morphinans and Kidney-Diseases

The analgesic efficacy and safety of butorphanol tartrate are discussed in 2 groups of patients who underwent urological procedures. The first group of 83 patients is presented as a retrospective review of the postoperative use of butorphanol. The second group of patients was involved in a double-blind, randomized comparative trial of butorphanol (2 or 4 mg) and meperidine (80 mg) for the relief of moderate to severe pain due to renal colic. Eighty-three patients with documented upper urinary tract calculi were evaluated for efficacy; 120 patients were evaluated for safety. Butorphanol 4 mg (i.m.) was more effective than butorphanol 2 mg (i.m.) and equivalent to meperidine 80 mg (i.m.). There were no statistically significant differences among the three treatment groups in regard to side effects. Overall, in the urology patients studied, butorphanol was found to be an effective and well tolerated agent that possesses important safety advantages when compared with the narcotic analgesics.

Topics: Adolescent; Adult; Aged; Butorphanol; Colic; Double-Blind Method; Female; Humans; Kidney Diseases; Male; Meperidine; Middle Aged; Morphinans; Pain Measurement; Pain, Postoperative; Prostatic Diseases; Random Allocation; Retrospective Studies; Urinary Calculi

The analgesic efficacy and safety of parenteral butorphanol and meperidine were compared. The double-blind, randomized study involved 120 patients presenting with moderate to severe renal colic. Pain intensity and pain relief were evaluated by trained observers at fixed time intervals for four hours after study drug was administered. Eighty-three patients with documented upper urinary tract calculi were evaluated for efficacy. Butorphanol 4 mg was significantly more effective than butorphanol 2 mg and was equivalent to meperidine 80 mg. Overall efficacy assessments were "good" or "excellent" for 87 per cent, 72 per cent, and 85 per cent, respectively. There were no significant differences in side effects among treatment groups in the 83 evaluable and 27 inevaluable patients receiving study drugs. Butorphanol was effective and well-tolerated in this patient population, with important advantages over opiate analgesics.

Topics: Butorphanol; Clinical Trials as Topic; Colic; Double-Blind Method; Drug Tolerance; Humans; Kidney Diseases; Meperidine; Morphinans; Random Allocation

Renal fibrosis is the common feature of chronic kidney disease and mainly mediated by TGFβ-associated pro-fibrogenic signaling, which causes excessive extracellular matrix accumulation and successive loss of kidney functions. Sinomenine (SIN), an alkaloid derived from medicinal herb extensively used in treatment of rheumatoid arthritis and various inflammatory disorders, displays renal protective properties in experimental animals; however its pharmacological potency against renal fibrosis is not explored. In this study we report that SIN possesses strong anti-renal fibrosis functions in kidney cell and in mouse fibrotic kidney. SIN beneficially modulated the pro-fibrogenic protein expression in TGFβ-treated kidney cells and attenuated the renal fibrotic pathogenesis incurred by unilateral ureteral obstruction (UUO), which correlated with its activation of Nrf2 signaling - the key defender against oxidative stress with anti-fibrotic potentials. Further investigation on its regulation of Nrf2 downstream events revealed that SIN significantly balanced oxidative stress via improving the expression and activity of anti-oxidant and detoxifying enzymes, and interrupted the pro-fibrogenic signaling of TGFβ/Smad and Wnt/β-catenin. Even more impressively SIN achieved its anti-fibrotic activities in an Nrf2-dependent manner, suggesting that SIN regulation of Nrf2-associated anti-fibrotic activities constitutes a critical component of SIN's renoprotective functions. Collectively our studies have demonstrated a novel anti-fibrotic property of SIN and its upstream events and provided a molecular basis for SIN's potential applications in treatment of renal fibrosis-associated kidney disorders.

Topics: Animals; Antirheumatic Agents; Catalase; Fibrosis; Glutathione Peroxidase; HEK293 Cells; Humans; Kidney Diseases; Mice; Morphinans; NF-E2-Related Factor 2; Oxidative Stress; Signal Transduction; Superoxide Dismutase; Transforming Growth Factor beta1