Barbiturates are a class of sedative-hypnotic drugs. They are commonly used as antiepileptics (phenobarbital) and for the induction of general anesthesia (thiopental). Some states administer barbiturates for physician-assisted suicide/euthanasia and use them for capital punishment by lethal injection. Their use in clinical practice has largely been replaced by benzodiazepines such as alprazolam, diazepam, and lorazepam due to the lower risk of overdose and available antidote to reverse toxicity. Barbiturates are used as a laboratory buffer and can be found in clinical and research laboratories. Barbiturates are controlled substances that pose a high risk for abuse given their psychoactive effects. Restrictions on access to barbiturates have caused the number of overdoses to decline. Common barbiturates include the following: Methohexital and thiopental are used as anesthetics. Phenobarbital and primidone are used in the treatment of seizures. Amobarbital is used as an investigative agent in the Wada test (neurological assessment of cerebral hemispheres)  Butalbital, in combination with other medications, is used for headaches and muscle pain.

This study investigated the occurrence of four non-steroidal anti-inflammatory drugs (NSAIDs) and four benzodiazepines/anti-depressants (ADs) in municipal wastewater in Mardan city, Pakistan, and in River Kabul and River Indus receiving untreated sewage. Liquid chromatography with a triple quadrupole tandem mass spectrometry (LC-MS/MS) was used for the analysis of paracetamol, diclofenac, ibuprofen, and codeine (NSAIDs) and diazepam, bromazepam, lorazepam, and temazepam (ADs). Except codeine and lorazepam, all the target compounds were observed in sewage and surface water in various concentrations. In sewage, paracetamol was found at the higher end (32.4 μg/L) of the reported ranges in literature for other countries. Results of river samples showed that the target compounds were usually lower in concentration than the respective EC50 values for aquatic organisms. However, the levels for paracetamol and ibuprofen were critical depicting the consequence of untreated disposal. Environmental risk assessment by estimating the risk quotient (RQ) as the ratio of measured environmental concentration and predicted no-effect concentration showed medium to high (RQ > 1 and 0.1 < RQ < 1) risk from paracetamol and ibuprofen to aquatic organisms in River Kabul and Kalpani stream, Pakistan.

Pharmaceutically active compounds are carried into aquatic bodies along with domestic sewage, industrial and agricultural wastewater discharges. Psychotropic drugs, which can be toxic to the biota, have been detected in natural waters in different parts of the world. Conventional water treatments, such as activated sludge, do not properly remove these recalcitrant substances, so the development of processes able to eliminate these compounds becomes very important. Advanced oxidation processes are considered clean technologies, capable of achieving high rates of organic compounds degradation, and can be an efficient alternative to conventional treatments. In this study, the degradation of alprazolam, clonazepam, diazepam, lorazepam, and carbamazepine was evaluated through TiO2/UV-A, H2O2/UV-A, and TiO2/H2O2/UV-A, using sunlight and artificial irradiation. While using TiO2 in suspension, best results were found at [TiO2] = 0.1 g L-1. H2O2/UV-A displayed better results under acidic conditions, achieving from 60 to 80% of removal. When WWTP was used, degradation decreased around 50% for both processes, TiO2/UV-A and H2O2/UV-A, indicating a strong matrix effect. The combination of both processes was shown to be an adequate approach, since removal increased up to 90%. H2O2/UV-A was used for disinfecting the aqueous matrices, while mineralization was obtained by TiO2-photocatalysis.

Background: Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are accompanied by a myriad of cardiometabolic side-effects. The specific reasons for clozapine's high propensity to cause adverse cardiometabolic events remain unknown, but it is believed that autonomic dysfunction may play a role in many of these. Objective: This systematic review summarizes the literature on autonomic dysfunction and related cardiovascular side effects associated with clozapine treatment. Method: A search of the EMBASE, MEDLINE, and EBM Cochrane databases was conducted using the search terms antipsychotic agents, antipsychotic drug*, antipsychotic*, schizophrenia, schizophren*, psychos*, psychotic*, mental ill*, mental disorder*, neuroleptic*, cardiovascular*, cardiovascular diseases, clozapine*, clozaril*, autonomic*, sympathetic*, catecholamine*, norepinephrine, noradrenaline, epinephrine, adrenaline. Results: The search yielded 37 studies that were reviewed, of which only 16 studies have used interventions to manage cardiovascular side effects. Side effects reported in the studies include myocarditis, orthostatic hypotension and tachycardia. These were attributed to sympathetic hyperactivity, decreased vagal contribution, blockade of cholinergic and adrenergic receptors, reduced heart rate variability and elevated catecholamines with clozapine use. Autonomic neuropathy was identified by monitoring blood pressure and heart rate changes in response to stimuli and by spectral analysis of heart rate variability. Metoprolol, lorazepam, atenolol, propranolol, amlodipine, vasopressin and norepinephrine infusion were used to treat tachycardia and fluctuations in blood pressure, yet results were limited to case reports. Conclusion: The results indicate there is a lack of clinical studies investigating autonomic dysfunction and a limited use of interventions to manage cardiovascular side effects associated with clozapine. As there is often no alternative treatment for refractory schizophrenia, the current review highlights the need for better designed studies, use of autonomic tests for prevention of cardiovascular disease and development of novel interventions for clozapine-induced side effects.

Chronic mild stress (CMS) has been demonstrated to contribute to atherosclerosis. 6-gingerol (6-Gin), a phenolic component of ginger (Zingiber officinale), has been shown to exert numerous pharmacological properties, such as anti-inflammatory and cardioprotective effects. Here we investigated the role of CMS in the development of atherosclerosis in high-fat diet (HFD)-fed ApoE-/- mice and evaluated the potential therapeutic effects of 6-Gin. Mice were exposed to CMS for 20 weeks, at week 5, they were fed with a high-fat diet (HFD), then received 6-Gin (20 mg/kg/day, intragastrically) treatment. Antiatherosclerotic simvastatin (Sim) and antidepressant lorazepam (Lor) were used for positive drugs. The behavioral and atherosclerotic changes, plasma lipid profiles as well as inflammatory cytokine levels were measured. Our results showed that CMS-exposed mice exhibited reduced body weight gain, sucrose preference and locomotor activity, which are representative of some of the core symptoms of depression. Furthermore, CMS challenge aggravated atherosclerotic lesions, as indicated by increased plaque formation, elevation of plasma total cholesterol, triglyceride, low-density lipoprotein cholesterin, and proinflammatory cytokines including TNF-α, IL-1β, and IL-6. In addition, the expression levels of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), acetyl-CoA carboxylase (ACC), hHMG-CoA reductase (HMGCR), fatty acid synthase (FAS), sterol regulatory element binding protein (SREBP)-1 and SREBP-2 in the liver tissues were altered after CMS exposure. 6-Gin not only improved the behavioral changes, but also alleviated atherosclerotic lesions, and reversed the expression levels of lipid profiles and inflammatory cytokines in stressed mice. Moreover, the antiatherosclerotic effects of 6-Gin is mediated in part by the AMPK signaling pathway, which is closely associated with cholesterol synthesis and lipid accumulation. Together, these results suggest that 6-Gin attenuates arteriosclerosis in ApoE-/- mice exposed to CMS and HFD, and it may be a potential therapeutic agent for the treatment of atherosclerosis.