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In unanaethetised rats with a single injection of compound 48/80, a mast cell degranulator (0.75 mg kg-1, i.p.), gastric lesions occurred with increased serum serotonin and histamine levels and reduced gastric mucosal blood flow at 0.5 h after the injection and developed at 3 h. Pretreatment with either cyproheptadine (a serotonin and histamine antagonist) or methysergide (a serotonin antagonist) prevented the formation of gastric mucosal lesions with attenuation of reduced gastric mucosal blood flow at 0.5 h after compound 48/80 injection, while pretreatment with either amitriptyline (a selective inhibitor of histamine release from mast cells), tripelennamine (a histamine H1-receptor antagonist), famotidine (a histamine H2-receptor antagonist) or cimetidine (a histamine H2-receptor antagonist) had no effect. Pretreatment with either cyproheptadine, methysergide, amitriptyline or tripelennamine prevented the development of gastric mucosal lesions at 3 h after compound 48/80 injection, while pretreatment with either famotidine or cimetidine had no effect. These results indicate that in unanaesthetised rats with a single compound 48/80 treatment, acutely released endogenous serotonin causes gastric mucosal lesions, while released endogenous histamine mainly contributes to the lesion development and that gastric acid plays little role in the pathogenesis of the compound 48/80-induced acute gastric lesions.
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A retrospective, cross-sectional study was conducted, involving older adults (aged 65 years and older), using 2009-2010 Medical Expenditure Panel Survey (MEPS) data. The 2012 AGS Beers Criteria were used to define potentially inappropriate anticholinergic medications on the basis of the list of medications to avoid using in older adults irrespective of the diagnosis. Descriptive analyses were used to examine the nature and extent of potentially inappropriate anticholinergic medication use. Multivariable logistic regression within the conceptual framework of the Andersen Behavioral Model was used to identify the factors associated with potentially inappropriate anticholinergic use in older adults.
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Increasing the duration of local anesthesia and/or creating greater differential blockade (i.e., selective block of pain-transmitting nerve fibers) has been attempted by modifying currently available agents. Most drugs show a different profile depending on the model or species studied. This study was designed to investigate the differential nerve-blocking properties of amitriptyline and its quaternary ammonium derivative in rats and sheep.
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Large volume pRBC transfusions are associated with multiple adverse clinical sequelae, including lung inflammation. Microparticles are formed in stored pRBCs over time and have been shown to contribute to lung inflammation after transfusion.
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In the context of chronic physical illness, such as breast cancer, depression is associated with increased morbidity, longer periods of hospitalization, and greater overall disability. Prompt diagnosis and effective treatment is. therefore, essential. Several small studies have established the efficacy of tricyclic antidepressants (TCAs) in this setting, and the selective serotonin reuptake inhibitors (SSRIs) would appear to be an alternative therapeutic option because of their established efficacy and better tolerability profile. This was a multicenter. double-blind, parallel-group study in which 179 women with breast cancer were randomized to treatment with either the SSRI paroxetine (20-40 mg/day), or the TCA, amitriptyline (75-150 mg/day). After 8-weeks treatment, depressive symptomatology had improved markedly and to a similar extent in both groups on the Montgomery Asberg Depression Rating Scale. Clinical global impression (CGI) Global improvement and Patient global evaluation scales indicated that patients were minimally to much improved at study endpoint: a change from moderately/mildly ill to borderline ill on the CGI severity of Illness scale. A steady improvement in quality of life was also observed in both groups. There were no clinically significant differences between the groups. In total, 47 (53.4%) patients in the paroxetine group and 53 (59.6%) patients in the amitriptyline group had adverse experiences, the most common of which were the well-recognized side-effects of the antidepressant medications or chemotherapy. Anticholinergic effects were almost twice as frequent in the amitriptyline group (19.1%) compared with paroxetine (11.4%). This study has demonstrated that paroxetine is a suitable alternative to amitriptyline for the treatment of depression in patients with breast cancer.
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The mechanisms underlying the pathogenesis of migraine and their possible association with serotonin (5-hydroxytryptamine; 5-HT) have not yet been elucidated. One of the major obstacles in achieving this goal is the lack of information on the mechanisms by which the monoamine could possibly trigger and/or modulate the basic pathophysiological features of the condition, that is, cranial vasodilatation and neurogenic inflammation. This information should provide a useful theoretical framework to insight the nature of the postulated fundamental triggering mechanism in the brain that ultimately results in head pain. Novel avenues for research and drug development may be envisaged upon the recent observations showing that 5-HT is actually able to produce vasodilatation of intra- and extra-cranial blood vessels through a mechanism pharmacologically resembling the 5-HT(7) receptor type, and that the messenger RNA (mRNA) encoding for this receptor is highly expressed in cranial vessels. Other lines of evidence have suggested that the 5-HT(7) receptor may play an excitatory role in neuronal systems and that it may be involved in hyperalgesic pain and neurogenic inflammation. On the basis of these observations, it is proposed that the 5-HT(7) receptor may well represent a link between the abnormal phenomena of 5-HT processing and neurotransmission that are observed in migraine patients, and the vascular and neurogenic alterations that account for migraine headache. This view is supported by the fact that most of the migraine prophylactic 5-HT receptor antagonists display relatively high affinity for the 5-HT(7) receptor, which significantly correlates with their pharmaceutically active oral doses.
The traditional and new antidepressive drugs appeared to be equally effective in the treatment of moderate depressive disorders, but new drugs: Selective Serotonin Reuptake Inhibitors show less adverse effects, compared to the traditional, tricyclic antidepressants.
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Objective: The objective of this study was to determine current practices in the Lorraine region in the treatment of neuropathic pain and to assess the challenges faced by general practitioners (GPs). Methods: We conducted a qualitative study by the focus group technique, by constituting a balanced panel of GPs to meet diversification requirements. The number of focus groups was defined to obtain data saturation. The lead author of this study acted as an observer, while a facilitator was responsible for moderating the debate. Analysis of transcripts was performed in two ways: firstly, several readings of the transcripts to highlight the main ideas emerging from these discussions, and secondly, integration of verbatim transcripts in NVivo 10 software to allow complementary computer analysis. Results: The GPs interviewed reported that they prescribed Clonazepam (Rivotril®), Carbamazepine (Tegretol®) and Amitriptyline (Laroxyl®) less often than ten years ago, and Gabapentin (Neurontin®), Pregabalin (Lyrica®), Venlafaxin (Effexor®) and Duloxetine (Cymbalta®) more often than ten years ago. They reported many difficulties in the daily management of these patients, especially concerning the psychological or psychiatric components associated with this pain, comorbidities, iatrogenic effects, the inefficacy of the available molecules, the difficulties of access to a specialist (including pain centres), acceptance of treatment by patients, limiting requirements (restrictive marketing authorisations, withdrawal of certain products…). Conclusion: The treatment of neuropathic pain raises a number of difficulties for GPs, but changes in prescribing habits reflect a constant adaptation of clinical practices.
Human platelet-rich plasma clots, formed with Reptilase, do not retract. Electron microscopy of such a clot reveals platelets of normal shape and ultrastructural features surrounded by fibrin. When ADP is added before Reptilase, the clot strongly retracts. A sequential ultrastructural study of this process shows that, before visible fibrin formation, the platelets form small clusters and show shape change, granule centralization and pseudopod formation. Upon immobilization of the platelets by fibrin, the pseudopods develop into large cytoplasmatic protrusions, which allow cell contact. During the retraction process, the platelet granules remain intact; some granule fusion only becomes apparent in fully retracted clots. When Thrombofax is added to platelet-rich plasma before Reptilase, the clots formed also retract. With this aggregation inducer, granule fusion occurs earlier and in more platelets. Platelet pseudopod enlargement and fibrin concentration around the platelet mass are similar to that in ADP-treated samples. Inhibitors of granule fusion and secretion (suprofen, indomethacin) do not modify ADP-Reptilase nor Thrombofax-Reptilase clot retraction but reduce the incidence of granule fusion in Thrombofax-Reptilase clots. Retraction of Thrombofax-Reptilase clots is unaffected by concentrations of apyrase which completely block ADP-Reptilase clot retraction. Prostaglandin E1, papaverine and amitryptiline inhibit both ADP-and Thrombofax-Reptilase clot retraction, platelet pseudopod formation and cell-to-cell adhesion. These findings suggest that interaction of fibrin with the mass of fused granules (granulomere) or platelet secretion are not responsible for clot retraction. Rather, contraction around adhesion sites formed by cytoplasmic protrusions from adjacent platelets would seem to be involved.
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A fast and selective ultraperformance liquid chromatographic-tandem mass spectrometric method was developed and validated for the simultaneous quantification of amitriptyline, citalopram, clomipramine, desipramine, desmethylcitalopram, desmethylclomipramine, desmethyldosulepin, desmethyldoxepin, desmethylfluoxetine, desmethylvenlafaxine, didesmethylcitalopram, dosulepin, doxepin, duloxetine, fluoxetine, fluvoxamine, imipramine, maprotiline, mianserin, mirtazapine, moclobemide, nortriptyline, paroxetine, reboxetine, sertraline, trazodone, and venlafaxine in 100 μL of plasma. After liquid-liquid extraction with 1-chlorobutane, analytes were separated on a BEH (Ethylene Bridged Hybrid) C18 analytical column with gradient elution. The compounds were ionized and detected over 7-minute analysis time by electrospray ionization tandem mass spectrometry with multiple reaction monitoring. Limits of quantification and limits of detection ranged from 2.5 to 10 ng/mL and 0.2 to 10 ng/mL, respectively. Intra- and interassay imprecision were lower than 15% for all the compounds except for mirtazapine, moclobemide, and desmethylclomipramine [relative standard deviation (RSD) < 20%], and the bias of the assay was lower than 15% for all the compounds except for fluvoxamine (bias < 20.5%), evaluated with 5 commercial quality control and 3 "in-house" quality control. The extraction was found to be reproducible (RSD < 16%) (except for duloxetine RSD 21.9%) and with recoveries varying from 59% to 86%. Furthermore, the stability studies demonstrated that the processed samples were stable in the autosampler for 24 hours for all the compounds. The method was successfully applied to the analysis of authentic samples from forensic toxicology cases and external quality control assays from the Society of Toxicology and Forensic Chemistry (GTFCh). The method was completely validated and can be of interest to clinical and forensic laboratories.
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The results of this trial indicate that the influence of cyclobenzaprine over pain, swelling and trismus does not justify prescribing additional medication for patients undergoing third-molar extraction.
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A fatal toxicity index (deaths per million National Health Service prescriptions) was calculated for antidepressant drugs on sale during the years 1975-84 in England, Wales, and Scotland. The tricyclic drugs introduced before 1970 had a higher index than the mean for all the drugs studied (p less than 0.001). In this group the toxicity of amitriptyline, dibenzepin, desipramine, and dothiepin was significantly higher, while that of clomipramine, imipramine, iprindole, protriptyline, and trimipramine was lower. The monoamine oxidase inhibitors had intermediate toxicity, and the antidepressants introduced since 1973, considered as a group, had significantly lower toxicity than the mean (p less than 0.001). Of these newer drugs, maprotiline had a fatal toxicity index similar to that of the older tricyclic antidepressants, while the other newly introduced drugs had lower toxicity indices, with those for mianserin, nomifensine, trazodone, and viloxazine reaching significance. Provided that these drugs are equally effective clinically, serious consideration should be given to prescribing antidepressants with a lower fatal toxicity.
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A woman in her mid-50s contacted her social worker and expressed intent to commit suicide by ingesting prescription medications. On arrival of emergency responders, the patient was found unconscious with an empty bottle of amitriptyline. Time of ingestion was estimated using the social worker's contact with local authorities. The patient's presentation at the emergency department (ED) exemplified tricyclic antidepressant toxidrome with a poor prognosis, based on measurable criteria and physical findings. Respiratory and cardiovascular collapse was managed emergently. Haemodynamic status and EKG findings responded in a stepwise fashion with therapy in the ED and intensive care unit. Full clinical recovery took 7 days, and the patient was subsequently transferred to an in-patient psychiatric facility for further evaluation. Eight days later, she was discharged home with no neurological sequelae.
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The effect of clonidine on amitriptyline-induced cardiotoxicity was investigated in an experimental rat mode. A continuous infusion of amitriptyline (30 mg/kg/h) was given until the animal died, usually within 2 hours. Fifteen minutes after starting the amitriptyline infusion, 50 micrograms/kg of clonidine was given intravenously over five minutes. This led to an increase in blood pressure and left ventricular end-diastolic pressure. There was no significant change in cardiac contractility. Heart rate decreased. These changes can be explained by an increase in afterload due to peripheral vasoconstriction. No signs of reduced sympathetic outflow were seen on the ECG. The peripheral effects of clonidine dominated over the central effects, which may be due to a competitive inhibition of amitriptyline at central noradrenergic sites. An increased afterload pushes the heart towards failure and increases mortality. In this model, clonidine did not reverse amitriptyline-induced cardiovascular toxicity. It may even be potentially harmful if used to treat tricyclic antidepressant poisoning.
Our findings can be useful for clinicians when they switch antidepressants and for researchers when they compare various antidepressants in their research.
To evaluate the efficacy of ultrasound-guided spinal nerve posterior ramus pulsed radiofrequency treatment for lower back post-herpetic neuralgia.
To determine the role of cytochrome P(450) (CYP)2C19 in N-demethylation of amitriptyline (AT) in healthy Chinese subjects.
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This case report describes a successful outcome of mirtazapine treatment in a patient with difficult post-thoracotomy pain. A 63-year-old man received thoracotomy for the resection of esophageal tumor. The pain continued 2 years after the operation. Allodynia was present in the region of the intercostal nerves from the surgical wound. Remedies such as clonazepam, amitriptyline, gabapentin, and acetaminophen were not effective, and epidural block effect was only temporal. The patient experienced a reduction in shooting pain after taking pregabalin; however, he still suffered from persistent pain and, mirtazapine was additionally administrated. One month after this, shooting and persistent pain was reduced, and the patient's appetite was improved, which had been present since the thoracotomy. Since then, his weight slightly increased and the administration of mirtazapine was stopped in accordance with the patient's request. The pain became worse again. Therefore, mirtazapine, commonly used as an antidepressant agent, was considered to be beneficial for neuropathic pain as an analgesic adjuvant.
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Genotypes and allele types of rs4646440 and rs2242480 were found to be significantly associated with the severity of withdrawal symptoms rated by COWS (p = 0.012, 0.0096, 0.017 and 0.012, respectively) as well as the side effects rated by TESS (p = 0.0089, 0.028, 0.0027 and 0.0085, respectively). The allele types associated with more severe withdrawal symptoms are also associated with more severe side effects and less betel nut (Areca catechu) use (p = 0.009 for rs4646440, p = 0.0063 for rs2242480). Further analyses on specific withdrawal symptoms in COWS showed that the genetic variants in rs4646440 are significantly associated with heart rate (allele type p = 0.0019).
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This review evaluates trials of antidepressants for acute and chronic postsurgical pain.
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Patients treated with narcotics plus nonnarcotic analgesics were associated with higher mean health care costs. Patient cohorts treated with some of the more common oral therapies for interstitial cystitis, including pentosan polysulfate sodium, amitriptyline, and hydroxyzine, were associated with lower costs. Physician visits were fewest among patients treated with pentosan polysulfate sodium plus amitriptyline and hydroxyzine. Physician visits were higher for cohorts that included dimethyl sulfoxide plus cystoscopy or bladder irrigation, or narcotics plus nonnarcotic analgesics.
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This paper reports on the clinical status, help-seeking and subsequent treatment experiences of 150 women one year after they had completed out-patient maintenance treatment by amitriptyline and/or psychotherapy for a depressive episode. While the majority of patients were asymptomatic at follow-up, a substantial minority had a return of acute symptoms and 2 per cent made minor suicide attempts during the year. Admission to hospital was rare. However, only 30 per cent of the patients did not seek any treatment during the year and the majority received some psychotropic medication. The findings support the long-term need for prompt access to treatment by patients who have recovered from an acute depression.