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Preclinical Research & Development The combination of nonsteroidal anti-inflammatory drugs (NSAIDs) with herbal products having analgesic and anti-inflammatory effects may increase their beneficial effects and limit their side effects. In this study, the effects of an interaction between α-bisabolol and the NSAID, diclofenac on nociception (formalin test), inflammation (paw inflammation produced by carrageenan) and gastric injury in rat was assessed. Diclofenac, α-bisabolol, or diclofenac-α-bisabolol combinations produced antinociceptive and anti-inflammatory effects in rat (p < .05). The systemic administration of diclofenac, but not α-bisabolol, produced gastric damage while the diclofenac-α-bisabolol combinations produced limited gastric damage. Effective dose (ED40 ) values were determined for each individual drug and analyzed isobolographically. The theoretical ED40 values for the antinociceptive (98.89 mg/kg) and the anti-inflammatory (41.2 mg/kg) effects differed from the experimental ED40 values (antinociception: 38.7 mg/kg and anti-inflammation: 13.4 mg/kg). We concluded that the interactions between diclofenac and α-bisabolol are synergistic. These data suggest that the diclofenac-α-bisabolol combinations can interact to produce minor gastric damage, thereby offering a safer therapeutic alternative for the clinical management of inflammation and/or inflammatory pain.
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Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Diclofenaco/uso terapêutico , Edema/tratamento farmacológico , Nociceptividade/efeitos dos fármacos , Sesquiterpenos/uso terapêutico , Animais , Carragenina , Sinergismo Farmacológico , Edema/induzido quimicamente , Formaldeído , Masculino , Sesquiterpenos Monocíclicos , Ratos Wistar , Estômago/efeitos dos fármacos , Estômago/patologiaRESUMO
Preclinical Research The coadministration of non-steroidal anti-inflammatory drugs (NSAIDs) with medicinal plant extracts may increase anti-inflammatory activity, thus permitting the use of lower NSAID doses and limiting the side effects. The aim of this study was to explore the interactions between an ethanolic extract of M. chamomilla extract (MCE) with two NSAIDs, diclofenac and indomethacin on carrageenan-induced paw inflammation and gastric injury in rats. Diclofenac, indomethacin and MCE, or combinations with MCE produced an anti-inflammatory effect. Effective dose (ED) values were estimated for the individual drugs, and isobolograms were constructed. The final experimental ED values were 483.7 mg/kg for diclofenac + MCE combination, and 212.6 mg/kg for indomethacin + MCE. These values were lower (p < 0.05) than the theoretical ED values (1186.9 mg/kg for diclofenac + MCE combination, and 1183.8 mg/kg for indomethacin + MCE). These data suggest that the interactions between NSAIDs and MCE that mediate the anti-inflammatory effects at the systemic level are synergistic and may have therapeutic advantages for the clinical treatment of inflammatory processes. Drug Dev Res 78 : 360-367, 2017. © 2017 Wiley Periodicals, Inc.
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Carragenina/efeitos adversos , Diclofenaco/administração & dosagem , Indometacina/administração & dosagem , Inflamação/tratamento farmacológico , Matricaria/química , Extratos Vegetais/administração & dosagem , Animais , Diclofenaco/uso terapêutico , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Indometacina/uso terapêutico , Inflamação/induzido quimicamente , Masculino , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Resultado do TratamentoRESUMO
The aim of this study was to evaluate the relaxant and anti-inflammatory effects of two thalidomide analogs as phosphodiesterase-4 (PDE-4) inhibitors in pregnant rat uterus. Uteri from Wistar female rats were isolated at 19 day of pregnancy. Uterine samples were used in functional studies to evaluate the inhibitory effects of the thalidomide analogs, methyl 3-(4-nitrophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4NO2PDPMe) and methyl 3-(4-aminophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4APDPMe), on prostaglandin-F2α (PGF2α)-induced phasic, K+-induced tonic, and Ca2+-induced contractions. Accumulation of cAMP was quantified in uterine homogenates by ELISA. Anti-inflammatory effect was assessed by using ELISA for determination of the pro-inflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin (IL)-1ß, and anti-inflammatory IL-10, from uterine explants stimulated with lipopolysaccharide (LPS). Nifedipine, forskolin and rolipram were used as positive controls where required. Both thalidomide analogs induced a significant inhibition of the uterine contractions induced by the pharmaco- and electro-mechanic stimuli. Nifedipine and forskolin were more potent than the analogs to inhibit the uterine contractility, but these were more potent than rolipram, and 4APDPMe was equieffective to nifedipine. Thalidomide analogs increased uterine cAMP-levels in a concentration-dependent manner. The LPS-induced TNFα and IL-1ß uterine secretion was diminished in a concentration-dependent fashion by both analogs, whereas IL-10 secretion was increased significantly. The thalidomide analogs induced utero-relaxant and anti-inflammatory effects, which were associated with the increased cAMP levels as PDE-4 inhibitors in the pregnant rat uterus. Such properties place these thalidomide analogs as potentially safe and effective tocolytic agents in a field that urgently needs improved pharmacological treatments, as in cases of preterm labor.
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Nursing staff spend more time with patients with pain than any other health staff member. For this reason, the nurse must possess the basic knowledge to identify the presence of pain in patients, to measure its intensity and make the steps necessary for treatment. Therefore, a prospective, descriptive, analytical, and cross-sectional study was conducted to investigate the knowledge and attitudes regarding pediatric pain in two different populations. The questionnaire, Pediatric Nurses Knowledge and Attitudes Survey Regarding Pain (PKNAS), was applied to 111 hospital pediatric nurses and 300 university nursing students. The final scores for pediatric nurses and nursing students were 40.1 ± 7.9 and 40.3 ± 7.5, respectively. None of the sociodemographic variables predicted the scores obtained by the participants (P > 0.05). There was a high correlation between the PKNAS scores of pediatric nurses and nursing students (r = 0.86, P < 0.001). It was observed that the degree of knowledge about pain and its treatment was very low in both groups. Due to this deficiency, pain in children remains inadequately managed, which leads to suffering in this population. It is necessary to increase the continued training in this subject in both areas.
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Introducción: la notificación de reacciones adversas a medicamentos es una obligación a nivel mundial. Aunque se han establecido muchas metodologías para esta acción, en la actualidad existen problemas. Objetivo: determinar la frecuencia de sospecha de reacciones adversas a la administración de medicamentos en pacientes y comparar la accesibilidad del llenado del formato de la NOM220 de la Secretaría de Salud y la Tarjeta Amarilla propuesta por la Organización Mundial de la Salud. Métodos: estudio transversal y observacional. Participaron 50 médicos responsables de las clínicas de diabetes del Estado de Hidalgo. Inicialmente, los médicos fueron capacitados para identificar las sospechas de reacciones adversas a la administración de medicamentos en los pacientes atendidos. Se realizó un diseño cruzado, en el que el 50 por ciento de los médicos utilizaron por tres meses el formato de la NOM220 y 50 por ciento la Tarjeta Amarilla. Después intercambiaron formatos y los utilizaron durante los tres meses siguientes. Al cabo de este periodo, respondieron un cuestionario para determinar la utilidad, claridad, tiempo de llenado y practicidad de ambos formatos. Se realizó estadística descriptiva y análisis bivariado para determinar los factores asociados a las sospecha de reacciones adversas a medicamentos, con el software SPSS (versión 17). Resultados: se registraron 46 sospechas de reacciones adversas a medicamentos en 46 pacientes con el formato de la NOM220 y 78 sospechas de reacciones adversas a medicamentos con la Tarjeta Amarilla en 78 pacientes. Todas las sospechas de reacciones adversas a la administración de medicamentos fueron tipo A. Los médicos recomiendan la utilización de la Tarjeta Amarilla, consideran claro el formato, sencillo, legible, fácil de llenar, entendible y accesible (p< 0,05). Conclusiones: los resultados permiten proponer la Tarjeta Amarilla como una alternativa más accesible para la notificación de sospechas de reacciones adversas a medicamentos, o se hagan adecuaciones al formato de la NOM220(AU)
Introduction: the reporting of adverse drug reactions is a global obligation. Although many methods have been implemented, there are still problems at present. Objective: to determine the frequency of suspected adverse reactions in patients and to compare the access to filling out the NOM220 formats of the Secretaría de Salud and the Yellow Card suggested by the World Health Organization. Methods: a cross-sectional and observational study was made. Fifty physicians responsible for the diabetes clinics in the state of Hidalgo participated in the study. First, the physicians were trained to identify the suspected adverse drug reactions in their patients. A crossover design was created where 50 percent of physicians used the NOM220 format and 50 percent the Yellow Card. Three months later, they exchanged the formats and used them during the following three months. After this period, questionnaire was administered to determine the usefulness, clarity, filling out time and convenience of the formats. Descriptive statistics and bivariate analyses were applied to determine the factors associated with the suspected adverse drug reactions with SPSS software (version 17). Results: a total of 46 suspected adverse reactions were registered in 46 patients using NOM220 format and 78 with the Yellow Card in 78 patients. All the suspected adverse reactions were type A. The physicians recommended the use of Yellow Card since they considered that it is practical, simple, readable, understandable, accessible and requires less time to fill it out (p< 0.05). Conclusions: the results allow selecting the Yellow Card as the most accessible choice for reporting suspected drug adverse reactions; additionally, they suggest that adjustments should be also made in the NOM220 format(AU)
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Humanos , Animais , Masculino , Diabetes Mellitus/etnologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Farmacovigilância , Estudos Transversais , Estudos Prospectivos , Estudo Observacional , MéxicoRESUMO
There is evidence that systemic sulfonylureas block diclofenac-induced antinociception in normal rat, suggesting that diclofenac activates ATP-sensitive K(+) channels. However, there is no evidence for the systemic interaction between different non-steroidal anti-inflammatory drugs (NSAIDs) and sulfonylureas in streptozotocin (STZ)-diabetic rats. Therefore, this work was undertaken to determine whether two sulfonylureas, glibenclamide and glipizide, have any effect on the systemic antinociception that is induced by diclofenac (30 mg/kg), lumiracoxib (56 mg/kg), meloxicam (30 mg/kg), metamizol (56 mg/kg) and indomethacin (30 mg/kg) using the non-diabetic and STZ-diabetic rat formalin test. Systemic injections of NSAIDs produced dose-dependent antinociception during the second phase of the test in both non-diabetic and STZ-diabetic rats. Systemic pretreatment with glibenclamide (10 mg/kg) and glipizide (10 mg/kg) blocked diclofenac-induced systemic antinociception in the second phase of the test (P<0.05) in both non-diabetic and STZ-diabetic rats. In contrast, pretreatment with glibenclamide or glipizide did not block lumiracoxib-, meloxicam-, metamizol-, and indomethacin-induced systemic antinociception (P>0.05) in both groups. Results showed that systemic NSAIDs are able to produce antinociception in STZ-diabetic rats. Likewise, data suggest that diclofenac, but not other NSAIDs, activated K(+) channels to induce its systemic antinociceptive effect in the non-diabetic and STZ-diabetic rat formalin test.
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Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Canais KATP/agonistas , Canais KATP/fisiologia , Medição da Dor/efeitos dos fármacos , Analgésicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Diabetes Mellitus Experimental/metabolismo , Masculino , Medição da Dor/métodos , Ratos , Ratos WistarRESUMO
The aim of this study was to compare the efficacy of diclofenac, for the treatment of acute pain originated by lower-limb fracture and surgery, with that of diclofenac plus B vitamins. This was a single-center, prospective, randomized, and double-blinded clinical trial. Patients with lower-limb closed fractures rated their pain on a 10 cm visual analog scale (VAS). Patients were then randomized to receive diclofenac or diclofenac plus B vitamins (thiamine, pyridoxine, and cyanocobalamin) intramuscularly twice daily. Patient evaluations of pain intensity were recorded throughout two periods: twenty-four hours presurgery and twenty-four hours postsurgical. One hundred twenty-two patients completed the study. The subjects' assessments of limb pain on the VAS showed a significant reduction from baseline values regardless of the treatment group. Diclofenac plus B vitamins combination was more effective to reduce the pain than diclofenac alone. The results showed that the addition of B vitamins to diclofenac increased its analgesic effect. The novelty of this paper consists in that diclofenac and diclofenac plus B vitamins were useful for treatment of acute pain originated by lower-limb fracture and surgery.
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OBJECTIVE: To evaluate the interaction type of the human uterine relaxant effect of the paracetamol-pyrilamine combination (PPC) in vitro. STUDY DESIGN: Uterine strips were contracted with KCl (60 mM) and treated with vehicle or increasing concentrations of paracetamol (100-3200 µM), pyrilamine (3.2-100 µM) or the PPC. The relaxing effects of the drugs alone and in combination were measured. Isobolographic analysis was used to determine the pharmacologic interaction type. RESULTS: Paracetamol, pyrilamine and the PPC produced a significant relaxing effect on non-pregnant human uterine strips pre-contracted with KCl (60 mM). The EC30 values for paracetamol and pyrilamine on the uterine contraction were 2391.3±595.3 µM and 14.7±1.7 µM, respectively. The derived experimental EC30 for the PPC was 401.8±129.8 µM. This value was significantly lower (p<0.05) than the theoretical EC30 expected for a purely additive interaction, which was 1203.0±297.7 µM for the PPC. The interaction index (γ) was 0.33±0.14 for PPC, being statistically different from unity. CONCLUSION: Data suggest that low doses of the PPC can interact synergistically and therefore this drug association may represent a therapeutic advantage for the clinical treatment of dysmenorreic pain.
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Acetaminofen/farmacologia , Analgésicos não Narcóticos/farmacologia , Antagonistas dos Receptores Histamínicos H1/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Miométrio/efeitos dos fármacos , Pirilamina/farmacologia , Adulto , Interpretação Estatística de Dados , Sinergismo Farmacológico , Dismenorreia/tratamento farmacológico , Feminino , Humanos , Técnicas In Vitro , Pessoa de Meia-Idade , Fármacos Neuromusculares Despolarizantes/farmacologia , Concentração Osmolar , Cloreto de Potássio/farmacologia , Contração Uterina/efeitos dos fármacos , Adulto JovemRESUMO
It has been shown that the association of non-steroidal anti-inflammatory drugs with plant extracts can increase their antinociceptive activity, allowing the use of lower doses and, thus, limiting side effects. Therefore, the aim of this study was to examine the effects of the interaction between naproxen and citral on nociception and gastric injury in rats. Naproxen, citral, or combinations of naproxen and citral produced an antinociceptive effect. The administration of naproxen produced significant gastric damage, but this effect was not obtained with either citral or the naproxen-citral combination. The ED(50) value was estimated for the individual drugs and an isobologram was constructed. The derived theoretical ED(50) for the antinociceptive effect (423.8 mg/kg) was not significantly different from the observed experimental value (359.0 mg/kg); hence, the interaction between naproxen and citral mediating the antinociceptive effect is additive. These data suggest that the naproxen-citral combination interacts at the systemic level, produces minor gastric damage, and potentially has therapeutic advantages for the clinical treatment of inflammatory pain.
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Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/efeitos adversos , Monoterpenos/uso terapêutico , Naproxeno/efeitos adversos , Naproxeno/uso terapêutico , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Monoterpenos Acíclicos , Analgésicos/efeitos adversos , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Mucosa Gástrica/efeitos dos fármacos , Monoterpenos/efeitos adversos , Medição da Dor , Ratos , Ratos Wistar , Índice de Gravidade de DoençaRESUMO
The combination of non-steroidal anti-inflammatory drugs with herbs having analgesic effects can increase their antinociceptive activity and limit their side effects. The aim of the present study was to examine the effects on inflammation and gastric injury in rats resulting from the interaction between naproxen and citral. Naproxen, citral, or fixed-dose naproxen-citral combinations were administered orally and their anti-inflammation (carrageenan-induced paw edema) and gastric damage were assessed in rats. The pharmacological interaction type was evaluated by the isobolographic analysis. Naproxen, citral, or combinations of naproxen and citral produced anti-inflammatory effects. The sole administration of naproxen produced significant gastric damage, but this effect was not obtained with either citral or combinations. ED(30) values were estimated for the individual drugs, and isobolograms were constructed. The derived theoretical ED(30) for the anti-inflammatory effect was 504.4 mg/kg; this was significantly higher than the observed experimental value (190.6 mg/kg). These results indicate that a synergistic interaction underlies the anti-inflammatory effect. The data suggests that the naproxen-citral combination can interact and to produce minor gastric damage and may have therapeutic advantages for the clinical treatment of inflammation.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Inflamação/tratamento farmacológico , Monoterpenos/uso terapêutico , Naproxeno/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Gastropatias/prevenção & controle , Monoterpenos Acíclicos , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/farmacologia , Carragenina , Sinergismo Farmacológico , Edema/tratamento farmacológico , Edema/etiologia , Interações Ervas-Drogas , Masculino , Monoterpenos/farmacologia , Naproxeno/efeitos adversos , Naproxeno/farmacologia , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Gastropatias/etiologia , Gastropatias/patologiaRESUMO
Pharmacovigilance is the permanent collection and assessment of the safety data of drugs in the interest of precise knowledge of the safety profile. We monitored notifications of suspected adverse reactions (AR) produced by psychoactive medications (ARPM) in a Psychiatry Hospital, during a 4-month period. Yellow cards for adverse reaction reporting were distributed to the medical personal at the Hospital Psiquiátrico Villa Ocaranza, Pachuca Hidalgo, Mexico. For each notification, the ARPM was analyzed in order to verify causality. One hundred twelve hospitalized patients entered the study (44 male and 68 female). The mean +/- SD age of the patients was 46 +/- 4.5 years. The major diagnoses found were: schizophrenia (35.7%), severe mental retardation (17 %), moderate mental retardation (MMR)/epilepsy (12.5%), MMR (8.03%), and others (26.7%). During the study there were 721 therapeutic regimens prescribed to patients on psychiatric service. Patients were receiving an average of 5.3 +/- 1.1 (range 4 to 8) psychiatric medications. The psychiatrists reported only 5 ARPMs in five patients (prevalence: 4.46%). Among the drugs involved were neuroleptics (47.8%), antiepileptic (39.1%), and others (13.04%). The organs and systems affected by the ARs were the central nervous system, skin, endocrinological and gastrointestinal. A causal association between the medication and the AR were classified as probable in three cases, as possible in one case, as doubtful in one case and as definite in no case.
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Farmacovigilância , Psicotrópicos/uso terapêutico , Adulto , Feminino , Hospitais Psiquiátricos , Humanos , Masculino , México , Pessoa de Meia-IdadeRESUMO
Tissue degeneration, infection, inflammation, cancer, trauma, surgery and limb fractures all produce pain. Each of these physiological abnormalities requires a therapeutic approach different from the last. In acute pain, caused by fracture, several classes of analgesics have been utilized. These basic remedies for analgesia, however, are still confined to a small number of medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), local anesthetics and opioids. In addition, most of these drugs have side effects, limiting their use in clinical practice. The purpose of this study was to compare the efficacy of three NSAIDs to relief acute pain caused by ankle fracture. Sixty subjects with ankle fracture were randomized to receive ketorolac, diclofenac, or etoricoxib, every 12 hours in a prospective, double-blind study. Forty-nine patients completed the study. The subjects' assessments of ankle pain on the visual analog scale and a Likert scale showed a significant reduction from baseline over 24 hr, regardless the treatment group. All treatments showed a similar profile in pain reduction. Etoricoxib, diclofenac and ketorolac twice daily are a rapid and effective treatment for acute pain. All the regimens were well tolerated in this study.
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Dor Aguda/tratamento farmacológico , Traumatismos do Tornozelo/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Diclofenaco/uso terapêutico , Fraturas Ósseas/tratamento farmacológico , Cetorolaco/uso terapêutico , Piridinas/uso terapêutico , Sulfonas/uso terapêutico , Adulto , Traumatismos do Tornozelo/fisiopatologia , Método Duplo-Cego , Etoricoxib , Fraturas Ósseas/fisiopatologia , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
There is evidence that local peripheral administration of gabapentin produces antinociception through the activation of the ATP-sensitive K+-channel. However, this interaction has not been evaluated systemically, nor in diabetic rat. This work was undertaken to determine whether glibenclamide has any effect on the systemic antinociception induced by gabapentin. Inflammatory pain was induced by injection of formalin in diabetic rats. Reduction of flinching behavior was considered as antinociception. Systemic administration of gabapentin (10-56 mg/kg, i.p.) produced a dose-dependent antinociception in both phases of the formalin test. Also, glibenclamide (1-10 mg/kg, s.c.) blocked the gabapentin-induced antinociception. Given alone glibenclamide did not significantly modify formalin-induced nociception in diabetic rats. Our data suggest that gabapentin is able to reduce formalin-induced nociception in streptozotocin-injected rats. In addition, these data are consistent with gabapentin-mediated activation of ATP-sensitive-K+ channels to produce systemic antinociception in the formalin test in diabetic rats.
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Aminas/uso terapêutico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Glibureto/uso terapêutico , Medição da Dor , Ácido gama-Aminobutírico/uso terapêutico , Animais , Diabetes Mellitus Experimental/fisiopatologia , Interações Medicamentosas , Gabapentina , Canais KATP/efeitos dos fármacos , Masculino , Ratos , Ratos WistarRESUMO
Heliopsis longipes is an herbaceous plant found in Mexico. Heliopsis longipes is traditionally used for its analgesic and anesthetic properties. Plant extracts may represent a therapeutic advantage for the clinical treatment of pain. Therefore, the main objective of this study was to determine the possible antihyperalgesic effect produced by the Heliopsis longipes ethanolic extract (HLEE) in the Hargreaves model of thermal hyperalgesia in the mouse. HLEE was administrated systemically to mice and the antihyperalgesic effect was evaluated using the thermal hyperalgesia test. Oral Administration of HLEE produced a dose-dependent antihyperalgesic effect. Previously, it was reported that Heliopsis longipes extract was able to release GABA in mice temporal cortex slices. Therefore, it is likely that the antihyperalgesic effect observed in our study could result from GABA liberation and its inhibition of excessive excitation of nociceptive circuits in the thalamus and cortex evoked by tissue injury. Our results suggest that HLEE may represent a therapeutic advantage for the clinical treatment of inflammatory pain.
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Asteraceae , Hiperalgesia/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Animais , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
The Casimiroa pringlei essential oil was analyzed to determine its chemical composition. Its effect on rat uterine smooth muscle was studied and compared with verapamil. Pure commercial piperitone, eucalyptol, and alpha-terpineol, the major constituents of C. pringlei essential oil, were tested on the uterine tonic contraction induced by high-potassium depolarizing solution (KCl 60 mM).
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Casimiroa , Óleos Voláteis/farmacologia , Parassimpatolíticos/farmacologia , Contração Uterina/efeitos dos fármacos , Útero/efeitos dos fármacos , Análise de Variância , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Casimiroa/química , Cromatografia Gasosa , Feminino , Espectrometria de Massas , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Parassimpatolíticos/química , Parassimpatolíticos/isolamento & purificação , Extratos Vegetais , Óleos de Plantas/química , Óleos de Plantas/isolamento & purificação , Óleos de Plantas/farmacologia , Cloreto de Potássio/farmacologia , Ratos , Verapamil/farmacologiaRESUMO
Lepechinia caulescens Ortega Epling (Lamiaceae) is a perennial herb used in Mexican folk medicine to treat diabetes, hypertension, gastrointestinal infections, dysmenorrhea and as abortifacient. In this study, a bioassay-guided fractionation of the hexanes extract of the leaves, evaluating the capacity to relax contraction of rat uterus rings induced by KCl (60mM), was made. The results indicated that, from the four isolated terpenes, spathulenol (1) was the most potent spasmolytic agent, followed by methyl 9alpha,13alpha-epidioxyabiet-8(14)-en-18-oate (2), 9alpha-hydroxydehydroabietyl alcohol (4) and dehydroabietic acid (3) studied at 10 and 30 microg/mL. The spasmolytic activity of 1 was totally reverted by addition of increasing extracellular Ca2+ concentrations ([Ca2+]o), while incubation of uterus rings with 1 in calcium free solutions reduced the contraction produced by [Ca2+]o in a concentration-dependent manner. Moreover, the presence of L-NAME (100 microM) or propranolol (10 microM) did not block the spasmolytic effect. These results suggest that 1 induces a greater blocking action on voltage-operated calcium channels. EtOAc and MeOH extracts of the leaves, which showed slight relaxing activity, led to 4 and rosmarinic acid (5).
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Lamiaceae/química , Parassimpatolíticos/farmacologia , Extratos Vegetais/farmacologia , Contração Uterina/efeitos dos fármacos , Animais , Cálcio/metabolismo , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/metabolismo , Feminino , Técnicas In Vitro , Medicina Tradicional , México , Parassimpatolíticos/química , Parassimpatolíticos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Cloreto de Potássio , Ratos , Ratos Wistar , Terpenos/isolamento & purificação , Terpenos/farmacologia , Útero/efeitos dos fármacos , Útero/metabolismoRESUMO
It has been shown that the association of opioids analgesic agents with non-steroidal anti-inflammatory drugs (NSAIDs) can increase their antinociceptive activity, allowing the use of lower doses and thus limiting side effects. Therefore, the goal of the present study was to examine the possible pharmacological interaction between acemetacin and two opioids in the Hargreaves model of thermal hyperalgesia in the mouse. Acemetacin, codeine, nalbuphine or fixed-dose ratios acemetacin-codeine and acemetacin-nalbuphine combinations were administrated systemically to mice and the antihyperalgesic effect was evaluated using the thermal hyperalgesia test. All treatments produced a dose-dependent antihyperalgesic effect. ED40 values were estimated for all the treatments and an isobologram was constructed. The derived theoretical ED40 for the acemetacin-codeine and acemetacin-nalbuphine combinations were 55.9+/-4.9 mg/kg and 40.3+/-3.8 mg/kg, respectively, being significantly higher than the actually observed experimental ED40, 14.5+/-1.7 mg/kg and 12.7+/-2.2 mg/kg, respectively. These results correspond to synergistic interactions between acemetacin and opioids on the Hargreaves model of thermal hyperalgesia. Highest doses of the individual drugs or the combinations did not affect motor coordination in the balancing test on a rota-rod. Data suggest that low doses of the acemetacin-opioids combination can interact synergistically at systemic level and therefore this drugs association may represent a therapeutic advantage for the clinical treatment of inflammatory pain.
Assuntos
Analgésicos Opioides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Temperatura Alta , Hiperalgesia/tratamento farmacológico , Indometacina/análogos & derivados , Animais , Área Sob a Curva , Codeína/uso terapêutico , Interpretação Estatística de Dados , Interações Medicamentosas , Indometacina/uso terapêutico , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nalbufina/uso terapêuticoRESUMO
OBJECTIVES: The primary was to assess the frequency of therapeutic non-compliance due to ADRs in a cohort of patients with recently diagnosed systemic hypertension. The secondary objectives were to evaluate the blood pressure control during the follow-up in the whole cohort and in patients who received non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: A cohort of 73 recently diagnosed ambulatory hypertensive patients was followed-up for 6 months. Validated questionnaires for identification of therapeutic scheme changes and ADRs were applied monthly, during each medical visit. RESULTS: Family physicians selected monotherapy in 79% of patients. The frequency of therapeutic non-compliance was 44%; non-compliance secondary to ADR was 7%. Systolic and diastolic blood pressure at the beginning of the study were 140 +/- 15/90 +/- 15 mm Hg for the whole cohort. At the end of the study the figures were 130 +/- 11/85 +/- 6 (p < 0.001). Patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) had higher blood pressure levels than the groups of patients not receiving such kind of drugs (134 +/- 10 vs. 128 +/- 8 mm Hg, p = 0.025 and 88 +/- 7 vs. 83 +/- 5 mm Hg, p = 0.05). CONCLUSIONS: The drugs used in the present study as monotherapy are considered acceptable choices for hypertension treatment. The frequency of therapeutic non-compliance was within the limits reported in the literature and the frequency of therapeutic non-compliance secondary to ADRs in this cohort was lower than that reported in the literature. Higher blood pressure was found in the group of patients receiving NSAIDs.
Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Cooperação do Paciente/estatística & dados numéricos , Atenção Primária à Saúde , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Estudos de Coortes , Comorbidade , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Objectives. The primary was to assess the frequency of therapeutic non-compliance due to ADRs in a cohort of patients with recently diagnosed systemic hypertension. The secondary objectives were to evaluate the blood pressure control during the follow-up in the whole cohort and in patients who received non-steroidal anti-inflammatory drugs (NSAIDs). Methods. A cohort of 73 recently diagnosed ambulatory hypertensive patients was followed-up for 6 months. Validated questionnaires for identification of therapeutic scheme changes and ADRs were applied monthly, during each medical visit. Results. Family physicians selected monotherapy in 79% of patients. The frequency of therapeutic non-compliance was 44%; non-compliance secondary to ADR was 7%. Systolic and diastolic blood pressure at the beginning of the study were 140 ± 15/90 ± 15 mm Hg for the whole cohort. At the end of the study the figures were 130 ± 11/85 ± 6 (p < 0.001). Patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) had higher blood pressure levels than the groups of patients not receiving such kind of drugs (134 ± 10 vs. 128 ± 8 mm Hg, p = 0.025 and 88 ± 7 vs. 83 ± 5 mm Hg, p = 0.05). Conclusions. The drugs used in the present study as monotherapy are considered acceptable choices for hypertension treatment. The frequency of therapeutic non-compliance was within the limits reported in the literature and the frequency of therapeutic non-compliance secondary to ADRs in this cohort was lower than that reported in the literature. Higher blood pressure was found in the group of patients receiving NSAIDs.
Objetivos. El objetivo primario fue evaluar la frecuencia de falta de cumplimiento terapéutico debido a la presencia de reacciones adversas a medicamentos (RAMs) con el uso de antihipertensivos; los objetivos secundarios fueron evaluar el control de la presión arterial durante el seguimiento y en aquellos pacientes que recibieron fármacos antiinflamatorios no esteroideos. Métodos. Se integró una cohorte de 73 pacientes hipertensos de reciente diagnóstico, a los que se les vigiló durante seis meses. En cada visita médica mensual se les aplicaron cuestionarios validados, para identificar cambios en el esquema terapéutico y RAMs. Resultados. Los médicos familiares emplearon monoterapia en 79% de los pacientes. La falta de cumplimiento terapéutico se presentó en 44%; el incumplimiento terapéutico secundario a RAMs se observó en 7% de los casos. En todos los pacientes la presión arterial sistólica y diastólica al inicio del estudio fue 140 ± 15/90 ± 15 mm Hg y al final del estudio las cifras fueron 130 ± 11 / 85 ± 6 (p < 0.001). Los pacientes que recibieron fármacos antiinflamatorios no esteroideos (AINEs) tuvieron cifras de presión arterial más elevadas que pacientes que no recibieron este tipo de fármacos (134 ± 10 vs. 128 ± 8, p = 0.025 y 88 ±7 vs. 83 ± 5 mm Hg, p - 0.05). Conclusiones. Los fármacos empleados en este estudio como monoterapia son fármacos aceptados para el tratamiento de la hipertensión. La frecuencia de falta de cumplimiento terapéutico se ubicó dentro de los límites descritos en la literatura y la falta de cumplimiento terapéutico secundario a RAMs fue menor que lo informado en la literatura. Se observaron cifras de presión arterial elevadas en pacientes que recibieron AINEs.