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1.
Int J Pharm Compd ; 23(6): 496-503, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31751946

RESUMO

The objective of this study was to investigate the effect of Lipoderm Cream, VersaBase Gel, and Emollient Cream on the release and permeation of gabapentin formulated for neuropathic pain. Gabapentin of different strengths (1%, 5%, and 10%) was compounded with the bases, diffusion of the drug from thebases, and permeation through artificial skin model studied with Franz diffusionsystem. Steady-state flux, cumulative permeation, and lag times were calculated,and release mechanisms modelled with first order, second-order, Higuchi, Korsmeyer-Peppas, and Hixon-Crowell kinetic models. Gabapentin recovery from VersaBase Gel, Lipoderm Cream, and Emollient Cream was 100.8 ± 2.7%, 101.3 ± 1.2%, and 104.9 ± 3.3%, respectively. Gabapentin completely diffused out of the three bases within 6 hours of application according to the Higuchi model. Flux of the drug appeared to be concentration-dependent with no permeation occurring at 1% strength. Whereas, 5% and 10% strengths in Lipoderm Cream permeated the skin rapidly, the same concentrations in Emollient Cream and VersaBase Gel required 60-minutes and 120-minutes lag times, respectively. For the three bases, a strong correlation was observed between lag times and flux. The overall permeation in VersaBase Gel and Lipoderm Base was not significantly different (P>0.05). However, Emollient Cream resulted in a significantly lower total permeation compared to other bases (P<0.05). As the formulations are for pain management, products with no lag times and higher flux are preferable. Although VersaBase Gel and Emollient Cream displayed some gabapentin permeability, it is important to consider gabapentin stability in these bases prior to use.


Assuntos
Analgésicos , Gabapentina , Neuralgia , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Composição de Medicamentos , Gabapentina/administração & dosagem , Gabapentina/farmacologia , Humanos , Manejo da Dor , Pele , Absorção Cutânea
2.
Am J Vet Res ; 80(11): 1007-1009, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31644338

RESUMO

OBJECTIVE: To determine the effect of oral administration of gabapentin (20 mg/kg) on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS: 6 healthy adult dogs (3 males and 3 females with a mean ± SD body weight of 24.8 ± 1.3 kg). PROCEDURES: Each dog was anesthetized twice. Dogs were initially assigned to 1 of 2 treatments (gabapentin [20 mg/kg, PO] followed 2 hours later by anesthesia maintained with isoflurane or anesthesia maintained with isoflurane alone). A minimum of 7 days later, dogs received the other treatment. The MAC of isoflurane was determined by use of an iterative bracketing technique with stimulating electrodes placed in the maxillary buccal mucosa. Hemodynamic variables and vital parameters were recorded at the lowest end-tidal isoflurane concentration at which dogs did not respond to the stimulus. Effect of treatment on outcome variables was analyzed by use of a paired t test. RESULTS: Mean ± SD MAC of isoflurane was significantly lower when dogs received gabapentin and isoflurane (0.71 ± 0.12%) than when dogs received isoflurane alone (0.91 ± 0.26%). Mean reduction in MAC of isoflurane was 20 ± 14%. Hemodynamic variables did not differ significantly between treatments. Mean time to extubation was significantly less when dogs received gabapentin and isoflurane (6 ± 4 minutes) than when dogs received isoflurane alone (23 ± 15 minutes). CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of gabapentin 2 hours before anesthesia maintained with isoflurane had a MAC-sparing effect with no effect on hemodynamic variables or vital parameters of dogs.


Assuntos
Anestésicos Inalatórios/farmacocinética , Cães/metabolismo , Gabapentina/farmacologia , Isoflurano/farmacocinética , Alvéolos Pulmonares/efeitos dos fármacos , Administração Oral , Anestésicos Inalatórios/administração & dosagem , Animais , Pressão Sanguínea/efeitos dos fármacos , Feminino , Gabapentina/administração & dosagem , Hemodinâmica/efeitos dos fármacos , Isoflurano/administração & dosagem , Masculino , Alvéolos Pulmonares/metabolismo
3.
Niger J Clin Pract ; 22(9): 1301-1303, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31489871

RESUMO

Neuropathic pain responds poorly to common analgesics that effectively control nociceptive pain because its pathophysiology is different and it is usually associated with co-morbidities such as sleep disturbance, depression and anxiety. Patients with this chronic pain are sometimes left with neurolysis as the last resort. A 65-year-old male multiply-injured retiree presented with disabling pain following traumatic brachial plexus injury sustained from road traffic accident 5 years earlier. Other injuries resolved with therapy except the chronic severe burning and electrifying pain (VAS score 9) in the paralyzed left upper limb associated with allodynia and insomnia which was unresponsive to conventional analgesics. PainDETECT score was 29. A test supraclavicular block with 0.25% Bupivacaine was done, followed by chemical neurolysis one month later. He was placed on oral Gabapentin. The pain score a week post injection was 3 and has remained same 18 months post injection. Patient's level of satisfaction on 5 point Likert scale was 5. Chronic neuropathic pain following traumatic brachial plexus injury could be successfully managed by chemical neurolysis and oral gabapentin.


Assuntos
Analgésicos/administração & dosagem , Neuropatias do Plexo Braquial/complicações , Neuropatias do Plexo Braquial/tratamento farmacológico , Plexo Braquial/lesões , Gabapentina/administração & dosagem , Bloqueio Nervoso/métodos , Neuralgia/tratamento farmacológico , Extremidade Superior/lesões , Adulto , Idoso , Analgésicos/uso terapêutico , Neuropatias do Plexo Braquial/fisiopatologia , Bupivacaína/administração & dosagem , Gabapentina/uso terapêutico , Humanos , Hiperalgesia/etiologia , Masculino , Bloqueio Nervoso/efeitos adversos , Neuralgia/etiologia , Medição da Dor , Sono/efeitos dos fármacos , Distúrbios do Início e da Manutenção do Sono/etiologia , Resultado do Tratamento
4.
BMC Pharmacol Toxicol ; 20(1): 51, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462283

RESUMO

BACKGROUND: Chemotherapy induced peripheral neuropathy (CIPN) has been attributed to chemotherapeutic agents such as cisplatin which adversely affect disease outcome leading to increased cancer related morbidity. The clinical efficacy of systemic gabapentin in neuropathic pain management is limited by central side-effects in addition to a scarceness of conclusive evidence of its efficacy in CIPN management. The topical route therefore may provide a relatively safe alternative for neuropathic pain treatment in general and CIPN in particular. METHODS: Cisplatin induced neuropathic nociception was established in rats after a single weekly cisplatin injection (3.0 mg/kg, intraperitoneally) for 4 weeks. The evoked neuropathic sensation of allodynia was assessed by plantar application of von Frey monofilaments as the paw withdrawal threshold (PWT), whereas the expression of heat-hypoalgesia was determined on a hot-plate as paw withdrawal latency (PWL). Gabapentin gel (10% w/w) was applied three-times daily on the hind paws while in a concurrent systemic study, gabapentin was administered daily (75 mg/kg, intraperitoneally) for 4 weeks. To assess any evidence of neurological adverse symptoms of cisplatin and the central side-effect propensity of systemic or topical gabapentin, evaluation of motor coordination (rotarod test) and gait (footprint analysis) were performed. RESULTS: Cisplatin invoked a progressive development of neuropathic hind paw allodynia (decreased PWT, days 7-28) and heat hypoalgesia (increased PWL, days 21-28). Topical gabapentin significantly delayed the expression of both allodynia on protocol days 21 and 28 and heat-hypoalgesia (day 28). Systemic gabapentin displayed a comparative anti-neuropathic predisposition through a sustained suppression of tactile allodynia on days 14 and 21-28 as well as thermal hypoalgesia (days 21 and 28). Systemic gabapentin also impaired motor coordination and gait thus affirming its clinically documented central side effects, but these outcomes were not evident after topical treatment. CONCLUSIONS: Both topical and systemic gabapentin exhibit a propensity to attenuate CIPN in a cisplatin paradigm. Gabapentin applied topically may therefore provide an adjunctive or alternative route for CIPN management upon cessation of systemic medications due to intolerable side-effects.


Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Gabapentina/uso terapêutico , Neuralgia/induzido quimicamente , Neuralgia/tratamento farmacológico , Administração Tópica , Animais , Gabapentina/administração & dosagem , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Masculino , Neuralgia/etiologia , Ratos , Ratos Sprague-Dawley
5.
Drug Des Devel Ther ; 13: 1985-1992, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354243

RESUMO

Background: The most common cause of polyneuropathy is diabetes mellitus. Neuropathic pain is seen in 26% of diabetic population. Therapeutic techniques for this disease can become challenging. Method: This study was a prospective comparative double-blind randomized study which was conducted during an eight-week period. Totally, 104 painful diabetic peripheral polyneuropathy (PDPP) patients who had a minimum Visual Analog Scale (VAS) of 40 millimeters, received no pain-controlling medication, and had no other severe disease at its final stage were randomly assigned to two groups (n=52) through the four block method. One group received Duloxetine and the other received Gabapentin. The effectiveness was measured through primary effectiveness (VAS scale) and secondary effectiveness (Sleep Interference Score, and Clinical Global Impression of Change (CGIC)). Medication compliance was assessed by enumerating the number of patients who refused treatment because of side effects. The Fisher's exact T-test and ANOVA were used for data analysis. This study was approved by the Ethics Committee of Jundishapur, University of Medical sciences Ahvaz, Iran, under reference number: IR.AJUMS.REC.1395.78. In addition, this study was registered and approved in the Iranian Registry of Clinical Trials (IRCT ID: IRCT20161023030455N2) (http://irct.ir/). Results: VAS, Sleep Interference Score, and CGIC were significantly improved (P<0.05) through time in both groups, [For GBP: VASBaseline=64±20.03, VASweek1=55.32±18.76, VASweek4=44.68±15.82, VASweek8=39.43±14.32; For DLX: VASBase-line=62±21.18, VASweek1=58.76±20.37, VASweek4=45.84±16.21, VASweek8=36.78±15.62] while a significant difference between the two groups was not observed (P<0.05). However, such significant improvements were not observed in the Duloxetine group at the end of the first week (P=674). Improvement in Sleep Interference Score and CGIC were similar to the results for the VAS scale. Side effects in the Duloxetine group (n=2) compared to the Gabapentin group (n=9) were significantly less (P<0.001). As a result, medication acceptance in the Duloxetine group (n=47) was significantly better than the Gabapentin (n=41) group (P<0.001). Conclusion: Both Duloxetine and Gabapentin are effective for the treatment of PDPP. On the one hand, Gabapentin shows the effect earlier while has more side effects. Conversely, Duloxetine has better medication compliance. Trial registration: The method of this study was approved by the Ethics Committee of Jundishapur University of Medical Sciences, Ahvaz, Iran, under reference number: IR.AJUMS.REC.1395.78. In addition, this study was registered and approved in the Iranian Registry of Clinical Trials (IRCT ID: IRCT20161023030455N2) (http://irct.ir/).


Assuntos
Analgésicos/uso terapêutico , Neuropatias Diabéticas/tratamento farmacológico , Cloridrato de Duloxetina/uso terapêutico , Gabapentina/uso terapêutico , Neuralgia/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Idoso , Analgésicos/administração & dosagem , Método Duplo-Cego , Cloridrato de Duloxetina/administração & dosagem , Feminino , Gabapentina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Manejo da Dor , Estudos Prospectivos , Adulto Jovem
6.
Drug Ther Bull ; 57(8): 125-127, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31345958

RESUMO

The interactions between opioids and gabapentin are more clinically relevant than ever. Prescriptions dispensed for gabapentin increased from 39 million in 2012 to 64 million in 2018 in the USA and are ever increasing. Authors present a challenging case of these interactions. A 58-year-old man presented to the emergency department with acute respiratory failure and altered mental status. He was on high dose opioids and gabapentin as prescription medications. Despite full intensive care support and resolution of his respiratory failure with non-invasive positive pressure ventilation, the patient did not regain consciousness. After ruling out other causes, the diagnosis of gabapentin withdrawal was considered. Gabapentin was administered by a nasogastric tube that quickly resulted in a reversal of his symptoms. We concluded that severe gabapentin withdrawal should be considered in patients on higher doses of gabapentin when it is stopped abruptly. In such patients, gabapentin should be replaced. As most patients are unable to swallow in this situation and intravenous formulation is not available, nasogastric tube can be used for replacement.


Assuntos
Analgésicos Opioides/efeitos adversos , Analgésicos/efeitos adversos , Encefalopatias/induzido quimicamente , Gabapentina/efeitos adversos , Analgésicos/administração & dosagem , Analgésicos Opioides/administração & dosagem , Interações Medicamentosas , Gabapentina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/etiologia
7.
Curr Opin Anaesthesiol ; 32(5): 629-634, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31335335

RESUMO

PURPOSE OF REVIEW: Gabapentinoid use has increased substantially in the past several years after initial promising data with regard to acute perioperative pain control. The purpose of this review is to critically appraise the evidence for the use of gabapentinoids for acute pain management and its impact on the development of chronic pain after surgery. RECENT FINDINGS: Recent meta-analyses have revealed that prior data likely have overestimated the beneficial effects of gabapentinoids in acute perioperative pain while underestimating the associated adverse effects. The utility of gabapentinoids in the setting of enhanced recovery pathways and for the prevention of chronic postsurgical pain is still unclear. Moreover, there has been increasing concern regarding the potential for misuse and abuse of gabapentinoids. SUMMARY: Current evidence does not support the routine use of gabapentinoids as part of a multimodal analgesic regimen in enhanced recovery pathways. We recommend being selective with regard to using gabapentinoids for acute postoperative pain management after careful consideration of the potential side effect profile based on patient comorbidities as well as the expected severity of postoperative pain. Large, high-quality trials are needed to identify the impact of gabapentinoids in the context of multimodal anagelsia.


Assuntos
Analgesia/efeitos adversos , Analgésicos/efeitos adversos , Gabapentina/efeitos adversos , Manejo da Dor/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Dor Aguda/diagnóstico , Dor Aguda/tratamento farmacológico , Dor Aguda/etiologia , Analgesia/métodos , Analgésicos/administração & dosagem , Dor Crônica/diagnóstico , Dor Crônica/tratamento farmacológico , Dor Crônica/etiologia , Gabapentina/administração & dosagem , Gabapentina/análogos & derivados , Humanos , Metanálise como Assunto , Manejo da Dor/métodos , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Índice de Gravidade de Doença , Procedimentos Cirúrgicos Operatórios/efeitos adversos
8.
PLoS One ; 14(6): e0217335, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31166976

RESUMO

BACKGROUND: Postherpetic neuralgia (PHN) is the most common complication of herpes zoster (HZ). Previous trials have reported that gabapentin can relieve chronic neuropathic pain, but its effect on prevention of PHN is unclear. OBJECTIVE: To assess the efficacy of a 5-week course of gabapentin on acute herpetic pain and on the prevention of PHN at 12 weeks in patients with acute HZ. METHODS: This was a randomized, double blind, placebo-controlled trial conducted in 17 primary care health centers in Mallorca, Spain. All patients were older than 50 years, presented with HZ within 72 h of rash onset, and had moderate-severe pain (≥4 on a 10-point visual analogue scale [VAS]). Ninety-eight patients were randomized to receive gabapentin or placebo. All patients received valaciclovir for 7 days and analgesia if needed. The treatment period was 5 weeks, followed by 7 weeks of follow-up. Gabapentin was initiated at 300 mg/day and gradually titrated to a maximum of 1800 mg/day. The main outcome measure was pain at 12 weeks. RESULTS: Seventy-five patients completed the study, 33 in the gabapentin group and 42 in the control group. A total of 18.2% of patients in the gabapentin group and 9.5% in the control group reported pain at 12 weeks (p = 0.144). Four patients in the gabapentin group (12.1%), but no patients in the placebo group, reported pain of 4 or more on a 10-point VAS. Patients taking gabapentin reported worse health-related quality of life and poorer sleep quality. Three patients discontinued the trial due to adverse effects from gabapentin. CONCLUSION: Addition of gabapentin to the usual treatment of HZ within 72 h of rash onset provided no significant relief from acute herpetic pain or prevention of PHN. TRIAL REGISTRATION: ISRCTN Registry identifier: ISRCTN79871784.


Assuntos
Gabapentina/administração & dosagem , Herpes Zoster/tratamento farmacológico , Neuralgia Pós-Herpética/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Gabapentina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Sono/efeitos dos fármacos , Espanha
9.
Pharmacol Rep ; 71(4): 573-582, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31170658

RESUMO

BACKGROUND: Macrophages, involved in the pathogenesis of pain, express a variety of receptors enabling responsiveness to certain medications, including adjuvant analgesics (AAs), that are effective in neuropathic pain and include drugs not primarily indicated for pain treatment, such as anticonvulsants or antidepressants. Their analgesic effects are likely associated with immunomodulatory activity, that remain undefined. Thus, current research aimed at examining the impact of AAs on morphine-induced effects exerted on mouse immunity. METHODS: Macrophages from mice treated with morphine with or without gabapentin, amitriptyline or venlafaxine, were either subjected to phagocytosis assay, cultured to evaluate the generation of cytokines, or were pulsed with either corpuscular antigen or hapten and transferred to naive recipients to induce humoral or cellular response, respectively. Active contact hypersensitivity was also elicited in drug-treated mice. RESULTS: We observed that repeatedly administered morphine and AAs reduced antigen phagocytosis by macrophages. Further, amitriptyline with morphine enhanced basal secretion of cytokines by macrophages, and all drugs tended to decrease LPS-stimulated release of pro-inflammatory cytokines. Morphine and AAs impacted the expression of phagocytosis and antigen-presentation markers on macrophages, which led to the reduced ability of morphine-affected macrophages to induce B-cell secretion of specific antibodies, and the addition of AAs strengthened this effect. Finally, gabapentin and venlafaxine suppressed the contact hypersensitivity reaction, while amitriptyline seemed to have the opposite effect. CONCLUSIONS: Our study demonstrated a significant anti-inflammatory activity of AAs across a broad spectrum of macrophage immune functions, which is likely critical to their analgesic activity supporting the beneficial effect of morphine.


Assuntos
Adjuvantes Farmacêuticos/farmacologia , Analgésicos Opioides/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Morfina/farmacologia , Fagocitose/efeitos dos fármacos , Adjuvantes Farmacêuticos/administração & dosagem , Amitriptilina/administração & dosagem , Amitriptilina/farmacologia , Analgésicos Opioides/administração & dosagem , Animais , Apresentação do Antígeno/efeitos dos fármacos , Citocinas/metabolismo , Gabapentina/administração & dosagem , Gabapentina/farmacologia , Imunidade Humoral/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Masculino , Camundongos Endogâmicos CBA , Morfina/administração & dosagem , Fagocitose/imunologia , Cloridrato de Venlafaxina/administração & dosagem , Cloridrato de Venlafaxina/farmacologia
10.
Yale J Biol Med ; 92(2): 201-204, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31249480

RESUMO

We present a totally blind adolescent with refractory insomnia due to a combination of Non-24 hour sleep-wake disorder and restless leg syndrome that was successfully treated with tasimelteon, iron replacement, and gabapentin. To our knowledge, this is the first published report of treatment of N24 with tasimelteon in an adolescent. In addition, this case highlights the importance of recognizing and treating multifactorial causes of insomnia.


Assuntos
Cegueira/complicações , Síndrome das Pernas Inquietas/complicações , Transtornos do Sono do Ritmo Circadiano/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/complicações , Adolescente , Benzofuranos/administração & dosagem , Benzofuranos/uso terapêutico , Ciclopropanos/administração & dosagem , Ciclopropanos/uso terapêutico , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Gabapentina/administração & dosagem , Gabapentina/uso terapêutico , Humanos , Ferro/administração & dosagem , Ferro/uso terapêutico , Transtornos do Sono do Ritmo Circadiano/complicações , Transtornos do Sono do Ritmo Circadiano/fisiopatologia
11.
J Dermatol ; 46(7): 622-625, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31106887

RESUMO

Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome is a recently recognized syndrome caused by mutations in the desmoglein 1 (DSG1) and desmoplakin (DSP) genes. Only two cases of SAM-DSP have been reported. We report on a 2-year-old girl presenting with pustular lakes within areas of erythema and large accumulations of intraepidermal neutrophils, which initially led to our misdiagnosis of generalized pustular psoriasis. No mutation was found in either the IL36RN or CARD14 genes by Sanger sequencing. The distinctive manifestations of erythroderma with severe itching, hypotrichosis, enamel defects, onychodystrophy, palmoplantar keratoderma and the crucial result of de novo missense mutation in exon 14 of the DSP gene (c.1828T>C, p.S610P) discovered by next-generation sequencing finally confirmed the diagnosis of SAM syndrome. The eruptions significantly improved after a 4-week treatment with oral acitretin and topical pimecrolimus. Oral gabapentin was prescribed simultaneously for 4 months, relieving her skin pruritus and suggesting that early treatment with pimecrolimus, acitretin and gabapentin for SAM-DSP syndrome is effective. It may even inhibit multiple allergies induced by skin barrier injury. In this work we also review the clinical features, differential diagnoses and pathological manifestations of SAM-DSP syndrome.


Assuntos
Acitretina/administração & dosagem , Dermatite Esfoliativa/diagnóstico , Desmoplaquinas/genética , Gabapentina/administração & dosagem , Hipersensibilidade/diagnóstico , Síndrome de Emaciação/diagnóstico , Administração Cutânea , Administração Oral , Pré-Escolar , Análise Mutacional de DNA , Dermatite Esfoliativa/tratamento farmacológico , Dermatite Esfoliativa/genética , Dermatite Esfoliativa/patologia , Diagnóstico Diferencial , Erros de Diagnóstico , Feminino , Humanos , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/genética , Hipersensibilidade/patologia , Mutação de Sentido Incorreto , Psoríase/diagnóstico , Índice de Gravidade de Doença , Pele/efeitos dos fármacos , Pele/patologia , Síndrome , Tacrolimo/administração & dosagem , Tacrolimo/análogos & derivados , Resultado do Tratamento , Síndrome de Emaciação/tratamento farmacológico , Síndrome de Emaciação/genética , Síndrome de Emaciação/patologia
12.
Neurol Sci ; 40(9): 1799-1811, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31041611

RESUMO

Vincristine (VCR) is a well-known anticancer drug which frequently induced painful neuropathy and impairs the quality of life of patients. The present study was designed to investigate the alleviative potential of a novel cyclohexenone derivative (CHD), i.e., ethyl 6-(4-methoxyphenyl)-2-oxo-4-phenylcyclohexe-3-enecarboxylate, against VCR-induced neuropathic pain in mice model. VCR was administered intraperitoneally for 10 days in two cycles to induce neuropathic pain. Static and dynamic mechanical allodynia was evaluated using von Frey hair filaments and cotton buds, respectively. Paw thermal hyperalgesia was determined through a hot plate analgesiometer. The tail cold immersion hyperalgesia and paw cold allodynia were determined by available standard protocols. The formalin nociception was induced via subplantar injection of formalin. The antioxidant potential was evaluated via 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity. The outcome of this study revealed that CHD (30-45 mg/kg) and gabapentin (75 mg/kg) significantly enhanced the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in static and dynamic allodynia, respectively, and increased the PWL in thermal hyperalgesia and tail withdrawal latency (TWL) as compared to the VCR-treated group. CHD significantly augmented the paw withdrawal duration (PWD) in paw cold allodynia, while the same compound only increased the paw elevation and paw licking in the delayed phase of formalin nociception. Moreover, CHD significantly inhibited the DPPH free radical scavenging action (IC50 = 56), butylated hydroxytoluene (BHT) (IC50 = 39), and ascorbic acid (IC50 = 2.93). In conclusion, CHD exhibited a profile of potential attenuative effect against the VCR-induced neuropathic pain which might be attributed to its possible antinociceptive and antioxidant effect.


Assuntos
Analgésicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Gabapentina/farmacologia , Hiperalgesia , Cetonas/farmacologia , Neuralgia , Vincristina/farmacologia , Analgésicos/administração & dosagem , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antioxidantes/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Gabapentina/administração & dosagem , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Hiperalgesia/fisiopatologia , Cetonas/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Neuralgia/induzido quimicamente , Neuralgia/tratamento farmacológico , Neuralgia/fisiopatologia , Vincristina/administração & dosagem
13.
Perm J ; 232019.
Artigo em Inglês | MEDLINE | ID: mdl-30939265

RESUMO

CONTEXT: Epidemiologic analyses of gabapentin use and cancer risk in Kaiser Permanente Northern California were previously carried out in a collaborative study and independently evaluated in a UK database. OBJECTIVE: To update these epidemiologic analyses with 7.5 more years of follow-up. DESIGN: Case-control analyses using conditional logistic regression to estimate relative risk by odds ratios using the prior collaboration's criteria for identifying positive drug-cancer associations and our more stringent criteria requiring stronger association, lower p values, and evidence of dose response. New associations were reanalyzed with additional control for limited measures of smoking and alcohol use. MAIN OUTCOME MEASURES: Gabapentin-cancer associations. RESULTS: No previously found associations met our stringent criteria, but cancers of the mouth/pharynx, esophagus, liver, and vagina did. All odds ratios for 3 or more and 8 or more prescriptions were moderately reduced by control for smoking and alcohol. Substantial elevations of risk of mouth/pharynx, liver, and vaginal cancers were associated with only 1 prescription dispensed. Sensitivity analyses aimed at possible confounding and other biases did not change our conclusions but did reveal a markedly increased risk of vaginal cancer in gabapentin users with epilepsy compared with users without. CONCLUSION: The reduced magnitude of relative risk with control for smoking and alcohol use suggests confounding by known risk factors. Biologically implausible elevated risk from just 1 prescription suggests confounding by indication. Either or both of these concerns applies to each of the 4 cancer sites associated with gabapentin use. Updated analyses show little if any evidence for carcinogenic effects of gabapentin.


Assuntos
Analgésicos/administração & dosagem , Gabapentina/administração & dosagem , Neoplasias/epidemiologia , California/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Masculino , Medição de Risco , Sensibilidade e Especificidade , Reino Unido/epidemiologia
14.
BMJ Case Rep ; 12(4)2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-31005866

RESUMO

The interactions between opioids and gabapentin are more clinically relevant than ever. Prescriptions dispensed for gabapentin increased from 39 million in 2012 to 64 million in 2018 in the USA and are ever increasing. Authors present a challenging case of these interactions. A 58-year-old man presented to the emergency department with acute respiratory failure and altered mental status. He was on high dose opioids and gabapentin as prescription medications. Despite full intensive care support and resolution of his respiratory failure with non-invasive positive pressure ventilation, the patient did not regained consciousness. After ruling out other causes, the diagnosis of gabapentin withdrawal was considered. Gabapentin was administered by a nasogastric tube that quickly resulted in a reversal of his symptoms. We concluded that severe gabapentin withdrawal should be considered in patients on higher doses of gabapentin when it is stopped abruptly. In such patients, gabapentin should be replaced. As most patients are unable to swallow in this situation and intravenous formulation is not available, nasogastric tube can be used for replacement.


Assuntos
Analgésicos Opioides/efeitos adversos , Gabapentina/efeitos adversos , Morfina/efeitos adversos , Insuficiência Respiratória/induzido quimicamente , Síndrome de Abstinência a Substâncias/diagnóstico , Analgésicos Opioides/administração & dosagem , Encefalopatias/induzido quimicamente , Dor Crônica/tratamento farmacológico , Gabapentina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Síndrome de Abstinência a Substâncias/etiologia
15.
Reg Anesth Pain Med ; 44(5): 578-585, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30867278

RESUMO

BACKGROUND: Choice of postcesarean delivery analgesic protocol may improve pain experience and reduce analgesic requirements. METHODS: Cesarean delivery patients were randomly assigned either to choose their postcesarean delivery analgesia protocol or to have no choice and receive routine care. Choices were low (50 µg intrathecal morphine), medium (identical to routine care: 150 µg intrathecal morphine), or high (300 µg intrathecal morphine with 600 mg oral gabapentin). All groups received scheduled acetaminophen and ibuprofen. The primary outcome was oxycodone requirements 0-48 hours postdelivery in those offered versus not offered a choice. RESULTS: Of 160 women enrolled, 120 were offered a choice and 40 were not offered a choice. There was no difference in oxycodone requirements or pain associated with choice, but those who had a choice expressed more satisfaction than those who did not have a choice (mean (95% CI) difference 5% (0% to 10 %), p=0.005). In the choice group, the high dose group required more oxycodone (5 (0 to 15) mg 0-24 hours after delivery and 15 (10 to 25) mg at 24-48 hours; p=0.05 and p=0.001) versus the low and medium groups. The low dose group had less pruritus (p=0.001), while the high dose group had more vomiting (p=0.01) requiring antiemetic treatment (p=0.04). CONCLUSION: Having a choice compared with no choice routine care did not reduce oxycodone requirements or pain scores. However, women have insight into their analgesic needs; women offered a choice and who chose the higher dose analgesic protocol required more oxycodone, and women who chose the lower dose protocol required less oxycodone. Despite providing additional analgesic (six times more intrathecal morphine plus gabapentin in high dose vs low dose protocols), we still did not equalize postcesarean oxycodone requirement differences between groups. TRIAL REGISTRATION NUMBER: NCT02605187.


Assuntos
Analgésicos Opioides/administração & dosagem , Cesárea/efeitos adversos , Sistemas de Liberação de Medicamentos/métodos , Dor Pós-Operatória/tratamento farmacológico , Preferência do Paciente , Administração Oral , Adulto , Analgésicos/administração & dosagem , Cesárea/psicologia , Sistemas de Liberação de Medicamentos/psicologia , Feminino , Gabapentina/administração & dosagem , Humanos , Injeções Espinhais , Morfina/administração & dosagem , Dor Pós-Operatória/psicologia , Preferência do Paciente/psicologia , Gravidez , Estudos Prospectivos , Método Simples-Cego
16.
JAMA Netw Open ; 2(3): e190168, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30821824

RESUMO

Importance: Acute postoperative pain is associated with the development of persistent postsurgical pain, but it is unclear which aspect is most estimable. Objective: To identify patient clusters based on acute pain trajectories, preoperative psychosocial characteristics associated with the high-risk cluster, and the best acute pain predictor of remote outcomes. Design, Setting, and Participants: A secondary analysis of the Stanford Accelerated Recovery Trial randomized, double-blind clinical trial was conducted at a single-center, tertiary, referral teaching hospital. A total of 422 participants scheduled for thoracotomy, video-assisted thoracoscopic surgery, total hip replacement, total knee replacement, mastectomy, breast lumpectomy, hand surgery, carpal tunnel surgery, knee arthroscopy, shoulder arthroplasty, or shoulder arthroscopy were enrolled between May 25, 2010, and July 25, 2014. Data analysis was performed from January 1 to August 1, 2018. Interventions: Patients were randomized to receive gabapentin (1200 mg, preoperatively, and 600 mg, 3 times a day postoperatively) or active placebo (lorazepam, 0.5 mg preoperatively, inactive placebo postoperatively) for 72 hours. Main Outcomes and Measures: A modified Brief Pain Inventory prospectively captured 3 surgical site pain outcomes: average pain and worst pain intensity over the past 24 hours, and current pain intensity. Within each category, acute pain trajectories (first 10 postoperative pain scores) were compared using a k-means clustering algorithm. Fifteen descriptors of acute pain were compared as predictors of remote postoperative pain resolution, opioid cessation, and full recovery. Results: Of the 422 patients enrolled, 371 patients (≤10% missing pain scores) were included in the analysis. Of these, 146 (39.4%) were men; mean (SD) age was 56.67 (11.70) years. Two clusters were identified within each trajectory category. The high pain cluster of the average pain trajectory significantly predicted prolonged pain (hazard ratio [HR], 0.63; 95% CI, 0.50-0.80; P < .001) and delayed opioid cessation (HR, 0.52; 95% CI, 0.41-0.67; P < .001) but was not a predictor of time to recovery in Cox proportional hazards regression (HR, 0.89; 95% CI, 0.69-1.14; P = .89). Preoperative risk factors for categorization to the high average pain cluster included female sex (adjusted relative risk [ARR], 1.36; 95% CI, 1.08-1.70; P = .008), elevated preoperative pain (ARR, 1.11; 95% CI, 1.07-1.15; P < .001), a history of alcohol or drug abuse treatment (ARR, 1.90; 95% CI, 1.42-2.53; P < .001), and receiving active placebo (ARR, 1.27; 95% CI, 1.03-1.56; P = .03). Worst pain reported on postoperative day 10 was the best predictor of time to pain resolution (HR, 0.83; 95% CI, 0.78-0.87; P < .001), opioid cessation (HR, 0.84; 95% CI, 0.80-0.89; P < .001), and complete surgical recovery (HR, 0.91; 95% CI, 0.86-0.96; P < .001). Conclusions and Relevance: This study has shown a possible uniform predictor of remote postoperative pain, opioid use, and recovery that can be easily assessed. Future work is needed to replicate these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT01067144.


Assuntos
Dor Aguda , Gabapentina/administração & dosagem , Medição da Dor/métodos , Dor Pós-Operatória , Cuidados Pré-Operatórios/métodos , Dor Aguda/diagnóstico , Dor Aguda/etiologia , Dor Aguda/prevenção & controle , Idoso , Analgésicos/administração & dosagem , Analgésicos Opioides/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/psicologia , Prognóstico , Psicologia , Medição de Risco/métodos , Fatores de Risco , Resultado do Tratamento , Suspensão de Tratamento
17.
Neurotox Res ; 36(1): 81-90, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30830678

RESUMO

Neurodegeneration in diabetic retina has been widely considered as initiating factor that may lead to vascular damage, the classical hallmark of diabetic retinopathy. Diabetes induced altered glutamate metabolism in the retina, especially through glutamate excitotoxicity might play a major role in the neurodegeneration. Increased level of branched chain amino acids (BCAAs) measured in diabetic retina might cause an increase in the neurotoxic level of glutamate by transamination of citric acid cycle intermediates. In order to analyze the transamination of BCAAs and their influence on neurodegenerative factors, we treated streptozotocin-induced diabetic rats with gabapentin, a leucine analogue and an inhibitor of branched chain amino transferase (BCATc). Interestingly, gabapentin lowered the retinal level of BCAAs in diabetic rats. Furthermore, gabapentin treatments ameliorated the reduced antioxidant glutathione level and increased malondialdehyde (MDA), the marker of lipid peroxidation in diabetic rat retinas. In addition, gabapentin also reduced the expression of proapoptotic caspase-3, a marker of apoptosis and increased anti-apoptotic marker Bcl-2 in diabetic retinas. Thus, these results suggest that gabapentin stimulates glutamate disposal, and ameliorates apoptosis and oxidative stress in diabetic rat retina. The influence of gabapentin may be due to its capacity to increase the ratio of BCKA to BCAA which in turn would reduce glutamate excitotoxicity in diabetic retina.


Assuntos
Apoptose/efeitos dos fármacos , Retinopatia Diabética/metabolismo , Gabapentina/administração & dosagem , Ácido Glutâmico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Aminoácidos/metabolismo , Animais , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Glutationa/metabolismo , Peroxidação de Lipídeos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Estreptozocina/administração & dosagem , Transaminases/antagonistas & inibidores
18.
Knee Surg Sports Traumatol Arthrosc ; 27(7): 2167-2172, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30826856

RESUMO

PURPOSE: Dexamethasone and gabapentin are used in multimodal pain management protocols to reduce postoperative pain after total knee arthroplasty. For both analgesic adjuvants, the optimal dose regimen to reduce opioid usage is still unclear. METHODS: The opioid consumption of patients undergoing primary TKA before and after a change of the analgesic adjuvant medication in our protocol (old protocol: 4 mg of dexamethasone daily for 2 days, 600 mg gabapentin daily for 1 week; new protocol: 10 mg dexamethasone daily for 2 days, 300 mg gabapentin every 8 h for 1 week) were retrospectively compared. All surgeries were performed under spinal anesthesia. Peri- and postoperative pain medication remained unchanged. RESULTS: A total of 186 patients who received TKA between 11/29/2016 and 06/09/2017 were screened. Six patients who received general anesthesia, 4 patients who underwent simultaneous bilateral TKA, and 16 patients with ongoing opioid consumption at the time of surgery were excluded, leaving 80 patients in each group. Opioid consumption within 24 h [morphine equivalents in mg: mean 50.5, standard deviation (SD) 30.0 (old) vs. 39.8, SD 24.2 (new); P = 0.0470], cumulative consumption over 48 h (97.3, SD 64.4 vs. 70.4, SD 51.2; P = 0.0040) and cumulative consumption over 72 h (108.1, SD 79.5 vs. 82.5, SD 72.6; P = 0.0080), were all significantly lower in the new protocol. CONCLUSION: Increased postoperative administration of dexamethasone and gabapentin after TKA is associated with lower opioid consumption. Within the first 48 h, up to about 25% of opioids can be spared, comparing high-dose to low-dose protocols. LEVEL OF EVIDENCE: Therapeutic Level III.


Assuntos
Analgésicos Opioides/administração & dosagem , Artroplastia do Joelho/efeitos adversos , Dexametasona/administração & dosagem , Gabapentina/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Idoso , Analgésicos/uso terapêutico , Raquianestesia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Medição da Dor , Dor Pós-Operatória/etiologia , Período Pós-Operatório , Estudos Retrospectivos
19.
Mayo Clin Proc ; 94(3): 484-489, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30718068

RESUMO

Postherpetic neuralgia (PHN) is the most common complication of varicella zoster virus (VZV) reactivation and a cause of considerable physical and psychosocial morbidity. No known treatment effectively prevents the development of PHN in patients with VZV reactivation. In this study, our objective was to evaluate the efficacy of premedication with gabapentin for reducing the risk of PHN in patients with diabetic and nondiabetic neuropathy. We retrospectively searched the electronic health records of patients with diabetic and nondiabetic neuropathy treated with gabapentin at Mayo Clinic before diagnosis of VZV reactivation. In total, PHN developed in 7 patients with diabetic neuropathy receiving gabapentin (n=62 [11.3%]) compared with 26 not receiving premedication with gabapentin (n=50 [52.0%]) (odds ratio, 0.12; 95% CI, 0.05-0.31; P<.001); PHN developed in 11 patients with nondiabetic neuropathy receiving gabapentin (n=109 [10.1%]) compared with 108 not receiving premedication with gabapentin (n=217 [49.8%]) (odds ratio, 0.11; 95% CI, 0.06-0.22; P<.001). In this cohort of patients with neuropathy, gabapentin administration before the onset of VZV reactivation significantly reduced the risk of PHN.


Assuntos
Antivirais/administração & dosagem , Neuropatias Diabéticas/prevenção & controle , Gabapentina/administração & dosagem , Herpes Zoster/tratamento farmacológico , Neuralgia Pós-Herpética/prevenção & controle , Neuropatias Diabéticas/virologia , Feminino , Herpes Zoster/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia Pós-Herpética/virologia , Resultado do Tratamento
20.
Int J Mol Sci ; 20(4)2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30769838

RESUMO

Gabapentinoids (gabapentin and pregabalin) and antidepressants (tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors) are often used to treat chronic pain. The descending noradrenergic inhibitory system from the locus coeruleus (LC) to the dorsal horn of the spinal cord plays an important role in the analgesic mechanisms of these drugs. Gabapentinoids activate the LC by inhibiting the release of γ-aminobutyric acid (GABA) and inducing the release of glutamate, thereby increasing noradrenaline levels in the spinal cord. Antidepressants increase noradrenaline levels in the spinal cord by inhibiting reuptake, and accumulating noradrenaline inhibits chronic pain through α2-adrenergic receptors in the spinal cord. Recent animal studies, however, revealed that the function of the descending noradrenergic inhibitory system is impaired in chronic pain states. Other recent studies found that histone deacetylase inhibitors and antidepressants restore the impaired noradrenergic descending inhibitory system acting on noradrenergic neurons in the LC.


Assuntos
Dor Crônica/tratamento farmacológico , Norepinefrina/antagonistas & inibidores , Receptores Adrenérgicos alfa 2/genética , Inibidores de Captação de Serotonina/administração & dosagem , Animais , Antidepressivos Tricíclicos/administração & dosagem , Dor Crônica/genética , Dor Crônica/fisiopatologia , Antagonistas GABAérgicos/administração & dosagem , Antagonistas GABAérgicos/metabolismo , Gabapentina/administração & dosagem , Humanos , Locus Cerúleo/efeitos dos fármacos , Locus Cerúleo/fisiopatologia , Norepinefrina/genética , Norepinefrina/metabolismo , Pregabalina/administração & dosagem , Inibidores de Captação de Serotonina/metabolismo , Medula Espinal/efeitos dos fármacos , Medula Espinal/fisiopatologia , Corno Dorsal da Medula Espinal/efeitos dos fármacos , Corno Dorsal da Medula Espinal/fisiopatologia
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