ABSTRACT
According to the high consumption of the mixture of B vitamins and diclofenac in several countries, this combination has constituted a frequently used option in pain therapy from inflammatory origin. Although the evidence obtained from inflammatory pain animal models has shown the existence of analgesic synergy between diclofenac and the B vitamins mixture, the corresponding clinical evidence is scarce. A double-blind, randomized clinical trial study was designed to characterize the analgesic effect and safety of diclofenac and B vitamins against diclofenac alone in patients with severe osteoarthritis. Forty eight patients programmed to total knee arthroplasty with a pain level ≥7 in a 1-10 cm visual analogue scale were allocated to receive a single intramuscular injection of sodium diclofenac (75 mg) alone or combined with thiamine (100 mg), pyridoxine (100 mg) and cyanocobalamin (5 mg), and the pain level was evaluated during 12 h post-injection. Diclofenac+B vitamins mixture showed a superior analgesic effect during the assessed period and also a better assessment of the pain relief perception by patients than diclofenac alone. This study constitutes a clinical support on the improvement of the analgesic effect of diclofenac by B vitamins in patients with osteoarthritis programmed to total knee arthroplasty, as a clinical model of inflammatory pain.
Subject(s)
Analgesics/pharmacology , Diclofenac/pharmacology , Osteoarthritis/drug therapy , Vitamin B Complex/pharmacology , Aged , Diclofenac/adverse effects , Double-Blind Method , Drug Synergism , Female , Humans , Male , Middle AgedABSTRACT
The pharmacokinetics of meloxicam, a potent analgesic and antiinflammatory drug used in several rheumatic diseases, has been studied in rats that received oral doses of 3.2, 5.6 or 10 mg/kg of meloxicam. Blood samples were obtained at selected times during 24 h after administration, and meloxicam concentrations were determined by a validated high-performance liquid chromatography (HPLC) method, using micro-whole-blood samples, developed in our laboratory. After administration of meloxicam, blood concentrations increased reaching a dose-dependent maximal concentration in about 2 h. Then, concentrations decayed with a half-life of 9 h. An increase in C(max) and AUC as a function of the dose was observed, and no statistically significant difference was observed in AUC/dose or C(max)/dose between doses. However, linearity could not be concluded because of the wide variability observed.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Thiazines/pharmacokinetics , Thiazoles/pharmacokinetics , Administration, Oral , Animals , Anti-Inflammatory Agents, Non-Steroidal/blood , Area Under Curve , Chromatography, High Pressure Liquid , Dose-Response Relationship, Drug , Half-Life , Male , Meloxicam , Rats , Rats, Wistar , Thiazines/blood , Thiazoles/bloodSubject(s)
Formaldehyde , Inflammation/prevention & control , Pain Measurement/drug effects , Pain/prevention & control , Vitamin B Complex/pharmacology , Animals , Behavior, Animal/drug effects , Female , Inflammation/chemically induced , Naloxone/pharmacology , Narcotic Antagonists/pharmacology , Pain/chemically induced , Rats , Rats, WistarSubject(s)
Airway Obstruction/drug therapy , Asthma/drug therapy , Bronchodilator Agents/pharmacokinetics , Bronchodilator Agents/therapeutic use , Theophylline/pharmacokinetics , Theophylline/therapeutic use , Adult , Airway Obstruction/metabolism , Airway Obstruction/physiopathology , Algorithms , Asthma/metabolism , Asthma/physiopathology , Bronchodilator Agents/administration & dosage , Female , Forced Expiratory Volume , Humans , Infusions, Intravenous , Male , Middle Aged , Models, Biological , Theophylline/administration & dosageSubject(s)
Blood Pressure/drug effects , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , Piperazines/pharmacology , Receptors, Adrenergic, alpha-1/classification , Animals , Autonomic Fibers, Preganglionic/physiology , Electric Stimulation , Male , Rats , Rats, Wistar , Vagotomy , Vasomotor System/drug effectsABSTRACT
The aim of the present study was to assess the role of vascular alpha 1D-adrenoceptors in the sympathetic vasopressor response in vivo. Specifically, we evaluated the effect of a selective alpha 1D-adrenoceptor antagonist, BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4,5)dec ane-7,9- dione 2HCl), on the vasopressor response induced by preganglionic (T7-T9) sympathetic stimulation in the pithed rat. The vasopressor response was dose-dependently sensitive to inhibition by intravenous BMY 7378 (0.1, 0.31, 1 and 3.1 mg/kg), doses of 1 and 3.1 mg/kg being equally effective. Like BMY 7378, 5-methylurapidil (0.1, 0.31, 1 and 3.1 mg/kg) antagonized the vasopressor response to spinal stimulation; doses of 1 and 3.1 mg/kg were also equally effective. In combination experiments, BMY 7378 (1 mg/kg, i.v.) and the alpha 1A-adrenoceptor antagonist, 5-methylurapidil (1 mg/kg, i.v.), showed an additive effect. The present results demonstrate that the alpha 1D-adrenoceptor subtype plays an important role in the pressor response to sympathetic nerve stimulation in the pithed rat, and confirm the participation of the alpha 1A-adrenoceptor subtype in the same response.