- QTc Time Correlates with Amitriptyline and Venlafaxine Serum Levels in Elderly Psychiatric Inpatients. [Journal Article]
- PPharmacopsychiatry 2018 Feb 21
- CONCLUSIONS: Amitriptyline and venlafaxine induce QT prolongation depending on drug concentrations in blood. Its extent, however, is very low when drug serum levels are within the therapeutic range. Future pharmacokinetic studies that correlate drug serum level and QT time should classify the cardiac risk of drugs based on the grade of the regression line in relation to the therapeutic range.
- Combination pharmacotherapy for the treatment of fibromyalgia in adults. [Review]
- CDCochrane Database Syst Rev 2018 Feb 19; 2:CD010585
- CONCLUSIONS: There are few, large, high-quality trials comparing combination pharmacotherapy with monotherapy for fibromyalgia, consequently limiting evidence to support or refute the use of combination pharmacotherapy for fibromyalgia.
- Antidepressants as antipruritic agents: A review. [Review]
- ENEur Neuropsychopharmacol 2018 Feb 15
- Pruritus is a concomitant symptom of various underlying disorders viz. dermatological, systemic and psychiatric disorders that provoke the person to scratch the skin. Many natural as well as, antipru...
Pruritus is a concomitant symptom of various underlying disorders viz. dermatological, systemic and psychiatric disorders that provoke the person to scratch the skin. Many natural as well as, antipruritic therapies are usually practiced in the treatment of pruritus including general preventive measures, topical therapies such as cooling agents, antihistamines, anesthetics, capsaicin, corticosteroids, immunomodulators and; systemic therapies including administration of antihistamines, opioid antagonists/agonists, antiepileptic drugs/neuroleptics (e.g., gabapentin and pregabalin), antidepressants (e.g., doxepin, amitriptyline, paroxetine, fluvoxamine, sertraline, escitalopram and mirtazapine) (Patel and Yosipovitch, 2010; Reich et al., 2011; Martín and Padilla, 2015; Eskeland et al., 2016). Topical therapies are the mainstay of treatment of delicate and localized pruritus while other systemic drug therapies are used to treat stern and generalized pruritus. The reported antipruritic activity of some antidepressant drugs has intrigued this review to focus on the types of pruritus, pruritus mechanism, the antipruritic mechanism of antidepressants and to comprehend the role of antidepressants in the management of pruritus.
- Early and long period follow-up results of low glycemic index diet for migraine prophylaxis. [Journal Article]
- AGRIAgri 2018; 30(1):8-11
- CONCLUSIONS: The results of the study revealed that low glycemic index diet intake can be an effective and reliable method to reduce migraine attacks.
- Posttranscriptional regulation of UGT2B10 hepatic expression and activity by alternative splicing. [Journal Article]
- DMDrug Metab Dispos 2018 Feb 09
- The detoxification enzyme UDP-glucuronosyltransferase UGT2B10 is specialized in the N-linked glucuronidation of many drugs and xenobiotics. Preferred substrates possess tertiary aliphatic amines and ...
The detoxification enzyme UDP-glucuronosyltransferase UGT2B10 is specialized in the N-linked glucuronidation of many drugs and xenobiotics. Preferred substrates possess tertiary aliphatic amines and heterocyclic amines such as tobacco carcinogens and several anti-depressants and anti-psychotics. We hypothesized that alternative splicing (AS) constitutes a mean to regulate steady state levels of UGT2B10 and enzyme activity. We established the transcriptome of UGT2B10 in normal and tumoral tissues of multiple individuals. Highest expression was in the liver, where ten AS transcripts represented 50% of the UGT2B10 transcriptome in 50 normal livers and 44 hepatocellular carcinomas. One abundant class of transcripts involves a novel exonic sequence and leads to two alternative (alt.) variants with novel in-frame C-termini of 10 or 65 amino acids. Their hepatic expression was highly variable among individuals, correlated with canonical transcript levels, and was 3.5 fold higher in tumors. Evidence for their translation in liver tissues was acquired by mass spectrometry. In cell models, they co-localized with the enzyme and influenced the conjugation of amitriptyline and levomedetomidine by repressing or activating the enzyme (40-70%; P<0.01), in a cell context-specific manner. A high turnover rate for the alt. proteins, regulated by the proteasome, was observed in contrast to the more stable UGT2B10 enzyme. Moreover, a drug-induced remodelling of UGT2B10 splicing was demonstrated in the HepaRG hepatic cell model, which favored alt. variants expression over the canonical transcript. Our findings support a significant contribution of AS in the regulation of UGT2B10 expression in the liver with an impact on enzyme activity.
- Updates in palliative care - overview and recent advancements in the pharmacological management of cancer pain. [Journal Article]
- CMClin Med (Lond) 2018; 18(1):17-22
- Pain is a common symptom in many types of cancer. Interdisciplinary team management, including pain assessment, explanation to the patient/family, treating the reversible, non-pharmacological treatme...
Pain is a common symptom in many types of cancer. Interdisciplinary team management, including pain assessment, explanation to the patient/family, treating the reversible, non-pharmacological treatments and reassessment are essential. This article focuses on the pharmacological management of cancer pain, and overviews and updates on the recent advances in this field. Both non-opioid and opioid analgesia as well as coanalgesics (adjuvants) are reviewed. Within non-opioid analgesia the risks of non-steroidal anti-inflammatory drugs (NSAIDs) are considered and recommendations for NSAIDs in patients at risk of gastrointestinal and cardiovascular toxicity are made. For opioid analgesics, side effects of opioids are discussed alongside practical guidance on opioid prescribing and converting between opioids. Newer drugs such as tapentadol are considered in this update. Amitriptyline, duloxetine, gabapentin and pregabalin, and the guidance for their use are reviewed in the coanalgesics (adjuvants) section.
- Randomized double-blind controlled study of bedtime low dose amitriptyline in chronic neck pain. [Journal Article]
- EJEur J Pain 2018 Feb 13
- CONCLUSIONS: Low-dose amitriptyline is effective for the management of idiopathic CNP with few side effects and high patients' satisfaction. This article is protected by copyright. All rights reserved.
- Dried blood spots and parallel artificial liquid membrane extraction-A simple combination of microsampling and microextraction. [Journal Article]
- ACAnal Chim Acta 2018 Jun 07; 1009:56-64
- In this paper, parallel artificial liquid membrane extraction (PALME) was used for the first time to clean-up dried blood spots (DBS) prior to ultra-high performance liquid chromatography-tandem mass...
In this paper, parallel artificial liquid membrane extraction (PALME) was used for the first time to clean-up dried blood spots (DBS) prior to ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Fundamental studies exploring amongst others desorption from the DBS in alkaline or acidic aqueous conditions, total extraction time and absolute recoveries were executed. Desorption and PALME were performed using a set of two 96-well plates, one of them housing the sample and the other comprising the supported liquid membrane (SLM) and the acceptor solution. In one procedure, amitriptyline and quetiapine (basic model analytes) were desorbed from the DBS using 250 μL of 10 mM sodium hydroxide solution (aqueous), and subsequently extracted through the SLM consisting of 4 μL of 1% trioctylamine in dodecyl acetate, and further into an acceptor solution consisting of 50 μL of 20 mM formic acid. In a second procedure, ketoprofen, fenoprofen, flurbiprofen, and ibuprofen (acidic model analytes) were desorbed from the DBS into 20 mM formic acid, extracted through an SLM with dihexyl ether, and further into an acceptor solution of 25 mM ammonia. Within 60 min of PALME, both basic and acidic model analytes were effectively desorbed from the DBS and extracted into the acceptor solution, which was injected directly into the analytical instrument. Recoveries between 63 and 85% for the six model analytes were obtained. PALME provided excellent clean-up from the DBS samples, and acceptor solutions were free from phospholipids. Linearity was obtained with r2 > 0.99 for five of the six analytes. Accuracy, precision and UHPLC-MS/MS matrix effects were in accordance with the European Medicines Agency (EMA) guideline. Based on these experiments, PALME shows great potential for future processing of DBS in a short and simple way, and with the presented setup, up to 96 DBS can be processed within a total extraction time of 60 min.
- Inhibition of the G9a/GLP histone methyltransferase complex modulates anxiety-related behavior in mice. [Journal Article]
- APActa Pharmacol Sin 2018 Feb 08
- Epigenetic gene-regulation abnormalities have been implicated in various neuropsychiatric disorders including schizophrenia and depression, as well as in the regulation of mood and anxiety. In additi...
Epigenetic gene-regulation abnormalities have been implicated in various neuropsychiatric disorders including schizophrenia and depression, as well as in the regulation of mood and anxiety. In addition, epigenetic mechanisms are involved in the actions of psychiatric drugs. Current anxiolytic drugs have significant shortcomings, and development of new medications is warranted. Two proteins, G9a (also known as EHMT2 or KMT1C) and GLP (G9a-like protein, also known as EHMT1 or KMT1D), which methylate lysine 9 of histone H3 (H3K9), could be promising anxiolytic targets. Postnatal genetic knock-out of G9a reduces anxiety-related behavior, consistent with the reduction of G9a levels by some medications used to treat anxiety (amitriptyline, imipramine and paroxetine). Conversely, there is increased anxiety-like behavior in mice with GLP haplodeficiency. We sought to determine whether two pharmacological inhibitors of G9a/GLP, UNC0642 and A-366, would have similar effects to genetic G9a/GLP insufficiency. We found that G9a/GLP inhibition with either compound reduced anxiety-like behaviors when administered to adult mice, in conjunction with decreased H3K9 methylation in the brain. In contrast, exposure to these compounds from embryonic day 9.5 (E9.5) until birth increased anxiety-like behaviors and decreased social interaction in adulthood, while H3K9 methylation was at normal levels in the brains of the adult mice. These findings reinforce genetic evidence that G9a/GLP has different effects on anxiety-like behavior at different stages of brain development, and suggest that targeting this histone methyltransferase pathway could be useful for developing new anxiolytic drugs. These data also suggest that antidepressant exposure in utero could have negative effects in adulthood, and further investigation of these effects is warranted.
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- Comparison of Predicted Intrinsic Hepatic Clearance of 30 Pharmaceuticals in Canine and Feline Liver Microsomes. [Journal Article]
- XXenobiotica 2018 Feb 06; :1-29
- Known cytochrome P450 (CYP) substrates in humans are used in veterinary medicine, with limited knowledge of the similarity or variation in CYP metabolism. Comparison of canine and feline CYP metaboli...
Known cytochrome P450 (CYP) substrates in humans are used in veterinary medicine, with limited knowledge of the similarity or variation in CYP metabolism. Comparison of canine and feline CYP metabolism via liver microsomes report that human CYP probes and inhibitors demonstrate differing rates of intrinsic clearance (CLint). The purpose of this study was to utilize a high-throughput liver microsome substrate depletion assay, combined with microsomal and plasma protein binding to compare the predicted hepatic clearance (CLhep) of thirty therapeutic agents used off-label in canines and felines, using both the well-stirred and parallel tube models. In canine liver microsomes, 3/30 substrates did not have quantifiable CLint, while midazolam and amitriptyline CLintwas too rapid for accurate determination. A CLhepwas calculated for 29/30 substrates in feline microsomes. Overall, canine CLhepwas faster compared to the feline, with fold differences ranging from 2-20 fold. A comparison between the well-stirred and parallel tube model indicates that the parallel tube model reports a slighter higher CLhepin both species. The differences in CYP metabolism between canine and feline highlight the need for additional research into CYP expression and specificity.