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.

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.

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.