1.Adrenaline antagonizes proarrhythmic effect induced by Shuanghuanglian Injection
Lei LIU ; Xuehua LI ; Wei WANG ; Zhuoka LUO ; Kesu CHEN ; Zhongyue WANG ; Long CHEN
Chinese Journal of Pharmacology and Toxicology 2014;(3):334-339
OBJECTIVE Toexploretheantagonisticeffectofadrenaline(Adr)onproarrhythmiain-duced by Chinese herbal intravenous injection of Shuanghuanglian Injection (SHL).METHODS ① In vivo ECG recording was made to analyze effects of jugular intravenous (iv)injection of SHL alone and SHL plus adrenaline on ECG in guinea pigs.SHL and/or adrenaline were injected accumulatively in this order:SHL 276 mg·kg -1→2760 mg·kg -1→adrenaline 0.0078 mg·kg -1→adrenaline 0.039 mg·kg -1 .② In vitro ECG recording was made to analyze effects of SHL and SHL plus adrenaline on ECG in isola-ted hearts of guinea pigs.SHL and/or adrenaline were perfused in this order:SHL 0.3 g·L-1→SHL 1 .5 g·L-1→SHL 1 .5 g·L-1 +Adr 0.42 mg·L-1→SHL 1 .5 g·L-1→control perfusion solution.③ Single ventricular myocyte action potential was recorded to analyze the effect of SHL alone and SHL plus adren-aline on the action potential durations at 50% (APD50 )and 90% (APD90 )repolarization levels.SHL alone was perfused in such order:SHL 0.3 g·L-1 →SHL 1 .5 g·L-1 →SHL 3 g·L-1 +adrenaline 0.83 mg·L-1 .RESULTS ①SHL (2760 mg·kg -1 )significantly reduced heart rate and prolonged QRS and QTc intervals in vivo ECG.Adrenaline (0.0078 mg·kg -1 and 0.039 mg·kg -1 )significantly amelio-rated the proarrhyth mia of SHL by shortening QTc,P-R intervals and increasing heart rate.② SHL (1 .5 g·L-1 )remarkably reduced heart rate and prolonged P-R interval in isolated guinea pig hearts in vitro.Adrenaline (0.42 mg·L-1 )significantly increased heart rate and shortened the QTc interval.③ SHL (3 g·L-1 )remarkably prolonged the APD50 and APD90.Adrenaline abolished the prolonged effectofSHLonAPD50APD90.CONCLUSION Adrenalinemightbeclinicallyusedtotreatsevere adverse drug reactions induced by SHL based on its antagonistic effect on arrhythmia.
2.Effect of promethazine on eIectrophysioIogicaI action of guinea pig hearts
Wenbin SHANG ; Zhuoka LUO ; Xuehua LL ; Lei LLU ; Wei WANG ; Kesu CHEN ; Zhongyue WANG ; Long CHEN
Chinese Journal of Pharmacology and Toxicology 2014;(5):691-696
OBJECTIVE To explore the effect and underlying mechanism of promethazine(PMZ) on proarrhythmia in guinea pigs. METHODS ① InvivoECG recordings were made to analyze effects of jugular intravenous(iv)injection of PMZ on ECG in guinea pigs. PMZ was injected in this order:3.83→7.67→15.33→38.33 mg·kg-1 cumulatively. ② In vitroECG recordings were made to analyze effects of PMZ on ECG in isolated hearts of guinea pigs. PMZ was perfused in such order:0. 1 → 1 → 10 →50 μmol·L-1 . ③ L-type Ca2+ currents from ventricular myocytes in guinea pigs were recorded to investi-gate the PMZ's blocking effect. PMZ was perfused in such order:0.1→1→10→50 μmol·L-1→washout.④ hNav1.5 and hERG currents were recorded to investigate the PMZ's blocking effects. PMZ-perfused in such order:1→3→10→30 μmol·L-1 for hNav1.5 current analysis,and 0.3→1→3→10 μmol·L-1 for hERG current analysis. RESULTS ① PMZ(15.33 mg·kg-1 )significantly prolonged QRS intervals in guinea pigs invivoECG(P﹤0.05). PMZ(38.33 mg·kg-1 )prolonged QRS,QTc,and P-R intervals but reduced the heart rate( P﹤0.05). PMZ(10 μmol·L-1 )reduced the heart rate of isolated guinea pig hearts. PMZ 50 μmol·L-1 prolonged QRS and QTc intervals and further reduced the heart rate(P﹤0.05).③ PMZ inhibited the L-type Ca2+ current from ventricular myocytes in guinea pigs in a concentration-dependent manner with the lC50 of(8.9±1.0)μmol·L-1 . ④ PMZ inhibited the hNav1.5 and hERG currents in a concentration-dependent manner with the lC50 of 6.1±1.5 and(1.6±0.2)μmol·L-1 ,respectively. CONCLUSION PMZ might cause arrhythmia at overdoses and incombination with other drugs which have potential blocking effect on /Na ,Ca2+ and /kr currents. The proarrhythmic effect of PMZ might be mediated by the blocking effect on /Na ,Ca2+ and /kr currents.
3.Effect Analysis of Comprehensive Intervention for Rational Use of Ribonucleic Acid Ⅱ for Injection in Our Hospital
Mingzhu ZHANG ; Dan HUO ; Lixia HE ; Zhuoka LUO
China Pharmacy 2017;28(32):4572-4576
OBJECTIVE:To explore the effect of comprehensive intervention mode on the rational use of Ribonucleic acid Ⅱ for injection,and to provide reference for the management of adjuvant drugs for cancer therapy.METHODS:The rational use of ribonucleic acid Ⅱ was interfered by establishing evaluation criteria,reviewing medical record,establishing tumor therapy adjuvant management work group,classifying drug prescription right,examining and approving off-label drug use,strengthening the assessment and training,clinical pharmacists intervention.The utilization of ribonucleic acid Ⅱ was analyzed statistically in our hospital during Apr.-Jun.2015 (before intervention),Jul.-Sept.2015 (after the first intervention),Oct.-Dec.2015 (after the second intervention) and Jan.-Mar.2016 (after the third intervention).RESULTS:The reasonable rate of Ribonucleic acid Ⅱ for injection was 77.34% before intervention,and 83.25%,83.64%,95.12% after the first,second and third intervention respectively;the difference was statistically significant compared to before intervention (P<0.05).The irrational types included inappropriate indications,unsuitable treatment course,inappropriate usage and dosage,and unsuitable drug combination,etc.The percentage of these irrational types decreased from 2.96%,4.93%,13.79% and 0.99% before intervention to 1.63%,0,3.25% and 0 after the third intervention,respectively.The utilization rate of Ribonucleic acid Ⅱ for injection was reduced from 8.81% before intervention to 3.93% after the third intervention,the differences were statically significant (P<0.05).CONCLUSIONS:The comprehensive intervention model combined with multiple intervention methods can promote the rational use of Ribonucleic acid Ⅱ for injection.It is suggested to further study and evaluate the intervention effect of this model on other adjuvant drugs for cancer therapy.