Cholinergic crisis caused by ingesting topical carpronium chloride solution: A case report.

A cholinergic crisiss is a state characterized by excess acetylcholine owing to the ingestion of cholinesterase inhibitors or cholinergic agonists. We report the first case of a cholinergic crisis after the ingestion of a carpronium chloride solution, a topical solution used to treat alopecia, seborrhea sicca, and vitiligo. An 81-year-old woman with no prior medical history was transported to our emergency department because the patient had disturbance of consciousness after ingesting three bottles of FUROZIN® solution (90 mL, 4500 mg as carpronium chloride). A family member who found the patient called for emergency medical services (EMS) personnel, who contacted the patient ten minutes after ingestion. The patient's Glasgow Coma Scale score was 12 (E4V3M5), and vital signs were as follows: blood pressure, 80/40 mmHg; heart rate, 40 beats/min. The patient vomited repeatedly in the ambulance. On arrival to the ED, the patient's systolic blood pressure and heart rate temporarily decreased to 80 mmHg and 40 beats/min, respectively. Seventy-eight minutes after ingestion, gastric lavage was performed. The patient's symptoms, which included excess salivation, sweating, and hot flush, improved 24 h after ingestion, and the patient's vital signs stabilized without atropine or vasopressors. On the second day of admission, the patient was examined by a psychiatrist and discharged without suicidal ideation. Carpronium chloride has a chemical structure similar to that of acetylcholine; therefore, it exhibits both cholinergic and local vasodilatory activities. There is limited information on the pharmacokinetics of ingested carpronium chloride; therefore, physicians should be made aware that ingesting a carpronium chloride solution may cause a cholinergic crisis.

Safety and Tolerability of the Anxiolytic and Nootropic Drug Phenibut: A Systematic Review of Clinical Trials and Case Reports.

Phenibut is a nootropic drug that exerts anxiolytic and antinociceptive effects by acting on the GABAB receptor and the α2-δ subunit of voltage-dependent calcium channels. An increased number of reports of dependence to and intoxication by phenibut purchased online on the one hand and the wide prescription of phenibut in Eastern Europe for more than half a century on the other hand have resulted in a number of controversies regarding its use. In this review, we have summarized currently available information from case reports of phenibut dependence and intoxication and safety data from clinical trials. We included 14 dependence and intoxication case reports (16 patients) and reviewed 11 phenibut clinical trials (583 patients). The clinical symptoms in the case reports included cardiovascular effects, insomnia, anxiety and agitation, hallucinations, and depressed level of consciousness. In addition, the doses used (0.5-100 g/day) were much higher than the recommended daily dose (0.25-2 g/day). An analysis of phenibut side effects described in the clinical trials showed adverse events in only 5.66% of patients, and the most reported side effect was somnolence (1.89%). There are discrepancies in the reported side effects of phenibut in clinical trials compared to those reported in cases of online-purchased phenibut dependence and intoxication. The current systematic review provides evidence that, at therapeutic doses, phenibut is safe and well tolerated with minor adverse effects, but questions regarding the quality of phenibut obtained online and the contribution of alcohol and other drug abuse to phenibut dependence and intoxication remain open.

Phenibut exposures and clinical effects reported to a regional poison center.

BACKGROUND: Phenibut is a synthetically produced central nervous system (CNS) depressant that is structurally similar to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Phenibut has been identified as a drug of abuse with numerous clinical effects in overdose and a withdrawal syndrome with chronic use. The purpose of this study is to report the incidence of exposure calls regarding phenibut to a poison center, describe the reasons for its use and clinical effects. METHODS: Study subjects were identified using Toxicall®, the electronic medical record utilized by the Minnesota Poison Control System. All phenibut exposure calls from January 2000 through December 2018 were included. Analysis was performed on incidence of exposure calls, reported reasons for use, signs and symptoms, coingestants, and outcome. RESULTS: There were 56 exposure calls over 19 years with 48 (85.7%) calls within the past five years. Over 50% of patients had CNS effects and 10.7% had withdrawal concerns. Twenty-seven patients (48%) had abuse as the reason for use and 13 (23%) used phenibut to treat anxiety. There were documented coingestants in 35.7% of patients. No patients died due to reported phenibut use, though 11 patients (19.6%) were intubated. CONCLUSION: Exposure calls to a regional poison center regarding phenibut have increased over the past five years. CNS depression was common, and associated with significant clinical outcomes including respiratory failure requiring intubation. As phenibut is easily attainable and exposures appear to be increasing, physicians should be aware of phenibut-associated CNS and respiratory depression and be prepared to manage airways appropriately.

Intentional Drug Overdose Involving Pregabalin and Gabapentin: Findings from the National Self-Harm Registry Ireland, 2007-2015.

INTRODUCTION: Intentional drug overdose (IDO) is a significant public health problem. Concerns about the misuse of gabapentinoids, i.e. pregabalin and gabapentin, including their consumption in IDO have grown in recent years. This paper examines the trends in the prevalence of gabapentinoids taken in IDO, the profile of individuals taking them, and associated overdose characteristics. METHODS: Presentations to emergency departments involving IDO, recorded by the National Self-Harm Registry Ireland between 1 January 2007 and 31 December 2015 were examined. Data items included patient demographics, drug names, total tablet quantity consumed and alcohol involvement. RESULTS: Gabapentinoids were involved in 2115 (2.9%) of the 72,391 IDOs recorded. Presentations involving a gabapentinoid increased proportionally from 0.5% in 2007 to 5.5% in 2015. The majority of IDOs involving a gabapentinoid were made by females (59.9%), with over one-third (37.2%) involving alcohol. Compared with IDOs involving other drugs, presentations with a gabapentinoid were made by persons who were older (median 37 vs. 32 years) and involved a significantly greater median quantity of tablets (30 vs. 21, p ≤ 0.001), with over one-quarter (27.4%) of these involving the ingestion of 50 tablets or more. Admission to hospital was significantly more common following IDOs with a gabapentinoid compared with those without (49.4% vs. 41.4%, p ≤ 0.001). CONCLUSIONS: This study identified the increasing use of gabapentinoids in IDO, describing the profile and overdose characteristics of presentations. It is important for clinicians to exercise vigilance while prescribing gabapentinoids, including being aware of other medications that their patients may have access to. Our findings support the need for routine monitoring for signs of misuse among those prescribed gabapentinoids.

Treatment of Gabapentin Toxicity With Peritoneal Dialysis: Assessment of Gabapentin Clearance.

Gabapentin is almost exclusively cleared by the kidney and thus presents challenges in patients with kidney failure. Gabapentin is known to be effectively cleared by hemodialysis, but the efficiency of clearance by peritoneal dialysis (PD) has not been previously described. We report a case of gabapentin toxicity in a patient on long-term PD who was treated with continuous automated cycling PD. We find that continuous PD provides significant clearance of gabapentin. With 2-L exchanges every 2 hours, we document an apparent elimination half-life of 41.33 hours, which is substantially shorter than the reported elimination half-life of 132 hours in the absence of kidney function. Further, our patient's symptoms of gabapentin toxicity gradually improved and had fully resolved after about 36 hours of dialysis. Gabapentin clearance by PD was estimated at 94% of urea clearance. We conclude that intensive PD provides gabapentin clearance that approximates that of urea and is an effective but slow method to treat gabapentin overdose and toxicity.

Acute behavioural disturbance associated with phenibut purchased via an internet supplier.

CONTEXT: Toxicity from recreational substances marketed for other purposes is a well-documented clinical entity. We present two cases of phenibut toxicity procured via the internet. CASE DETAILS: A 20-year-old female presented to the emergency department (ED) having used phenibut the prior day. The main finding was a decreased level of consciousness, however when roused she became delirious. Supportive care only was required with no specific intervention. The patient made a full recovery over a 24-hour period and admitted to use of phenibut purchased online. Plasma phenibut concentration was 29.7 µg/ml. A 38-year-old male presented to ED with an agitated delirium. The prior evening he had used tetrahydrocannabinol or THC, alcohol and phenibut, the latter purchased via the internet. His behavioural state had a suboptimal response to parenteral sedation. He was subsequently intubated for airway protection in the context of ongoing sedation to optimally manage his behavioural state. Post extubation the next morning he admitted using phenibut. Plasma phenibut concentration was 36.5 µg/ml. DISCUSSION: Altered mental status was the predominant manifestation of phenibut toxicity in these cases. Clinicians to be aware of how phenibut toxicity may present as the internet has widened access to such substances.

An acute gabapentin fatality: a case report with postmortem concentrations.

Gabapentin (GBP) (Neurontin®, Horizant®, Gralise®) is a widely prescribed medication used primarily for the treatment of epilepsy and neuropathic pain. GBP has a favorable adverse effect profile in therapeutic dosing with the most common reported effects being dizziness, fatigue, drowsiness, weight gain, and peripheral edema. Even with intentional GBP self-poisonings, serious effects are rare. A 47-year-old female was found dead at work with her daughter's bottle of GBP 600 mg. There were 26 tablets missing and the decedent's only known medication was hydrocodone/acetaminophen. Following initial detection by an alkaline drug screen (GC-MS), analysis utilizing specific liquid chromatography-mass spectrometry revealed an elevated postmortem GBP peripheral blood concentration of 37 mg/L, central blood 32 mg/L, liver 26 mg/kg, vitreous 32 mg/L, and gastric contents 6 mg. Screening for volatiles, drugs of abuse, alkaline compounds, and acid/neutral compounds was negative with the exception of ibuprofen (<2 mg/L) detected in peripheral blood. This report presents a fatality that appears to be associated with an isolated and acute GBP ingestion.

Profiles of pregabalin and gabapentin abuse by postmortem toxicology.

Pregabalin (PRG) and gabapentin (GBP) are used in the treatment of neuropathic pain and epilepsy, and PRG also in generalized anxiety disorder. There is increasing evidence that PRG possesses considerable abuse potential. PRG may have a higher addiction potential than GBP due to its rapid absorption and faster onset of action. Our objective is to estimate the proportion of all PRG- and GBP-related fatalities attributable to PRG and GBP abuse. We investigated all medico-legal death cases in Finland in which PRG or GBP was found in postmortem toxicology during 2010-2011. PRG was found in 316 cases and GBP in 43 cases. Drug abuse was associated with 48.1% of the PRG and 18.6% of the GBP findings. PRG poisoning accounted for 10.1% of all PRG cases and GBP poisoning for 4.7% of all GBP cases. In the drug abuser cases, PRG poisoning represented 19.1%, and GBP poisoning 12.5%. The median blood concentration of PRG was 15 mg/L in the abuser group and 5.8 mg/L in the other cases. For GBP, these concentrations were 12 mg/L and 8.3mg/L, respectively. In the PRG abuser group, 91.4% of cases showed concomitant opioid use, while in the rest of these cases neither alcohol nor opioids were detected, but other central nervous system acting drugs were found in each abuser case. In the GBP abuser group, 87.5% of cases showed concomitant opioid use. PRG abuse with high doses is increasingly common and can be fatal when combined with opioids.

Quantification of pregabalin using hydrophilic interaction HPLC-high-resolution MS in postmortem human samples: eighteen case reports.

Pregabalin is a drug for treating epilepsy, anxiety disorders and neuropathic pain. Cases of poisoning are rare, though some have been fatal. Concentrations of pregabalin in postmortem human samples and its distribution have very rarely been documented. As the literature is so scarce, we propose to report the concentrations in autopsy samples of 18 people who had been taking Lyrica(®), including one case of a mixed overdose involving pregabalin. Analysis was carried out using an original Hydrophilic Interaction LIquid Chromatography (HILIC) technique coupled with a high-resolution mass spectrometer (m/z 160.1334 ± 5 ppm). The sensitivity of the technique enables a quick and simple treatment of the samples by protein precipitation. The method was validated in the whole blood with detection and quantification limits of 0.025 and 0.060 µg/mL, respectively. Pregabalin was a likely factor in the cause of death in 3 of the 18 cases. In the other individuals, the concentrations ranged from 0.4 to 17.0 in the peripheral blood, 1.5 to 11.1 in the central blood, 126.6 to 2004.6 in the urine and 10.5 to 58.3 µg/mL in the bile, with median values of 5.6, 4.6, 534.6 and 17.7, respectively.

Gabapentin overdose in a military beneficiary.

We report the case of a 59-year-old military beneficiary that presented to the emergency department after ingesting approximately 90 g of gabapentin immediate-release capsules during a deliberate self-harm attempt. Her serum gabapentin level was 72.8 mcg/mL approximately 3 hours after ingestion. Her renal function panel, complete blood count, and liver function panel were normal. Her urine drug screen, aspirin, ethanol, and acetaminophen level were negative. Her electrocardiogram was normal, including a normal QTc interval. Her only symptoms were nausea and mild sedation. She was admitted for observation with no sequelae noted. She was transferred to a psychiatric facility at that time for further evaluation and treatment. We report a case of gabapentin overdose that presented to the emergency department. Given the large volume ingestion with minimal morbidity, it appears that gabapentin has a wide therapeutic margin and may be safe in overdose.

A case of pregabalin intoxication.

Pregabalin, or S-(+)-3-isobutylgaba, is a lipophilic analogue of GABA. Although pregabalin is structurally related to GABA, it is inactive at GABA receptors and does not appear to mimic GABA physiologically. Pregabalin is a potent ligand for the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system. It is currently being licensed for epilepsy, neuropathic pain, and generalized anxiety disorder. There are few case reports that have demonstrated safety of pregabalin in case of intoxication. We report here a case of pregabalin toxicity with a moderate pregabalin concentration that was successfully managed with conservative treatment only. The case report describes a 54-year-old man who was treated with pregabalin for generalized anxiety disorder. After having experienced a significant stress on a job the patient ingested huge amount of pregabalin (4,2 r) together with bromazepam (21 mg) and chlorimipramine (125 mg). On presentation he was conscious and alert with a stable condition of cardiovascular and respiratory systems. The serum pregabalin concentration was 20.8 mg/L but the patient did not have any signs of toxicity. Thanks to his good and stable somatic condition the patient was managed with supportive treatment only. Although anecdotal, our case report points toward safety of pregabalin following deliberate self-poisoning. Our observation is in accordance with the recent international literature underlining that pregabalin was listed as the drug ingested in only 1% of fatalities, usually in combination with other drugs.

Complete atrioventricular block due to overdose of pregabalin.

Pregabalin, a synthetic derivate of the inhibitory neurotransmitter γ-aminobutyric acid, shows antiepileptic, analgesic, anticonvulsant, anxiolytic, and sleep-modulating activities. The major advantage of pregabalin is its relative reliability, easy use, high tolerance, and lack of negative interaction with other drugs. A 65-year-old woman with medical histories of diabetes mellitus, lumbar spondylosis, diabetic nephropathy, chronic renal failure, and anemia of chronic disease was admitted with the complaint of dizziness and syncope. She had been taking pregabalin 300 mg daily for 8 months. Electrocardiogram revealed complete atrioventricular (AV) block and right bundle-brunch block with a heart rate of 39 per minute. Her creatinine was 1.8 mg/dL, and creatinine clearance was 50 mL/min. Pregabalin treatment was discontinued. Four days later, the complete AV block resolved spontaneously to Mobitz type II block and to sinus rhythm with right bundle-brunch block on the seventh day. To our knowledge, this is the first case of complete AV block associated with pregabalin. We believe that AV block occurred as a result of pregabalin's effect on L-type Ca++ channels in the heart. Pregabalin's different effects on electrocardiogram and on the heart in different individuals may have an association with the patterns of distribution of the L-type calcium channels in myocardium.

Suicide by gabapentin overdose.

Gabapentin is an antiepileptic drug that is prescribed for both FDA-approved and multiple off-label conditions, and has a relatively safe side-effect profile. Rare cases of overdose-related adverse effects have been reported in the literature. Described herein are the circumstances and autopsy findings of a 62-year-old woman with a history of depression, whose death was caused by intentional ingestion of excess gabapentin. The postmortem peripheral blood gabapentin concentration as determined by high-performance liquid chromatography/tandem mass spectroscopy was 88 µg/mL. Previously reported cases of individuals surviving gabapentin overdoses are discussed and compared with this case. Based on a review of the available literature, this appears to be the first published report of a death due solely to gabapentin toxicity.

Significant pregabalin toxicity managed with supportive care alone.

There are two previously reported cases describing the management of pregabalin self-poisoning and one further case of management of therapeutic pregabalin accumulation. The peak reported pregabalin concentrations in these cases ranged from 13 mg/L to approximately 60 mg/L. Previous case reports have suggested that both supportive care and enhanced elimination are appropriate managements for pregabalin toxicity. A 54-year-old male presented following ingestion of 8.4 g of pregabalin. Initially, he had no clinical features of toxicity, although he developed significant neurological depression and coma approximately 3 h post-ingestion. He was managed with supportive care (including endotracheal intubation and mechanical ventilation) until his level of consciousness improved. Subsequent toxicological screening confirmed isolated pregabalin ingestion, with a serum pregabalin concentration of 66.5 mg/L at the time he clinically deteriorated. The pharmacokinetic properties of pregabalin indicate the potential value of extra-corporeal elimination methods such as haemodialysis. Clinical toxicologists should be aware that whilst there is a pharmacokinetic basis for the use of extra-corporeal methods in those with severe toxicity arising from excessive plasma pregabalin concentrations, there are case reports, including this one, where patients have been managed with supportive measures only.

Treatment of pregabalin toxicity by hemodialysis in a patient with kidney failure.

Pregabalin is prescribed for neuropathic pain. We report the first case of pregabalin toxicity in a hemodialysis patient and her successful treatment with hemodialysis. The patient was a 30-year-old woman on long-term hemodialysis therapy who experienced significant myoclonus of the arms and legs when her dose of pregabalin was mistakenly increased. The drug has 3 properties that contribute to making it amenable to removal by hemodialysis: relatively low molecular weight (159.23 Da), relatively low volume of distribution (0.5 L/kg), and not bound to plasma proteins. We achieved hemodialysis clearance of 88.8 mL/min, which was associated with resolution of symptoms immediately after hemodialysis.

A multi-drug intoxication fatality involving Xyrem (GHB).

Gamma-hydroxybutyrate (GHB) is best known as a recreational depressant drug, whose use has also been implicated in drug facilitated sexual assault cases. It is also available as a therapeutic agent (Xyrem) used for the treatment of daytime sleepiness or cataplexy associated with narcolepsy. This is a report of a case of a 53-year-old woman undergoing treatment with Xyrem for narcolepsy. The decedent was also prescribed tramadol, gabapentin, cetirizine, modafinil, carisoprodol, and Xyrem. Toxicological analysis of the blood revealed GHB 165.6 mg/L, and 90.7 mg/L in the urine. Blood GHB concentrations in the range 156-260 mg/L have been reported to induce moderately sound sleep. The combined use of central nervous system depressant drugs, together with her problematic sleep apnea, and snoring (both contraindications for GHB use) were determined to have caused this subject's death. The manner of death was determined to be accidental.