Alcohol-related posterior reversible encephalopathy syndrome: a case report of a patient managed with a benzodiazepine-sparing regimen for alcohol withdrawal.

We report a case of posterior reversible encephalopathy syndrome (PRES) during treatment for alcohol withdrawal syndrome with gabapentin and clonidine. The patient developed severe hypertension, confusion and tremor, culminating in bilateral vision loss and a seizure. Imaging revealed posterior cerebral edema. Treatment with benzodiazepines, antihypertensives, and anti-seizure medications led to resolution. One year later, imaging showed resolution of the findings. We review the associated literature and propose the recognition of a PRES sub-entity, Alcohol-Related PRES (ARPRES), which can appear in the setting of alcohol withdrawal syndrome, chronic alcohol use, and acute alcohol intoxication, with or without hypertension.

Cardiovascular risk of gabapentin and pregabalin in patients with diabetic neuropathy.

BACKGROUND: Gabapentin and pregabalin are commonly prescribed medications to treat pain in patients with diabetic neuropathy. Gabapentin and pregabalin can cause fluid retention, which is hypothesized to be associated with cardiovascular diseases. However, whether long-term use of gabapentin and pregabalin is associated with adverse cardiovascular diseases remains unknown. This study aims to examine the association between gabapentin use, pregabalin use and several adverse cardiovascular events. METHODS: This retrospective cohort study used propensity score matching within patient electronic health records (EHRs) from a multicenter database with 106 million patients from 69 health care organizations in the US. The study population comprised 210,064 patients who had a diagnosis of diabetic neuropathy and were prescribed diabetic neuropathy medications in their EHRs. The exposure cohort comprised patients who were prescribed gabapentin or pregabalin to treat diabetic neuropathy. The comparison cohort comprised patients who were not prescribed either gabapentin or pregabalin but were prescribed other drugs to treat diabetic neuropathy. The outcomes of interest were myocardial infarcts, strokes, heart failure, peripheral vascular disease, and venous thromboembolic events. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for 3-month and 5-year risk for adverse cardiovascular events between the propensity score-matched cohorts. RESULTS: Both gabapentin and pregabalin were associated with increased risk of 5-year adverse cardiovascular events compared with the comparison group. In patients prescribed gabapentin, the highest risk was observed for deep venous thrombosis (HR: 1.58, 95% CI 1.37-1.82), followed by pulmonary embolism (HR: 1.5, 95% CI 1.27-1.76), peripheral vascular disease (HR: 1.37, 95% CI 1.27-1.47), stroke (HR: 1.31, 95% CI 1.2-1.43), myocardial infarction (HR: 1.25, 95% CI 1.14-1.38) and heart failure (HR: 1.14, 95% CI 1.07-1.21). In patients prescribed pregabalin, the highest risk was observed for deep venous thrombosis (HR: 1.57, 95% CI 1.31-1.88), followed by peripheral vascular disease (HR: 1.35, 95% CI 1.22-1.49), myocardial infarction (HR: 1.29, 95% CI 1.13-1.47), pulmonary embolism (HR: 1.28, 95% CI 1.04-1.59), stroke (HR: 1.26, 95% CI 1.12-1.42), and heart failure (HR: 1.2, 95% CI 1.11-1.3). There were significant associations between short-term (3 month) gabapentin use and heart failure, myocardial infarction, peripheral vascular disease, deep venous thrombosis, and pulmonary embolism. Short-term (3 month) pregabalin use was associated with deep venous thrombosis, peripheral vascular disease. CONCLUSION: In patients with diabetic neuropathy who were prescribed gabapentin and pregabalin, there is an increased risk for heart failure, myocardial infarction, peripheral vascular disease, stroke, deep venous thrombosis, and pulmonary embolism with long-term use. Our findings suggest that increased risk for adverse cardiovascular events, along with other side effects, the efficacy of pain control and the degree of tolerance of the patient, should be considered when prescribing gabapentin and pregabalin long-term in patients with diabetic neuropathy.

Potential Role of Heterocyclic Aromatic Amines in Neurodegeneration.

Heterocyclic aromatic amines (HAAs) are mainly formed in the pyrolysis process during high-temperature cooking of meat. Meat consumption is very typical of the western diet, and the amount of meat consumption in the eastern countries is growing rapidly; HAAs represents widespread exposure. HAAs are classified as possible human carcinogens; numerous epidemiological studies have demonstrated regular consumption of meat with HAAs as risk factor for cancers. Specific HAAs have received major attention. For example, 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine has been extensively studied as a genotoxicant and mutagen, with emergent literature on neurotoxicity. Harmane has been extensively studied for a role in essential tremors and potentially Parkinson's disease (PD). Harmane levels have been demonstrated to be elevated in blood and brain in essential tremor patients. Meat consumption has been implicated in the etiology of neurodegenerative diseases; however, the role of toxicants formed during meat preparation has not been studied. Epidemiological studies are currently examining the association between HAAs and risk of neurodegenerative diseases such as essential tremors and PD. Studies from our laboratory and others have provided strong evidence that HAA exposure produces PD and Alzheimer's disease-relevant neurotoxicity in cellular and animal models. In this review, we summarize and critically evaluate previous studies on HAA-induced neurotoxicity and the molecular basis of potential neurotoxic effects of HAAs. The available studies provide strong support for the premise that HAAs may impact neurological function and that addressing gaps in understanding of adverse neurological outcomes is critical to determine whether these compounds are modifiable risk factors.

Structural basis for inhibition of a voltage-gated Ca2+ channel by Ca2+ antagonist drugs.

Ca2+ antagonist drugs are widely used in therapy of cardiovascular disorders. Three chemical classes of drugs bind to three separate, but allosterically interacting, receptor sites on CaV1.2 channels, the most prominent voltage-gated Ca2+ (CaV) channel type in myocytes in cardiac and vascular smooth muscle. The 1,4-dihydropyridines are used primarily for treatment of hypertension and angina pectoris and are thought to act as allosteric modulators of voltage-dependent Ca2+ channel activation, whereas phenylalkylamines and benzothiazepines are used primarily for treatment of cardiac arrhythmias and are thought to physically block the pore. The structural basis for the different binding, action, and therapeutic uses of these drugs remains unknown. Here we present crystallographic and functional analyses of drug binding to the bacterial homotetrameric model CaV channel CaVAb, which is inhibited by dihydropyridines and phenylalkylamines with nanomolar affinity in a state-dependent manner. The binding site for amlodipine and other dihydropyridines is located on the external, lipid-facing surface of the pore module, positioned at the interface of two subunits. Dihydropyridine binding allosterically induces an asymmetric conformation of the selectivity filter, in which partially dehydrated Ca2+ interacts directly with one subunit and blocks the pore. In contrast, the phenylalkylamine Br-verapamil binds in the central cavity of the pore on the intracellular side of the selectivity filter, physically blocking the ion-conducting pathway. Structure-based mutations of key amino-acid residues confirm drug binding at both sites. Our results define the structural basis for binding of dihydropyridines and phenylalkylamines at their distinct receptor sites on CaV channels and offer key insights into their fundamental mechanisms of action and differential therapeutic uses in cardiovascular diseases.

Disperse azo dyes, arylamines and halogenated dinitrobenzene compounds in synthetic garments on the Swedish market.

BACKGROUND: Azobenzene disperse dyes (azo DDs) are well-known as textile allergens, but the knowledge of their occurrence in garments is low. The numerous azo DDs and dye components found in textiles constitute a potential health risk, but only seven azo DDs are included in the European baseline patch test series (EBS). OBJECTIVES: To investigate non-regulated azo DDs and dye components in synthetic garments on the Swedish market. METHODS: High-performance liquid chromatography/mass spectrometry, gas chromatography/mass spectrometry and computerized data mining. RESULTS: Sixty-two azo DDs were detected, with Disperse Red 167:1 occurring in 67%, and 14 other DDs each found in >20% of the garments. Notably, the EBS dyes were less common, three even not detected, while arylamines were frequently detected and exceeded 1 mg/g in several garments. Also, halogenated dinitrobenzenes were identified in 25% of the textiles. CONCLUSION: Azo DDs and dye components, in complex compositions and with large variations, occurred frequently in the synthetic garments. The arylamines were shown to occur at much higher levels compared to the azo DDs, suggesting the former constitute a potentially higher health risk. The role of arylamines and halogenated dinitrobenzenes in textile allergy has to be further investigated.

Mortality from bladder cancer in dyestuff workers exposed to aromatic amines: A 73-year follow-up.

OBJECTIVE: To update the analysis of mortality of a cohort of dyestuff workers, in Northern Italy, heavily exposed to carcinogenic aromatic amines. METHODS: We updated to 2018 overall and cause-specific mortality in a cohort of 590 male workers heavily exposed to carcinogenic aromatic amines in a dyestuff factory from 1922 to 1972. Workers were censored at age 85. Expected cases for the period 1946-2018 were computed using Piedmont mortality rates and standardized mortality ratios (SMR) were computed. RESULTS: Between 1946 and 2018, 470 deaths were reported. The overall SMR was 1.59 (95% confidence interval [CI] 1.45-1.74) and SMR from all cancers was 2.05 (95% CI = 1.77-2.37); Compared to a previous report, there were 4 additional  deaths from bladder cancer,  for a total of 60 deaths compared  with 4.0 expected  (SMR 14.86, 95% CI 11.34-19.12).The SMR for bladder cancer increased with younger age at first exposure  and longer duration of exposure, while it  decreased with time since last exposure, albeit it was still 3.5, 30 or more years since last exposure. An increased risk was observed among workers exposed to fuchsine or ortho-toluidine (SMR=16.3; 95% CI = 6.0-35.5). CONCLUSIONS: This 73 year follow up confirms the results from previous analyses, with an increased overall mortality and, an increased mortality from all cancers and especially for bladder cancer. The excess risk of bladder cancer persisted several decades after stopping exposure.

Gabapentin controlled substance status.

Gabapentin is approved to treat postherpetic neuralgia and epilepsy with partial-onset seizures. The large majority of gabapentin prescribing is off label. Gabapentin may be abused for euphoria, potentiating the high from opiates, reduction of alcohol cravings, a cocaine-like high, as well as sedation or sleep. Individuals at the highest risk for abusing gabapentin include those with opioid abuse, mental illness, or previous history of prescription drug abuse. States are now taking action to track gabapentin use through prescription monitoring programs, and some states have reclassified it as a Schedule V controlled substance. This commentary summarizes gabapentin's abuse potential, identifies state-level actions regarding gabapentin monitoring, and discusses possible clinical implications and ways to enhance patient safety when prescribing gabapentin.

Is gabapentin a safe and effective treatment for nonneuropathic pain?

ABSTRACT: A review of the recent literature found that compared with placebo or other pain medications, gabapentin did not significantly reduce nonneuropathic pain. The drug also is associated with an increased risk of adverse reactions, including somnolence, dizziness, and nausea. Given the lack of efficacy and risk of adverse reactions, gabapentin should not be used for nonneuropathic pain.

Identification of late asthmatic reactions following specific inhalation challenge.

Specific inhalation challenge (SIC) is the reference standard for the diagnosis of occupational asthma. Current guidelines for identifying late asthmatic reactions are not evidence based. OBJECTIVES: To identify the fall in forced expiratory volume in 1 s (FEV1) required following SIC to exceed the 95% CI for control days, factors which influence this and to show how this can be applied in routine practice using a statistical method based on the pooled SD for FEV1 from three control days. METHODS: Fifty consecutive workers being investigated for occupational asthma were asked to self-record FEV1 hourly for 2 days before admission for SIC. These 2 days were added to the in-hospital control day to calculate the pooled SD and 95% CI. RESULTS: 45/50 kept adequate measurements. The pooled 95% CI was 385 mL (SD 126), or 14.2% (SD 6.2) of the baseline FEV1, but was unrelated to the baseline FEV1 (r=0.06, p=0.68), or gender, atopy, smoking, non-specific reactivity or treatment before or during SIC. Thirteen workers had a late asthmatic reaction with ≥2 consecutive FEV1 measurements below the 95% CI for pooled control days, 4/13 had <15% and 9/13 >15% late fall from baseline. The four workers with ≥2 values below the 95% CI all had independent evidence of occupational asthma. CONCLUSION: The pooled SD method for defining late asthmatic reactions has scientific validity, accounts for interpatient spirometric variability and diurnal variation and can identify clinically relevant late asthmatic reactions from smaller exposures. For baseline FEV1 <2.5 L, a 15% fall is within the 95% CI.

Behaviour of Vascular Smooth Muscle Cells on Amine Plasma-Coated Materials with Various Chemical Structures and Morphologies.

Amine-coated biodegradable materials based on synthetic polymers have a great potential for tissue remodeling and regeneration because of their excellent processability and bioactivity. In the present study, we have investigated the influence of various chemical compositions of amine plasma polymer (PP) coatings and the influence of the substrate morphology, represented by polystyrene culture dishes and polycaprolactone nanofibers (PCL NFs), on the behavior of vascular smooth muscle cells (VSMCs). Although all amine-PP coatings improved the initial adhesion of VSMCs, 7-day long cultivation revealed a clear preference for the coating containing about 15 at.% of nitrogen (CPA-33). The CPA-33 coating demonstrated the ideal combination of good water stability, a sufficient amine group content, and favorable surface wettability and morphology. The nanostructured morphology of amine-PP-coated PCL NFs successfully slowed the proliferation rate of VSMCs, which is essential in preventing restenosis of vascular replacements in vivo. At the same time, CPA-33-coated PCL NFs supported the continuous proliferation of VSMCs during 7-day long cultivation, with no significant increase in cytokine secretion by RAW 264.7 macrophages. The CPA-33 coating deposited on biodegradable PCL NFs therefore seems to be a promising material for manufacturing small-diameter vascular grafts, which are still lacking on the current market.

Recent advances in heterocyclic aromatic amines: An update on food safety and hazardous control from food processing to dietary intake.

Heterocyclic aromatic amines (HAAs) as probable carcinogenic substances are mainly generated in meat products during thermal processing. Numerous studies have contributed to the analysis, formation, and mitigation of HAAs during food processing. However, few articles have comprehensively reviewed food safety aspects from both food processing and dietary intake regarding the formation, mitigation, metabolism, biomarkers for exposure, hazard control, and risk assessment of HAAs, and related food safety researches. Several factors may influence the generation of HAAs, including processing temperature, processing time, and chemical composition of the meat. Nonetheless, these mutagenic compounds are attenuated to different levels by the addition of natural or synthetic flavorings and antioxidant-rich marinades, as well as pretreatments using technique such as microwave heating. After dietary intake, different types of HAAs are metabolized in humans by several enzymes, including cytochrome P450s, peroxidases, N-acetyltransferases, sulfotransferases, uridine diphosphate-glucuronosyltransferases, and glutathione S-transferases. Their primary metabolites are further conjugated with DNA or ultimately excreted in urine and feces. The 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in hair as well as DNA, hemoglobin, and serum albumin adducts has been considered as biomarkers for exposure assessment. Dietary intake information obtained from questionnaires and the results of epidemiological investigations have shown a positive relationship between the intakes of red meat and processed meat and high risk of cancer incidence. As several cancers have been reported to be associated with HAAs, HAAs should be both effectively reduced during food processing and controlled from dietary intake to facilitate human health.

Carcinogens and DNA damage.

Humans are variously and continuously exposed to a wide range of different DNA-damaging agents, some of which are classed as carcinogens. DNA damage can arise from exposure to exogenous agents, but damage from endogenous processes is probably far more prevalent. That said, epidemiological studies of migrant populations from regions of low cancer risk to high cancer risk countries point to a role for environmental and/or lifestyle factors playing a pivotal part in cancer aetiology. One might reasonably surmise from this that carcinogens found in our environment or diet are culpable. Exposure to carcinogens is associated with various forms of DNA damage such as single-stand breaks, double-strand breaks, covalently bound chemical DNA adducts, oxidative-induced lesions and DNA-DNA or DNA-protein cross-links. This review predominantly concentrates on DNA damage induced by the following carcinogens: polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, mycotoxins, ultraviolet light, ionising radiation, aristolochic acid, nitrosamines and particulate matter. Additionally, we allude to some of the cancer types where there is molecular epidemiological evidence that these agents are aetiological risk factors. The complex role that carcinogens play in the pathophysiology of cancer development remains obscure, but DNA damage remains pivotal to this process.

Surveillance of the armed forces as a sentinel system for detecting adverse effects of dietary supplements in the general population.

OBJECTIVE: Half the US population takes dietary supplements, but surveillance systems available to regulatory and public health authorities to determine whether specific dietary supplements present a risk are inadequate and numerous severe injuries and deaths have occurred from their consumption. Uniformed military personnel regularly use dietary supplements and are more likely to use potentially dangerous supplements than civilians. Recently, the supplement 1,3-dimethylamylamine (DMAA) was marketed for physical performance-enhancement and weight loss. However, after over 100 reports of illness attributed to DMAA, including six deaths, the Food and Drug Administration issued a warning to cease its sale. DESIGN: When DMAA was legal (2010-2011), we conducted, using convenience samples, supplement surveys of service members and determined prevalence of use and self-reported symptoms of DMAA use. SUBJECTS: We surveyed 4374 armed forces personnel using a standardized dietary supplement survey administered by local health-care professionals. RESULTS: Overall, 11 % of survey respondents used dietary supplements labelled as containing DMAA at least once/week. Regular users were over two times more likely to report tachycardia (P<0·0001), tremors (P<0·0001) and dizziness (P=0·0004), and over three times more likely to report numbness/tingling (P<0·0001) than non-users. CONCLUSIONS: Military services could readily monitor adverse events associated with dietary supplements using electronic surveys and medical records. Since armed forces personnel are much more likely than civilians to use potentially dangerous dietary supplements like DMAA, near real-time surveillance of them using electronic surveys and medical records would provide early warning to regulatory agencies and the medical and public health communities when high-risk dietary supplements are introduced.

Gabapentin for Chronic Neuropathic Pain.

Clinical Question: Is gabapentin associated with pain relief in people with chronic neuropathic pain? Bottom Line: Oral gabapentin (1200-3600 mg/d for 4-12 weeks) for patients with moderate or severe neuropathic pain from postherpetic neuralgia (PHN) or painful diabetic neuropathy (PDN) is associated with pain reduction of at least 50% in 14% to 17% more patients than placebo.

Feasibility study for interspecialistic collaboration in active research of urothelial neoplasms of professional origin.

INTRODUCTION: In Italy only a small fraction of cancer is reported to the supervisory body and recognised as professional by the insurance institution. Among the causes of this sub-notification, especially for lowgrade etiologic fractional cancers such as bladder cancers are the lack of knowledge of carcinogenicity in the occupational field and the consequent incomplete medical history collections. OBJECTIVES: Diagnosis of occupational bladder neoplasms and activation of systematic surveillance of tumors of professional origin through an "active research" program. METHODS: From July 2010 to July 2017, all patients diagnosed with Bladder Cancer in the departments of Urology of Area Vasta 3 ASUR Marche underwent a first interview and a further anamnestic study in selected cases.When an occupational exposure was recognised, more information for preventive, social security and criminal justice has been acquired. RESULTS: The study highlighted 18 cases of bladder tumors due to occupational exposure to aromatic amines and polycyclic aromatic hydrocarbons, which are the most important risk factor for BC after tobacco smoking. CONCLUSIONS: Our study confirmed that active research is an useful tool both for the activation of epidemiological surveillance and for the regional registration of professional tumors. In addition active research of occupational exposure allow obtaining information that can be used for preventive purposes, for criminal justice and for the initiation of medico-legal actions and improvement of working conditions aimed at guaranteeing workers' rights.

On the addictive power of gabapentinoids: a mini-review.

The gabapentinoids gabapentin and pregabalin have been related to addiction citing pharmacovigilance data, some case presentations and increasing reports mainly from methadone maintenance treatment programs or emergency medicine. Most of these reports were based on patients with another current or previous substance use disorder (SUD). According to the ICD-10 dependence criteria, physical dependence (withdrawal symptoms, tolerance) was reported most frequently alongside regular use of gabapentinoids. Far less patients showed key symptoms of behavioral dependence (craving, loss of control, or addictive behavior). Through a literature review, we found 2 and 13 case reports about gabapentionoid-seeking behavior or craving for gabapentin and pregabalin, respectively. Those patients without a history of another SUD, but being behaviorally dependent on gabapentinoids, deemed more appropriate to reflect the true addictive power of these drugs. We found solely 4 such cases, all referring to pregabalin and none for gabapentin. Taking into account that gabapentinoids have become widely distributed and easily obtainable via the internet or black-markets, one would expect many more of these cases, if gabapentinoids had considerable addictive power. Moreover, we are not aware of any patient who sought detoxification treatment owing to the misuse of gabapentinoids. Unlike for traditional psychoactive drugs, there is only very scarce evidence for gabapentinoids to be misused in a long-term manner and to be rewarding and reinforcing in animal experiments. Further, we assessed the hazardous potential of gabapentin and pregabalin in relation to that of traditional substances of abuse. Altogether, we support the view that gabapentinoids are quite rarely addictive in the general population. In patients with a history of SUD, however, gabapentinoids (notably pregabalin) should avoided or, if thought to be beneficial, administered with caution by using a strict prescription and therapy monitoring.

Benefits and safety of gabapentinoids in chronic low back pain: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Chronic Low Back Pain (CLBP) is very common, with a lifetime prevalence between 51% and 80%. In majority, it is nonspecific in nature and multifactorial in etiology. Pregabalin (PG) and Gabapentin (GB) are gabapentinoids that have demonstrated benefit in neuropathic pain conditions. Despite no clear rationale, they are increasingly used for nonspecific CLBP. They necessitate prolonged use and are associated with adverse effects and increased cost. Recent guidelines from the National Health Service (NHS), England, expressed concerns on their off-label use, in addition to the risk of misuse. We aimed to assess the effectiveness and safety of gabapentinoids in adult CLBP patients. METHODS: Electronic databases of MEDLINE, EMBASE, and Cochrane were searched from their inception until December 20th, 2016. We included randomized control trials reporting the use of gabapentinoids for the treatment of CLBP of >3 months duration, in adult patients. Study selection and data extraction was performed independently by paired reviewers. Outcomes were guided by Initiative on Methods, Measurement and Pain Assessment in Clinical Trials guidelines, with pain relief and safety as the primary outcomes. Meta-analyses were performed for outcomes reported in 3 or more studies. Outcomes were reported as mean differences (MDs) or risk ratios (RRs) with their corresponding 95% confidence intervals (CIs), and I2 in percentage representing the percentage variability in effect estimates that could be explained by heterogeneity. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to assess the quality of evidence. RESULTS: Out of 1,385 citations, eight studies were included. Based on the interventions and comparators, studies were analyzed in 3 different groups. GB compared with placebo (3 studies, n = 185) showed minimal improvement of pain (MD = 0.22 units, 95% CI [-0.5 to 0.07] I2 = 0%; GRADE: very low). Three studies compared PG with other types of analgesic medication (n = 332) and showed greater improvement in the other analgesic group (MD = 0.42 units, 95% CI [0.20 to 0.64] I2 = 0; GRADE: very low). Studies using PG as an adjuvant (n = 423) were not pooled due to heterogeneity, but the largest of them showed no benefit of adding PG to tapentadol. There were no deaths or hospitalizations reported. Compared with placebo, the following adverse events were more commonly reported with GB: dizziness-(RR = 1.99, 95% CI [1.17 to 3.37], I2 = 49); fatigue (RR = 1.85, 95% CI [1.12 to 3.05], I2 = 0); difficulties with mentation (RR = 3.34, 95% CI [1.54 to 7.25], I2 = 0); and visual disturbances (RR = 5.72, 95% CI [1.94 to 16.91], I2 = 0). The number needed to harm with 95% CI for dizziness, fatigue, difficulties with mentation, and visual disturbances were 7 (4 to 30), 8 (4 to 44), 6 (4 to 15), and 6 (4 to 13) respectively. The GRADE evidence quality was noted to be very low for dizziness and fatigue, low for difficulties with mentation, and moderate for visual disturbances. Functional and emotional improvements were reported by few studies and showed no significant improvements. CONCLUSIONS AND RELEVANCE: Existing evidence on the use of gabapentinoids in CLBP is limited and demonstrates significant risk of adverse effects without any demonstrated benefit. Given the lack of efficacy, risks, and costs associated, the use of gabapentinoids for CLBP merits caution. There is need for large high-quality trials to more definitively inform this issue. TRIAL REGISTRATION: PROSPERO CRD42016034040.

An Atypical Withdrawal Syndrome in Neonates Prenatally Exposed to Gabapentin and Opioids.

We report a retrospective case series of 19 infants exposed to both opioids and gabapentin prenatally. We describe a unique behavioral phenotype in 15 of these infants and report a treatment strategy.

Gabapentin acutely increases the apnea-hypopnea index in older men: data from a randomized, double-blind, placebo-controlled study.

Although drugs with sedative properties may increase the risk of airway collapse during sleep, their acute effects on the apnea-hypopnea index in older adults are under-reported. We investigated the acute effects of gabapentin (GABA) on sleep breathing in older men without sleep apnea. A double-blind, randomized, placebo-controlled cross-over pilot study using a bedtime dose of gabapentin 300 mg was conducted in eight non-obese older men. Polysomnography measured the effects of the intervention. The apnea-hypopnea index was higher in the gabapentin arm than in the placebo arm (22.4 ± 6.1 versus 12.2 ± 4.3, P ≤ 0.05, d: 0.67), as was the oxygen desaturation index (20.6 ± 5.8 versus 10.8 ± 3.9, P ≤ 0.05, d: 0.68). The number needed to harm was four. A subset analysis demonstrated that differences in sleep respiratory parameters were present only during non-rapid eye movement sleep, as well as only in the supine position. No adverse events were reported. Hence, gabapentin worsened sleep breathing acutely compared with placebo. Long-term clinical trials are warranted to elucidate the clinical relevance of these findings for the safety profile of GABAergic agents.

Antiepileptic drugs: Impacts on human serum paraoxonase-1.

Serum paraoxonase (PON1) is a key enzyme related to high-density lipoprotein (HDL)-cholesterol particle. It can prevent the oxidation of low-density lipoprotein (LDL) and HDL. The present article focuses on the in vitro inhibition role of some antiepileptic drugs (AEDs) such as valproic acid, gabapentin, primidone, phenytoin, and levetiracetam on human paraoxonase (hPON1). Therefore, PON1 was purified from human serum with a specific activity of 3976.36 EU/mg and 13.96% yield by using simple chromatographic methods. The AEDs were tested at various concentrations, which showed reduced in vitro hPON1 activity. IC50 values for gabapentin, valproic acid, primidone, phenytoin, and levetiracetam were found to be 0.35, 0.67, 0.87, 6.3, and 53.3 mM, respectively. Ki constants were 0.261 ± 0.027, 0.338 ± 0.313, 0.410 ± 0.184, 10.3 ± 0.001, and 43.01 ± 0.003 mM, respectively. Gabapentin exhibited effective inhibitory activity as compared with the other drugs. The inhibition mechanisms of all compounds were noncompetitive.