Benzodiazepines (BZDs) are widely used for treatment of anxiety and insomnia, however, this class... more Benzodiazepines (BZDs) are widely used for treatment of anxiety and insomnia, however, this class of drugs is also commonly abused. Many different BZDs and analogs have been produced that are not FDA-approved. We tested 15 of these with the ThermoFisher CEDIA® BZD-immunoassay. With the exception of ketazolam, all compounds showed significant reactivity, highlighting the need for mass spectrometry confirmation assays. We developed a liquid-chromatography high-resolution mass spectrometry method for the detection of these 15 non-FDA approved BZDs. The limit of detection for most compounds ranged from 1 to 50 ng/mL, with mostly positive matrix effects observed in urine and negative matrix effects in serum. In a clinical research case, clonazolam and etizolam were detected in serum at 10.2 and 281 ng/mL, with an apparent elimination half-life of 3.6 and 4.8 hours, respectively. Although we did not detect non-FDA approved BZDs in 211 urine samples that were previously determined to be BZ...
Clinical toxicology (Philadelphia, Pa.), Jan 5, 2016
Novel psychoactive substances (NPS) are being created and introduced at an unprecedented rate, ca... more Novel psychoactive substances (NPS) are being created and introduced at an unprecedented rate, causing frequent, large-scale epidemics. Current identification of NPS in clinical settings in the USA is limited to the retrospective case or small cluster analysis. The purpose of this study was to assess the utility of non-targeted comprehensive drug screening in the agitated patients in an emergency department (ED) setting. This is a prospective, observational case series that was conducted in the ED of an urban Level I Trauma Center with an annual census of approximately 65,000 patients per year. Since it is common clinical practice at this facility for haloperidol to be used as a second-line chemical restraint when initial dose(s) of benzodiazepines are deemed insufficient, we surmised that the subset of ED patients with psychomotor agitation severe enough to receive both these pharmaceuticals would be likely users of NPS. For 1 month, biweekly pharmacy medication audits identified 4...
Journal of clinical pharmacy and therapeutics, 2014
Post-operative gastrointestinal ileus is a common complication that can cause erratic absorption ... more Post-operative gastrointestinal ileus is a common complication that can cause erratic absorption of oral pharmaceuticals. This is a case of near-fatal, antihypertensive medication overdose due to gastric ileus in a 40-year-old patient following combined kidney-pancreas transplant. After being transitioned from intravenous to oral antihypertensive medications, the patient sustained pulseless bradycardia requiring resuscitative measures. Suspicion of accumulated medication bolus due to gastric ileus was confirmed by supratherapeutic serum labetalol measurement of 493 ng/mL (therapeutic range: 30-180 ng/mL). Judicious use of oral pharmaceuticals, particularly those with relatively narrow therapeutic ranges, is warranted in patients with post-operative ileus.
Context. Synthetic cannabinoids have been manufactured, sold, and consumed for recreational purpo... more Context. Synthetic cannabinoids have been manufactured, sold, and consumed for recreational purposes since at least 2004; their use has been associated with adverse psychiatric, cardiovascular, renal, pulmonary, and neurologic effects. We report simultaneous canine and human clinical cases associated with exposure to a novel synthetic cannabinoid, PB-22 (QUPIC). Case report. A 22-yearold man brought his dog to a veterinary clinic after it had a seizure. During the course of the canine ' s evaluation, the human patient was witnessed to have a generalized tonic-clonic seizure. He was intubated for agitation and combativeness after his arrival to the emergency department (ED). He was extubated the next day without discernable sequelae. The canine patient received intravenous hydration and was also discharged to home after a period of close observation. The man later endorsed smoking three containers of a substance called " Crazy Monkey " daily for several weeks, but would not disclose how his dog had been exposed. The convulsant effects of " Crazy Monkey " were confi rmed in this patient when, three months later, he was sedated, paralyzed, intubated, and admitted to another local hospital for seizures in the context of smoking the same product. Discussion. Laboratory analysis of samples obtained from the human and canine patients. A sample of the product (labeled " Crazy Monkey ") revealed the presence of PB-22 (QUPIC), a novel synthetic cannabinoid. Additionally, serum and urine samples from the human patient contained metabolites of a second compound, UR-144. Conclusion. We present a laboratory-confi rmed case report of human and canine neurotoxicity associated with a novel synthetic cannabinoid, PB-22 (QUIPIC).
The goal of this study was to describe the clinical effects and time of onset of hypoglycemia in ... more The goal of this study was to describe the clinical effects and time of onset of hypoglycemia in pediatric sulfonylurea poisoning. This was a retrospective, descriptive study of pediatric (<6 years old) sulfonylurea exposures with hypoglycemia (glucose concentration <60 mg/dL) that were consulted on by the California Poison Control System for the 8-year period between January 1, 2002, and December 31, 2009. Of the 1943 consultations for pediatric sulfonylurea exposure in the study period, 300 children developed hypoglycemia. Ten percent had hypoglycemia occurring or persisting ≥ 12 hours after ingestion despite receiving treatment. All 5 children with seizures experienced these before hospital presentation. The mean (SD) time to onset of hypoglycemia in children not given any prophylactic treatment was 2.0 (1.2) hours. The mean (SD) times in children receiving prophylactic food only, intravenous glucose only, and both food and intravenous glucose were 5.9 (3.9), 5.7 (2.5), and 8.9 (3.6) hours, respectively. Ranges were 1 to 18, 1.5 to 9, and 2.5 to 15 hours. Seven of 40 patients (18%) receiving prophylactic food only had an onset of hypoglycemia >8 hours after sulfonylurea ingestion. Pediatric sulfonylurea exposure can result in significant poisoning. Severe effects such as seizures occurred only in cases of unrecognized sulfonylurea ingestion. The onset of hypoglycemia after pediatric sulfonylurea ingestion can be delayed by as much as 18 hours by either free access to food or administration of intravenous glucose.
It is unclear how much diphenhydramine (DPH) is toxic in humans. Previous dose-response studies h... more It is unclear how much diphenhydramine (DPH) is toxic in humans. Previous dose-response studies have had conflicting results. Objective. We sought to evaluate DPH dose-response using a unique method that utilizes acetaminophen (APAP) serum concentrations to estimate DPH doses in patients ingesting APAP/DPH in a fixed-combination product. We retrospectively analyzed APAP/DPH-only exposures in patients 2-80 years of age using case data from 15 U.S. poison centers. DPH dose was extrapolated from measured serum APAP concentrations. A clinically significant response (CSR) was predefined in terms of eight specific manifestations (e.g., coma) that would warrant emergency department intervention. Nominal logistic regression was used to model the probability of each recorded manifestation across DPH dose ranges examining fits for mg, mg/kg, log10 mg, and log10 mg/kg DPH doses. The threshold value where patients reliably became symptomatic was determined by further examining receiver operating characteristic curves. There were 509 cases that met inclusion criteria. Forty-five patients (9%) developed CSRs. A higher percentage of patients developed CSR at ≥ 7.5 mg/kg DPH and ≥1 g total DPH cutoff points (p < 0.05, Fisher's exact test). The best model for predicting the probability of CSR was a logistic fit of log(10) mg/kg dose (p < 0.05). By this model, for every 1 log(10) unit increase of mg/kg DPH dose, the odds of developing a CSR increased 47-fold (95% CI 17, 154). Receiver operating characteristic analyses showed a dose-related progression of symptoms. The cut-point with greatest sensitivity (98%) versus 1-specificity (57%) corresponded to an extrapolated mg/kg DPH dose of 8.2 mg/kg (95% CI 5.6, 10.5). Our findings support the current American Association of Poison Control Centers' guideline recommendation to refer patients to the hospital for evaluation if they have ingested greater than or equal to 7.5 mg/kg of DPH.
diabetes failed to demonstrate any significant associations. Conclusion: Although we found that e... more diabetes failed to demonstrate any significant associations. Conclusion: Although we found that endothelial cell and inflammatory marker levels were statistically similar in diabetics and non-diabetics, patients taking statins had significantly decreased levels of endothelial cell markers compared to patients not taking statins, independent of DM. Future studies should address the utility of using endothelial cell markers as a way to monitor the effectiveness of statin treatment, as well as to explore the therapeutic potential of statins to modulate endothelial cell activation. Eventually, novel therapies for diabetes or CVD may be developed that directly target specific endothelial cell markers.
A 28-year-old man presented with acute flaccid paralysis and respiratory failure that persisted f... more A 28-year-old man presented with acute flaccid paralysis and respiratory failure that persisted for 2 weeks after suicidal ingestion of unknown substances. Extensive clinical, nerve, laboratory, and neuroimaging testing excluded alternative causes of this neuromuscular syndrome. Prompted by clues provided by family members, liquid chromatography time-of-flight mass spectrometry was used to investigate for the presence of poison hemlock. Testing of the residue in a jar used for the ingestion of a poisonous concoction confirmed the presence of the nicotinic alkaloid coniine. Analysis of patient serum suggested the presence of conhydrine. Concentrations of amitriptyline and diazepam were also found to be supratherapeutic, but only through the first few days of hospitalization. Herein we describe a case of reversible coma, flaccid quadriparesis, and neuromuscular respiratory failure caused by intentional ingestion of poison hemlock.
Tricyclic antidepressant (TCA) ingestions are a relatively common pediatric ingestion, with signi... more Tricyclic antidepressant (TCA) ingestions are a relatively common pediatric ingestion, with significant potential for both cardiac and neurological toxicity. Previous studies on pediatric TCA ingestions have found the threshold of toxicity to be 5 mg/kg. We report a case of an 8-year-old girl who presented to the emergency department with depressed mental status and seizure-like movements. An extensive workup was pursued to evaluate the cause of her mental status, which only revealed a positive urine toxicology screen for TCA. Quantified serum levels of amitriptyline were 121 ng/mL (therapeutic range, 50-300 ng/mL) and nortriptyline were 79 ng/mL (therapeutic range 70-170 ng/mL), 18 hours after onset of symptoms. Subsequent history obtained after her mental status returned to normal revealed that she had ingested amitriptyline at a dose of 0.8 mg/kg. Tricyclic antidepressant ingestion has a high potential for toxicity in pediatric patients. This case suggests, contrary to previous literature, that toxicity may occur even with small doses.
The objectives of this study were to evaluate the effect of octreotide on number of hypoglycemic ... more The objectives of this study were to evaluate the effect of octreotide on number of hypoglycemic episodes and blood glucose concentrations (BGCs) in a case series of young children who received octreotide for treatment of sulfonylurea-induced hypoglycemia and to identify the frequency of adverse effects associated with octreotide's use for this indication. A retrospective review of 9 years of National Poison Data System pediatric sulfonylurea overdoses treated with octreotide was conducted. Inclusion criteria were age younger than 6 years with acute sulfonylurea overdose managed in a health care facility. Redacted poison center charts were obtained, and data on pretreatment and posttreatment number of hypoglycemic episodes and BGCs as well as medical outcomes and adverse reactions were extracted and analyzed. There were 121 octreotide cases. Patients experienced a median of 2.0 and 0.0 hypoglycemic episodes before and after treatment, respectively (P < 0.0001). The median lowest BGC was significantly higher after octreotide administration (P < 0.001). In 73% of children, only 1 dose of octreotide was given. Hyperglycemia was noted in 3 children who also received dextrose in whom adverse effects to therapy were coded. Octreotide administration decreases number of hypoglycemic events and increases BGCs. The majority of children who receive octreotide require only 1 dose. There were no adverse effects documented in these children who received octreotide as an antidote for sulfonylurea-induced hypoglycemia.
Benzodiazepines (BZDs) are widely used for treatment of anxiety and insomnia, however, this class... more Benzodiazepines (BZDs) are widely used for treatment of anxiety and insomnia, however, this class of drugs is also commonly abused. Many different BZDs and analogs have been produced that are not FDA-approved. We tested 15 of these with the ThermoFisher CEDIA® BZD-immunoassay. With the exception of ketazolam, all compounds showed significant reactivity, highlighting the need for mass spectrometry confirmation assays. We developed a liquid-chromatography high-resolution mass spectrometry method for the detection of these 15 non-FDA approved BZDs. The limit of detection for most compounds ranged from 1 to 50 ng/mL, with mostly positive matrix effects observed in urine and negative matrix effects in serum. In a clinical research case, clonazolam and etizolam were detected in serum at 10.2 and 281 ng/mL, with an apparent elimination half-life of 3.6 and 4.8 hours, respectively. Although we did not detect non-FDA approved BZDs in 211 urine samples that were previously determined to be BZ...
Clinical toxicology (Philadelphia, Pa.), Jan 5, 2016
Novel psychoactive substances (NPS) are being created and introduced at an unprecedented rate, ca... more Novel psychoactive substances (NPS) are being created and introduced at an unprecedented rate, causing frequent, large-scale epidemics. Current identification of NPS in clinical settings in the USA is limited to the retrospective case or small cluster analysis. The purpose of this study was to assess the utility of non-targeted comprehensive drug screening in the agitated patients in an emergency department (ED) setting. This is a prospective, observational case series that was conducted in the ED of an urban Level I Trauma Center with an annual census of approximately 65,000 patients per year. Since it is common clinical practice at this facility for haloperidol to be used as a second-line chemical restraint when initial dose(s) of benzodiazepines are deemed insufficient, we surmised that the subset of ED patients with psychomotor agitation severe enough to receive both these pharmaceuticals would be likely users of NPS. For 1 month, biweekly pharmacy medication audits identified 4...
Journal of clinical pharmacy and therapeutics, 2014
Post-operative gastrointestinal ileus is a common complication that can cause erratic absorption ... more Post-operative gastrointestinal ileus is a common complication that can cause erratic absorption of oral pharmaceuticals. This is a case of near-fatal, antihypertensive medication overdose due to gastric ileus in a 40-year-old patient following combined kidney-pancreas transplant. After being transitioned from intravenous to oral antihypertensive medications, the patient sustained pulseless bradycardia requiring resuscitative measures. Suspicion of accumulated medication bolus due to gastric ileus was confirmed by supratherapeutic serum labetalol measurement of 493 ng/mL (therapeutic range: 30-180 ng/mL). Judicious use of oral pharmaceuticals, particularly those with relatively narrow therapeutic ranges, is warranted in patients with post-operative ileus.
Context. Synthetic cannabinoids have been manufactured, sold, and consumed for recreational purpo... more Context. Synthetic cannabinoids have been manufactured, sold, and consumed for recreational purposes since at least 2004; their use has been associated with adverse psychiatric, cardiovascular, renal, pulmonary, and neurologic effects. We report simultaneous canine and human clinical cases associated with exposure to a novel synthetic cannabinoid, PB-22 (QUPIC). Case report. A 22-yearold man brought his dog to a veterinary clinic after it had a seizure. During the course of the canine ' s evaluation, the human patient was witnessed to have a generalized tonic-clonic seizure. He was intubated for agitation and combativeness after his arrival to the emergency department (ED). He was extubated the next day without discernable sequelae. The canine patient received intravenous hydration and was also discharged to home after a period of close observation. The man later endorsed smoking three containers of a substance called " Crazy Monkey " daily for several weeks, but would not disclose how his dog had been exposed. The convulsant effects of " Crazy Monkey " were confi rmed in this patient when, three months later, he was sedated, paralyzed, intubated, and admitted to another local hospital for seizures in the context of smoking the same product. Discussion. Laboratory analysis of samples obtained from the human and canine patients. A sample of the product (labeled " Crazy Monkey ") revealed the presence of PB-22 (QUPIC), a novel synthetic cannabinoid. Additionally, serum and urine samples from the human patient contained metabolites of a second compound, UR-144. Conclusion. We present a laboratory-confi rmed case report of human and canine neurotoxicity associated with a novel synthetic cannabinoid, PB-22 (QUIPIC).
The goal of this study was to describe the clinical effects and time of onset of hypoglycemia in ... more The goal of this study was to describe the clinical effects and time of onset of hypoglycemia in pediatric sulfonylurea poisoning. This was a retrospective, descriptive study of pediatric (<6 years old) sulfonylurea exposures with hypoglycemia (glucose concentration <60 mg/dL) that were consulted on by the California Poison Control System for the 8-year period between January 1, 2002, and December 31, 2009. Of the 1943 consultations for pediatric sulfonylurea exposure in the study period, 300 children developed hypoglycemia. Ten percent had hypoglycemia occurring or persisting ≥ 12 hours after ingestion despite receiving treatment. All 5 children with seizures experienced these before hospital presentation. The mean (SD) time to onset of hypoglycemia in children not given any prophylactic treatment was 2.0 (1.2) hours. The mean (SD) times in children receiving prophylactic food only, intravenous glucose only, and both food and intravenous glucose were 5.9 (3.9), 5.7 (2.5), and 8.9 (3.6) hours, respectively. Ranges were 1 to 18, 1.5 to 9, and 2.5 to 15 hours. Seven of 40 patients (18%) receiving prophylactic food only had an onset of hypoglycemia >8 hours after sulfonylurea ingestion. Pediatric sulfonylurea exposure can result in significant poisoning. Severe effects such as seizures occurred only in cases of unrecognized sulfonylurea ingestion. The onset of hypoglycemia after pediatric sulfonylurea ingestion can be delayed by as much as 18 hours by either free access to food or administration of intravenous glucose.
It is unclear how much diphenhydramine (DPH) is toxic in humans. Previous dose-response studies h... more It is unclear how much diphenhydramine (DPH) is toxic in humans. Previous dose-response studies have had conflicting results. Objective. We sought to evaluate DPH dose-response using a unique method that utilizes acetaminophen (APAP) serum concentrations to estimate DPH doses in patients ingesting APAP/DPH in a fixed-combination product. We retrospectively analyzed APAP/DPH-only exposures in patients 2-80 years of age using case data from 15 U.S. poison centers. DPH dose was extrapolated from measured serum APAP concentrations. A clinically significant response (CSR) was predefined in terms of eight specific manifestations (e.g., coma) that would warrant emergency department intervention. Nominal logistic regression was used to model the probability of each recorded manifestation across DPH dose ranges examining fits for mg, mg/kg, log10 mg, and log10 mg/kg DPH doses. The threshold value where patients reliably became symptomatic was determined by further examining receiver operating characteristic curves. There were 509 cases that met inclusion criteria. Forty-five patients (9%) developed CSRs. A higher percentage of patients developed CSR at ≥ 7.5 mg/kg DPH and ≥1 g total DPH cutoff points (p < 0.05, Fisher's exact test). The best model for predicting the probability of CSR was a logistic fit of log(10) mg/kg dose (p < 0.05). By this model, for every 1 log(10) unit increase of mg/kg DPH dose, the odds of developing a CSR increased 47-fold (95% CI 17, 154). Receiver operating characteristic analyses showed a dose-related progression of symptoms. The cut-point with greatest sensitivity (98%) versus 1-specificity (57%) corresponded to an extrapolated mg/kg DPH dose of 8.2 mg/kg (95% CI 5.6, 10.5). Our findings support the current American Association of Poison Control Centers' guideline recommendation to refer patients to the hospital for evaluation if they have ingested greater than or equal to 7.5 mg/kg of DPH.
diabetes failed to demonstrate any significant associations. Conclusion: Although we found that e... more diabetes failed to demonstrate any significant associations. Conclusion: Although we found that endothelial cell and inflammatory marker levels were statistically similar in diabetics and non-diabetics, patients taking statins had significantly decreased levels of endothelial cell markers compared to patients not taking statins, independent of DM. Future studies should address the utility of using endothelial cell markers as a way to monitor the effectiveness of statin treatment, as well as to explore the therapeutic potential of statins to modulate endothelial cell activation. Eventually, novel therapies for diabetes or CVD may be developed that directly target specific endothelial cell markers.
A 28-year-old man presented with acute flaccid paralysis and respiratory failure that persisted f... more A 28-year-old man presented with acute flaccid paralysis and respiratory failure that persisted for 2 weeks after suicidal ingestion of unknown substances. Extensive clinical, nerve, laboratory, and neuroimaging testing excluded alternative causes of this neuromuscular syndrome. Prompted by clues provided by family members, liquid chromatography time-of-flight mass spectrometry was used to investigate for the presence of poison hemlock. Testing of the residue in a jar used for the ingestion of a poisonous concoction confirmed the presence of the nicotinic alkaloid coniine. Analysis of patient serum suggested the presence of conhydrine. Concentrations of amitriptyline and diazepam were also found to be supratherapeutic, but only through the first few days of hospitalization. Herein we describe a case of reversible coma, flaccid quadriparesis, and neuromuscular respiratory failure caused by intentional ingestion of poison hemlock.
Tricyclic antidepressant (TCA) ingestions are a relatively common pediatric ingestion, with signi... more Tricyclic antidepressant (TCA) ingestions are a relatively common pediatric ingestion, with significant potential for both cardiac and neurological toxicity. Previous studies on pediatric TCA ingestions have found the threshold of toxicity to be 5 mg/kg. We report a case of an 8-year-old girl who presented to the emergency department with depressed mental status and seizure-like movements. An extensive workup was pursued to evaluate the cause of her mental status, which only revealed a positive urine toxicology screen for TCA. Quantified serum levels of amitriptyline were 121 ng/mL (therapeutic range, 50-300 ng/mL) and nortriptyline were 79 ng/mL (therapeutic range 70-170 ng/mL), 18 hours after onset of symptoms. Subsequent history obtained after her mental status returned to normal revealed that she had ingested amitriptyline at a dose of 0.8 mg/kg. Tricyclic antidepressant ingestion has a high potential for toxicity in pediatric patients. This case suggests, contrary to previous literature, that toxicity may occur even with small doses.
The objectives of this study were to evaluate the effect of octreotide on number of hypoglycemic ... more The objectives of this study were to evaluate the effect of octreotide on number of hypoglycemic episodes and blood glucose concentrations (BGCs) in a case series of young children who received octreotide for treatment of sulfonylurea-induced hypoglycemia and to identify the frequency of adverse effects associated with octreotide's use for this indication. A retrospective review of 9 years of National Poison Data System pediatric sulfonylurea overdoses treated with octreotide was conducted. Inclusion criteria were age younger than 6 years with acute sulfonylurea overdose managed in a health care facility. Redacted poison center charts were obtained, and data on pretreatment and posttreatment number of hypoglycemic episodes and BGCs as well as medical outcomes and adverse reactions were extracted and analyzed. There were 121 octreotide cases. Patients experienced a median of 2.0 and 0.0 hypoglycemic episodes before and after treatment, respectively (P < 0.0001). The median lowest BGC was significantly higher after octreotide administration (P < 0.001). In 73% of children, only 1 dose of octreotide was given. Hyperglycemia was noted in 3 children who also received dextrose in whom adverse effects to therapy were coded. Octreotide administration decreases number of hypoglycemic events and increases BGCs. The majority of children who receive octreotide require only 1 dose. There were no adverse effects documented in these children who received octreotide as an antidote for sulfonylurea-induced hypoglycemia.
Uploads
Papers by Derrick Lung