乙胺丁醇引发哮喘样症状

1名65岁男性患者,于淋巴结结核手术后,给予异烟肼0.3g/d、利福平0.45g/d、吡嗪酰胺0.5g,2次/d、乙胺丁醇片0.75g/d。用药18d后患者出现畏寒、乏力、咳嗽、胸闷,服用对乙酰氨基酚、阿莫西林。次日患者咳嗽加剧,并出现发热(T38℃),呼吸困难,不能平卧,口唇发绀,双肺哮鸣音,对症处理后缓解。停用抗结核药物,哮喘样症状消失。1周后,给予患者异烟肼,之后每3d分别加用利福平和吡嗪酰胺,未出现哮喘样症状。但当加服乙胺丁醇后数小时内再次出现哮喘样症状。     

利福平相关肾病综合征

1例17岁女性患者因肺结核给予吡嗪酰胺、乙胺丁醇、利福平、异烟肼治疗。2个月后吡嗪酰胺及乙胺丁醇停用,利福平0.45g/d和异烟肼0.3g/d继续应用。又过3个月,患者出现双下肢可凹性水肿,伴乏力、憋气、尿中泡沫多。遂停用利福平及异烟肼。实验室检查：血浆白蛋白（Alb）12.6g/L,血脂（TG）2.11mmol/L,24h尿蛋白5.511～8.283g,肌酐清除率（CCr）181ml/min。给予口服泼尼松龙、对症治疗,并给予吡嗪酰胺、乙胺丁醇、异烟肼巩固疗效。15d后症状好转出院,随访无复发。     

异烟肼相关多器官功能障碍综合征

1例74岁女性患者,因结核性胸膜炎给予链霉素、异烟肼、利福平及吡嗪酰胺。用药1周后出现肝肾损害。停用抗结核药,肝肾功能恢复正常。再次抗结核治疗,出现发热及皮肤瘙痒。停药及抗过敏治疗后症状好转。再次口服异烟肼0.2g,吡嗪酰胺1.0g,乙胺丁醇0.75g。30min后出现畏寒、发热、恶心、呕吐,意识障碍,唇周发绀。T40.5℃,P120次/min。随后出现少尿,颈强直;左侧上、下肢肌力2级,右侧上、下肢肌力0级。实验室检查：ALT41U/L,AST99U/L,BUN13.57mmol/L,SCr481μmol/L;肌红蛋白2470μg/L,肌钙蛋白0.52μg/L,LDH442U/L,α-羟丁酸脱氢酶315U/L,CK2789U/L,CK-MB50U/L,血清淀粉酶384U/L。行对症支持治疗,2d后症状好转。再次给予吡嗪酰胺、乙胺丁醇、左氧氟沙星抗结核治疗,治疗2个月未出现不良反应。     

异烟肼与乙胺丁醇合用引起过敏性休克

1例68岁女性患者,为排除结核口服异烟肼0.3g、乙胺丁醇0.75g、利福平0.45g进行诊断性治疗。服药5min后,患者突然感头晕,BP80/57mmHg,血氧饱和度0.90。给予葡萄糖氯化钠注射液静脉滴注,10min后血压恢复正常,症状缓解。次日,停用利福平,口服其他2种药物。服药后10min,患者出现头晕、大汗淋漓、四肢冰冷,BP64/42mmHg。经补液,吸氧,用肾上腺素、多巴胺及间羟胺等药物,2h后血压升至102/60mmHg。此后停用异烟肼及乙胺丁醇,改用口服利福平及吡嗪酰胺,未出现上述症状。     

军团菌合并支原体衣原体感染致非典型肺炎1例

<正>患者,女,38岁。于入院前45 d因感全身不适、气短乏力,继而头痛、发热,伴有咳嗽、咳黄脓痰,偶带有血丝,体温最高达40.5℃,在当医院先后给青霉素、阿莫西林舒巴坦、头孢哌酮钠、奥硝唑抗感染治疗2周后仍发热,考虑为肺结核给异烟肼、利福平、乙胺丁醇、吡嗪酰胺抗结核治疗后,体温     

乙胺丁醇致手指甲紫绀、舌下溃疡及视力减退

患者男,53岁。因结核性胸膜炎,于2002年4月26日入院,入院查体T37.1℃,P90次/min,R20次/min;肝功能:ALT40.9U/L,AST27.2U/L。当日始予抗结核治疗,异烟肼0.3g,利福平0.45g,吡嗪酰胺1.0g,1次/d口服。入院后23d检查肝功能:ALT93U/L,AST54U/L。停用利福平,吡嗪酰胺,仅用异烟肼0.3g,1次/d口服;加服肌苷片0.4g,3次/d;甘草酸二铵0.1g,3次/d;乙胺丁醇0.75g,1次/d。2天后患者手指甲出现紫绀,呈紫黑色,按压无痛感,面色、掌面红润如常,同时伴舌下大面积溃疡,有厚重舌苔,用手指轻刮,有豆腐样物刮出;同时伴有视物模糊,双眼视力由1.5下降到左0.3…     

基于斑马鱼模型的抗结核药物肝脏毒性比较研究#br#

目的 以肝脏绿色荧光转基因斑马鱼Tg(L-FABP:EGFP)为模型,研究一线抗结核药物异烟肼、吡嗪酰胺和乙胺丁醇对斑马鱼肝脏的影响以及比较其肝毒性大小。方法 用不同浓度的异烟肼、吡嗪酰胺和乙胺丁醇分别处理发育至72h的斑马鱼,于加药后24、48和72hpe(hour post-exposure)观察斑马鱼的死亡率、畸形率和肝脏形态变化情况,荧光显微镜下观察药物对斑马鱼肝脏荧光面积和荧光强度的影响。结果 随着给药浓度的增加和给药时间的延长,异烟肼、吡嗪酰胺和乙胺丁醇导致斑马鱼死亡率、畸形率升高。在72hpe,与空白对照组相比,1、2.5和5mmol/L吡嗪酰胺组斑马鱼肝脏荧光面积显著下降,5mmol/L异烟肼组斑马鱼肝脏荧光面积显著下降,10、20和30mmol/L乙胺丁醇组斑马鱼肝脏荧光面积显著下降。5mmol/L浓度下,异烟肼导致斑马鱼肝脏荧光面积降低程度高于吡嗪酰胺。结论 异烟肼、吡嗪酰胺和乙胺丁醇均有肝脏毒性,乙胺丁醇肝毒性最小。1和2.5mmol/L浓度下吡嗪酰胺导致斑马鱼发生肝损伤程度强于异烟肼,但5mmol/L下异烟肼肝脏损伤程度强于吡嗪酰胺,其有关机制需进一步研究。     

抗菌药物临床应用指导原则

抗结核分枝杆菌和非结核分枝杆菌药 本类药物主要包括异烟肼、利福平、乙胺丁醇、吡嗪酰胺、对氨水杨酸，以及异烟肼-利福平-吡嗪酰胺(卫非特)和异烟肼-利福平(卫非宁)两个复方制剂。     

肺结核患者胸腺五肽及抗结核药物联合用药与单纯应用抗结核药物疗效的对照分析

目的探讨肺结核的患者应用胸腺五肽及抗结核药物组与单纯应用抗结核药物组疗效对照分析。方法对36例合并肺结核的患者(均为初治患者),随机分成两组:A组和B组。A组给予异烟肼0.3 g每日1次口服,利福平0.45 g每日1次静点,乙胺丁醇0.6 g每日1次口服,吡嗪酰胺0.45 g每日1次口服。B组给予胸腺五肽1 mg每日1次静点,异烟肼0.3 g每日1次口服,利福平0.45 g每日1次静点,乙胺丁醇0.6 g每日1次口服,吡嗪酰胺0.45 g每日1次口服。治疗12周后,拍胸片,以胸片示病灶吸收程度作为疗效的评判指标。根据资料不同采用χ2检验。结果 36例患者完成了全过程的观察,其中21例好转,7例未愈,8例无效。给予单纯性抗结核药物组18例患者,其中8例好转,3例未愈,7例无效;给予胸腺五肽及抗结核药物联合用药组18例患者,其中13例好转,4例未愈,1例无效,两组比较,χ2=6.12>χ20.05,2=5.991,P<0.05,差异有统计学意义,二者有相关性。结论肺结核患者给予胸腺五肽及抗结核药物联合应用比单纯性应用抗结核药物,有较高的好转率,治疗效果好。     

抗结核药临床应用分析

目的:评价我院抗结核药的应用情况及发展趋势。方法:对我院2005年抗结核药的种类、构成比、人均日费用等进行回顾性分析。结果:临床应用以口服药为主,DDDS前5位药品分别为:异烟肼片、乙胺丁醇、利福平、吡嗪酰胺、利福喷汀。目前在结核病的常规治疗中,异烟肼片,乙胺丁醇,利福平,吡嗪酰胺仍是最主要的抗结核一线药物。结论:结核病的药物治疗是人类控制结核病的主要手段,合理使用抗结核药,定能遏制结核病疫情的发展。     

3种抗结核药物致大鼠肝脏损伤血清ALT与肝脏病理相关性研究

目的探讨主要抗结核药物致肝脏损伤血清丙氨酸氨基转移酶(ALT)与肝脏病理相关性研究。方法健康成年SD大鼠64只,随机分为8组。异烟肼(INH)组、利福平(RFP)组、吡嗪酰胺(PZA)组、IHH RFP组、RFP PZA组、INH PZA组、INH RFP PZA组。对照组:生理盐水。分别灌药10d后处死大鼠,留取颈动脉血,制备血清测ALT,取肝脏标本,在显微镜、投射电镜下观察肝脏病理变化。结果在抗结核药物PZA单药组、多药组,随着ALT的增高,大鼠肝脏组织病理及电镜表现均出现不同程度病理性改变。结论单药组、两药组、三药组3种抗结核方案中ALT的增高差异有统计学意义(P<0.05或0.01),同时有病理性的肝细胞的特征性变化,单药组以PZA组改变明显。     

Pharmacokinetic and pharmacodynamic behaviour of antitubercular drugs encapsulated in alginate nanoparticles at two doses

This study was designed to evaluate the pharmacokinetics and tissue distribution of free and alginate-encapsulated antitubercular drugs in mice at different doses. Alginate nanoparticles encapsulating isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA) and ethambutol (EMB) were prepared by controlled cation-induced gelification of alginate. The formulation was orally administered to mice at two dose levels (D1 and D2). A comparison was made in mice receiving free drugs at equivalent doses. Drugs were analysed by high performance liquid chromatography (HPLC). The average size of alginate nanoparticles was found to be 235.5+/-0.0 nm with a polydispersity index of 0.44; drug encapsulation was 70-90% for INH and PZA, 80-90% for RIF and 88-95% for EMB. In the free drug groups, plasma levels of RIF and INH were higher and PZA and EMB levels were lower in the D1 group (per body surface area of mice) compared with the D2 group (recommended human dose). The plasma drug levels of all drugs were higher in the D1 encapsulated group compared with D2, resulting in higher values of area under the plasma drug concentration-time curve (AUC(0-infinity)). The relative bioavailabilities of all drugs encapsulated in alginate nanoparticles were significantly higher compared with free drugs. Drug levels were maintained at or above the minimum inhibitory concentration (MIC(90)) until Day 15 in organs after administration of encapsulated drugs, whilst free drugs stayed at or above the MIC(90) up to Day 1 only irrespective of dose. The levels of drugs in various organs remained above the MIC at both doses for equal periods, demonstrating their equiefficiency. Alginate nanoparticles hold great potential in reducing dosing frequency of antitubercular drugs.     

汕头市住院肺结核患者结核分枝杆菌耐药情况分析

目的分析汕头市住院肺结核患者结核分枝杆菌耐药情况。方法回顾性抽样分析2008年1月-2010年12月100例住院肺结核患者结核分枝杆菌对INH、RFP、SM和EMB的耐药性试验结果,观察初治组和复治组对抗结核药物的耐药率。结果复治组INH、RFP和EMB耐药率明显高于初治组（分别为：59．5％vs．25．4％、40．5％vs．7．9％和43．2％vs．11．1％,）,2组比较差异均有极显著性（P〈0．01）;复治组SM耐药率与初治组比较,差异无显著性（18．9％vs．20．6％,P〉0．05）。结论抗结核药物耐药性试验对肺结核患者特别是复治患者是必需的,要重新重视SM的应用。     

临床药师参与1例哌拉西林他唑巴坦致药物热抗感染治疗方案调整临床分析

目的探讨临床药师在药物热抗感染治疗方案制订中的作用。方法临床药师参与1例哌拉西林他唑巴坦致药物热抗感染治疗过程,经分析二次发热为药物热,找出导致药物热的原因,并根据相关原则重新制订抗感染治疗方案。结果医师采纳临床药师建议,重新制订抗感染治疗方案后,患者未再次发热,感染症状缓解。结论临床药师参与哌拉西林他唑巴坦致药物热的抗感染治疗,保证了疗效,避免了抗菌药物的升级。     

三种不同方法检测结核分枝杆菌药物敏感性分析

目的探讨仪器液体比例法（BacT／ALERT 3D与MGIT960系统）与L—J比例法测试结核分枝杆菌药物敏感性结果的一致性。方法用BacT/ALERT3D快速药敏法、MGIT960快速药敏法、L—J比例法同时对107株结核分枝杆菌进行INH、SM、RFP及EMB四种抗结核药物的耐药性测定。结果（1）INH、SM、RFP及EMB用BacT／ALERT3D法、MGIT960法、L—J比例法药敏测试结果一致率分别为：93％、90％、95％、90％。（2）BacT／ALERT3D法、MGIT960法、L—J比例法对INH、SM、RFP、EMB的耐药率分别是：27％、28％、24％;12％、13％、19％;25％、25％、22％;7％、6％、9％。三种方法四种药物的耐药性均无显著性差异（P〉0．05）.（3）BacT／ALERT3D法、MGIT960法、L—J比例法完成药敏测试平均时间为10．5天、7．7天、28天,经统计存在差异显著性（P〈0．00）.结论BacT/ALERT3D法、MGIT960法、L-J比例三法对INH、SM、RFP、EMB药敏测试结果具有高的可比性。MGIT960法药敏检测时间最短。     

The disposition of antituberculous drugs in plasma of elderly patients. II. Isoniazid, rifampicin and pyrazinamide

The pharmacokinetics of isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) were studied in 18 elderly patients (67-89 years of age) and 19 young adult patients (19-59 years of age) on the first day and at one month of treatment for pulmonary tuberculosis. Elderly patients exhibited more side effects but there were no age-related changes in the pharmacokinetics of any of the three drugs when used in this combination. The clearance for INH and RIF at steady-state were significantly lower than after first-dose, while that of PZA remained unchanged. At steady-state the clearances for INH and RIF were not characteristic of polymorphic metabolism and auto-enzyme induction, respectively. Elderly patients are more sensitive to antituberculous (anti-TB) drugs; therefore, a modification in the dosage for this patient group should be considered.     

Probing Location of Anti-TB Drugs Loaded in Brij 96 Microemulsions Using Thermoanalytical and Photophysical Approach

The aim of this work is to monitor the changes in microstructure in nonionic Brij 96 microemulsions and to locate the solubilization loci of antituberculosis drugs (of variable solubility using photophysical and thermoanalytical properties. Using properties such as spectral shift, Stroke's shift, and anisotropy for two dyes, that is, Nile red (NR) and tris(2,2′-bipyridine)ruthenium(II) dichloride (RC), the structure of microemulsions has been investigated. With the help of spectral and deconvoluted analysis, it has been seen that rifampicin (RIF) shows a strong interaction with NR and isoniazid (INH) and pyrazinamide (PZA) with RC. It has been concluded that RIF molecules are mainly present at the interface toward oil side and INH toward hydrophilic side, whereas PZA remains in free water. The findings have been correlated with aqueous solubility drugs and partition coefficients. Differential scanning calorimetry elucidates the state of water in microheterogeneous environment and variation of different states, that is, free, bound, interphasal, and nonfreezable water with dilution. In addition, it confirmed the stability and location of the drugs in the prepared Brij 96 microemulsion formulations. A good agreement between both the studies has been achieved. These findings will help in elucidating the drug delivery properties of anti-TB drugs-loaded microemulsion formulations in future.     

全自动分枝杆菌检测仪对肺结核患者的耐药性监测

目的应用BACT／ALERT3D120全自动分枝杆菌检测仪对初治和复治肺结核患者进行耐药情况分析。方法对分离菌株进行抗结核药物链霉素（SM）、异烟肼（INH）、利福平（RFP）、乙胺丁醇（EMB）的耐药性测定。结果结核分枝杆菌的总耐药率为35．19％，初治耐药率为33．93％，初治多重耐药率为4．99％，复治耐药率为45．36％，复治多重耐药率为12．37％，与初治耐药率比较，复治耐药率有不同程度升高。结论全自动分枝杆菌检测仪能快速有效检测初治和复治肺结核患者的耐药情况，为临床用药提供参考。     

太原市结核病医院结核菌耐药现状分析

目的了解太原市结核病医院结核菌耐药现状。方法采用回顾性调查的方法,收集近3年经过药敏测定的116例肺结核患者药敏结果。结果总耐药率79%,总耐多药率25%;初始耐药率68%,初始耐多药率12%;获得性耐药率91%,获得性耐多药率39%,耐多药率逐年增加。耐单药顺位由高到低依次为乙胺丁醇(EMB)、异烟肼(INH)、链霉素(SM)、利福平(RFP)、吡嗪酰胺(PZA)、对氨基水杨酸钠(PAS)。结论高耐药率尤其是高耐多药率是我院结核菌的耐药特点,也反映我省当前比较严峻的结核菌耐药形势。     

234例痰菌阳性肺结核患者的耐药性分析

目的对234例住院患者痰标本获得的结核杆菌做耐药性检测,为临床制订抗痨方案提供一定的参考依据。方法统计2012年1月～2013年8月234例痰培养阳性患者痰标本的耐药情况,同时分别做一线药物：异烟肼（INH）、利福平（RFP）、乙胺丁醇（EMB）、链霉素（SM）的药敏试验,了解各药在初治和复治患者中的耐药情况。结果234例中。175例存在耐药情况,109例初治患者和125例复治患者对INH的耐药例数分别为43、73例,耐药率分别为18．4％、31．2％,对RFP的耐药例数分别为36、52例,耐药率分别为15．4％、22．2％,对EMB的耐药例数分别为14、35例．耐药率分别为5．98％、14．96％,对SM的耐药例数分别为21、33例,耐药率分别为8．97％、14．1％。结论初治和复治患者均对INH的耐药率最高,复治患者的耐药率明显高于初治患者。