Trending gabapentin exposures in Kentucky after legislation requiring use of the state prescription drug monitoring program for all opioid prescriptions.

OBJECTIVE: Gabapentin is a gamma-aminobutyric acid (GABA) analog approved by the Food and Drug Administration (FDA) for partial seizures and post-herpetic neuralgia. Due to its wide therapeutic window and minimal adverse effects, it is frequently prescribed for additional off-label uses. The purpose of this study was to characterize the number, exposure reason, medical outcomes, and disposition of gabapentin exposures reported to one regional poison control center (PCC). METHODS: A retrospective cross-sectional review of exposures reported to one regional PCC was performed from January 1, 2012 to December 31, 2015. The primary outcomes were the number of gabapentin-only exposures and multi-agent exposures including gabapentin reported. Exposure reason, medical outcome, and disposition were identified for each exposure. RESULTS: There were 424 gabapentin-only exposures during the study period. The number of exposures increased each year, from 39 in 2012 to 160 in 2015. There were 1321 multi-agent exposures that included gabapentin. These exposures increased from 165 in 2012 to 440 in 2015. Comparatively, total human exposures reported to the regional PCC decreased during the study period. The majority of gabapentin-only and multi-agent exposures was intentional versus unintentional. Nine patients (2%) had a major medical outcome and three patients (1%) died in the gabapentin-only group. Comparatively, 76 patients (6%) had a major medical outcome and 12 patients (1%) died in the multi-agent group. Almost half of the multi-agent exposures required admission to the intensive care unit (ICU). CONCLUSIONS: Both gabapentin-only and multi-agent exposures increased significantly from 2012 to 2015, with the majority of cases intentional ingestion, specifically suspected suicide. The increased number of gabapentin exposures coincided with Kentucky's implementation of prescription opioid reform legislation. Providers are encouraged to call their local PCC, regardless of exposure type, to effectively monitor and evaluate exposure trends.

A case series of patients with lamotrigine toxicity at one center from 2003 to 2012.

INTRODUCTION: Lamotrigine is a phenyltriazine compound that inhibits voltage-gated sodium channels, decreasing release of glutamate and aspartate, and inhibits serotonin, norepinephrine and dopamine reuptake. Reports of toxicity in the literature are limited to case reports and primarily involve coingestants. This case series is intended to report the clinical manifestations of lamotrigine toxicity. METHODS: This retrospective case series from 2003 to 2012 studies the effects of lamotrigine toxicity when not confounded by coingestants. Admission records at an inpatient toxicology center were reviewed for lamotrigine-only exposure based on history with supporting laboratory data when available. After identification, these charts were reviewed again to characterize vital signs, neurological examination findings, specific laboratory and electrocardiography parameters, and complications. RESULTS: Fifty-seven patients were identified with possible lamotrigine toxicity. Nine patients, including three toddlers, had lamotrigine-only ingestions. Three of these patients had seizures, four were hypertensive, five were tachycardic, and four experienced tachypnea. Mental status was altered in all nine (depressed (n = 4), agitated (n = 5) or both (n = 3)). Five patients were hyperreflexic and experienced intermittent myoclonus, and two had inducible clonus. On electrocardiogram, two patients experienced QRS prolongation (114-116 ms), and four had QTc prolongation (463-586 ms). No patient had life-threatening symptoms or signs. Serum levels of lamotrigine were available in seven patients, and averaged 35.4 mg/L (17-90 mg/L). The therapeutic range for sLTG is 3-14 mg/L. CONCLUSIONS: Lamotrigine toxicity manifested with minor-moderate neurologic and/or electrocardiographic effects. Toxicity reflects the known pharmacologic actions of lamotrigine: serotonin, norepinephrine and dopamine reuptake inhibition, and sodium channel blockade.

Methylenedioxymethamphetamine-related deaths in Taiwan: 2001-2008.

Methylenedioxymethamphetamine (MDMA) has been one of most popular drugs in the "club" scene in Taiwan. This epidemic was studied through the examination of toxicological data obtained from the 59 fatalities tested positive for MDMA during the period of January 2001 to December 2008. Ketamine was found in 28 of these cases, signifying the popularity of this drug in Taiwan. The annual number of deaths in each of the 8 years in this period was 4, 7, 9, 14, 8, 9, 2, and 6, respectively. Among these 59 deaths, 39 (66.1%) were men, and the mean, median, and range of ages were 24.6, 23, and 14-46, respectively. Causes of death ruled by the attending pathologists and the distributions for these fatalities were acute intoxication, 40 and mechanical injury, 19, including 3 hanging and 2 drowning. The manners of death were ruled as accidental, 44; homicidal, 6; suicidal, 7; and undetermined, 2. In this study, postmortem whole blood was analyzed by gas chromatography-mass spectrometry with a limit of quantitation at 0.05 microg/mL for both MDMA and MDA. The mean, median, and range of MDMA concentrations in the cases, where MDMA acute intoxication was ruled as the cause of death, were 4.75, 2.60, and 0.12-40.41 microg/mL. MDA was found in 30 of these 40 cases with the following mean, median, and range data: 0.19, 0.13, and 0.05-1.81 microg/mL. The corresponding data of MDMA and MDA in the remaining 19 MDMA-related deaths were significantly lower: 1.25, 0.97, 0.08-3.05 and 0.11, 0.09, 0.06-0.24 microg/mL, respectively.

[Serotonin syndrome caused by an overdose of dextromethorphan, Medicon].

We report the first case of serotonin syndrome caused by overdose of dextromethorphan in Japan. A 34-year-old woman with schizophrenia received a dextromethorphan (Medicon) for a catarrhal symptom from two individual departments of the university hospital by chance. The daily amount of dextromethorphan was up to 180 mg for several days in addition to other regular antipsychotic drugs including risperidone, amitriptyline and levomepromazine. Finally, she was found in deep comatose state (GCS coma scale: E1V1M1) and the trachea was intubated in the emergency room. After admission to intensive care unit, the consciousness gradually improved; however, she was confused and agitated. The situation was normalized within next 24 hours and she was weaned from the mechanical ventilation next day. Serotonin syndrome demonstrates various signs and might be overlooked in an emergency room. Dextromethorphan is considered as a safe antitussive drug; however, the unexpected interaction should be suspected during chronic medical treatment.

Postmortem memantine concentrations.

Postmortem fluid and tissue concentrations of memantine (Namenda), a drug recently approved for the treatment of Alzheimer's Disease by the FDA, are reported in a suspicious death. In addition, memantine concentrations considered to be incidental findings in three other cases are included to aid in the interpretation in future toxicological investigations. Memantine was extracted from biological samples by a standard liquid-liquid basic drug method followed by analysis utilizing a gas chromatograph-mass spectrometer operated in SIM mode. Blood concentrations ranged from 0.03 to 1.8 mg/L, and the liver concentration was 6.1 mg/kg.

Influence of the glia limitans on pial arteriolar relaxation in the rat.

We examined whether damage to the glia limitans (GL), via exposure to the gliotoxin l-alpha-aminoadipic acid (l-alphaAAA), alters hypercapnia-induced pial arteriolar dilation in vivo. Anesthetized female rats were prepared with closed cranial windows. Pial arteriolar diameters were measured using intravital microscopy. l-alphaAAA (2 mM) was injected into the space under the cranial windows 24 h before the study, and injury to the GL was confirmed by light microscopy. l-alphaAAA was associated with a reduction in pial arteriolar CO(2) reactivity to 40-50% of the level seen in vehicle-treated controls, with no further reduction in the CO(2) response after nitric oxide (NO) synthase (NOS) inhibition via N(omega)-nitro-l-arginine (l-NNA). Subsequent blockade of prostanoid synthesis, via indomethacin (Indo), reduced CO(2) reactivity to 10-15% of normal. In vehicle-treated controls, l-NNA, followed by Indo, reduced the response to approximately 50% and then to 15-20% of the normocapnic value, respectively. On the other hand, l-alphaAAA had no effect on vascular responses to the endothelium-dependent vasodilator acetylcholine or the NO donor SNAP and did not alter cortical somatosensory evoked responses. This indicates an absence of any direct l-alphaAAA actions on pial arterioles or influence on neuronal transmission. Furthermore, l-alphaAAA did not alter the vasodilation elicited by topical application of an acidic artificial cerebrospinal fluid solution, suggesting that the GL influences the pial arteriolar relaxation elicited by hypercapnic, but not local extracellular (EC), acidosis. That differences exist in the mechanisms mediating hypercapnia- versus EC acidosis-induced pial arteriolar dilations was further exemplified by the finding that topical application of a neuronal NOS (nNOS)-selective blocker (ARR-17477) reduced the response to hypercapnia (by approximately 65%) but not the response to EC acidosis. Disruption of GL gap junctional communication, using an antisense oligodeoxynucleotide (ODN) connexin43 knockdown approach, was accompanied by a 33% lower CO(2) reactivity versus missense ODN-treated controls. These results suggest that the GL contribution to the hypercapnic vascular response appears to involve the NO-dependent component rather than the prostanoid-dependent component and may involve gap junctional communication. We speculate that the GL may act to facilitate the spread, to pial vessels, of hypercapnia-induced vasodilating signals arising in the comparatively few scattered nNOS neurons that lie well beneath the GL.

A multiple drug fatality involving MK-801 (dizocilpine), a mimic of phencyclidine.

MK-801 (dizocilpine) is a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) family of glutamate receptors in the central nervous system. It is an anticonvulsant and also shares several pharmacological properties with phencyclidine and ketamine. It is not observed routinely as a substance of abuse. The deceased, a 45-year-old white male, obtained MK-801 surreptitiously in an attempt to treat a self-diagnosed depression. He was discovered the next morning, unresponsive on the bathroom floor. An empty bottle, labeled to contain 25mg of MK-801, was found near the body. The autopsy was performed at the Joseph A Jachimczyk Forensic Center, Houston, TX. Body weight at autopsy was 88kg. Lungs were edematous and congested (right: 775g; left 700g). The heart had proportionate chambers and was otherwise unremarkable. The kidneys (right: 220g; left 225g) were smooth surfaced. The brain (1550g) was congested and without trauma. Microscopic evaluation of the heart, kidneys and lungs showed normal histology and confirmed pulmonary congestion and edema. Samples of heart blood, liver, bile, vitreous humor, stomach contents and urine were collected at autopsy. There were 550ml of stomach contents. Drugs in blood were screened by EMIT II Plus immunoassay procedures and by gas chromatography/mass spectrometry (GC/MS) of an organic solvent extract of basified blood. Alcohol was determined by gas chromatography with headspace injection. MK-801, benzodiazepines and alcohol were detected in blood. Amounts of MK-801 present in blood, bile, liver, vitreous humor and urine were 0.15, 0.29, 0.92, less than 0.1 and 0.36 mg/l (kg), respectively. The cause of death was benzodiazepine, dizocilpine and ethanol toxicity and the manner accidental.