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Dose-response : a Publication of... 2022Radiation-induced lung injuries (RILI) is one of the serious complications of radiotherapy posed by the damage of alveolar cells and inflammation over-reaction. We aimed...
Radiation-induced lung injuries (RILI) is one of the serious complications of radiotherapy posed by the damage of alveolar cells and inflammation over-reaction. We aimed to investigate the potential protective effects of doxepin on RILI (20 Gy total dose at 3 Gy/min of X-ray irradiation), as well as its underlying mechanism. For animal experiments, such parameters as Immunohistochemistry and hematoxylin and eosin (H&E) staining, WBC (white blood cell), CRP (C-reactive protein), Western blot, and q-PCR were detected. The results indicated that both survival status and weight increase of irradiated rats treated by doxepin (3 mg/kg/day, rat) were higher than those of treated with irradiation alone (Dosing started the day before irradiation). Further, histological examinations showed doxepin could tenuate the radiation injury, as indicated as alveolar inflammatory exudation and there was only mild interstitial inflammation infiltration. Western blotting and q-PCR showed that expression of NF-κβ in X group were higher than that in XMD group. For the first time, we reported doxepin functioned as a radioprotectant candidate, which provide a promising application of doxepin for protecting radiotherapy injuries.
PubMed: 35693872
DOI: 10.1177/15593258221107193 -
Current Neuropharmacology 2022In contrast to that of other monoamine neurotransmitters, the association of the histaminergic system with neuropsychiatric disorders is not well documented. In the last... (Review)
Review
In contrast to that of other monoamine neurotransmitters, the association of the histaminergic system with neuropsychiatric disorders is not well documented. In the last two decades, several clinical studies involved in the development of drugs targeting the histaminergic system have been reported. These include the H3R-antagonist/inverse agonist, pitolisant, used for the treatment of excessive sleepiness in narcolepsy, and the H1R antagonist, doxepin, used to alleviate symptoms of insomnia. The current review summarizes reports from animal models, including genetic and neuroimaging studies, as well as human brain samples and cerebrospinal fluid measurements from clinical trials, on the possible role of the histaminergic system in neuropsychiatric disorders. These studies will potentially pave the way for novel histamine-related therapeutic strategies.
Topics: Animals; Brain; Histamine; Piperidines; Receptors, Histamine
PubMed: 34521328
DOI: 10.2174/1570159X19666210909144930 -
The Medical Letter on Drugs and... Jun 2020
Topics: Humans; Orexin Receptor Antagonists; Pyridines; Pyrimidines; Sleep Initiation and Maintenance Disorders
PubMed: 32724021
DOI: No ID Found -
The effect of smoking on the plasma concentration of tricyclic antidepressants: a systematic review.Acta Neuropsychiatrica Feb 2022Smoking is highly prevalent in the psychiatric population, and hospital admittance usually results in partial or complete smoking cessation. Tobacco use is known to... (Review)
Review
Smoking is highly prevalent in the psychiatric population, and hospital admittance usually results in partial or complete smoking cessation. Tobacco use is known to affect the metabolism of certain psychoactive drugs, but whether smoking influences the plasma concentration of tricyclic antidepressants (TCAs) remains unclear. This article investigates the possible effect of smoking on the plasma concentration of TCAs. A systematic review of the literature available on PubMed and EMBASE as of October 2020 was carried out using PRISMA guidelines. Studies reporting plasma concentrations of any TCA in both a smoking and a non-smoking group were included and compared. Ten eligible studies were identified and included. In the eight studies investigating the effect of smoking on amitriptyline and/or nortriptyline, five studies found no significant effect. Two studies investigating the effect of smoking on imipramine found a significant effect, and one study investigating the effect of smoking on doxepin found no significant effect. The majority of studies included in this review were influenced by small study populations and other methodical issues. The effect of smoking on the plasma concentration of TCAs is still not entirely clear. There is a possibility that smoking affects the distribution of TCA metabolites, but this is probably not of clinical importance.
Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Imipramine; Nortriptyline; Smoking
PubMed: 34497000
DOI: 10.1017/neu.2021.28 -
Northern Clinics of Istanbul 2021Urticarial vasculitis (UV) is an uncommon disease clinically presenting with pruritic urticarial plaques of the skin. The disease is classified as normocomplementic and...
OBJECTIVE
Urticarial vasculitis (UV) is an uncommon disease clinically presenting with pruritic urticarial plaques of the skin. The disease is classified as normocomplementic and hypocomplementemic types according to their complement levels. We aimed to evaluate demographic characteristics, laboratory findings, and response to treatment of patients diagnosed as UV in our clinic.
METHODS
Between January 2015 and January 2019, the files of the patients were retrospectively reviewed. Demographic data, clinical features, laboratory findings, suspected triggering factors, disease course, treatment modalities, and treatment results of the patients were recorded.
RESULTS
A total of 16 patients (nine males [56.25%], seven females [43.75%]) were included in the study.The mean age at diagnosis was 45.2±10.4 years and the duration of the disease was 72.1±62 months. Twelve (75%) patients had angioedema and two (12.5%) patients had residual hyperpigmentation. The most common extracutaneous finding was arthralgia (43.7%). No hypocomplementemia was detected in the patients. The most common abnormal laboratory findings were CRP elevation (37.5%) and ANA positivity (n=4/15, 26.7%). Analgesic and antibiotic drugs use were the most common possible triggering factors for the disease (n=9, 56%). Oral antihistamines, oral corticosteroids, azathioprine, colchicine, dapsone, hydroxychloroquine, doxepin, and omalizumab were among the treatments given to the patients. Complete remission was achieved in three patients.
CONCLUSION
Compared with other studies, we found that angioedema was more frequent, postinflammatory hyperpigmentation was lower and long-term treatment was needed to control UV attacks. There are a few studies on UV and we think that more and larger patient groups are needed for standardization of treatment.
PubMed: 34909591
DOI: 10.14744/nci.2020.55476 -
Phytomedicine : International Journal... Nov 2023Lycium barbarum L. is a typical Chinese herbal and edible plant and are now consumed globally. Low molecular weight L. barbarum L. oligosaccharides (LBO) exhibit better...
BACKGROUND
Lycium barbarum L. is a typical Chinese herbal and edible plant and are now consumed globally. Low molecular weight L. barbarum L. oligosaccharides (LBO) exhibit better antioxidant activity and gastrointestinal digestibility in vitro than high molecular weight polysaccharides. However, the LBO on the treatment of liver disease is not studied.
PURPOSE
Modification of the gut microbial ecosystem by LBO is a promising treatment for liver fibrosis.
STUDY DESIGN AND METHODS
Herein, LBO were prepared and characterized. CCl-treated mice were orally gavaged with LBO and the effects on hepatic fibrosis and mitochondrial abnormalities were evaluated according to relevant indicators (gut microbiota, faecal metabolites, and physiological and biochemical indices).
RESULTS
The results revealed that LBO, a potential prebiotic source, is a pyranose cyclic oligosaccharide possessing α-glycosidic and β-glycosidic bonds. Moreover, LBO supplementation restored the configuration of the bacterial community, enhanced the proliferation of beneficial species in the gastrointestinal tract (e.g., Bacillus, Tyzzerella, Fournierella and Coriobacteriaceae UCG-002), improved microbial metabolic alterations (i.e., carbohydrate metabolism, vitamin metabolism and entero-hepatic circulation), and increased antioxidants, including doxepin, in mice. Finally, LBO administration reduced serum inflammatory cytokine and hepatic hydroxyproline levels, improved intestinal and hepatic mitochondrial functions, and ameliorated mouse liver fibrosis.
CONCLUSION
These findings indicate that LBO can be utilized as a prebiotic and has a remarkable ability to mitigate liver fibrosis.
Topics: Animals; Mice; Antioxidants; Liver Cirrhosis; Lycium; Oligosaccharides; Gastrointestinal Microbiome
PubMed: 37690228
DOI: 10.1016/j.phymed.2023.155068 -
The Primary Care Companion For CNS... Apr 2020The number of prescriptions for antidepressants (ADs) in England and Wales has almost doubled in the past decade. The objective of this article is to describe the...
OBJECTIVE
The number of prescriptions for antidepressants (ADs) in England and Wales has almost doubled in the past decade. The objective of this article is to describe the current prescribing rates of different antidepressants by general practice (GP) practice.
METHODS
We collated the prescribing behavior in each GP practice in the year April 1, 2017, to March 31, 2018. The monthly GP practice prescribing data reports for medication prescribing for each British National Formulary code and practice, as well as the prescriptions, quantity, and costs were examined in relation to prescribing practice.
RESULTS
The data showed that 2.1 billion doses of antidepressant were prescribed to a total population of 52 million people. That equates to 11% of individuals taking ≥ 1 antidepressants on any day. Selective serotonin reuptake inhibitors (SSRIs) were the most prescribed class of ADs, with sertraline the most prescribed SSRI. The other most prescribed ADs were citalopram, fluoxetine, and mirtazapine. Some older agents, such as trimipramine and doxepin, are prescribed at a very high tariff.
CONCLUSIONS
Broadly, the findings are in keeping with National Institute for Health and Care Excellence guidance in that the bulk of prescriptions were for SSRIs. Regular audit of patient treatment at a general practice level will ensure appropriate targeted use of licensed medications as supported by the evidence base.
Topics: Antidepressive Agents; Drug Prescriptions; England; General Practitioners; Humans; Practice Patterns, Physicians'; Selective Serotonin Reuptake Inhibitors
PubMed: 32302071
DOI: 10.4088/PCC.19m02552 -
Long-Term Use of Insomnia Medications: An Appraisal of the Current Clinical and Scientific Evidence.Journal of Clinical Medicine Feb 2023While evidence supports the benefits of medications for the treatment of chronic insomnia, there is ongoing debate regarding their appropriate duration of use. A panel... (Review)
Review
While evidence supports the benefits of medications for the treatment of chronic insomnia, there is ongoing debate regarding their appropriate duration of use. A panel of sleep experts conducted a clinical appraisal regarding the use of insomnia medications, as it relates to the evidence supporting the focus statement, "No insomnia medication should be used on a daily basis for durations longer than 3 weeks at a time". The panelists' assessment was also compared to findings from a national survey of practicing physicians, psychiatrists, and sleep specialists. Survey respondents revealed a wide range of opinions regarding the appropriateness of using the US Food and Drug Administration (FDA)-approved medications for the treatment of insomnia lasting more than 3 weeks. After discussion of the literature, the panel unanimously agreed that some classes of insomnia medications, such as non-benzodiazepines hypnotics, have been shown to be effective and safe for long-term use in the appropriate clinical setting. For eszopiclone, doxepin, ramelteon and the newer class of dual orexin receptor antagonists, the FDA label does not specify that their use should be of a limited duration. Thus, an evaluation of evidence supporting the long-term safety and efficacy of newer non-benzodiazepine hypnotics is timely and should be considered in practice recommendations for the duration of pharmacologic treatment of chronic insomnia.
PubMed: 36836164
DOI: 10.3390/jcm12041629 -
Journal of Medical Toxicology :... Oct 2023Chronic tricyclic antidepressant toxicity is rarely described in children. Symptoms include confusion, ataxia, and seizures. Toxicity may result from dosing error,...
INTRODUCTION
Chronic tricyclic antidepressant toxicity is rarely described in children. Symptoms include confusion, ataxia, and seizures. Toxicity may result from dosing error, CYP2C19 and CYP2D6 genetic variability, and drug-drug interactions. Chronic doxepin toxicity has not been previously reported in children. Doxepin is prescribed for insomnia and depression, with a maximum off-label dose of 3 mg/kg in children. We present a case of chronic doxepin toxicity mimicking epilepsy in a child attributable to three potential factors: supratherapeutic dosing, pharmacogenomic variability, and drug-drug interactions.
CASE REPORT
A 10-year-old boy with insomnia, diagnosed with epilepsy 6 months prior, presented to an emergency department with confusion, ataxia, and increasing seizure frequency. He was prescribed doxepin for insomnia and four antiepileptics for seizures. After admission, he had two seizures and remained confused. EKGs showed QRS prolongation, suggesting doxepin toxicity. Doxepin-nordoxepin combined serum concentration was 1419 ng/mL (therapeutic 100-300 ng/mL), confirming doxepin toxicity. Outpatient records showed onset of confusion and seizures as doxepin dose was gradually uptitrated to 300 mg nightly (4.41 mg/kg). Symptoms worsened following addition of clobazam (CYP2D6 inhibitor) and topiramate (CYP2C19 inhibitor). Following doxepin discontinuation, all symptoms resolved. CYP2D6 testing showed intermediate metabolizer phenotype (CYP2D6*1/*4; activity score = 1.0; copy number = 2.0). No seizures have occurred in more than one year since doxepin discontinuation.
DISCUSSION
Caution must be exercised when prescribing doxepin. Pharmacogenomics, dose, drug-drug interactions, and age should be considered. Chronic toxicity should be contemplated in patients taking doxepin without acute overdose who present with persistent neurologic abnormalities including seizure.
Topics: Male; Child; Humans; Doxepin; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2D6; Sleep Initiation and Maintenance Disorders; Epilepsy; Seizures; Ataxia
PubMed: 37682427
DOI: 10.1007/s13181-023-00966-y -
Pharmaceuticals (Basel, Switzerland) Mar 2021Doxepin is commonly prescribed for depression and anxiety treatment. Doxepin-related disruptions to metabolism and renal/hepatic adverse effects remain unclear; thus,...
Doxepin is commonly prescribed for depression and anxiety treatment. Doxepin-related disruptions to metabolism and renal/hepatic adverse effects remain unclear; thus, the underlying mechanism of action warrants further research. Here, we investigated how doxepin affects lipid change, glucose homeostasis, chromium (Cr) distribution, renal impairment, liver damage, and fatty liver scores in C57BL6/J mice subjected to a high-fat diet and 5 mg/kg/day doxepin treatment for eight weeks. We noted that the treated mice had higher body, kidney, liver, retroperitoneal, and epididymal white adipose tissue weights; serum and liver triglyceride, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and creatinine levels; daily food efficiency; and liver lipid regulation marker expression. They also demonstrated exacerbated insulin resistance and glucose intolerance with lower Akt phosphorylation, GLUT4 expression, and renal damage as well as higher reactive oxygen species and interleukin 1 and lower catalase, superoxide dismutase, and glutathione peroxidase levels. The treated mice had a net-negative Cr balance due to increased urinary excretion, leading to Cr mobilization, delaying hyperglycemia recovery. Furthermore, they had considerably increased fatty liver scores, paralleling increases in adiponectin, FASN, PNPLA3, mRNA, and mRNA levels. In conclusion, doxepin administration potentially worsens renal injury, nonalcoholic fatty liver disease, and diabetes.
PubMed: 33809508
DOI: 10.3390/ph14030267