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Journal of Multidisciplinary Healthcare 2016Herpes zoster, also known as shingles, is a distinctive clinical condition caused by the reactivation of latent varicella zoster (chickenpox) virus following an initial... (Review)
Review
Herpes zoster, also known as shingles, is a distinctive clinical condition caused by the reactivation of latent varicella zoster (chickenpox) virus following an initial infection. Approximately 1 million cases of herpes zoster occur annually in the US, and one in every three people develops herpes zoster during their lifetime. Postherpetic neuralgia is a neuropathic pain syndrome characterized by pain that persists for months to years after resolution of the herpes zoster rash. It stems from damage to peripheral and central neurons that may be a byproduct of the immune/inflammatory response accompanying varicella zoster virus reactivation. Patients with postherpetic neuralgia report decreased quality of life and interference with activities of daily living. Approaches to management of postherpetic neuralgia include preventing herpes zoster through vaccination and/or antiviral treatment, and administering specific medications to treat pain. Current guidelines recommend treatment of postherpetic neuralgia in a hierarchical manner, with calcium channel α2-δ ligands (gabapentin and pregabalin), tricyclic antidepressants (amitriptyline, nortriptyline, or desipramine), or topical lidocaine patches as first-line drugs. The safety and tolerability of pharmacologic therapies for pain are important issues to consider as postherpetic neuralgia affects primarily an older population. Patients should be educated on appropriate dosing, titration if applicable, the importance of adherence to treatment for optimal effectiveness, and possible side effects. Health-care professionals play a key role in helping to ameliorate the pain caused by postherpetic neuralgia through early recognition and diligent assessment of the problem; recommending evidence-based treatments; and monitoring treatment adherence, adverse events, responses, and expectations. Nurse practitioners are especially crucial in establishing communication with patients and encouraging the initiation of appropriate pain-relieving treatments.
PubMed: 27703368
DOI: 10.2147/JMDH.S106340 -
Journal of Virology Mar 2019Bovine herpesvirus 1 (BoHV-1) is an alphaherpesvirus that causes disease in cattle populations worldwide. Sphingomyelin (SM) is the most abundant sphingolipid in the...
Bovine herpesvirus 1 (BoHV-1) is an alphaherpesvirus that causes disease in cattle populations worldwide. Sphingomyelin (SM) is the most abundant sphingolipid in the mammalian cell membrane, where it preferentially associates with cholesterol to form lipid raft domains. SM is a substrate for the lysosome-resident enzyme acid sphingomyelinase, which plays a role in cell membrane repair following injury. Treatment of cells with noncytotoxic concentrations of -derived sphingomyelinase successfully reduced cell surface-exposed sphingomyelin but did not significantly inhibit BoHV-1 entry and infection, as measured by the beta-galactosidase reporter assay. Interestingly, entry of the porcine alphaherpesvirus pseudorabies virus (PRV) was inhibited by sphingomyelin-depletion of cells. Treatment of BoHV-1 particles with sphingomyelinase inhibited viral entry activity, suggesting that viral SM plays a role in BoHV-1 entry, while cellular SM does not. Treatment of cells with noncytotoxic concentrations of the functional inhibitors of host acid sphingomyelinase, imipramine and amitriptyline, which induce degradation of the cellular enzyme, did not significantly inhibit BoHV-1 entry. In contrast, inhibition of cellular acid sphingomyelinase inhibited PRV entry. Entry of the human alphaherpesvirus herpes simplex virus 1 (HSV-1) was independent of both host SM and acid sphingomyelinase, in a manner similar to BoHV-1. Together, the results suggest that among the alphaherpesviruses, there is variability in entry requirements for cellular sphingomyelin and acid sphingomyelinase activity. Bovine herpesvirus 1 (BoHV-1) is an ubiquitous pathogen affecting cattle populations worldwide. Infection can result in complicated, polymicrobial infections due to the immunosuppressive properties of the virus. Available vaccines limit disease severity and spread but do not prevent infection. The financial and animal welfare ramifications of BoHV-1 are significant. In order to develop more effective prevention and treatment regimens, a more complete understanding of the initial steps in viral infection is necessary. We recently identified a low pH endocytosis pathway for BoHV-1. Here, we examine the role of cellular factors responsible for membrane integrity and repair in alphaherpesviral entry. This study allows comparisons of the BoHV-1 entry pathway with those of other alphaherpesviruses (pseudorabies virus [PRV] and herpes simplex virus 1 [HSV-1]). Lastly, this is the first report of sphingomyelin and lysosomal sphingomyelinase playing a role in the entry of a herpesvirus. The results may lead to the development of more effective prevention and treatment regimens.
Topics: Amitriptyline; Animals; Cattle; Cattle Diseases; Cell Line; Chlorocebus aethiops; Dogs; Herpesvirus 1, Bovine; Herpesvirus 1, Suid; Imipramine; Madin Darby Canine Kidney Cells; Membrane Microdomains; Sphingomyelin Phosphodiesterase; Sphingomyelins; Vero Cells; Virus Internalization
PubMed: 30541840
DOI: 10.1128/JVI.01547-18 -
Brazilian Journal of Otorhinolaryngology 2017Vestibular migraine (VM) is now accepted as a common cause of episodic vertigo. Treatment of VM involves two situations: the vestibular symptom attacks and the period... (Observational Study)
Observational Study
INTRODUCTION
Vestibular migraine (VM) is now accepted as a common cause of episodic vertigo. Treatment of VM involves two situations: the vestibular symptom attacks and the period between attacks. For the latter, some prophylaxis methods can be used. The current recommendation is to use the same prophylactic drugs used for migraines, including β-blockers, antidepressants and anticonvulsants. The recent diagnostic definition of vestibular migraine makes the number of studies on its treatment scarce.
OBJECTIVE
To evaluate the efficacy of prophylactic treatment used in patients from a VM outpatient clinic.
METHODS
Review of medical records from patients with VM according to the criteria of the Bárány Society/International Headache Society of 2012 criteria. The drugs used in the treatment and treatment response obtained through the visual analog scale (VAS) for dizziness and headache were assessed. The pre and post-treatment VAS scores were compared (the improvement was evaluated together and individually, per drug used). Associations with clinical subgroups of patients were also assessed.
RESULTS
Of the 88 assessed records, 47 were eligible. We included patients that met the diagnostic criteria for VM and excluded those whose medical records were illegible and those of patients with other disorders causing dizziness and/or headache that did not meet the 2012 criteria for VM. 80.9% of the patients showed improvement with prophylaxis (p<0.001). Amitriptyline, Flunarizine, Propranolol and Topiramate improved vestibular symptoms (p<0.001) and headache (p<0.015). The four drugs were effective in a statistically significant manner. There was a positive statistical association between the time of vestibular symptoms and clinical improvement. There was no additional benefit in hypertensive patients who used antihypertensive drugs as prophylaxis or depressed patients who used antidepressants in relation to other prophylactic drugs. Drug association did not show statistically significant results in relation to the use of a single drug.
CONCLUSIONS
Prophylactic medications used to treat VM improve the symptoms of this disease, but there is no statistically significant difference between the responses of prophylactic drugs. The time of vestibular symptom seems to increase the benefit with prophylactic treatment.
Topics: Adult; Aged; Amitriptyline; Female; Flunarizine; Fructose; Humans; Longitudinal Studies; Male; Middle Aged; Migraine Disorders; Propranolol; Retrospective Studies; Topiramate; Treatment Outcome; Vestibular Diseases
PubMed: 27320656
DOI: 10.1016/j.bjorl.2016.04.022 -
Korean Journal of Anesthesiology Feb 2019The pain-relief properties of tricyclic antidepressants can be attributed to several actions. Recent observations suggest that adenosine is involved in the...
BACKGROUND
The pain-relief properties of tricyclic antidepressants can be attributed to several actions. Recent observations suggest that adenosine is involved in the antinociceptive effect of amitriptyline. The A3 adenosine receptor (A3AR) is the only adenosine subtype overexpressed in inflammatory and cancer cells. This study was performed to investigate the role of A3AR in the anti-nociceptive effect of amitriptyline.
METHODS
Spinal nerve-ligated neuropathic pain was induced by ligating the L5 and L6 spinal nerves of male Sprague-Dawley rats. The neuropathic rats were randomly assigned to one of the following three groups (8 per group): a neuropathic pain with normal saline group, a neuropathic pain with amitriptyline group, and a neuropathic pain with amitriptyline and 3-ethyl-5-benzyl- 2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS) group. Amitriptyline or saline was administered intraperitoneally and 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191), an A3AR antagonist, was injected subcutaneously immediately before amitriptyline administration. The level of extracellular signal-regulated kinase P44/42 (ERK1/2), cyclic AMP response element-binding protein (CREB), and proinflammatory cytokines were assessed using immunoblotting or reverse-transciption polymerase chain reaction.
RESULTS
Amitriptyline increased the mechanical withdrawal threshold of the neuropathic rats. The level of phospho-ERK1/2 and phospho-CREB proteins, and proinflammatory cytokines produced by spinal nerve ligation were significantly reduced by amitriptyline administration. However, the use of MRS-1191 before amitriptyline administration not only reduced the threshold of mechanical allodynia, but also increased the signaling protein and proinflammatory cytokine levels, which were reduced by amitriptyline.
CONCLUSIONS
The results of this study suggest that the anti-nociceptive effect of amitriptyline involves the suppression of ERK1/2 and CREB signaling proteins, and A3AR activation also affects the alleviation of the inflammatory response.
Topics: Adenosine A3 Receptor Antagonists; Amitriptyline; Animals; Cyclic AMP Response Element-Binding Protein; Cytokines; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; MAP Kinase Signaling System; Male; Neuralgia; Rats; Rats, Sprague-Dawley; Receptor, Adenosine A3
PubMed: 29969887
DOI: 10.4097/kja.d.18.00022 -
Translational Psychiatry Feb 2021Antidepressant medications are known to modulate the central nervous system, and gut microbiota can play a role in depression via microbiota-gut-brain axis. But the...
Antidepressant medications are known to modulate the central nervous system, and gut microbiota can play a role in depression via microbiota-gut-brain axis. But the impact of antidepressants on gut microbiota function and composition remains poorly understood. Thus this study assessed the effect of serotonin reuptake inhibitor antidepressant fluoxetine (Flu) and tricyclic antidepressant amitriptyline (Ami) administration on gut microbiota composition, diversity, and species abundance, along with microbial function in a chronic unpredictable mild stress (CUMS)-induced depression rat model. Oral administration of Ami and Flu significantly altered the overall gut microbiota profile of CUMS-induced rats, as assessed using the permutational multivariate analysis of variance test. At the phylum level, 6-week of antidepressant treatment led to a decreased Firmicutes/Bacteroidetes ratio due to an enhanced Bacteroidetes and reduced Firmicutes relative abundance. Flu was more potent than Ami at altering the Firmicutes and Bacteroidetes levels in the CUMS rats. At the family level, both antidepressants significantly increased the abundance of Porphyromonadaceae. However, an increased Bacteroidaceae level was significantly associated with Ami, not Flu treatment. Furthermore, at the genus level, an increase in the relative abundance of Parabacteroides, Butyricimonas, and Alistipes was observed following Ami and Flu treatment. Subsequent metagenomics and bioinformatics analysis further indicated that Ami and Flu likely also modulated metabolic pathways, such as those involved in carbohydrate metabolism, membrane transport, and signal transduction. Additionally, both antidepressants affected antibiotic resistome, such as for aminoglycoside (aph3iiiA), multidrug (mdtK, mdtP, mdtH, mdtG, acrA), and tetracycline (tetM) resistance in CUMS rats. These data clearly illustrated the direct impact of oral administration of Flu and Ami on the gut microbiome, thus set up the foundation to reveal more insights on the therapeutic function of the antidepressants and their overall contribution to host health.
Topics: Amitriptyline; Animals; Antidepressive Agents; Fluoxetine; Gastrointestinal Microbiome; Rats; Stress, Psychological
PubMed: 33602895
DOI: 10.1038/s41398-021-01254-5 -
Cureus Jun 2018Amitriptyline is a widely prescribed tricyclic antidepressant (TCA) with a very concerning cardiotoxicity profile, but it is one that has not been discussed much in...
Amitriptyline is a widely prescribed tricyclic antidepressant (TCA) with a very concerning cardiotoxicity profile, but it is one that has not been discussed much in literature. Here, we present a case of amitriptyline toxicity presenting as myocarditis with pericardial involvement. A 21-year-old male with no previous cardiac history presented to the emergency department (ED) with a decreased level of consciousness after an amitriptyline overdose as a suicidal attempt. For concerns with airway protection, the patient was intubated and subsequently admitted to the intensive care unit (ICU). An electrocardiogram (EKG) showed sinus tachycardia, prolonged QRS complex, prolonged QTc interval, and nonspecific ST-T wave changes. Intravenous fluid resuscitation and sodium bicarbonate were administered with a target blood pH of 7.5 to 7.55. Two days later, the patient was taken off mechanical ventilation and improved clinically. However, troponin levels began to rise with a peak level of 4.08 µg/L. He then began having fevers, elevated white blood cell counts (WBCs), and elevated inflammatory markers. Transthoracic echo (TTE) revealed an ejection fraction (EF) of 45%-50%, no wall segment motion abnormalities, and a mild-to-moderate pericardial effusion. Cardiac magnetic resonance (CMR) was done, which revealed changes indicative of acute myocarditis, moderate pericardial effusion, a calculated EF of 45% with a moderate left ventricular dilation, and no coronary artery stenosis or anomalous coronary artery origin. Given the patient's age, the absence of cardiac risk factors, and the presence of an amitriptyline overdose along with his EKG, TTE, and CMR findings, we hypothesize that this myocarditis with pericardial involvement is due to amitriptyline-induced direct toxicity.
PubMed: 30430045
DOI: 10.7759/cureus.2840 -
Brain, Behavior, & Immunity - Health Jan 2021Amitriptyline is prescribed to reduce the intensity of chronic neuropathic pain. There is a paucity of validated evidence in humans regarding amitriptyline's mechanism...
Examination and characterisation of the effect of amitriptyline therapy for chronic neuropathic pain on neuropeptide and proteomic constituents of human cerebrospinal fluid.
INTRODUCTION
Amitriptyline is prescribed to reduce the intensity of chronic neuropathic pain. There is a paucity of validated evidence in humans regarding amitriptyline's mechanism of action. We examined the effect of amitriptyline therapy on cerebrospinal fluid (CSF) neuropeptides and proteome in patients with chronic neuropathic pain to identify potential mechanisms of action of amitriptyline.
METHODS
Patients with lumbar radicular neuropathic pain were selected for inclusion with clinical and radiological signs and a >50% reduction in pain in response to a selective nerve root block. Baseline (pre-treatment) and 8-week (post-treatment) pain scores with demographics were recorded. CSF samples were taken at baseline (pre-treatment) and 8 weeks after amitriptyline treatment (post-treatment). Proteome analysis was performed using mass spectrometry and secreted cytokines, chemokines and neurotrophins were measured by enzyme-linked immunosorbent assay (ELISA).
RESULTS
A total of 9/16 patients experienced a >30% reduction in pain after treatment with amitriptyline and GO analysis demonstrated that the greatest modulatory effect was on immune system processes. KEGG analysis also identified a reduction in PI3K-Akt and MAPK signalling pathways in responders but not in non-responders. There was also a significant decrease in the chemokine eotaxin-1 (p = 0.02) and a significant increase in the neurotrophin VEGF-A (p = 0.04) in responders.
CONCLUSION
The CSF secretome and proteome was modulated in responders to amitriptyline verifying many pre-clinical and models. The predominant features were immunomodulation with a reduction in pro-inflammatory pathways of neuronal-glia communications and evidence of a neurotrophic effect.
PubMed: 34589721
DOI: 10.1016/j.bbih.2020.100184 -
Therapeutic Advances in... 2024Tricyclic antidepressants (TCAs) remain widely prescribed for depression and many other conditions. There may be important differences between individual TCA in regard... (Review)
Review
Tricyclic antidepressants (TCAs) remain widely prescribed for depression and many other conditions. There may be important differences between individual TCA in regard to their overdose toxicity and their cardiac toxicity in clinical use. We conducted a systematic review to compare the toxicity of individual TCA in overdose and the risk of serious adverse cardiac events occurring with therapeutic doses. We used the fatal toxicity index (FTI) and case fatality ratio as markers of fatality in overdose, and hazard ratios or odds ratios for the risk of cardiovascular adverse events during normal clinical use. In all, 30 reports of mortality in overdose and 14 observational studies assessing the risk of cardiovascular adverse events in clinical use were included. FTI values were of the same order of magnitude (10-10) for all TCAs except lofepramine. Desipramine appears to be somewhat more likely than other TCAs to lead to death in overdose. Amitriptyline, clomipramine, dothiepin/dosulepin, doxepin, trimipramine and imipramine showed broadly similar toxicity and were usually reported to be less toxic than desipramine. Data on nortriptyline were contradictory. Lofepramine had the lowest risk of death in overdose. The rank order of overdose toxicity was broadly consistent between different FTI definitions and between markers used. With respect to the risk of cardiovascular events at clinically relevant exposure, amitriptyline, nortriptyline and lofepramine were associated with a greater risk of in-use cardiotoxicity. All measures of overdose toxicity were subject to external influences and confounding. The continued use of TCAs in depression and other conditions should be minimized when considering their undoubted toxicity in overdose and possible toxicity in normal clinical use.
PubMed: 38827015
DOI: 10.1177/20451253241243297 -
Arquivos de Neuro-psiquiatria Apr 2018Nonpharmacological treatments, such as the Nociceptive Trigeminal Inhibition Tension Suppression System (NTI-tss), are approved for migraine prophylaxis. We aimed at... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVES
Nonpharmacological treatments, such as the Nociceptive Trigeminal Inhibition Tension Suppression System (NTI-tss), are approved for migraine prophylaxis. We aimed at evaluating the effectiveness of the NTI-tss and to compare its efficacy with amitriptyline and with a sham intraoral device in the preventive treatment of migraine.
METHODS
Consecutive patients with migraine were randomized to receive 25 mg of amitriptyline/day (n = 34), NTI-tss (n = 33) and a non-occlusal splint (n = 30). The headache frequency was evaluated at six and 12 weeks.
RESULTS
The amitriptyline group showed, respectively, 60% and 64% reduction in attack frequency at six and 12 weeks (P = 0.000). In the NTI-tss and non-occlusal splint groups, reduction was 39% and 30%, respectively, at six weeks and 48% for both groups at 12 weeks.
CONCLUSIONS
Amitriptyline proved superior to the NTI-tss and the non-occlusal splint. Despite its approval by the United States Food and Drug Administration, the NTI-tss was not superior to a sham device.
Topics: Adult; Amitriptyline; Analgesics, Non-Narcotic; Female; Humans; Male; Migraine Disorders; Occlusal Splints; Treatment Outcome
PubMed: 29742243
DOI: 10.1590/0004-282x20180023