverse pharmacology and clinical effects of these agents are so broad that they do not produce a universal constellation of signs and symptoms. Detailed physical exams are essential for identifying clues leading one to suspect an alternative drug of abuse. Testing for the presence of these agents is often limited, and even when available, the results do not return in a timely fashion. Intoxications from these agents pose unique challenges for health care providers. Physician knowledge of the physiological effects of these alternative agents and the local patterns of drug of abuse are important for the accurate diagnosis and optimal care of poisoned patients. This review summarizes the current knowledge of alternative drugs of abuse and highlights their clinical presentations.

Polymorphisms in CYP2D6 may predict methamphetamine related heart failure.

BACKGROUND: Methamphetamine (METH) has been associated with a dilated cardiomyopathy. The first and rate-limiting step of metabolism is dependent on the polymorphic enzyme CYP2D6. OBJECTIVES: To evaluate if polymorphisms in CYP2D6 can be associated with the development of a methamphetamine-induced cardiomyopathy. METHODS: We performed a prospective case-control pilot study. Cases were defined by a urinary drug screen positive for amphetamine and evidence of heart failure by beta natriuretic peptide (BNP) greater than 300 pg/ml and symptoms of heart failure. Controls were defined with urinary drug screens positive for amphetamines but without evidence of heart failure defined by a BNP lesser than 300 pg/ml or symptoms of heart failure. Exclusion criteria were less than 18 years or greater than 60 years of age, urinary toxicology screen positive for additional stimulants, known coronary artery disease (CAD) defined by greater than 50% stenosis on catheterization or previous myocardial infarction, known cardiomyopathy of alternative etiology or inability to provide consent. Patients underwent gas chromatography confirmation-mass spectroscopy for methamphetamine, genotyping of CYP2D6, limited echocardiography, and participated in a modified 2007 National Survey of Drug Use and Health Stimulant Survey. Genotype results were analyzed with traditional classifications and "Activity Scores". RESULTS: Fifty-six patients completed the study with 19 cases and 37 controls. There was no statistically significant difference in days of use in a month, age, gender, or ethnicity between cases and controls. While not statistically significant, age and days of use did trend higher in cases. CYP2D6 genotype demonstrated that the lower the activity score/poor metabolizer group had less heart failure than extensive metabolizers/higher activity score. However, it did not reach statistical significance. When adjusting for higher days of use, extensive metabolizers had the highest odds of developing a dilated cardiomyopathy. (OR: 2.33, 95% CI: 0.54-10.13). Echo findings in all cases showed reduced ejection fractions with a mean of 18.6% (range: 10-35%) and 70% had a dilated cardiomyopathy. No cardiomyopathies were seen in the controls. Mean ejection fraction was 56.75% (range: 45-70%). The odds ratio of having a dilated cardiomyopathy in extensive metabolizers was 1.62 (95% CI: 0.47-5.5). CONCLUSION: Our study demonstrates a trend that individuals with decreased metabolic activity were less likely to develop heart failure. While not statistically significant, a signal is present that extensive metabolizers may be at increased risk for the development of a cardiomyopathy.

Formaldehyde levels in FEMA-supplied travel trailers, park models, and mobile homes in Louisiana and Mississippi.

In 2006, area physicians reported increases in upper respiratory symptoms in patients living in U.S. Federal Emergency Management Agency (FEMA)-supplied trailers following Hurricanes Katrina and Rita. One potential etiology to explain their symptoms included formaldehyde; however, formaldehyde levels in these occupied trailers were unknown. The objectives of our study were to identify formaldehyde levels in occupied trailers and to determine factors or characteristics of occupied trailers that could affect formaldehyde levels. A disproportionate random sample of 519 FEMA-supplied trailers was identified in Louisiana and Mississippi in November 2007. We collected and tested an air sample from each trailer for formaldehyde levels and administered a survey. Formaldehyde levels among all trailers in this study ranged from 3 parts per billion (ppb) to 590 ppb, with a geometric mean (GM) of 77 ppb [95% confidence interval (CI): 70-85; range: 3-590 ppb]. There were statistically significant differences in formaldehyde levels between trailer types (P < 0.01). The GM formaldehyde level was 81 ppb (95% CI: 72-92) among travel trailers (N = 360), 57 ppb (95% CI: 49-65) among mobile homes (N = 57), and 44 ppb (95% CI: 38-53) among park models (N = 44). Among travel trailers, formaldehyde levels varied significantly by brand. While formaldehyde levels varied by trailer type, all types tested had some levels ≥ 100 ppb.

Blood leak alarm interference by hydoxocobalamin is hemodialysis machine dependent.

CONTEXT: Hydroxocobalamin has been reported to interfere with the blood leak alarm on hemodialysis machines making it difficult to use this treatment modality after hydroxocobalamin infusion. OBJECTIVE: The objective was to determine if this interference with hydroxocobalamin occurs across hemodialysis machines by different manufacturers. Additionally, we aimed to see if this represented a colorimetric interference alone or if it is the optical properties of hydroxocobalamin. MATERIALS AND METHODS: Hydroxocobalamin was reconstituted per package insert. Food coloring was added to 0.9% saline to create the colors of the visual spectrum. Optical properties of absorbance and transmittance were measured. Hydroxocobalamin and the saline solutions were infused into the Fresenius 2008K™ and the Gambro Phoenix X36™ machines. Times were recorded from the start of the machine until the solution finished or the alarm triggered. RESULTS: When evaluating the Gambro Phoenix X36™ machine and dialysis circuit; the alarm did not trigger. In contrast, the blood leak alarm on the Fresenius 2008K™ machine was tripped by both the red solution and hydoxocobalamin infused per the package insert. The alarm stopped the machine between 128 and 132 seconds for the red solution and between 30 and 35 seconds with the hydroxocobalamin. Membranes of the circuits where the alarm tripped were examined and remained intact without blood. Results were validated on different machines with new circuits. DISCUSSION: Hydroxocobalamin infusion per package insert and the red saline solution prepared with Red Dye 40 both triggered the blood leak alarm and stopped the Fresenius 2008K™ machine. However, this was not true for the Gambro Phoenix X36™ machine as the alarm never triggered. The interference with the Fresenius 2008K™ appears colorimetric due to normal saline with Red Dye 40 triggering the alarm. CONCLUSION: We alert physicians to become familiar with the properties of individual dialysis machines prior to use of hydroxocobalamin. When facing difficulties with hemodialysis after the administration of hydroxocobalamin, consider attempting with a different manufactures machine or model if available or contact the manufacturer directly.

Predictors of ethylene glycol ingestion cases called into a regional poison center.

Poison center consultations for potential toxic alcohol poisonings are challenging because blood levels are typically not immediately available. The primary objective of this study was to determine whether readily obtainable laboratory values can be used to accurately and rapidly diagnose these poisonings. Over a 15-month period, patients with a history of toxic alcohol ingestion or a metabolic acidemia (pH ≤ 7.30 or serum bicarbonate ≤ 18 mEq/L) that prompted a poison center consultation were enrolled. A predictive logistic regression model was used to assess the combined ability of serum pH, calcium, osmolar gap, and anion gap levels to predict a final diagnosis of toxic alcohol poisoning. There were 102 subjects included in the analysis. A total of 44% (45/102) patients had a final diagnosis of ethylene glycol (EG) poisoning. Higher levels of calcium, osmolar gap, and anion gap were independently associated with statistically significant or marginally significant increases in the odds of a final diagnosis of EG poisoning. The c-index was estimated at 0.81, indicating that the model showed a reasonable ability to discriminate EG cases from others. The final model had a sensitivity and specificity of 78% and 89%, respectively, and positive and negative predictive values of 84% and 83% respectively. The combination of elevated calcium, osmolar gap, and anion gap is associated with a high likelihood of EG poisoning, but clinician gestalt is still essential for its diagnosis. Further refinement of the model is needed.

Race is not an independent predictor of biochemical recurrence after radical prostatectomy in an equal access medical center.

OBJECTIVES: To compare the racial differences in clinical and pathologic features between black and white men who underwent radical prostatectomy (RP) in an equal access health care center and to determine whether race is an independent predictor of biochemical recurrence. METHODS: A retrospective survey of 273 patients (125 black, 148 white) who underwent RP at the West Los Angeles Veterans Affairs Medical Center between 1991 and 1999 was undertaken. Patients were analyzed for racial differences in age at diagnosis, clinical stage, preoperative serum prostate-specific antigen (PSA), and Gleason score of the prostate biopsy specimens. Surgical specimens were studied to determine pathologic stage, Gleason score, incidence of seminal vesicle invasion, positive surgical margins, capsular penetration, and pelvic lymph node involvement. Patients were followed for PSA recurrence (greater than 0.2 ng/mL). Multivariate analysis was used to determine the clinical and pathologic variables that were significant in predicting biochemical recurrence after RP and to determine whether race was an independent predictor of biochemical failure. RESULTS: No significant differences were found between black and white men in the preoperative factors (clinical stage, age at diagnosis, biopsy Gleason score, and serum PSA) or in the pathologic features of the RP specimens (Gleason score, pathologic stage, incidence of positive surgical margins, capsular penetration, seminal vesicle invasion, or lymph node involvement). In addition, no differences were found between black and white men in the PSA recurrence rates after RP using Kaplan-Meier survival curves (P = 0.651). Multivariate analysis revealed that serum PSA (P = 0.010), biopsy Gleason score (P = 0. 003), younger age (P = 0.010), surgical Gleason score (P = 0.005), and lymph node involvement (P = 0.022) were all independent predictors of biochemical recurrence. Race was not a significant predictor of biochemical failure in multivariate analysis (P = 0. 199). CONCLUSIONS: In an equal access medical care facility, no differences were evident between black and white men in the preoperative clinical factors or the pathologic features of the RP specimens. In addition, no differences were observed in the PSA recurrence rates after RP. Serum PSA, biopsy Gleason score, younger age, surgical Gleason score, and lymph node involvement were all independent predictors of biochemical recurrence. Race was not an independent predictor of biochemical recurrence.

Clinical characteristics in black and white men with prostate cancer in an equal access medical center.

OBJECTIVES: To determine whether black men with newly diagnosed prostate cancer in an equal access health care center are more likely to present with metastatic disease, more poorly differentiated tumors, higher serum prostate-specific antigen (PSA) levels, and/or at younger ages compared with white men. METHODS: A retrospective survey was conducted that identified black and white men with newly diagnosed prostate cancer at the Los Angeles Regional Veterans Affairs Clinics between 1991 and 1997. Patient data were analyzed for racial differences in age at diagnosis, clinical stage, PSA level, and Gleason score of the prostate biopsy specimens. RESULTS: A total of 477 evaluable patients (230 black, 247 white) with newly diagnosed prostate cancer were identified. No significant differences in the average age (66.9 +/- 7.3 versus 67.9 +/- 7.5) or clinical stage at diagnosis were found between black and white men. Among black men, 87% presented with clinically localized disease (T1-2, Nx, M0) compared with 88% of white men. Only 6% of black men presented with distant disease (Tx, Nx, M1) compared with 4% of white men. Black men had higher median PSA levels than white men (14. 2 versus 9.4 ng/mL, P = 0.0001). Black men also had slightly higher average Gleason scores (6.2 versus 5.9, P = 0.025). CONCLUSIONS: This is the first study to show a low and equal percentage of black and white men presenting with metastatic prostate cancer. In this equal access center, no differences were found in patient age or clinical stage of prostate cancer between black and white men at the time of diagnosis. However, black men presented with higher serum PSA values and slightly higher Gleason scores.