Pharmacol Rep
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Sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, has recently been reported to influence the antidepressant activity of some antidepressant drugs. The present study was undertaken to investigate the involvement of the nitric oxide/cyclic guanosine 3',5'-monophosphate/PDE5 (NO/cGMP/PDE5) signaling pathway in the antidepressant activity of paroxetine and to assess the interaction between paroxetine and sildenafil, in the forced swim test in mice. ⋯ The results suggest that paroxetine may exert its antidepressant action by decreasing cGMP levels and sildenafil, as a drug which has the opposite effect on the processes mediated via the NO/cGMP/PDE5 signaling pathway, may decrease the efficacy of paroxetine. However, the co-administration of paroxetine with sildenafil resulted in a potent reduction (80%) of locomotor activity, which suggests that the reversal of antidepressant action of paroxetine may have been a result of locomotor deficits. Further studies are required to explain the mechanism underlying this phenomenon.
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Randomized Controlled Trial
Effects of different priming doses of fentanyl on fentanyl-induced cough: a double-blind, randomized, controlled study.
Fentanyl-induced cough is not an uncommon phenomenon during the induction of general anesthesia. A preliminary randomized controlled study was designed to observe the effects of different priming doses of fentanyl on fentanyl-induced cough during induction of anesthesia. ⋯ In summary, a priming dose of fentanyl 0.5 μg/kg suppressed fentanyl-induced cough during induction of anesthesia in clinical practice. Fentanyl-induced cough was positively correlated with the dose of fentanyl.
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Target controlled infusion (TCI) devices are increasingly used in clinical practice. These devices unquestionably aid optimization of drug dosage. ⋯ One has to realize the limitation of this approach: these models may be less accurate when applied to patients in extreme clinical conditions: in intensive care units, with a considerable loss of blood, severe hypothermia or temporary changes in the composition of plasma, e.g., hypoalbuminemia. In the future, data obtained under these "extreme" clinical circumstances, may be used to modify the dosage algorithms of propofol TCI systems to match the clinical scenario.
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The animal models are pivotal for understanding the characteristics of acute renal failure (ARF) and development of effective therapy for its optimal management. Since the etiology for induction of renal failure is multifold, therefore, a large number of animal models have been developed to mimic the clinical conditions of renal failure. Glycerol-induced renal failure closely mimics the rhabdomyolysis; ischemia-reperfusion-induced ARF simulate the hemodynamic changes-induced changes in renal functioning; drug-induced such as gentamicin, cisplatin, NSAID, ifosfamide-induced ARF mimics the renal failure due to clinical administration of respective drugs; uranium, potassium dichromate-induced ARF mimics the occupational hazard; S-(1,2-dichlorovinyl)-L-cysteine-induced ARF simulate contaminated water-induced renal dysfunction; sepsis-induced ARF mimics the infection-induced renal failure and radiocontrast-induced ARF mimics renal failure in patients during use of radiocontrast media at the time of cardiac catheterization. Since each animal model has been created with specific methodology, therefore, it is essential to describe the model in detail and consequently interpret the results in the context of a specific model.
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Clinical Trial
Pharmacokinetics and pharmacodynamics of propofol in patients undergoing abdominal aortic surgery.
Available propofol pharmacokinetic protocols for target-controlled infusion (TCI) were obtained from healthy individuals. However, the disposition as well as the response to a given drug may be altered in clinical conditions. The aim of the study was to examine population pharmacokinetics (PK) and pharmacodynamics (PD) of propofol during total intravenous anesthesia (propofol/fentanyl) monitored by bispectral index (BIS) in patients scheduled for abdominal aortic surgery. ⋯ The BIS index was linked to the effect site concentrations through a sigmoidal E(max) model with EC(50) = 2.19 mg/l. The body weight, age, blood pressure and gender were not identified as statistically significant covariates for all PK/PD parameters. The population PK/PD model was successfully developed to describe the time course and variability of propofol concentration and BIS index in patients undergoing surgery.