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1.
AAPS PharmSciTech ; 22(3): 95, 2021 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-33686480

RESUMEN

Vulvodynia is a chronic clinical condition associated with vulvar pain that can impair the sexual, social, and psychological life of women. There is a need for more research to develop novel strategies and therapies for the treatment of vulvodynia. Vulvodynia in experimental animal models induced via infections, allergens, and diabetes are tedious and with lessor induction rate. The objective of the study was to explore the possibility of inducing vulvodynia using a chemotherapeutic agent in a rodent model. Paclitaxel is commonly used in treating breast and ovarian cancer, whose dose-limiting side effect is peripheral neuropathy. Studies have shown that peripheral neuropathy is one of the etiologies for vulvodynia. Following paclitaxel administration (2 mg/kg i.p.), the intensity of vulvar hypersensitivity was assessed using a series of von Frey filaments (0.008 to 1 g) to ensure the induction of vulvodynia. Vulvodynia was induced from day 2 and was well sustained for 11 days. Furthermore, the induced vulvodynia was validated by investigating the potentiation of a flinch response threshold, upon topical application and systemic administration of gabapentin, a commonly used medication for treating neuropathic pain. The results demonstrate that vulvodynia was induced due to administration of paclitaxel. The fact that chemotherapeutic agent-induced vulvodynia was responsive to topical and parenterally administered gabapentin provides validity to the model. The study establishes a new, relatively simple and reliable animal model for screening drug molecules for vulvar hypersensitivity.


Asunto(s)
Antineoplásicos/efectos adversos , Vulvodinia/inducido químicamente , Analgésicos/uso terapéutico , Animales , Antineoplásicos Fitogénicos/efectos adversos , Modelos Animales de Enfermedad , Femenino , Gabapentina/uso terapéutico , Neuralgia/inducido químicamente , Neuralgia/psicología , Paclitaxel/efectos adversos , Dimensión del Dolor/efectos de los fármacos , Ratas , Ratas Sprague-Dawley
2.
BMJ Case Rep ; 14(3)2021 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-33731393

RESUMEN

Establishing accurate symptomatology associated with novel diseases such as COVID-19 is a crucial component of early identification and screening. This case report identifies an adult patient with a history of clotting dysfunction presenting with rare cutaneous manifestations of COVID-19, known as 'COVID-19 toes'', previously described predominantly in children. Additionally, this patient presented with possible COVID-associated muscle spasticity of the lower limbs, as well as a prolonged and atypical timeline of COVID-19 infection. The rare occurrence of 'COVID-19 toes'' in this adult patient suggests that her medical history could have predisposed her to this symptom. This supports the coagulopathic hypothesis of this manifestation of COVID-19 and provides possible screening questions for patients with a similar history who might be exposed to the virus. Additionally, nervous system complaints associated with this disease are rare and understudied, so this novel symptom may also provide insight into this aspect of SARS-CoV-2.


Asunto(s)
/complicaciones , Enfermedades del Pie/etiología , Espasticidad Muscular/etiología , Analgésicos/uso terapéutico , Vesícula/tratamiento farmacológico , Vesícula/etiología , Vesícula/patología , Femenino , Enfermedades del Pie/tratamiento farmacológico , Enfermedades del Pie/patología , Gabapentina/uso terapéutico , Humanos , Persona de Mediana Edad , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/patología , Dedos del Pie/patología
3.
Value Health ; 24(2): 196-205, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33518026

RESUMEN

OBJECTIVES: Little is known about relationships between opioid- and gabapentinoid-use patterns and healthcare expenditures that may be affected by pain management and risk of adverse outcomes. This study examined the association between patients' opioid and gabapentinoid prescription filling/refilling trajectories and direct medical expenditures in US Medicare. METHODS: This cross-sectional study included a 5% national sample (2011-2016) of fee-for-service beneficiaries with fibromyalgia, low back pain, neuropathy, or osteoarthritis newly initiating opioids or gabapentinoids. Using group-based multitrajectory modeling, this study identified patients' distinct opioid and gabapentinoid (OPI-GABA) dose and duration patterns, based on standardized daily doses, within a year of initiating opioids and/or gabapentinoids. Concurrent direct medical expenditures within the same year were estimated using inverse probability of treatment weighted multivariable generalized linear regression, adjusting for sociodemographic and health status factors. RESULTS: Among 67 827 eligible beneficiaries (mean age ± SD = 63.6 ± 14.8 years, female = 65.8%, white = 77.1%), 11 distinct trajectories were identified (3 opioid-only, 4 gabapentinoid-only, and 4 concurrent OPI-GABA trajectories). Compared with opioid-only early discontinuers ($13 830, 95% confidence interval = $13 643-14 019), gabapentinoid-only early discontinuers and consistent low-dose and moderate-dose gabapentinoid-only users were associated with 11% to 23% lower health expenditures (adjusted mean expenditure = $10 607-$11 713). Consistent low-dose opioid-only users, consistent high-dose opioid-only users, consistent low-dose OPI-GABA users, consistent low-dose opioid and high-dose gabapentinoid users, and consistent high-dose opioid and moderate-dose gabapentinoid users were associated with 14% to 106% higher healthcare expenditures (adjusted mean expenditure = $15 721-$28 464). CONCLUSIONS: Dose and duration patterns of concurrent OPI-GABA varied substantially among fee-for-service Medicare beneficiaries. Consistent opioid-only users and all concurrent OPI-GABA users were associated with higher healthcare expenditures compared to opioid-only discontinuers.


Asunto(s)
Analgésicos Opioides/uso terapéutico , Analgésicos/uso terapéutico , Gabapentina/uso terapéutico , Medicare/economía , Dolor/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Analgésicos/administración & dosificación , Analgésicos Opioides/administración & dosificación , Estudios Transversales , Utilización de Medicamentos , Planes de Aranceles por Servicios/economía , Femenino , Gabapentina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Estados Unidos
5.
Aust Vet J ; 99(3): 86-88, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33398883

RESUMEN

A 38-year-old white rhinoceros bull (Ceratotherium simum) was treated with phenylbutazone over a period of four years for chronic osteoarthritic and neuropathic pain of the thoracic limbs. Initially the lameness was sporadic and responded well to phenylbutazone (4 mg/kg PO SID). The lameness increased in severity during the winter months. Four years after treatment was initiated, there was an increase in the severity and incidence of the lameness. Analgesia was augmented by the addition of non-conventional analgesic drugs. Pentosan polysulfate was administered IM at 3 mg/kg once a week for two treatments and thereafter monthly when possible. Gabapentin was used at 8 mg/kg but produced ataxia and anorexia. The dose was reduced to 4-5 mg/kg PO SID. Amantadine (3 mg/kg PO BID) was added to the multimodal analgesia and produced a significant improvement in the clinical lameness. Chronic inflammation was monitored using both automated and manual fibrinogen methods. Eventually the rhinoceros was euthanized on humane grounds when treatment was unable to produce suitable clinical relief.


Asunto(s)
Analgesia , Dolor Crónico , Amantadina/uso terapéutico , Analgesia/veterinaria , Animales , Bovinos , Dolor Crónico/veterinaria , Eutanasia Animal , Gabapentina/uso terapéutico , Masculino , Poliéster Pentosan Sulfúrico , Perisodáctilos , Fenilbutazona
6.
BMC Neurol ; 21(1): 39, 2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33509130

RESUMEN

BACKGROUND: Ramsay Hunt syndrome (RHS) is caused by a reactivation of varicella-zoster virus (VZV) infection, and it is characterized by the symptoms of facial paralysis, otalgia, auricular rash, and/or an oral lesion. Elderly patients or immunocompromised patients, deep pain at the initial visit and no prompt treatment are significant predictors of postherpetic neuralgia (PHN). When PHN occurs, especially involved cranial polyneuropathy, multiple modalities should be administered for patients with the intractable PHN. The use of thermography in the follow-up of PHN secondary to RHS with multicranial nerve involvement has not yet been described yet in the literature. CASE PRESENTATION: The patient was a 78-year-old man with the chief complaint of a 3-month history of PHN secondary to RHS with polycranial nerve (V, VII, VIII, and IX) involvement. Multimodality therapy with oral gabapentin, pulsed radiofrequency (PRF) application to the Gasserian ganglion for pain in the trigeminal nerve region, linear-polarized near-infrared light irradiation for pain in the facial nerve region, and 2% lidocaine spray for pain in the glossopharyngeal nerve region was used to the treat patient, and follow-up evaluations included thermography. This comprehensive treatment obviously improved the quality of life, resulting in considerable pain relief, as indicated by a decrease in the numerical rating scale (NRS) score from 9 to 3 and a decrease in thermal imaging temperature from higher to average temperature on the ipsilateral side compared with the contralateral side. Lidocaine spray on the tonsillar branches of the glossopharyngeal nerve resulted in an improvement in odynophagia, and the NRS score decreased from 9 to 0 for glossopharyngeal neuralgia after three applications. CONCLUSION: Although the use of thermography in the follow-up of RHS with multiple cranial nerve (V, VII, VIII, and IX) involvement is very rare, in this patient, thermal imaging showed the efficacy of combination therapy (oral gabapentin, 2% lidocaine sprayed, PRF application and linear-polarized near-infrared light irradiation) and that is a good option for treatment.


Asunto(s)
Herpes Zóster Ótico/complicaciones , Herpes Zóster Ótico/diagnóstico , Neuralgia Posherpética/diagnóstico , Neuralgia Posherpética/etiología , Termografía/métodos , Anciano , Analgésicos/uso terapéutico , Anestésicos Locales/uso terapéutico , Estudios de Seguimiento , Gabapentina/uso terapéutico , Humanos , Lidocaína/uso terapéutico , Masculino , Neuralgia Posherpética/terapia , Fototerapia/métodos , Tratamiento de Radiofrecuencia Pulsada/métodos
7.
Cochrane Database Syst Rev ; 1: CD001415, 2021 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-33434292

RESUMEN

BACKGROUND: This is an updated version of the Cochrane Review previously published in 2018. Epilepsy is a common neurological disorder characterised by recurrent seizures. Most people with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug, but up to 30% develop drug-resistant epilepsy, especially people with focal seizures. In this review, we summarised the evidence from randomised controlled trials (RCTs) of gabapentin, when used as an add-on treatment for drug-resistant focal epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of gabapentin when used as an add-on treatment for people with drug-resistant focal epilepsy. SEARCH METHODS: For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid) on 11 August 2020. CRS Web includes randomised or quasi-randomised, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups including Epilepsy. We imposed no language restrictions. SELECTION CRITERIA: Randomised, placebo-controlled, double-blind, add-on trials of gabapentin in people with drug-resistant focal epilepsy. We also included trials using an active drug control group or comparing different doses of gabapentin. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: seizure frequency, seizure freedom, treatment withdrawal (any reason) and adverse effects. Primary analyses were intention-to-treat. We also undertook sensitivity best-case and worst-case analyses. We estimated summary risk ratios (RR) for each outcome and evaluated dose-response in regression models. MAIN RESULTS: We identified no new studies for this update, therefore, the results and conclusions are unchanged. In the previous update of this review, we combined data from six trials in meta-analyses of 1206 randomised participants. The overall risk ratio (RR) for reduction in seizure frequency of 50% or more compared to placebo was 1.89 (95% confidence interval (CI) 1.40 to 2.55; 6 studies, 1206 participants; moderate-certainty evidence). Dose regression analysis (for trials in adults) showed increasing efficacy with increasing dose, with 25.3% (95% CI 19.3 to 32.3) of people responding to gabapentin 1800 mg compared to 9.7% on placebo, a 15.5% increase in response rate (95% CI 8.5 to 22.5). The RR for treatment withdrawal compared to placebo was 1.05 (95% CI 0.74 to 1.49; 6 trials, 1206 participants; moderate-certainty evidence). Adverse effects were significantly associated with gabapentin compared to placebo. RRs were as follows: ataxia 2.01 (99% CI 0.98 to 4.11; 3 studies, 787 participants; low-certainty evidence), dizziness 2.43 (99% CI 1.44 to 4.12; 6 studies, 1206 participants; moderate-certainty evidence), fatigue 1.95 (99% CI 0.99 to 3.82; 5 studies, 1161 participants; low-certainty evidence) and somnolence 1.93 (99% CI 1.22 to 3.06; 6 studies, 1206 participants; moderate-certainty evidence). There was no evidence of a difference for the adverse effects of headache (RR 0.79, 99% CI 0.46 to 1.35; 6 studies, 1206 participants; moderate-certainty evidence) or nausea (RR 0.95, 99% CI 0.52 to 1.73; 4 trials, 1034 participants; moderate-certainty evidence). Overall, the studies were at low to unclear risk of bias due to information on each risk of bias domain not being available. We judged the overall certainty of the evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide CIs. AUTHORS' CONCLUSIONS: Gabapentin has efficacy as an add-on treatment in people with drug-resistant focal epilepsy, and seems to be fairly well-tolerated. However, the trials reviewed were of relatively short duration and provide no evidence for the long-term efficacy of gabapentin beyond a three-month period. The results cannot be extrapolated to monotherapy or to people with other epilepsy types. Further trials are needed to assess the long-term effects of gabapentin, and to compare gabapentin with other add-on drugs.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Epilepsia Refractaria/tratamiento farmacológico , Epilepsias Parciales/tratamiento farmacológico , Gabapentina/uso terapéutico , Ácido gamma-Aminobutírico/uso terapéutico , Adulto , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Niño , Quimioterapia Combinada/métodos , Gabapentina/administración & dosificación , Gabapentina/efectos adversos , Humanos , Análisis de Intención de Tratar , Pacientes Desistentes del Tratamiento/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto
10.
11.
J Chromatogr A ; 1637: 461844, 2021 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-33445033

RESUMEN

Charged aerosol detection (CAD) is an universal technique in liquid chromatography that is increasingly used for the quality control of drugs. Consequently, it has found its way into compendial monographs promoted by its simple and robust application. However, the response of CAD is inherently nonlinear due to its principle of function. Thus, easy and rapid linearization procedures, in particular regarding compendial applications, are highly desirable. One effective approach to linearize the detector's signal makes use of the built-in power function value (PFV) setting of the instrument. The PFV is basically a multiplication factor to the power law exponent of the equation describing the CAD's response, thereby altering the detector's signal output to optimize the quasi-linear range of the response curve. The experimental optimization of the PFV for a series of analytes is a time-consuming process, limiting the practicability of this approach. Here, two independent approaches for the determination of the optimal PFV based on an empirical model and a mathematical transformation in each case, are evaluated. Both approaches can be utilized to predict the optimal PFV for each analyte solely based on the experimental results of a series of calibration standards obtained at a single PFV. The approaches were applied to the HPLC-UV-CAD impurity analysis of the drug gabapentin to improve the observed nonlinear response of the impurities in the range of interest. The predicted optimal PFV of both approaches were in good agreement with the experimentally obtained optimal PFV of the analytes. As a result, the accuracy of the method was significantly improved when using the optimal PFV (90 - 105% versus 81 - 115% recovery rate for quantitation by either single-point calibration or linear regression) for the majority of the analytes. The final method with a PFV adjusted to 1.30 was validated with respect to ICH guideline Q2(R1).


Asunto(s)
Aerosoles/análisis , Cromatografía Líquida de Alta Presión/instrumentación , Calibración , Gabapentina/química , Ácido Mirístico/química , Ácido Palmítico/química , Control de Calidad , Reproducibilidad de los Resultados , Programas Informáticos
12.
Life Sci ; 267: 118940, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33359747

RESUMEN

AIMS: This study aimed to investigate the potential protective effects of vitamin E against gabapentin-induced chronic liver and kidney injury associated with the inhibition of biomarkers of apoptosis and tissue injury. MATERIALS AND METHODS: Four groups of adult male rats were included; control, gabapentin (100 mg/kg/day), Vitamin E (80 mg/kg/day), and a combination of gabapentin and Vitamin E for 90 days. Serum levels of AST, ALT, LDH, ALP, urea, and creatinine were measured in addition to malondialdehyde (MDA), and reduced glutathione (GSH) tissue levels. P53 gene expression, histological, and immunohistochemical examinations were performed in liver and kidney tissue samples. KEY FINDINGS: Gabapentin increased AST, ALT, LDH, ALP, urea, creatinine, MDA, and p53 gene expression and it reduced GSH. Moreover, gabapentin administration caused structural changes in the hepatic and renal architecture with a weak Periodic acid-Schiff (PAS) reaction that reflects glycogen deposition in the liver and kidney and a positive immunoreaction for BCL2-associated X protein (BAX) that reflects activated apoptosis. Vitamin E significantly (p<0.05) reversed the biochemical alterations associated with chronic gabapentin administration and improved the histopathological picture of hepatic and renal tissue with a partial inhibition of BAX. SIGNIFICANCE: Chronic administration of gabapentin causes hepatic and renal impairments, which is ameliorated by Vitamin E; possibly due to the inhibition of biomarkers of apoptosis and tissue injury.


Asunto(s)
Gabapentina/efectos adversos , Vitamina E/farmacología , Animales , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Biomarcadores/metabolismo , Creatinina/metabolismo , Gabapentina/metabolismo , Gabapentina/toxicidad , Glutatión/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Sustancias Protectoras/farmacología , Ratas , Ratas Wistar , Vitamina E/metabolismo
13.
An Acad Bras Cienc ; 92(4): e20191155, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33331440

RESUMEN

Gabapentin has antihyperalgesic action, decreasing central sensitization in neuropathic pain models; this effect depends on the mobilization of endogenous pain control pathways. This study aims to investigate the contribution of the endocannabinoid system to the antihyperalgesic action of gabapentin. Mus musculus Swiss, male, were submitted to PSL. On the 7th and 14th days post PSL, different groups were treated with CB1 receptor antagonist, AM281 via i.t. (2 µg/5 µl) or i.pl. (10 µg/20 µl) or CB2, AM630 via i.t. (5 µL i.t.) or (20 µL i.p.) and 15 min after gabapentin (30 mg / kg orally). Mechanical hyperalgesia was measured by the frequency of paw removal by the von Frey monofilament. Gabapentin demonstrated antihypernociceptive action, which was attenuated in animals pretreated with AM281 in both the i.t. and i.pl routes on the 7th and 14th days, differently from animals pretreated with AM630 that did not achieve a significant reduction with administration i.t. only on the 14th day with administration i.pl. The results show that endocannabinoid system contributes to the antihyperalgesic action of gabapetin in neuropathic pain by PSL, suggesting participation in the medullary and peripheral levels of CB1 receptors, and the peripheral performance of CB2 receptors.


Asunto(s)
Endocannabinoides , Neuralgia , Analgésicos/uso terapéutico , Animales , Modelos Animales de Enfermedad , Gabapentina , Hiperalgesia/tratamiento farmacológico , Masculino , Ratones , Neuralgia/tratamiento farmacológico , Nervio Ciático
14.
BMJ Case Rep ; 13(12)2020 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-33334741

RESUMEN

A 23-year-old woman diagnosed with type 1 diabetes mellitus in 2011 came to our outpatient office because of an inability to walk correctly. She was under a basal bolus insulin regimen. In the summer of 2016, she experienced a rapid improvement in her glycaemic control. A few weeks later, she started to complain of a severe burning pain in the soles of her feet (pain score 10/10). Neither macrovascular nor microvascular complications were detected. The patient was forced to walk barefoot due to an intense pain using shoes or socks and used to soak her feet in water for several hours daily. She also developed severe intolerance to environmental heat, both indoors and outdoors. A diagnosis of treatment-induced diabetic neuropathy was made. The patient was admitted to a general ward to start pain therapy. After a 6-month course of different neuropathic pain drugs, the patient was able to walk autonomously again.


Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Neuropatías Diabéticas/diagnóstico , Insulina/efectos adversos , Neuralgia/diagnóstico , Diabetes Mellitus Tipo 1/complicaciones , Neuropatías Diabéticas/inducido químicamente , Neuropatías Diabéticas/tratamiento farmacológico , Dibenzazepinas/administración & dosificación , Quimioterapia Combinada/métodos , Electromiografía , Femenino , Pie , Gabapentina/administración & dosificación , Humanos , Neuralgia/inducido químicamente , Neuralgia/tratamiento farmacológico , Tramadol/administración & dosificación , Resultado del Tratamiento , Prueba de Paso , Adulto Joven
16.
JAMA Netw Open ; 3(12): e2031647, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-33372975

RESUMEN

Importance: The use of gabapentinoids in multimodal postoperative analgesia is increasing; however, when coadministered with opioids, these drugs may potentiate central nervous system and respiratory depression. Objective: To evaluate the association between perioperative coadministration of gabapentinoids and opioids with inpatient opioid-related adverse events in surgical patients. Design, Setting, and Participants: This cohort study used propensity score trimming, stratification, and weighting of adults admitted for a major surgery between October 2007 and December 2017 who were treated with opioids on the day of surgery and included in the Premier Research database. Data analysis was conducted from February to April 2020. Exposure: Gabapentinoids (gabapentin or pregabalin) coadministered with opioids starting the day of surgery vs opioid therapy without gabapentinoids. Main Outcomes and Measures: Primary outcome was opioid overdose. Secondary outcomes included respiratory complications, unspecified adverse effects of opioid use, and a composite of these 3 outcomes. Patients were followed up for as long as 30 days from the day of surgery until deviation from the initial treatment regimen or discharge. Results: Gabapentinoids with opioids were administered to 892 484 of 5 547 667 eligible admissions (16.1%; mean [SD] age, 63.5 [11.8] years; 353 315 [39.6%] men). Among the 4 655 183 patients who received opioids only, the mean (SD) age was 63.7 (14.7) years, and 1 913 284 (41.1%) were men. Overall, 441 overdose events were identified, with absolute risks of 1.4 per 10 000 patients with gabapentinoid exposure and 0.7 per 10 000 patients receiving opioids only. Following propensity score trimming, the cohort included 737 383 patients exposed to gabapentinoids and 3 002 480 patients receiving opioids only. The primary analysis yielded the adjusted hazard ratio of 1.95 (95% CI, 1.49-2.55), and the number needed to treat for an additional overdose to occur was 16 914 patients (95% CI, 11 556-31 537 patients). Adjusted hazard ratios for secondary outcomes were 1.68 (95% CI, 1.59-1.78) for respiratory complications, 1.77 (95% CI, 1.61-1.93) for unspecified adverse effects of opioids, and 1.70 (95% CI, 1.62-1.79) for the composite outcome. The results were consistent across sensitivity analyses and subgroups identified by key clinical factors. Conclusions and Relevance: In this real-world cohort study of patients who underwent major surgery, concomitant use of gabapentinoids with opioids was associated with increased risk of opioid overdose and other opioid-related adverse events; however, the absolute risk of adverse events was low.


Asunto(s)
Analgésicos Opioides/efectos adversos , Sobredosis de Droga/epidemiología , Gabapentina/efectos adversos , Trastornos Relacionados con Opioides/epidemiología , Dolor Postoperatorio/tratamiento farmacológico , Anciano , Analgésicos Opioides/administración & dosificación , Sobredosis de Droga/etiología , Quimioterapia Combinada , Femenino , Gabapentina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Trastornos Relacionados con Opioides/etiología , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Factores de Riesgo , Estados Unidos
17.
Am J Vet Res ; 81(12): 973-984, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33251843

RESUMEN

OBJECTIVE: To determine the effects of gabapentin, tramadol, and meloxicam on tear production, intraocular pressure (IOP), pupillary diameter, tear break-up time, and corneal touch threshold in healthy dogs when given orally for 3 days. ANIMALS: 9 healthy research Beagles. PROCEDURES: A randomized, blinded, case-crossover study with a 6-sequence, 3-treatment, and 3-period design was performed. A 7-day acclimation period was followed by 3 treatment phases, each with a 3-day treatment period followed by a 7-day washout period for 3 different drugs. Block randomization was used to group dogs for treatments with drug A (gabapentin), B (tramadol), or C (meloxicam). Measurements of tear production, IOP, pupillary diameter, tear break-up time, and corneal touch threshold were performed on a schedule. A generalized mixed-effects linear regression model was created for each ocular variable, accounting for repeated measures within individuals. RESULTS: Intraocular pressure was the only variable to have differed substantially between the first 5 and last 2 days of the acclimation period. When treatment phase, day, time of day, dog identification, baseline value, and eye were accounted for, the mean IOP was lower for dogs during treatment phases with gabapentin or tramadol, compared with meloxicam, but this difference was not considered clinically meaningful. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that a minimum 5-day acclimation period is necessary for IOP measurements to return to baseline in dogs. The statistically identified effect of gabapentin and tramadol on IOP in dogs of the present study warrants further investigation. It is possible that at higher dosages, or in dogs with glaucoma, this effect may become clinically significant.


Asunto(s)
Tramadol , Animales , Estudios Cruzados , Perros , Gabapentina , Presión Intraocular , Meloxicam , Tonometría Ocular
18.
Yakugaku Zasshi ; 140(10): 1199-1206, 2020.
Artículo en Japonés | MEDLINE | ID: mdl-32999198

RESUMEN

Potential risks to the fetus or infant should be considered prior to medication during pregnancy and lactation. It is essential to evaluate the exposure levels of drugs and their related factors in addition to toxicological effects. Epilepsy is one of the most common neurological complications in pregnancy; some women continue to use antiepileptic drugs (AEDs) to control seizures. Benzodiazepines (BZDs) are widely prescribed for several women who experience symptoms such as anxiety and insomnia during the postpartum period. In this review, we describe the 1) transport mechanisms of AEDs across the placenta and the effects of these drugs on placental transporters, and 2) the transfer of BZDs into breast milk. Our findings indicated that carrier systems were involved in the uptake of gabapentin (GBP) and lamotrigine (LTG) in placental trophoblast cell lines. SLC7A5 was the main contributor to GBP transport in placental cells. LTG was transported by a carrier that was sensitive to chloroquine, imipramine, quinidine, and verapamil. Short-term exposure to 16 AEDs had no effect on folic acid uptake in placental cells. However, long-term exposure to valproic acid (VPA) affected the expression of folate carriers (FOLR1, SLC46A1). Furthermore, VPA administration changed the expression levels of various transporters in rat placenta, suggesting that sensitivity to VPA differed across gestational stages. Lastly, we developed a method for quantifying eight BZDs in human breast milk and plasma using LC/MS/MS, and successfully applied it to quantify alprazolam in breast milk and plasma donated by a lactating woman.


Asunto(s)
Anticonvulsivantes/metabolismo , Benzodiazepinas/metabolismo , Transporte Biológico/genética , Lactancia Materna , Gabapentina/metabolismo , Lactancia/metabolismo , Lamotrigina/metabolismo , Transportador de Aminoácidos Neutros Grandes 1/fisiología , Intercambio Materno-Fetal , Leche Humana/metabolismo , Placenta/metabolismo , Ácido Valproico/metabolismo , Anticonvulsivantes/efectos adversos , Benzodiazepinas/efectos adversos , Benzodiazepinas/uso terapéutico , Línea Celular , Epilepsia/tratamiento farmacológico , Femenino , Receptor 1 de Folato/genética , Receptor 1 de Folato/metabolismo , Gabapentina/efectos adversos , Expresión Génica/efectos de los fármacos , Humanos , Lamotrigina/efectos adversos , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Transportador de Folato Acoplado a Protón/genética , Transportador de Folato Acoplado a Protón/metabolismo , Ácido Valproico/efectos adversos
19.
Lancet ; 396(10255): 909-917, 2020 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-32979978

RESUMEN

BACKGROUND: Chronic pelvic pain affects 2-24% of women worldwide and evidence for medical treatments is scarce. Gabapentin is effective in treating some chronic pain conditions. We aimed to measure the efficacy and safety of gabapentin in women with chronic pelvic pain and no obvious pelvic pathology. METHODS: We performed a multicentre, randomised, double-blind, placebo-controlled randomised trial in 39 UK hospital centres. Eligible participants were women with chronic pelvic pain (with or without dysmenorrhoea or dyspareunia) of at least 3 months duration. Inclusion criteria were 18-50 years of age, use or willingness to use contraception to avoid pregnancy, and no obvious pelvic pathology at laparoscopy, which must have taken place at least 2 weeks before consent but less than 36 months previously. Participants were randomly assigned in a 1:1 ratio to receive gabapentin (titrated to a maximum dose of 2700 mg daily) or matching placebo for 16 weeks. The online randomisation system minimised allocations by presence or absence of dysmenorrhoea, psychological distress, current use of hormonal contraceptives, and hospital centre. The appearance, route, and administration of the assigned intervention were identical in both groups. Patients, clinicians, and research staff were unaware of the trial group assignments throughout the trial. Participants were unmasked once they had provided all outcome data at week 16-17, or sooner if a serious adverse event requiring knowledge of the study drug occurred. The dual primary outcome measures were worst and average pain scores assessed separately on a numerical rating scale in weeks 13-16 after randomisation, in the intention-to-treat population. Self-reported adverse events were assessed according to intention-to-treat principles. This trial is registered with the ISRCTN registry, ISCRTN77451762. FINDINGS: Participants were screened between Nov 30, 2015, and March 6, 2019, and 306 were randomly assigned (153 to gabapentin and 153 to placebo). There were no significant between-group differences in both worst and average numerical rating scale (NRS) pain scores at 13-16 weeks after randomisation. The mean worst NRS pain score was 7·1 (standard deviation [SD] 2·6) in the gabapentin group and 7·4 (SD 2·2) in the placebo group. Mean change from baseline was -1·4 (SD 2·3) in the gabapentin group and -1·2 (SD 2·1) in the placebo group (adjusted mean difference -0·20 [97·5% CI -0·81 to 0·42]; p=0·47). The mean average NRS pain score was 4·3 (SD 2·3) in the gabapentin group and 4·5 (SD 2·2) in the placebo group. Mean change from baseline was -1·1 (SD 2·0) in the gabapentin group and -0·9 (SD 1·8) in the placebo group (adjusted mean difference -0·18 [97·5% CI -0·71 to 0·35]; p=0·45). More women had a serious adverse event in the gabapentin group than in the placebo group (10 [7%] of 153 in the gabapentin group compared with 3 [2%] of 153 in the placebo group; p=0·04). Dizziness, drowsiness, and visual disturbances were more common in the gabapentin group. INTERPRETATION: This study was adequately powered, but treatment with gabapentin did not result in significantly lower pain scores in women with chronic pelvic pain, and was associated with higher rates of side-effects than placebo. Given the increasing reports of abuse and evidence of potential harms associated with gabapentin use, it is important that clinicians consider alternative treatment options to off-label gabapentin for the management of chronic pelvic pain and no obvious pelvic pathology. FUNDING: National Institute for Health Research.


Asunto(s)
Analgésicos/efectos adversos , Analgésicos/uso terapéutico , Dolor Crónico/tratamiento farmacológico , Gabapentina/efectos adversos , Gabapentina/uso terapéutico , Dolor Pélvico/tratamiento farmacológico , Adolescente , Adulto , Método Doble Ciego , Femenino , Humanos , Uso Fuera de lo Indicado , Resultado del Tratamiento , Adulto Joven
20.
Sr Care Pharm ; 35(10): 436-438, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-32972493

RESUMEN

While opioids have historically been the initial choice of analgesic for both acute and chronic pain, legislative and deprescribing trends as a result of the opioid epidemic have demonstrated an increase in the use of adjunctive therapies. These adjunctive agents are being utilized with increased frequency, especially in older adult patients, as a mechanism to mitigate any likelihood of dependency and in an effort to provide multimodal pain management. As this patient population can be more challenging because of comorbidities, the presence of polypharmacy, pharmacokinetic, and pharmacodynamic changes, it is important to evaluate the risk of any relevant adverse effects for opioids and adjuncts that can lead to higher risk of opioid toxicities. Gabapentin is one of the most commonly added adjunctive medications; however, its safety and efficacy in conjunction with opioids has not been exclusively considered in older adult patients in the perioperative setting. This report will summarize available evidence for gabapentin as an adjunctive therapy to opioids in older adult patients undergoing surgery.


Asunto(s)
Analgésicos Opioides/uso terapéutico , Dolor Crónico , Gabapentina/uso terapéutico , Anciano , Analgésicos/efectos adversos , Analgésicos Opioides/efectos adversos , Dolor Crónico/tratamiento farmacológico , Gabapentina/efectos adversos , Humanos , Manejo del Dolor
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