ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Celtis pallida Torr (Cannabaceae) is employed as a folk medicine for the treatment of inflammation, pain, skin infections, and diarrhea, among other diseases. AIM OF THE STUDY: The purpose of this work was to assess the chemical composition, the in vitro and in vivo toxicity, the antimicrobial, anti-inflammatory, antidiarrheal, antinociceptive, locomotor, and sedative effects of an ethanolic extract obtained from Celtis pallida aerial parts (CPE). MATERIALS AND METHODS: The composition of CPE was carried out by GC-MS. The in vitro and in vivo toxic activity of CPE was estimated with the comet assay (10-1000⯵g/ml) for 5â¯h in peripheral blood mononuclear cells, and the acute toxicity test (500-5000â¯mg/kg p.o.), for 14 days, respectively. The antimicrobial effect of CPE was evaluated using the minimum inhibitory concentration (MIC) assay, whereas the antidiarrheal activity (10-200â¯mg/kg p.o.) was calculated using the castor oil test. The antinociceptive effects of CPE (50-200â¯mg/kg p.o.) were estimated with the acetic acid and formalin tests, as well as the hot plate test. The sedative and locomotor activities of CPE (50-200â¯mg/kg p.o.) were assessed with the pentobarbital-induced sleeping time test and the rotarod test, respectively. RESULTS: The main compound found in CPE was the triterpene ursolic acid (22% of the extract). CPE at concentrations of 100⯵g/ml or higher induced genotoxicity in vitro and showed low in vivo toxicity (LD50 > 5000â¯mg/kg p.o.). Additionally, CPE lacked (MIC > 400⯵g/ml) antimicrobial activity but exerts antinociceptive (ED50 = 12.5⯱â¯1.5â¯mg/kg) and antidiarrheal effects (ED50 = 2.8â¯mg/kg), without inducing sedative effects or altering the locomotor activity. The antinociceptive activity of CPE suggests the participation of adrenoceptors, as well as the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway. CONCLUSION: C. pallida exerts its antinociceptive effects probably mediated by the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway.
Subject(s)
Analgesics/pharmacology , Cannabaceae , Pain Measurement/drug effects , Plant Components, Aerial , Plant Extracts/pharmacology , Analgesics/isolation & purification , Analgesics/toxicity , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/toxicity , Antidiarrheals/isolation & purification , Antidiarrheals/pharmacology , Antidiarrheals/toxicity , Dose-Response Relationship, Drug , Ethanol/pharmacology , Mice , Mice, Inbred BALB C , Mutagenicity Tests/methods , Pain Measurement/methods , Plant Extracts/isolation & purification , Plant Extracts/toxicity , UlmaceaeABSTRACT
ABSTRACT BACKGROUND AND OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to control arthroscopic pain. Addition of oral effective opioid "codeine" to NSAIDs may be more effective and decrease parenteral opioid consumption in the postoperative period. The aim of this study was to compare the efficacy and side effects of naproxen sodium and a new preparation naproxen sodium-codeine phosphate when administered preemptively for arthroscopic meniscectomy. METHODS: Sixty-one patients were randomized into two groups to receive either oral naproxen sodium (Group N) or naproxen sodium-codeine phosphate (Group NC) before surgery. The surgery was carried out under general anesthesia. Intravenous meperidine was initiated by patient-controlled analgesia (PCA) for all patients. The primary outcome measure was pain score at the first postoperative hour assessed by the Visual Analogue Scale (VAS). Sedation assessed by Ramsey Sedation Scale, first demand time of PCA, postoperative meperidine consumption, side effects and hemodynamic data were also recorded. RESULTS: The groups were demographically comparable. Median VAS scores both at rest and on movement were significantly lower in Group NC compared with Group N, except 18th hour on movement (p < 0.05). The median time to the first demand of PCA was shorter in Group N compared with Group NC (p < 0.001). Meperidine consumption was higher in Group N compared with Group NC (p < 0.001). There was no difference between groups with respect to side effects (p > 0.05). CONCLUSIONS: The combination of naproxen sodium-codeine phosphate provided more effective analgesia than naproxen sodium and did not increase side effects.
RESUMO JUSTIFICATIVA E OBJETIVOS: Os anti-inflamatórios não esteroides (AINEs) são frequentemente usados para controlar a dor após artroscopia. A adição de um opiáceo oral eficaz (codeína) aos AINEs pode ser mais efetiva e diminuir o consumo de opiáceo parenteral no pós-operatório. O objetivo deste estudo foi comparar a eficácia e os efeitos colaterais de naproxeno sódico e uma nova preparação, naproxeno sódico-fosfato de codeína, quando administrados preventivamente para meniscectomia artroscópica. MÉTODOS: Foram randomicamente divididos em dois grupos 61 pacientes para receber naproxeno sódico por via oral (Grupo N) ou naproxeno sódico-fosfato de codeína (Grupo NC) antes da cirurgia. A cirurgia foi feita sob anestesia geral. Meperidina intravenosa foi iniciada por meio de analgesia controlada pelo paciente (ACP) para todos os pacientes. O desfecho primário foi o escore de dor na primeira hora de pós-operatório, avaliada com a escala visual snalógica (EVA). A sedação foi avaliada com a escala de sedação de Ramsey. A primeira demanda de ACP, o consumo de meperidina no pós-operatório, os efeitos colaterais e os dados hemodinâmicos também foram registrados. RESULTADOS: Os grupos foram demograficamente comparáveis. As medianas dos escores EVA tanto em repouso quanto em movimento foram significativamente menores no Grupo NC comparado com o Grupo N; exceto para movimento na avaliação de 18 horas (p < 0,05). A mediana do tempo até a primeira demanda de ACP foi menor no Grupo N em comparação com o Grupo NC (p < 0,001). O consumo de meperidina foi maior no Grupo N em comparação com o Grupo NC (p < 0,001). Não houve diferença entre os grupos em relação aos efeitos colaterais (p > 0,05). CONCLUSÕES: A combinação de naproxeno sódico-fosfato de codeína forneceu analgesia mais efetiva que naproxeno sódico, sem aumentar os efeitos colaterais.
Subject(s)
Humans , Male , Female , Adult , Arthroscopy/methods , Naproxen/administration & dosage , Codeine/administration & dosage , Meniscus/surgery , Pain, Postoperative/drug therapy , Pain Measurement , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Naproxen/adverse effects , Double-Blind Method , Prospective Studies , Follow-Up Studies , Analgesia, Patient-Controlled/methods , Codeine/adverse effects , Drug Combinations , Analgesics, Opioid/administration & dosage , Meperidine/administration & dosage , Middle AgedABSTRACT
BACKGROUND AND OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to control arthroscopic pain. Addition of oral effective opioid "codeine" to NSAIDs may be more effective and decrease parenteral opioid consumption in the postoperative period. The aim of this study was to compare the efficacy and side effects of naproxen sodium and a new preparation naproxen sodium-codeine phosphate when administered preemptively for arthroscopic meniscectomy. METHODS: Sixty-one patients were randomized into two groups to receive either oral naproxen sodium (Group N) or naproxen sodium-codeine phosphate (Group NC) before surgery. The surgery was carried out under general anesthesia. Intravenous meperidine was initiated by patient-controlled analgesia (PCA) for all patients. The primary outcome measure was pain score at the first postoperative hour assessed by the Visual Analogue Scale (VAS). Sedation assessed by Ramsey Sedation Scale, first demand time of PCA, postoperative meperidine consumption, side effects and hemodynamic data were also recorded. RESULTS: The groups were demographically comparable. Median VAS scores both at rest and on movement were significantly lower in Group NC compared with Group N, except 18(th) hour on movement (p<0.05). The median time to the first demand of PCA was shorter in Group N compared with Group NC (p<0.001). Meperidine consumption was higher in Group N compared with Group NC (p<0.001). There was no difference between groups with respect to side effects (p>0.05). CONCLUSIONS: The combination of naproxen sodium-codeine phosphate provided more effective analgesia than naproxen sodium and did not increase side effects.
Subject(s)
Arthroscopy/methods , Codeine/administration & dosage , Meniscus/surgery , Naproxen/administration & dosage , Adult , Analgesia, Patient-Controlled/methods , Analgesics, Opioid/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Codeine/adverse effects , Double-Blind Method , Drug Combinations , Female , Follow-Up Studies , Humans , Male , Meperidine/administration & dosage , Middle Aged , Naproxen/adverse effects , Pain Measurement , Pain, Postoperative/drug therapy , Prospective StudiesABSTRACT
BACKGROUND AND OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to control arthroscopic pain. Addition of oral effective opioid "codeine" to NSAIDs may be more effective and decrease parenteral opioid consumption in the postoperative period. The aim of this study was to compare the efficacy and side effects of naproxen sodium and a new preparation naproxen sodium-codeine phosphate when administered preemptively for arthroscopic meniscectomy. METHODS: Sixty-one patients were randomized into two groups to receive either oral naproxen sodium (Group N) or naproxen sodium-codeine phosphate (Group NC) before surgery. The surgery was carried out under general anesthesia. Intravenous meperidine was initiated by patient-controlled analgesia (PCA) for all patients. The primary outcome measure was pain score at the first postoperative hour assessed by the Visual Analogue Scale (VAS). Sedation assessed by Ramsey Sedation Scale, first demand time of PCA, postoperative meperidine consumption, side effects and hemodynamic data were also recorded. RESULTS: The groups were demographically comparable. Median VAS scores both at rest and on movement were significantly lower in Group NC compared with Group N, except 18(th) hour on movement (p<0.05). The median time to the first demand of PCA was shorter in Group N compared with Group NC (p<0.001). Meperidine consumption was higher in Group N compared with Group NC (p<0.001). There was no difference between groups with respect to side effects (p>0.05). CONCLUSIONS: The combination of naproxen sodium-codeine phosphate provided more effective analgesia than naproxen sodium and did not increase side effects.