CYP2C19基因多态性对伏立康唑个体化用药的影响研究进展

目前,伏立康唑是临床抗真菌的常规用药之一,但伏立康唑体内代谢呈非线性药动学特性,CYP2C19遗传多态性以及多种药物与伏立康唑合用时均可影响伏立康唑药物浓度因此伏立康唑受CYP2C19基因多态性等多因素影响个体差异较大,不良反应严重,传统的给药模式已满足不了临床的需求。本文对基于CYP2C19基因多态性对伏立康唑药代动力学研究现状做一综述,以期为临床合理用药提供参考依据。     

临床药师开展伏立康唑不良反应重点监测的意义

伏立康唑是一种新型的三唑类抗真菌药,存在个体差异大、不良反应多、易发生药物相互作用等问题。2012年我院开展了临床药师在呼吸科对伏立康唑不良反应进行重点监测的项目,一是对伏立康唑的安全性做出进一步评价,促进合理用药,二是对单一药品不良反应重点监测这一模式的可行性及意义进行探究。经过为期6个月的临床监测,这一项目取得了阶段性的成果．使医务人员对伏立康唑不良反应的发生规律、临床特征、危险因素有了更加深入的认识。同时不良反应重点监测作为一种新的监测模式显示出其重要的现实意义。由此,可以把开展伏立康唑不良反应重点监测的经验、方法推广到对其他药品的不良反应监测中,在不断地尝试与探索中完善我国不良反应监测体系。     

伏立康唑治疗COPD合并肺真菌感染的不良反应分析

目的:分析伏立康唑治疗慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)合并肺部真菌感染导致的不良反应发生情况。方法:回顾性分析湖北医药学院附属东风医院2013年1月至2016年4月收治的慢性阻塞性肺疾病急性加重(acute exacerbation of chronic obstructive pulmonary disease,AECOPD)合并肺部真菌感染150例患者的临床资料。结果:150例患者中有32例接受伏立康唑治疗,其中8例发生伏立康唑相关不良反应,4例出现精神障碍。8例(25%)患者共发生了17例次伏立康唑相关不良反应,临床表现包括视觉障碍、皮疹、肝肾功能损害、低钾血症、精神障碍、尿失禁等,1/2病例同时出现多种不良反应,累及多个系统,发生在用药中的各个时间段,视觉障碍和精神症状发生时间较早,2~3 d内出现神经精神症状4例,发生率为12.5%。8例均合并使用了1种以上药物,包括左氧氟沙星、甲强龙、异丙嗪、胰岛素、他汀类、泮托拉唑、莫沙必利等。结论:伏立康唑在不同人群中的代谢差异很大,老年COPD患者应注意合并用药对伏立康唑代谢的影响,出现精神行为异常时,应立即停药或调整剂量。     

新一代广谱抗真菌药伏立康唑

综述第二代三唑类抗真菌药伏立康唑的作用机制、体内体外活性、药代动力学、药物相互作用、临床疗效、安全性等     

伏立康唑致尖端扭转型室性心动过速(TdP)的文献分析—非浓度依赖性的副反应

目的 探讨伏立康唑致尖端扭转型室性心动过速(TdP)的发生规律,为临床安全用药提供参考.方法 以"伏立康唑"和"尖端扭转型室性心动过速"与"Antifungal drugs""Cardiac toxicity""Voriconazole""torsades de pointes(TdP)"为检索词,检索1980年1月至2020年3月中国知网、维普、万方数据库和PubMed、Springer、Embase数据库收载的伏立康唑致TdP的个案报导文献,汇总进行文献分析.结果 共筛选出个案报道6篇,涉及9例患者.男女性别比2:7,15岁以下患者5例、年龄最小12岁,15岁3例,用药1周后出现Tdp 8例,9例均停止使用伏立康唑,1例停药后QTc恢复不到正常水平造成永久性损害.Tdp危险因素包括高剂量给药、低钾血症、低镁血症、严重的心动过缓、长QT症、联合引起QTc延长药物或有心血管基础疾病患者.结论 伏立康唑不依赖浓度和剂量诱发Tdp,作为预防措施,长期使用伏立康唑可监测心电图(心率、QTc)、不常规推荐测定血药浓度或CYP2C19基因代谢类型.     

注射用伏立康唑临床合理使用评价标准的建立

目的:建立注射用伏立康唑临床药物利用评价标准,对该药的药物利用情况进行回顾性评价,为合理应用伏立康唑提供依据。方法:以伏立康唑的应用指南作参考,在查阅相关文献基础上制定伏立康唑药物利用评价细则,并对我院2014年6月1日至2014年12月31日62例出院病历进行回顾性评价。结果:研究发现临床应用伏立康唑时在给药途径、溶媒选用和配制方面符合标准率均为100%,但在用药指征、配伍禁忌、病原学检查、滴注时间、用药疗程和用药监护等方面存在不合理现象,而且我院的医院信息系统(hospital information system,HIS)特殊级抗菌药物管理系统存在操作漏洞。结论:伏立康唑药物利用评价方法可用于该药的药物利用评价,评价结果说明我院注射用伏立康唑的使用还存在普遍不合理应用现象,需加强合理用药宣传和监管,我院的电子监管系统仍然有操作漏洞,需要进一步完善。     

复发性外阴阴道假丝酵母菌病发病危险因素与治疗分析

目的 调查分析复发性外阴阴道假丝酵母菌病(RVVC)发病的危险因素和相应治疗措施,为临床诊断治疗RVVC提供理论依据.方法 以我院2013年10月至2015年10月期间收治的230例RVVC患者为RVVC组,以同期收治的248例外阴阴道念珠菌病(VVC)为VVC组,对两组患者进行问卷调查.采用Logistic回归分析RVVC发病的相关因素,并比较氟康唑、伊曲康唑、伏立康唑、两性霉素B四种RVVC常规治疗药物的临床疗效及药敏性.结果 与VVC组相比,RVVC组有更高的比例有未控制的糖尿病、阴道病史、流产史、抗生素应用频次高、口服避孕药、应用免疫抑制剂、偏好紧身化纤内裤、长期使用护垫和宫内节育器,且有阴道反复冲洗及长期焦虑抑郁(P<0.05).Logistic回归分析表明,未控制的糖尿病、阴道病史、流产史、和抗生素应用频次高、口服避孕药、免疫抑制剂应用、紧身化纤内裤、护垫长期使用和宫内节育器是RVVC发病的独立危险因素(P<0.05).在临床疗效方面,以两性霉素B最优,且与氟康唑、伊曲康唑、伏立康唑比较差异具有统计学意义(P<0.05);两性霉素B的药敏性最高,且与氟康唑、伊曲康唑、伏立康唑比较差异具有统计学意义(P<0.05).结论 RVVC的易感因素复杂多样,包括疾病史、用药史和不良行为习惯等.RVVC的临床治疗药物应用方案并不一致,但临床医师应重视真菌培养和药敏试验,以针对RVVC发病危险因素对症治疗,从而提高RVVC的治愈率,减少RVVC的致病菌的耐药情况发生.     

急性白血病患者侵袭性真菌病的临床研究与分析

目的：分析急性白血病( AL)患者侵袭性真菌病( IFD)的相关危险因素和临床特点,为IFD的诊断和治疗提供指导。方法对1272例AL患者进行回顾性研究,统计分析IFD的相关危险因素及临床特点。结果 1272例AL患者中发生IFD 124例,感染率为9．75%,感染部位以肺部和血液为主;住院天数、粒细胞缺乏持续时间和广谱抗菌药物联合使用时间是侵袭性真菌感染的独立危险因素;病原菌以白色念珠菌为主,多对两性霉素B和伏立康唑敏感。结论 AL患者是IFD的易感人群,以白色念珠菌感染为主,在治疗原发病的同时,缩短住院天数、粒细胞恢复时间,加强支持治疗及合理使用广谱抗菌药物,可有效降低IFD的发生。     

HPLC-MS/MS同时检测大鼠血浆中阿托伐他汀和伏立康唑的浓度

目的建立并应用同时测定大鼠血浆中阿托伐他汀和伏立康唑浓度的液相质谱联用方法（HPLC-MS/MS）,研究阿托伐他 汀单独给药及与伏立康唑联合给药后,大鼠体内阿托伐他汀的药动学变化以及伏立康唑的浓度变化。方法采用醋酸钠酸化, 甲基叔丁基醚液-液萃取法处理血浆样品,经Thermo Hypersil Gold C1（8 2.1×100 mm, 1.9 μm）色谱柱分离,流动相为乙腈-0.1%甲 酸水溶液,梯度洗脱,分析时间6 min;质谱检测采用加热电喷雾离子源（H-ESI）正离子扫描方式,选择反应监测（SRM）模式检 测,选用m/z559.2→440.2（阿托伐他汀）、m/z350.2→281（伏立康唑）、m/z370.2→252（内标兰索拉唑）作为定量分析的离子。结 果阿托伐他汀在0.01~100 ng/mL（r=0.9957）,伏立康唑在0.025~100 ng/mL（r=0.9966）范围内线性关系良好,阿托伐他汀和伏 立康唑的日间和日内精密度均小于13%,提取回收率66.50%~82.67%,血浆样品稳定性符合测定要求。单独给药和联合给药后 大鼠血浆中阿托伐他汀的AUC0-24 h分别为（438.78±139.61）和（927.43±204.12)）h·μg·L-1,CLz/F分别为（23.89±8.14）和（10.43± 2.58）L·h-1·kg-1,Cmax分别为（149.62±131.10）和（159.37±36.83）μg·L-1,t1/2分别为（5.08±1.63）和（5.58±2.11）h,Tmax分别为（0.37± 0.14）和（3.60±1.52）h,其中AUC0-24 h和CLz/F,Tmax具有显著性差异（P<0.05）。同时可测定合并给药组中伏立康唑的血药浓度。 结论本方法简单快速,灵敏度高,可用于同时检测大鼠血浆中阿托伐他汀和伏立康唑的浓度。伏立康唑和阿托伐他汀联用,使 阿托伐他汀的部分药代动力学参数发生了改变。     

伏立康唑治疗血液系统恶性肿瘤并发侵袭性真菌感染的疗效分析

目的观察伏立康唑治疗血液系统恶性肿瘤并发侵袭性真菌感染的疗效。方法回顾性分析24例血液系统恶性肿瘤并发侵袭性真菌感染患者采用常规剂量的伏立康唑序贯治疗的情况。结果本组24例中1例因疾病进展死亡用药4d自然停药而无法评估,其余23例中痊愈5例,显效11例,无效7例,有效率为69.57%。治疗过程中出现视觉障碍5例,无需停药,均能缓解。肝功能损害2例,经护肝药物治疗后恢复正常。颜面潮红1例,出汗1例,恶心、胃部不适1例,经对症治疗及调整服药时间后好转。结论伏立康唑静脉注射或口服疗效均好,耐受性强,毒副作用轻,是治疗侵袭性真菌感染的有效药物。     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

Acupuncture Combined with Spinal Tui Na for Treatment of Primary Dysmenorrhea in 30 Cases

Objective: To observe the therapeutic effects in acupunture treatment of primary dysmenorrhea combined with spinal Tui Na, and study its mechanism. Methods: Thirty cases of the treatment group were treated by acupuncture combined with spinal Tui Na, and thirty cases in the control group were treated by routine acupuncture. Results: The total effective rate was 93.3% in the treatment group, and 73.3% in the control group, with a significant difference between the two groups (P<0.05). Conclusions: Acupuncture combined with spinal Tui Na has good prospects for treatment of primary dysmenorrhea.     

Luo Lingjie's Experience in Treating Chronic Nephropathy

In treating chronic nephropathy,Luo Lingjie,a chief physician,pays attention to regulating the balance between yin and yang,treating infection if present,and removing pathogenic factors.He prescribes gentle drugs and uses carefully strongly warming-tonifying ones,emphasizes the importance of persuading the patient to persist in treatment with medication and nurse one's health for recuperation,and is good at combined use of TCM and western medicine therapy and brings the merits of various therapies into full play,with obvious theraoeutic effects.     

Dr.Zhang Ren's Experience in the Acupuncture Treatment of Different Diseases with the Same Therapeutic Principle

Dr.Zhang Ren,the chief physician,is the chairman of Shanghai Acupuncture and Moxibustion Association.Having been engaged in medicine for about 40 years,he is experienced in treating various intractable diseases.In his long years of clinical practice,he advocates taking the TCM differentiation as the basis to seek for the acupuncture method for treatment of modern intractable diseases.The author of this essay had the fortune to follow Dr.Zhang in study.The following is a summary of Dr.Zhang's experience in the acupuncture treatment for different intractable diseases with the same therapeutic principle.     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

猪肺磷脂注射液联合经鼻持续气道正压通气对呼吸衰竭早产儿的临床疗效及肌酸激酶同工酶活性的影响

目的 探讨猪肺磷脂注射液联合经鼻持续气道正压通气(NCPAP)对呼吸衰竭早产儿的临床疗效及肌酸激酶同工酶活性(CK-MB)的影响.方法 选取呼吸衰竭早产儿80例,分为观察组和对照组各40例.对照组采用NCPAP给氧治疗,观察组给予NCPAP给氧联合猪肺磷脂气管内给药.观察两组患儿治疗前及治疗12h、24 h后PaO2、PaCO2、血氧饱和度(SaO2)、pH的变化情况,检测治疗前及治疗5d后血清CK-MB水平;评估两组患儿的临床治疗效果.结果 两组患儿PaO2、PaCO2、SaO2、pH比较,差异均有统计学意义(P＜0.05),其中观察组治疗后的PaO2、SaO2、pH均高于对照组,PaCO2则低于对照组.两组的PaO2、SaO2、pH均随观察时间延长而升高(P＜0.05),PaCO2均随观察时间的延长而降低(P＜0.05).观察组治疗有效率为87.5％,显著高于对照组的70.0％ (P ＜0.05).治疗5d后两组患儿血清CK-MB水平均较前降低(P＜0.05),且观察组明显低于对照组(P＜0.05).结论 猪肺磷脂注射液气管内给药联合NCPAP可以显著降低呼吸衰竭早产儿CK-MB的含量,提高治疗有效率,起到很好的呼吸循环支持作用.