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1.
Artigo em Inglês | MEDLINE | ID: mdl-32213465

RESUMO

In this study, the use of switchable hydrophilicity solvent with a simple and low-cost lab-made device for the extraction procedure in homogeneous liquid-liquid microextraction is proposed for the first time in the determination of antidepressants in human urine. The antidepressants studied consisted of fluoxetine, amitriptyline, nortriptyline, imipramine, desipramine and sertraline. The optimization of the main parameters that can influence on the extraction efficiency was performed through multivariate approaches. The analytes were separated and identified by gas chromatography coupled to mass spectrometry (GC-MS). The optimal extraction conditions consisted of using N,N-dimethylcyclohexylamine (DMCHA) as the switchable hydrophilicity solvent (SHS), 500 µL of urine sample previously diluted with ultrapure water at 1:1 ratio (v/v), 200 µL of a mixture of SHS:HCl 6 mol L-1 (1:1 v/v), 600 µL of NaOH 10 mol L-1 and 3 min of extraction time. A volume of 40 µL of diphenylamine at concentration of 500 µg L-1 (20 ng) was used as internal standard. The method developed was in-house validated, providing coefficients of determination higher than 0.995 for all analytes, limits of detection (LOD) from 0.02 to 0.88 µg L-1, limits of quantification (LOQ) from 0.05 to 2.92 µg L-1, relative recoveries of 68 to 102%, intra-day precision from 0.5 to 15.9%, inter-day precision from 4.2 to 19.3%, selectivity and robustness. The method proposed was successfully applied in five human urine samples from a Toxicological Information Center located in Porto Alegre (Brazil). The results demonstrated that the µP-SHS-HLLME approach is highly cost-effective, rapid, simple and environmentally-friendly with satisfactory analytical performance.


Assuntos
Antidepressivos/urina , Adulto , Amitriptilina/urina , Cicloexilaminas/química , Desipramina/urina , Fluoxetina/urina , Cromatografia Gasosa-Espectrometria de Massas , Química Verde , Humanos , Interações Hidrofóbicas e Hidrofílicas , Imipramina/urina , Limite de Detecção , Microextração em Fase Líquida , Nortriptilina/urina , Sertralina/urina , Solventes/química
2.
Toxicol Lett ; 325: 43-50, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32092452

RESUMO

As a consequence of the detoxification process, drugs and drug related metabolites can accumulate in the liver, resulting in drug induced liver injury (DILI), which is the major cause for dose limitation. Amitriptyline, a commonly used tricyclic anti-depressant, is known to cause DILI. The mechanism of Amitriptyline induced liver injury is not yet completely understood. However, as it undergoes extensive hepatic metabolism, unraveling the molecular changes in the liver upon Amitriptyline treatment can help understand Amitriptyline's mode of toxicity. In this study, Amitriptyline treated male rat liver tissue was analyzed using Matrix Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging (MALDI-MSI) to investigate the spatial abundances of Amitriptyline, lipids, and bile acids. The metabolism of Amitriptyline in liver tissue was successfully demonstrated, as the spatial distribution of Amitriptyline and its metabolites localize throughout treatment group liver samples. Several lipids appear upregulated, from which nine were identified as distinct phosphatidylcholine (PC) species. The detected bile acids were found to be lower in Amitriptyline treatment group. The combined results from histological findings, Oil Red O staining, and lipid zonation by MSI revealed lipid upregulation in the periportal area indicating drug induced macrovesicular steatosis (DIS).


Assuntos
Amitriptilina/toxicidade , Antidepressivos Tricíclicos/toxicidade , Ácidos e Sais Biliares/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Animais , Doença Hepática Induzida por Substâncias e Drogas/patologia , Fígado/química , Fígado/metabolismo , Fígado/patologia , Masculino , Espectrometria de Massas , Tamanho do Órgão/efeitos dos fármacos , Fosfatidilcolinas/metabolismo , Ratos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Regulação para Cima/efeitos dos fármacos
3.
PLoS One ; 15(2): e0228077, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32017772

RESUMO

N-of-1 trials allow inference between two treatments given to a single individual. Most often, clinical investigators analyze an individual's N-of-1 trial data with usual t-tests or simple nonparametric methods. These simple methods do not account for serial correlation in repeated observations coming from the individual. Existing methods accounting for serial correlation require simulation, multiple N-of-1 trials, or both. Here, we develop t-tests that account for serial correlation in a single individual. The development includes effect size and precision calculations, both of which are useful for study planning. We then use Monte Carlo simulation to evaluate statistical properties of these serial t-tests, namely, Type I and II errors, and confidence interval widths, and compare these statistical properties to those of analogous usual t-test. The serial t-tests clearly outperform the usual t-tests commonly used in reporting N-of-1 results. Examples from N-of-1 clinical trials in fibromyalgia patients and from a behavioral health setting exhibit how accounting for serial correlation can change inferences. These t-tests are easily implemented and more appropriate than simple methods commonly used; however, caution is needed when analyzing only a few observations.


Assuntos
Ensaios Clínicos como Assunto , Amitriptilina/uso terapêutico , Fibromialgia/tratamento farmacológico , Humanos , Método de Monte Carlo , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Tamanho da Amostra
4.
Internist (Berl) ; 61(3): 270-276, 2020 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-32030435

RESUMO

BACKGROUND: The treatment of polyneuropathy includes symptomatic therapy of sensory, motor and autonomic dysfunctions. AIM: This article provides an overview of the current treatment recommendations for polyneuropathy, focusing on pain. METHODS: Current treatment guidelines will be discussed based on a literature research. RESULTS: Calcium-channel anticonvulsants gabapentin/pregabalin as well as antidepressants duloxetine and amitriptyline are recommended as first line therapeutics. Alternatively, topical therapeutics can be used in the case of localized disorders. In individual cases, opioids or other antidepressants/anticonvulsants may be effective. Pharmacological treatment is often limited due to adverse events, which affect the central nervous system in particular. DISCUSSION: In general, treatment for polyneuropathy should follow a multimodal concept and include the treatment of other symptoms. When choosing pain medication, comorbidities, patient's age and adverse events need to be taken into consideration. Phenotype-based stratification may support specialized pain therapy and achieve the best medical treatment.


Assuntos
Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Neuralgia/tratamento farmacológico , Polineuropatias/tratamento farmacológico , Amitriptilina/uso terapêutico , Analgésicos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Humanos , Pregabalina/uso terapêutico
5.
Oral Dis ; 26(1): 193-199, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31705718

RESUMO

OBJECTIVE: Burning mouth syndrome (BMS) is a chronic intraoral burning sensation with no identifiable causes. In this study, we aim to demonstrate the effectiveness of treatment strategy using ethyl loflazepate monotherapy or in combination with milnacipran or amitriptyline. METHOD: A hospital-based, retrospective study was conducted in 86 patients. The patients were divided into remission group and non-remission group. The remission group comprised patients who were satisfied with their pain relief within a year of treatment initiation and did not require any follow-up treatment. The treatment was considered effective if the patient got remission within 1 year or was able to reduce the visual analogue scale (VAS) score to <20, in the absence of remission. RESULTS: The treatment strategy was effective in 76.7% of the patients. Significant reductions (p < .05) in VAS scores from 73.5 ± 14.2 at first visit to 14.7 ± 8.7 at last visit in the remission group, and from 79.7 ± 14.3 at first visit to 33.4 ± 23.7 after 1 year of treatment in the non-remission group were noted. CONCLUSION: The treatment strategy using ethyl loflazepate monotherapy or in combination with milnacipran or amitriptyline can be very effective in reducing pain in BMS patients.


Assuntos
Amitriptilina/uso terapêutico , Benzodiazepinas/uso terapêutico , Síndrome da Ardência Bucal/tratamento farmacológico , Milnaciprano/uso terapêutico , Manejo da Dor , Adulto , Idoso , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Retrospectivos
6.
Am J Physiol Endocrinol Metab ; 318(2): E131-E144, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31821039

RESUMO

We reported previously that increased acid sphingomyelinase (ASMase)-catalyzed hydrolysis of sphingomyelin, which leads to increases in ceramide and sphingosine 1 phosphate (S1P), played a key role in the synergistic upregulation of proinflammatory cytokines by palmitic acid (PA), a major saturated fatty acid, and lipopolysaccharide (LPS) in macrophages. Since macrophages are vital players in nonalcoholic steatohepatitis (NASH) and atherosclerosis, we assessed the effect of ASMase inhibition on NASH and atherosclerosis cooperatively induced by high-PA-containing high-fat diet (HP-HFD) and LPS in LDL receptor-deficient (LDLR-/-) mice. LDLR-/- mice were fed HP-HFD, injected with low dose of LPS and treated with or without the ASMase inhibitor amitriptyline. The neutral sphingomyelinase inhibitor GW4869 was used as control. Metabolic study showed that both amitriptyline and GW4869 reduced glucose, lipids, and insulin resistance. Histological analysis and Oil Red O staining showed that amitriptyline robustly reduced hepatic steatosis while GW4869 had modest effects. Interestingly, immunohistochemical study showed that amitriptyline, but not GW4869, strongly reduced hepatic inflammation. Furthermore, results showed that both amitriptyline and GW4869 attenuated atherosclerosis. To elucidate the underlying mechanisms whereby amitriptyline inhibited both NASH and atherosclerosis, but GW4869 only inhibited atherosclerosis, we found that amitriptyline, but not GW4869, downregulated proinflammatory cytokines in macrophages. Finally, we found that inhibition of sphingosine 1 phosphate production is a potential mechanism whereby amitriptyline inhibited proinflammatory cytokines. Collectively, this study showed that amitriptyline inhibited NASH and atherosclerosis through modulation of sphingolipid metabolism in LDLR-/- mice, indicating that sphingolipid metabolism in macrophages plays a crucial role in the linkage of NASH and atherosclerosis.


Assuntos
Amitriptilina/farmacologia , Amitriptilina/uso terapêutico , Aterosclerose/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Esfingolipídeos/metabolismo , Esfingomielina Fosfodiesterase/antagonistas & inibidores , Compostos de Anilina/farmacologia , Animais , Aterosclerose/induzido quimicamente , Aterosclerose/metabolismo , Compostos de Benzilideno/farmacologia , Glicemia/metabolismo , Citocinas/biossíntese , Dieta Hiperlipídica , Regulação para Baixo , Resistência à Insulina , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores de LDL/deficiência , Receptores de LDL/genética
7.
Int J Mol Sci ; 20(24)2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31835809

RESUMO

Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments for Farber disease are clinically available, and affected patients have a severely shortened lifespan. We have recently reported a novel acid ceramidase deficiency model that mirrors the human disease closely. Acid sphingomyelinase is the enzyme that generates ceramide upstream of acid ceramidase in the lysosomes. Using our acid ceramidase deficiency model, we tested if acid sphingomyelinase could be a potential novel therapeutic target for the treatment of Farber disease. A number of functional acid sphingomyelinase inhibitors are clinically available and have been used for decades to treat major depression. Using these as a therapeutic for Farber disease, thus, has the potential to improve central nervous symptoms of the disease as well, something all other treatment options for Farber disease can't achieve so far. As a proof-of-concept study, we first cross-bred acid ceramidase deficient mice with acid sphingomyelinase deficient mice in order to prevent ceramide accumulation. Double-deficient mice had reduced ceramide accumulation, fewer disease manifestations, and prolonged survival. We next targeted acid sphingomyelinase pharmacologically, to test if these findings would translate to a setting with clinical applicability. Surprisingly, the treatment of acid ceramidase deficient mice with the acid sphingomyelinase inhibitor amitriptyline was toxic to acid ceramidase deficient mice and killed them within a few days of treatment. In conclusion, our study provides the first proof-of-concept that acid sphingomyelinase could be a potential new therapeutic target for Farber disease to reduce disease manifestations and prolong survival. However, we also identified previously unknown toxicity of the functional acid sphingomyelinase inhibitor amitriptyline in the context of Farber disease, strongly cautioning against the use of this substance class for Farber disease patients.


Assuntos
Lipogranulomatose de Farber/enzimologia , Esfingomielina Fosfodiesterase/deficiência , Ceramidase Ácida/metabolismo , Amitriptilina/farmacologia , Animais , Ceramidas/metabolismo , Citocinas/metabolismo , Lipogranulomatose de Farber/patologia , Camundongos Endogâmicos C57BL , Esfingomielina Fosfodiesterase/metabolismo , Análise de Sobrevida , Ganho de Peso/efeitos dos fármacos
8.
Pak J Pharm Sci ; 32(4(Supplementary)): 1855-1860, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31680083

RESUMO

Amitriptyline, an agent universally used to treat depression, has an anti-inflammatory activity and a potential for lowering inflammatory mediators. Periodontal diseases like gingivitis and periodontitis if untreated contributes to gingival tissue destruction and bone resorption. These diseases are commonly treated with conventional non-steroidal anti-inflammatory agents and antibiotics along with standard periodontal treatment. The aim of this experimental, observational and randomized clinical control trial was to evaluate the anti-inflammatory effects of amitriptyline on clinical parameters and on inflammatory biomarkers in patients of periodontal diseases by developing 1% oral gel and mouthwash formulations. 30 patients participated in the study were grouped in three categories, patients received standard conventional treatment, patients received gel treatment for four weeks after standard treatment, patients received mouthwash for four weeks after standard periodontal treatment. Results showed that amitriptyline gel and mouthwash in 1% formulation showed promising results by significantly reducing periodontal parameters and inflammatory biomarkers (p<0.001) as compared to standard treatment. Thus, we suggest that gel and mouthwash formulation of amitriptyline is highly efficacious in treating the periodontal diseases.


Assuntos
Amitriptilina/administração & dosagem , Antissépticos Bucais/administração & dosagem , Doenças Periodontais/tratamento farmacológico , Periodontite/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Biomarcadores/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Feminino , Gengiva/efeitos dos fármacos , Gengiva/metabolismo , Gengivite/tratamento farmacológico , Gengivite/metabolismo , Humanos , Masculino , Doenças Periodontais/metabolismo , Periodontite/metabolismo
9.
Dokl Biochem Biophys ; 488(1): 307-310, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31768847

RESUMO

Using Fura-2AM microfluorimetry, we have shown for the first time that sigma-1 receptor agonist-tricyclic antidepressant amitriptyline-significantly inhibits store-dependent Ca2+ entry, induced by endoplasmic Ca2+-ATPase inhibitors thapsigargin and cyclopiazonic acid, in rat peritoneal macrophages. The results suggest a possible involvement of sigma-1 receptors in the regulation of store-dependent Ca2+ entry in macrophages.


Assuntos
Amitriptilina/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Macrófagos Peritoneais/metabolismo , Receptores sigma/agonistas , Animais , Indóis/farmacologia , Transporte de Íons/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores sigma/metabolismo , Tapsigargina/farmacologia
10.
Ideggyogy Sz ; 72(7-8): 279-281, 2019 Jul 30.
Artigo em Húngaro | MEDLINE | ID: mdl-31517461

RESUMO

Introduction - Complex regional pain syndrome is a di-stressing neuropathic pain condition without known etiology and evidence based treatment. Case presentation - Here a posttraumatic severe case of complex regional pain syndrome is presented, successfully treated by amitriptyline monotherapy. Amitriptyline is one of the most effective evidence based treatments of peri-pheral diabetic neuropathic pain and other neuropathic pain syndromes. Discussion - Amitriptyline seems to be effective to decrease pain, autonomic and motor symptoms in chronic regional pain syndrome. Conclusion - Controlled trials may be warranted to test the effectiveness of amitriptyline in complex regional pain syndrome.


Assuntos
Amitriptilina/uso terapêutico , Analgésicos não Entorpecentes/uso terapêutico , Síndromes da Dor Regional Complexa/tratamento farmacológico , Neuralgia/tratamento farmacológico , Antidepressivos Tricíclicos/uso terapêutico , Doença Crônica , Humanos , Neuralgia/etiologia , Resultado do Tratamento
11.
Clin Chim Acta ; 499: 81-86, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31491368

RESUMO

BACKGROUND: Many clinical toxicology laboratories receive urine specimens in urine cups that contain point of care (POC) drug testing strips. We conducted this study to evaluate the effect on the stability of commonly measured drugs in the clinical toxicology laboratory when urine is exposed to POC urine drug testing cups. METHODS: Drug free urine was spiked with 85 drugs that were measured by a validated liquid chromatography mass spectrometry (LCMS) method after exposure to POC urine drug testing cups at ambient and 2-6 °C temperatures. Alterations ≥20% were defined as significant changes in the drugs concentration. RESULTS: Concentrations of amitriptyline, cyclobenzaprine, fentanyl, fluoxetine, flunitrazepam, nortriptyline, paroxetine, and sertraline were significantly reduced when urine specimens were stored inside POC urine drug testing cups for 24 h at ambient temperature. Storage of urine in urine chemistry dipsticks reduced the concentration of several drugs. When spiked urine was exposed to an increasing number of POC urine drug testing strips, the concentrations of some drugs were reduced in a dose-dependent manner. The drugs that were absorbed by POC urine drug testing strips were partially back extracted from the strips. CONCLUSION: Exposure of urine specimens to POC urine drug testing strips reduces the concentration of several drugs measured by LCMS method.


Assuntos
Testes Imediatos , Amitriptilina/análogos & derivados , Amitriptilina/urina , Cromatografia Líquida , Armazenamento de Medicamentos , Fentanila/urina , Flunitrazepam/urina , Fluoxetina/urina , Humanos , Espectrometria de Massas , Nortriptilina/urina , Paroxetina/urina , Sertralina/urina
12.
Life Sci ; 233: 116752, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31415770

RESUMO

AIMS: Few studies have compared the interaction of single and repeated administration of amitriptyline (amit) with the nitrergic system and glutamatergic system in the experimental model of neuropathic pain. We aimed to evaluate the antinociceptive effect of single and repeated administration of amit and to assess whether glutamate preceded inducible nitric oxide synthase (iNOS) inhibition as a mechanism of the analgesic effect of amit in the neuropathic model of pain. MATERIALS AND METHODS: Male Wistar rats were subjected to left sciatic nerve ligation. The effect of single (25 mg kg-1) and repeated (10 mg kg-1 daily for 3 weeks) administration of amit intraperitoneally (i.p.) alone or in combination with aminoguanidine (AG i.p., 100 mg kg-1 for 3 days, a selective iNOS inhibitor) and MK-801 (0.05 mg kg-1 i.p., NMDA antagonist) on resting paw posture and mechanical hyperalgesia were studied. Glutamate level and iNOS protein expression in hippocampus were detected. KEY FINDINGS: Single and repeated administration of amit alone or in combination with AG or MK-801 demonstrated a significant decrease in resting pain score and increase in the pain threshold. Both glutamate and nitrite levels decreased in the hippocampi of single and repeated amit + MK-801 groups. Immunohistochemistry showed a marked decrease in iNOS immunoreactivity in rats treated with single and repeated amit + MK-801. SIGNIFICANCE: Our results suggest that glutamate-dependent mechanisms are involved in the analgesic responses to amit administration. Importantly, glutamatergic system and its upstream nitrergic system play an important role in the antinociceptive action of amit.


Assuntos
Amitriptilina/farmacologia , Analgésicos não Entorpecentes/farmacologia , Ácido Glutâmico/metabolismo , Neuralgia/tratamento farmacológico , Nitrogênio/metabolismo , Amitriptilina/administração & dosagem , Analgésicos não Entorpecentes/administração & dosagem , Animais , Modelos Animais de Doenças , Masculino , Neuralgia/metabolismo , Neuralgia/patologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Limiar da Dor , Ratos , Ratos Wistar
13.
Biomed Chromatogr ; 33(12): e4679, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31415098

RESUMO

Amitriptyline (AMI) has been in use for decades in treating depression and more recently for the management of neuropathic pain. A highly sensitive and specific LC-tandem mass spectrometry method was developed for simultaneous determination of AMI, its active metabolite nortriptyline (NOR) and their hydroxy-metabolites in human serum, using deuterated AMI and NOR as internal standards. The isobaric E-10-hydroxyamitriptyline (E-OH AMI), Z-10-hydroxyamitriptyline (Z-OH AMI), E-10-hydroxynortriptyline (E-OH NOR) and Z-10-hydroxynortriptyline (Z-OH NOR), together with their parent compounds, were separated on an ACE C18 column using a simple protein precipitation method, followed by dilution and analysis using positive electrospray ionisation with multiple reaction monitoring. The total run time was 6 min with elution of E-OH AMI, E-OH NOR, Z-OH AMI, Z-OH NOR, AMI (+ deuterated AMI) and NOR (+ deuterated NOR) at 1.21, 1.28, 1.66, 1.71, 2.50 and 2.59 min, respectively. The method was validated in human serum with a lower limit of quantitation of 0.5 ng/mL for all analytes. A linear response function was established for the range of concentrations 0.5-400 ng/mL (r2 > .999). The practical assay was applied on samples from patients on AMI, genotyped for CYP2C19 and CYP2D6, to understand the influence of metaboliser status and concomitant medication on therapeutic drug monitoring.


Assuntos
Amitriptilina , Cromatografia Líquida/métodos , Nortriptilina , Espectrometria de Massas em Tandem/métodos , Idoso , Amitriptilina/análogos & derivados , Amitriptilina/sangue , Amitriptilina/metabolismo , Monitoramento de Medicamentos , Humanos , Limite de Detecção , Modelos Lineares , Nortriptilina/análogos & derivados , Nortriptilina/sangue , Nortriptilina/metabolismo , Reprodutibilidade dos Testes
14.
Clin Chim Acta ; 498: 6-10, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31374190

RESUMO

BACKGROUND: External quality assessment schemes (EQAS) can provide important information regarding accuracy and comparability of different measurement methods if the sample matrices are composed of commutable material. The aim of this study was to assess the commutability of different matrices for the material used in an EQAS for amitriptyline and nortriptyline. METHODS: Proficiency testing material (PTM) and patient samples containing amitriptyline and nortriptyline were prepared, collected, pooled, and distributed to participating laboratories for analysis. Low, medium and high concentrations of both drugs in liquid pooled human, lyophilized human and lyophilized bovine serum were tested in this study. The measurement deviation of the PTM results to the patient serum regression line were normalized by dividing trough the average within-laboratory SD (SDwl) derived from the results reported in the official EQAS, resulting in a relative residual. The commutability decision limit was set at 3 SDwl. RESULTS: With 10 laboratories participating in this study, 45 laboratory couples were formed. All matrix types delivered several relative residuals outside the commutability decision limit. The number and the magnitude of relative residuals for both drugs were lower for liquid human sera as compared to lyophilized human and bovine sera. CONCLUSIONS: The PTM used for amitriptyline and nortriptyline is preferably prepared with human serum, although not all relative residuals are within the commutability decision limit.


Assuntos
Amitriptilina/sangue , Ensaio de Proficiência Laboratorial/métodos , Nortriptilina/sangue , Inibidores da Captação Adrenérgica/sangue , Animais , Antidepressivos Tricíclicos/sangue , Bovinos , Liofilização , Humanos , Laboratórios/normas , Modelos Lineares , Controle de Qualidade
15.
Int J Mol Sci ; 20(16)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31443157

RESUMO

Active rebuilding, stabilizing, and maintaining the lipid barrier of the skin is an encouraging disease management and care concept for dry skin, atopic dermatitis (eczema, neurodermatitis), and psoriasis. For decades, corticosteroids have been the mainstay of topical therapy for atopic dermatitis; however, innovations within the scope of basic therapy are rare. In (extremely) dry, irritated, or inflammatory skin, as well as in lesions, an altered (sphingo)lipid profile is present. Recovery of a balanced (sphingo)lipid profile is a promising target for topical and personalized treatment and prophylaxis. New approaches for adults and small children are still lacking. With an ingenious combination of commonly used active ingredients, it is possible to restore and reinforce the dermal lipid barrier and maintain refractivity. Lysosomes and ceramide de novo synthesis play a key role in attenuation of the dermal lipid barrier. Linoleic acid in combination with amitriptyline in topical medication offers the possibility to relieve patients affected by dry and itchy skin, mild to moderate atopic dermatitis lesions, and eczemas without the commonly occurring serious adverse effects of topical corticosteroids or systemic antibody administration.


Assuntos
Ceramidas/metabolismo , Dermatite Atópica/metabolismo , Amitriptilina/uso terapêutico , Animais , Antioxidantes/metabolismo , Apoptose/fisiologia , Humanos , Ácido Linoleico/uso terapêutico , Esfingolipídeos/metabolismo
16.
J Surg Res ; 244: 1-8, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31279258

RESUMO

BACKGROUND: The pathophysiology behind the subacute but persistent hypercoagulable state after traumatic brain injury (TBI) is poorly understood but contributes to morbidity induced by venous thromboembolism. Because platelets and their microvesicles have been hypothesized to play a role in post-traumatic hypercoagulability, administration of commonly used agents may ameliorate this coagulability. We hypothesized that utilization of aspirin, ketorolac, amitriptyline, unfractionated heparin, or enoxaparin would modulate the platelet aggregation response after TBI. METHODS: Concussive TBI was induced by weight drop. Mice were then randomized to receive aspirin, ketorolac, amitriptyline, heparin, enoxaparin, or saline control at 2 and 8 h after TBI. Mice were sacrificed at 6 or 24 h after injury to determine coagulability by rotational thromboelastometry (ROTEM), platelet function testing with impedance aggregometry, and microvesicle enumeration. Platelet sphingolipid metabolites were analyzed by mass spectrometry. RESULTS: ROTEM demonstrated increased platelet contribution to maximum clot firmness at 6 h after TBI in mice that received aspirin or amitriptyline, but this did not persist at 24 h. By contrast, adenosine diphosphate- and arachidonic acid-induced platelet aggregation at 6 h was significantly lower in mice receiving ketorolac, aspirin, and amitriptyline compared with mice receiving saline at 6 h after injury and only arachidonic acid-initiated platelet aggregation was decreased by aspirin at 24 h. There were no differences in microvesicle production at either time point. Platelet sphingosine-1-phosphate levels were decreased at 6 h in the group receiving amitriptyline and increased at 24 h along with platelet ceramide levels at 24 h in the amitriptyline group. CONCLUSION: After TBI, amitriptyline decreased platelet aggregability and increased contribution to clot in a manner similar to aspirin. The amitriptyline effects on platelet function and sphingolipid metabolites may represent a possible role of the acid sphingomyelinase in the hypercoagulability observed after injury. In addition, inhibition of platelet reactivity may be an underappreciated benefit of low molecular weight heparins, such as enoxaparin.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Inibidores da Agregação de Plaquetas/administração & dosagem , Tromboembolia Venosa/prevenção & controle , Amitriptilina/administração & dosagem , Animais , Aspirina/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/fisiopatologia , Modelos Animais de Doenças , Enoxaparina/administração & dosagem , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Agregação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/fisiologia , Testes de Função Plaquetária , Esfingolipídeos/metabolismo , Tromboelastografia , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia
17.
Bull Exp Biol Med ; 167(3): 356-362, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31346879

RESUMO

The pharmacokinetics of two fluoxetine capsulated dosage forms and two amitriptyline tablet forms after a single oral intake was studied in dogs and healthy volunteers. High significant correlations were detected between plasma concentrations of fluoxetine (r=0.96, p<0.00001, n=11) and amitriptyline (r=0.78, p<0.0224, n=8) in dogs and volunteers. A correlation of medium strength (though insignificant) was detected between nortriptyline concentrations in the plasma of dogs and volunteers (r=0.69, p<0.199, n=5). The bioavailability parameters of the test drugs in dogs and volunteers did not differ. Similar trends of fluoxetine and amitriptyline pharmacokinetic parameters were revealed in volunteers and animals. Methods for extrapolation of experimental pharmacokinetics parameters of fluoxetine and amitriptyline obtained on dogs for humans are proposed and validated.


Assuntos
Amitriptilina/farmacocinética , Fluoxetina/farmacocinética , Nortriptilina/sangue , Administração Oral , Amitriptilina/administração & dosagem , Amitriptilina/sangue , Animais , Disponibilidade Biológica , Cães , Feminino , Fluoxetina/administração & dosagem , Fluoxetina/sangue , Humanos , Masculino
18.
Ann Pharm Fr ; 77(5): 418-425, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31296331

RESUMO

Cyclobenzaprine hydrochloride, a skeletal muscle relaxant has been determined using an ecofriendly micellar HPLC method in its pure form and tablets. The chromatographic determination was performed using C8 monolithic column (100mm×4.6mm i.d., 5µm particle size) and micellar eluent which was composed of sodium dodecyl sulfate (0.15M), n-propanol (15%), 0.02M orthophosphoric acid (pH 4.5) and 0.3% triethylamine using UV detection of effluent was set at 225nm. The calibration plot showed good linearity over concentration range from 2-40µg/mL. The assay results were statistically validated for linearity, accuracy, precision and specificity according to ICH guidelines. Additionally, regarding USP guidelines, the uniformity of tablets content and in-vitro dissolution test of the tablets was tested using the proposed method. Simple and rapid applicability of the developed method allowed determination of the drug in its pure and tablet dosage forms. Moreover, the major advantage of micellar HPLC technique is to determine the drug in biological fluids without prior extraction steps. Depending on this, the estimation of cyclobenzaprine in spiked human urine was so simple without traditional tedious procedures. The proposed method offers the advantages of sensitivity and simplicity in addition to short analysis time which didn't exceed 6 minutes.


Assuntos
Amitriptilina/análogos & derivados , Química Verde/métodos , Relaxantes Musculares Centrais/análise , Amitriptilina/análise , Amitriptilina/urina , Cromatografia Líquida de Alta Pressão , Suco Gástrico/química , Guias como Assunto , Humanos , Limite de Detecção , Micelas , Relaxantes Musculares Centrais/urina , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Solubilidade , Espectrofotometria Ultravioleta , Comprimidos/análise
19.
Braz J Cardiovasc Surg ; 34(3): 290-296, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31310467

RESUMO

OBJECTIVE: In this study, we aimed to examine the effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts in coronary artery bypass graft surgeries. METHODS: 59 patients (40 males and 19 females; mean age 65.1 years, distribution: 45-84 years) who had coronary artery bypass graft surgery between February 2014 and May 2016 were included in the study. After the saphenous vein grafts with intact and denuded endothelium were precontracted with 3×10-6M phenylephrine, amitriptyline, fluoxetine and tranylcypromine were cumulatively added to isolated organ baths in the range of 10-11-3x10-5M, while venlafaxine was added in the range of 10-9-3×10-5M. Then, the antidepressant-induced relaxation responses were recorded isometrically. RESULTS: While the relaxation response of amitriptyline at -6.42 (Log M) was 74.6%, the response at -6.32 (Log M) was 75.5%. While the relaxation response at -6.46 (Log M) of fluoxetine was 68.02%, the response at -6.02 (Log M) was 72.12%. While the relaxation response of tranylcypromine at -7.53 (Log M) was 61.13%, the response at -7.23 (Log M) was 65.53%. While the relaxation response of venlafaxine at -6.21 (Log M) was 29.98%, the response at -5.90 (Log M) was 32.96%. CONCLUSION: The maximum relaxation at minimum and maximum therapeutic concentrations was obtained with amitriptyline, fluoxetine and tranylcypromine, and the minimum relaxation was obtained with venlafaxine. The relaxation responses were independent of the endothelium.


Assuntos
Amitriptilina/farmacologia , Antidepressivos/farmacologia , Fluoxetina/farmacologia , Veia Safena/efeitos dos fármacos , Veia Safena/transplante , Tranilcipromina/farmacologia , Cloridrato de Venlafaxina/farmacologia , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Ponte de Artéria Coronária/métodos , Endotélio Vascular/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/efeitos dos fármacos , Valores de Referência , Transplantes/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos
20.
Ann Glob Health ; 85(1)2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31298824

RESUMO

BACKGROUND: The dearth of information on the economic cost of childhood poisoning in sub-Saharan Africa necessitated this study. OBJECTIVE: This study has investigated the prevalence of childhood drug and non-drug poisoning, treatment modalities and economic costs in Nigeria. METHOD: A retrospective study of childhood drug and non-drug poisoning cases from January 2007 to June 2014 in the University of Port Harcourt Teaching Hospital (UPTH), Port Harcourt, Nigeria was carried out. Medical records were analysed for demographic and aetiological characteristics of poisoned children (0-14 years of age), as well as fiscal impact of poisoning cases. FINDINGS: Of the 100 poisoned patients, 46% were male and 54% female, with female/male ratio of 1.17:1. Most of the children were under five years of age. Paracetamol, amitriptyline, chlorpromazine, ferrous sulphate, kerosene, organophosphates, carbon monoxide, snake bite, alcohol and rodenticides were involved in the poisoning. The average cost of poison management per patient was about $168, which is high given the economic status of Nigeria. CONCLUSION: Childhood poisoning is still a significant cause of morbidity among children in Nigeria and accounts for an appreciable amount of health spending, therefore preventive strategies should be considered.


Assuntos
Etanol/envenenamento , Custos de Cuidados de Saúde , Envenenamento/economia , Envenenamento/epidemiologia , Mordeduras de Serpentes/epidemiologia , Acetaminofen/envenenamento , Adolescente , Distribuição por Idade , Amitriptilina/envenenamento , Analgésicos não Entorpecentes/envenenamento , Antipsicóticos/envenenamento , Intoxicação por Monóxido de Carbono/economia , Intoxicação por Monóxido de Carbono/epidemiologia , Criança , Pré-Escolar , Clorpromazina/envenenamento , Feminino , Compostos Ferrosos/envenenamento , Humanos , Lactente , Recém-Nascido , Querosene/envenenamento , Tempo de Internação , Masculino , Nigéria/epidemiologia , Intoxicação por Organofosfatos/economia , Intoxicação por Organofosfatos/epidemiologia , Envenenamento/etiologia , Prevalência , Estudos Retrospectivos , Rodenticidas/envenenamento , Distribuição por Sexo , Mordeduras de Serpentes/economia
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