The Z-drugs zolpidem, zopiclone, and zaleplon were hailed as the innovative hypnotics of the new millennium, an improvement to traditional benzodiazepines in the management of insomnia. Increasing reports of adverse events including bizarre behavior and falls in the elderly have prompted calls for caution and regulation. Z-drugs have significant hypnotic effects by reducing sleep latency and improving sleep quality, though duration of sleep may not be significantly increased. Z-drugs exert their effects through increased γ-aminobutyric acid (GABA) transmission at the same GABA-type A receptor as benzodiazepines. Their pharmacokinetics approach those of the ideal hypnotic with rapid onset within 30 min and short half-life (1–7 h). Zopiclone with the longest duration of action has the greatest residual effect, similar to short-acting benzodiazepines. Neuropsychiatric adverse events have been reported with zolpidem including hallucinations, amnesia, and parasomnia. Poisoning with Z-drugs involves predominantly sedation and coma with supportive management being adequate in the majority. Flumazenil has been reported to reverse sedation from all three Z-drugs. Deaths from Z-drugs are rare and more likely to occur with polydrug overdose. Z-drugs can be detected in blood, urine, oral fluid, and postmortem specimens, predominantly with liquid chromatography–mass spectrometry techniques. Zolpidem and zaleplon exhibit significant postmortem redistribution. Zaleplon with its ultra-short half-life has been detected in few clinical or forensic cases possibly due to assay unavailability, low frequency of use, and short window of detection. Though Z-drugs have improved pharmacokinetic profiles, their adverse effects, neuropsychiatric sequelae, and incidence of poisoning and death may prove to be similar to older hypnotics.

The clinical and forensic toxicology of Z-drugs.

原色韓國本草圖鑑 = Illustrated book of Korean medicinal herbs

Atomoxetine is a nonstimulant medication used to treat attention-deficit/hyperactivity disorder (ADHD). Cytochrome P450 (CYP)2D6 polymorphisms influence the metabolism of atomoxetine thereby affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for atomoxetine based on CYP2D6 genotype (updates at www.cpicpgx.org).

Clinical Pharmacogenetics Implementation Consortium Guideline for Cytochrome P450 (CYP)2D6 Genotype and Atomoxetine Therapy

Introduction : The imidazopyridine derivative zolpidem, which acts as a benzodiazepine (BZ) receptor agonist, is the most widely prescribed hypnotic drug in the US Areas covered : This review addresses the neuroreceptor properties of zolpidem; clinical pharmacokinetics, pharmacodynamics and drug interactions; efficacy as a hypnotic; adverse effects; tolerance, dependence and withdrawal; relation to motor vehicle accidents and complex sleep behaviors; and new dosage forms Expert opinion : Approved doses of zolpidem (10 mg for adults, 5 mg for the elderly) are consistently effective in reducing sleep latency and consequently increasing sleep duration in patients with insomnia However, favorable effects on sleep maintenance are observed less consistently Residual daytime effects are unlikely with recommended doses, and provided that at least 8 h elapse prior to arising Hypnotic efficacy is maintained with repeated nightly use, and the risk of rebound insomnia is low Dependence and abuse of zolpidem are

Zolpidem for insomnia

Coptis, a traditional medicinal plant, has been used widely in the field of traditional Chinese medicine for many years. More recently, the chemical composition and bioactivity of Coptis have been studied worldwide. Berberine is a main component of Rhizoma Coptidis. Modern medicine has confirmed that berberine has pharmacological activities, such as anti-inflammatory, analgesic, antimicrobial, hypolipidemic, and blood pressure-lowering effects. Importantly, the active ingredient of berberine has clear inhibitory effects on various cancers, including colorectal cancer, lung cancer, ovarian cancer, prostate cancer, liver cancer, and cervical cancer. Cancer, ranked as one of the world’s five major incurable diseases by WHO, is a serious threat to the quality of human life. Here, we try to outline how berberine exerts antitumor effects through the regulation of different molecular pathways. In addition, the berberine-mediated regulation of epigenetic mechanisms that may be associated with the prevention of malignant tumors is described. Thus, this review provides a theoretical basis for the biological functions of berberine and its further use in the clinical treatment of cancer.

/pdf/a-natural-isoquinoline-alkaloid-with-antitumor-activity-4sfosdamo9.pdf

A Natural Isoquinoline Alkaloid With Antitumor Activity: Studies of the Biological Activities of Berberine

Berberine-containing plants have been traditionally used in different parts of the world for the treatment of inflammatory disorders, skin diseases, wound healing, reducing fevers, affections of eyes, treatment of tumors, digestive and respiratory diseases, and microbial pathologies. The physico-chemical properties of berberine contribute to the high diversity of extraction and detection methods. Considering its particularities this review describes various methods mentioned in the literature so far with reference to the most important factors influencing berberine extraction. Further, the common separation and detection methods like thin layer chromatography, high performance liquid chromatography, and mass spectrometry are discussed in order to give a complex overview of the existing methods. Additionally, many clinical and experimental studies suggest that berberine has several pharmacological properties, such as immunomodulatory, antioxidative, cardioprotective, hepatoprotective, and renoprotective effects. This review summarizes the main information about botanical occurrence, traditional uses, extraction methods, and pharmacological effects of berberine and berberine-containing plants.

/pdf/berberine-botanical-occurrence-traditional-uses-extraction-49ijktbqhx.pdf

Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders

Acetaminophen (APAP) is one of the most used analgesics and antipyretic agents in the world. Intoxication with APAP is the main cause of acute liver toxicity in both the US and Europe. Spore-forming probiotic bacteria have the ability to resist harsh gastric and intestinal conditions. The aim of this study was to investigate the possible protective effect of Bacillus (B) species (sp) spores (B. licheniformis, B. indicus, B. subtilis, B. clausii, B. coagulans) against hepatotoxicity induced by APAP in rats. A total of 35 rats were randomly divided into seven groups: group I served as control; group II received silymarin; group III received MegaSporeBioticTM (MSB); group IV received APAP and served as the model of hepatotoxicity; group V received APAP and silymarin; group VI received APAP and MSB; group VII received APAP, silymarin and MSB. The livers for histopathological examination and blood samples were collected on the last day of the experiment. We determined aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total antioxidant capacity (TAC) levels and zonula occludens (ZO-1), tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) expression. APAP overdose increased AST and ALT. It slowly decreased TAC compared to the control group, but pretreatment with silymarin and MSB increased TAC levels. Elevated plasma concentrations were identified for ZO-1 in groups treated with APAP overdose compared with those without APAP or receiving APAP in combination with silymarin, MSB or both. The changes were positively correlated with the levels of other proinflammatory cytokines (TNF-α, IL-1β). In addition, histopathological hepatic injury was improved by preadministration of MSB or silymarin versus the disease model group. Bacillus sp spores had a protective effect on acute hepatic injury induced by APAP. Pretreatment with MSB resulted in a significant reduction in serum AST, ALT, TNF-α, IL-1β, ZO-1, TAC and also hepatocyte necrosis, similar to the well-known hepatoprotective agent-silymarin.

Probiotic Bacillus Spores Protect Against Acetaminophen Induced Acute Liver Injury in Rats.

Summary

What is known and Objective:  Ivabradine is a novel heart rate-lowering agent that selectively and specifically inhibits the depolarizing cardiac pacemaker If current in the sinus node Our objective was to evaluate a possible pharmacokinetic interaction between ivabradine and carbamazepine in healthy volunteers



Methods:  The study consisted of two periods: Period 1 (Reference), when each volunteer received a single dose of 10 mg ivabradine and Period 2 (Test), when each volunteer received a single dose of 10 mg ivabradine and 400 mg carbamazepine Between the two periods, the subjects were treated for 15 days with a single daily dose of 400 mg carbamazepine Plasma concentrations of ivabradine were determined during a 12-h period following drug administration, using a high-throughput liquid chromatography with mass spectrometry analytical method Pharmacokinetic parameters of ivabradine administered in each treatment period were calculated using non-compartmental and compartmental analysis to determine if there were statistically significant differences



Results and Discussion:  In the two periods of treatments, the mean peak plasma concentrations (Cmax) were 16·25 ng/mL (ivabradine alone) and 3·69 ng/mL (ivabradine after pretreatment with carbamazepine) The time taken to reach Cmax, tmax, were 0·97 and 1·14 h, respectively, and the total areas under the curve (AUC0-∞) were 52·49 and 10·33 ng h/mL, respectively These differences were statistically significant for Cmax and AUC0-∞ when ivabradine was administered with carbamazepine, whereas they were not for tmax, half-life and mean residence time



What is new and Conclusion:  TCarbamazepine interacts with ivabradine in healthy volunteers, and lowers its bioavailability by about 80% This magnitude of effect is likley to be clinically significant

Pharmacokinetic interaction between ivabradine and carbamazepine in healthy volunteers

Background Nowadays, growing attention was being given to the alternative ways to prevent or treat diseases. Nutraceuticals are used increasingly for this purpose. Many of these are being used as alternative therapy. Classic therapy with synthetic drugs, although very effective, has many side effects. The term "nutraceuticals" refers to the link between the nutritional and pharmaceutical domains. Also, lately, many studies have been done to investigate the role of microbiota in maintaining health. There is the hypothesis that some of the health benefits of nutraceuticals are due to their ability to change the microbiota. The aim of this review was to emphasize the link between the most commonly used nutraceuticals, the microbiota and the health benefits. Methods We selected the articles in PubMed, published up to July 2017, that provided information about most used nutraceuticals, microbiota and health benefits. In this review, we incorporate evidence from various types of studies, including observational, in vitro and in vivo, clinical studies or animal experiments. Results The results demonstrate that many nutraceuticals change the composition of microbiota and can interfere with health status of the patients. Discussion There is evidence which sustains the importance of nutraceuticals in people's health through microbiota but further studies are needed to complete the assessment of nutraceuticals in health benefit as a consequence of microbiota's changing.

An overview on the interplay between nutraceuticals and gut microbiota.

In recent years, increased attention has been paid to the relationship between microbiota and various diseases, especially immune-mediated diseases. Because conventional therapy for many autoimmune diseases is limited both in efficacy and safety, there is an increased interest in identifying nutraceuticals, particularly probiotics, able to modulate the microbiota and ameliorate these diseases. In this review, we analyzed the research focused on the role of gut microbiota and skin in immunity, their role in immune-mediated skin diseases (IMSDs), and the beneficial effect of probiotics in patients with this pathology. We selected articles published between 2009 and 2019 in PubMed and ScienceDirect that provided information regarding microbiota, IMSDs and the role of probiotics in these diseases. We included results from different types of studies including observational and interventional clinical trials or in vivo and in vitro experimental studies. Our results showed that probiotics have a beneficial effect in changing the microbiota of patients with IMSDs; they also influence disease progression. Further studies are needed to better understand the impact of new therapies on intestinal microbiota. It is also important to determine whether the microbiota of patients with autoimmune diseases can be manipulated in order to restore homeostasis of the microbiota.

https://www.mdpi.com/2076-2607/7/9/279/pdf

Maria Neag

Papers

Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders

Probiotic Bacillus Spores Protect Against Acetaminophen Induced Acute Liver Injury in Rats.

Pharmacokinetic interaction between ivabradine and carbamazepine in healthy volunteers

An overview on the interplay between nutraceuticals and gut microbiota.

Microbiota and Immune-Mediated Skin Diseases-An Overview.