RESUMEN
BACKGROUND: Pregabalin, an antiepileptic and chronic pain medication, has been used by various authors for preoperative analgesia. We have assessed the effect of pre-emptive administration of the drug to patients scheduled for elective abdominal hysterectomy. METHODS: Seventy-four ASA I and II patients were included in this prospective, double blind study. They were randomised to receive 75, 150, or 300 mg of pregabalin, or 7.5 mg of midazolam as a placebo, one hour before anaesthesia and surgery. Anaesthesia was induced with propofol and maintained with sevoflurane or desflurane. Fentanyl was used for analgesia and rocuronium for muscle relaxation. Immediately after surgery, patients received morphine intravenously in 2 mg increments until the NRS score was below 3. This was then followed by PCA. RESULTS: Morphine consumption and pain scores were only significantly lower in the 300 mg pregabalin group, when compared to the placebo and other treatment groups; there were no differences between placebos and lower doses of pregabalin. CONCLUSION: We conclude that pre-emptive administration of 300 mg pregabalin reduces postoperative pain and morphine consumption. Further studies on higher doses would appear to be justified.
Asunto(s)
Analgésicos Opioides/uso terapéutico , Analgésicos/uso terapéutico , Morfina/uso terapéutico , Dolor Postoperatorio/prevención & control , Medicación Preanestésica , Premedicación , Ácido gamma-Aminobutírico/análogos & derivados , Método Doble Ciego , Femenino , Humanos , Histerectomía , Dimensión del Dolor/métodos , Dolor Postoperatorio/tratamiento farmacológico , Pregabalina , Estudios Prospectivos , Resultado del Tratamiento , Ácido gamma-Aminobutírico/uso terapéuticoRESUMEN
This study was aimed at determining the analgesic effect of gabapentin and tiagabine, two antiepileptic drugs that were administered alone and in combination at a fixed ratio of 1:1, in the acute thermal pain model (hot-plate test) in mice. Linear regression analysis was used to evaluate the dose-response relationships between logarithms of antiepileptic drug doses and their resultant maximum possible antinociceptive effects in the mouse hot-plate test. From linear equations, we calculated doses that increased the antinociceptive effect by 50% (ED(50) values) for gabapentin, tiagabine and their combination. The type of interaction between gabapentin and tiagabine was assessed using the isobolographic analysis. Results indicated that both antiepileptic drugs produced the definite antinociceptive effect, and the experimentally derived ED(50) values for gabapentin and tiagabine, when applied alone, were 504.4 mg/kg and 5.67 mg/kg, respectively. With isobolography, the experimentally derived ED(50 mix) value for the fixed ratio combination of 1:1 was 139.31 mg/kg and significantly differed from the theoretically calculated ED(50 add) value, which was 255.04 mg/kg (p < 0.05), indicating the synergistic interaction between gabapentin and tiagabine in the hot-plate test in mice. In conclusion, the combination of tiagabine with gabapentin at a fixed ratio of 1:1 exerted a synergistic interaction in the mouse model of nociceptive pain. If the results from this study could be extrapolated to clinical settings, the combination of tiagabine with gabapentin might be beneficial for pain relief in humans.
Asunto(s)
Aminas/farmacología , Anticonvulsivantes/farmacología , Ácidos Ciclohexanocarboxílicos/farmacología , Ácidos Nipecóticos/farmacología , Dimensión del Dolor/efectos de los fármacos , Ácido gamma-Aminobutírico/farmacología , Aminas/administración & dosificación , Animales , Anticonvulsivantes/administración & dosificación , Ácidos Ciclohexanocarboxílicos/administración & dosificación , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Gabapentina , Masculino , Ratones , Modelos Estadísticos , Ácidos Nipecóticos/administración & dosificación , Tiagabina , Ácido gamma-Aminobutírico/administración & dosificaciónRESUMEN
The aim of this study was to determine the analgesic effect of gabapentin and tiagabine - two antiepileptic drugs, administered alone and in combination at the fixed-ratio of 1:1, in two phases of the formalin test in mice. Log-probit analysis was used to evaluate dose-response effects and calculate the ED(50) values for gabapentin, tiagabine, and their combination at the fixed-ratio of 1:1 in the phases I and II of the formalin test in mice. The types of interactions between both antiepileptic drugs were characterized using the isobolographic analysis. Results indicated that gabapentin and tiagabine produced the antinociceptive effect in both phases of the formalin test. The ED(50) values for gabapentin and tiagabine, administered singly, in the phase I of the formalin test were 29.59 and 2mg/kg, whereas in the phase II of the formalin test were 8.22 and 0.50 mg/kg, respectively. With isobolography, the ED(50 mix) values at the fixed-ratio combination of 1:1 were 7.30 mg/kg (phase I) and 0.48 mg/kg (phase II), indicating both additive and supra-additive (synergistic) interactions between gabapentin and tiagabine in the formalin test in mice. In conclusion, the combination of gabapentin with tiagabine at the fixed-ratio of 1:1 exerted additive interaction in the phase I and synergistic interaction in the phase II of the formalin test in mice. If the results from this study could be extrapolated to clinical settings, the combination of tiagabine with gabapentin might be beneficial in the pain relief in humans.