Objectives:Terlipressin improves renal function in hepatorenal syndrome (HRS) is a known fact. However the reason for lack of its long-term survival benefits despite improvement in renal function remains unclear. The aim of this study was to analyze the survival benefits of terlipressin in HRS and to address the issue of non-responder state to terlipressin.Materials and Methods:Electronic databases and relevant articles were searched for all types of studies related to HRS and use of terlipressin in HRS. Reduction in all-cause mortality rate was the primary outcome measure. Reduction in mortality rate due to HRS and other causes of death were also analyzed.Results:With total 377 patients analyzed from eight eligible studies; terlipressin reduced all-cause mortality rate by 15% (Risk Difference: -0.15%, 95% CI:-0.26 to -0.03). Reduction in the mortality rate due to HRS at three months was 9% (Risk Difference:-0.09%, 95% CI:-0.18 to 0.00).Conclusion:Terlipressin has long term survival benefits perhaps at least up to three months but only with HRS as a cause of death not for other causes of death. Benefits and role of antioxidants like N- Acetylcysteine (NAC) in non-responder patients’ needs to be studied further. Long-term use of low dose terlipressin (<4mg/d) plus albumin and addition of antioxidant NAC to this regimen may help in improving both HRS reversal rate and survival rate in non-responders to terlipressin.

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 “tirapazamine”. 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.

Objective:To analyze the role of calcium in anxiety and its effect on anxiolytic activity of diazepam and verapamil.Materials and Methods:Study was conducted using female albino rats in light and dark arena; a nonconflicting animal experimental model for anxiety. Animals were divided into six groups with six animals in each group. Test drugs, calcium gluconate (10 mg/kg), diazepam (1 mg/kg), verapamil (5 mg/kg), calcium + diazepam, and calcium + verapamil were administered intraperitoneally. Percentage of time spent in light arena and number of entries into light arena were the two parameters observed for 5 min after 30 min of drug administration. ANOVA test was used for statistical analysis.Results:Compared to the control group, diazepam group, and calcium group, only calcium + diazepam group showed considerable increase in mean percentage of time spent in light arena. However, this increase was statistically insignificant. In the case of total number of entries into light arena, animals in calcium + diazepam group showed statistically significant increase in total number of entries into light arena when compared to calcium group and diazepam group.Conclusion:Results of the study suggest that calcium may enhance the anxiolytic activity of diazepam, but has no effect on anxiolytic activity of verapamil.

Objectives:To analyze the impact of various drugs used in conservative therapy on renal failure and mortality in hepatorenal syndrome (HRS) at a tertiary care teaching hospital.Materials and Methods:Retrospective review of hospital admission records was conducted for case records with HRS as diagnosis. Demographic and clinical data and drug utilization pattern were collected in a pre-designed patient information sheet. Impact of various drugs especially hepatoprotector antioxidant, silymarin, on survival benefits in terms of number of patients alive, change in mean arterial pressure (MAP) and change in serum creatinine at the end of treatment period were estimated by univariate and followed by multivariate analysis.Results:Of the total 89 case records, 31 met the eligibility criteria and were included in the analysis. On multivariate analysis, a significant correlation between use of intravenous fluids (IVFs) and survival benefits was observed (P < 0.05); wherein patients treated with IVFs had an increase in log odds of survival by 2.42 (95% CI = 1.06 to 121.13) as compared to patient not treated with IVF. However, MAP was not affected by any of the treatment modalities. While change in serum creatinine level was not significantly (P = 0.06, regression correlation = −0.3) correlated with duration of treatment with IVFs.Conclusion:Use of IVFs may be associated with better short-term survival benefits and favor HRS reversal. Use of silymarin as hepatoprotector antioxidant has no beneficial effects on HRS reversal or survival benefits.

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