ABSTRACT
Background: The benefits of achieving better response by adding tirapazamine, a specific hypoxic cancer cell killer to chemo and or radiotherapy is contradictory. This study aims at analyzing the efficacy and safety of tirapazamine, apart from understanding the reasons for its doubtful and inconsistent benefits.Methods: Electronic database search in PUBMED, EMBASE, Cochrane library was conducted using search term 搕irapazamine�. Randomized or cross-over studies comparing effects of tirapazamine vs other active treatment or placebo in patients >18yrs with any type of cancers were included under analysis. Overall Survival rate was the primary outcome measure while the incidences of grade-3 and 4 adverse drug reactions were the secondary outcome measure. Inverse variance method and both random and fixed effect models were used in the analysis by RevMan 5.3 software.Results: Total six studies were eligible with 1034 patients included in the analysis. Tirapazamine failed to show significant effect on overall survival rate at the end of one year (HR: 0.96, 95% CI: 0.88, 1.05), two year (HR: 1.04, 95% CI: 0.98, 1.12), three year (HR: 1.01, 95% CI: 0.89, 1.15) and five year (HR: 0.97, 95% CI: 0.77, 1.23) compared to placebo group. There was a significantly higher incidence of muscle cramps (Risk Difference, RD: 0.06, 95% CI: 0.02, 0.11) and dermal adverse events (RD: 0.03, 95% CI: 0.01, 0.06) in tirapazamine group.Conclusions: With the available evidences from clinical trials and preclinical studies, use of tirapazamine may not be justifiable and so is to side line this drug as another failed drug.
ABSTRACT
Mechanism of action of both magnesium and zinc in mediating their antidepressant activities is supposed to be through NMDA receptor antagonism. In the background of similarity in mechanism of action of zinc and magnesium as antidepressant through antagonism of NMDA receptors and evidences for anticonvulsant actions of magnesium being mediated through NMDA receptors blockade; present study was designed to test whether zinc has an additional anticonvulsant activity. Thirty six albino rats of either sex were divided in to 6 groups with 6 animals in each group. Group-I received distilled water (1ml/kg body weight) was control group. Group-II receiving phenytoin sodium (20mg/kg body weight) was the standard group. Group-III, IV and V were test groups receiving zinc sulfate at doses of 30mg/kg, 150mg/kg and 300mg/kg respectively. Animals were screened for anticonvulsant activity by Maximum Electroshock (MES) method and for generalized CNS depressant effect by photo-actometer method. With regard to anticonvulsant activity there was no statistically significant differences between any of the zinc sulfate treated groups with control and standard drug phenytoin. There was no evidence for possible anticonvulsant activity of zinc after single dose treatment at three selected doses in presence of generalized CNS depressant effect.
ABSTRACT
Incidence of obesity continues to rise worldwide with each year especially in developed countries. On the other hand success achieved with pharmacotherapy of obesity is disappointing, with some of the unmet needs in management strategies for obesity. Zonisamide an anti-epileptic drug has been found to have significant weight reduction properties with favorable safety profile. Present meta-analysis has been done with the aim of analyzing the efficacy of zonisamide in obesity. Electronic data bases were searched for all types of studies related to use of zonisamide in obesity and binge eating disorder. Change in body weight following treatment with zonisamide was the primary outcome measure analyzed. Both fixed and random effect models were used for statistical analysis of the data. With total 111 patients analyzed from 3 eligible studies; a significant reduction in weight from baseline by 5.88 kg (MD: -5.88; 95% CI:-7.51 to -4.25) at 16 weeks could be expected by treatment with zonisamide. As the data on safety profile of zonisamide especially long term was either incomplete or not available, analysis of safety profile was not carried out. Future studies analyzing the efficacy and long term safety of zonisamide on large population and for long term are preferred.