Tetracaine topical anesthesia for myringotomy

OBJECTIVES/HYPOTHESIS: To study the efficacy and safety of topical tetracaine anesthesia for office myringotomy and myringotomy with a tube. STUDY DESIGN: Retrospective review of patients undergoing office myringotomy, with or without tube insertion, performed over a 4-year period. METHODS: A topical solution of 8% tetracaine base in 70% isopropyl alcohol was used in 381 ears. Five to 10 drops of the solution were applied to the tympanic membrane for 10 to 15 minutes and aspirated. Myringotomy was performed either with a myringotomy knife or with a CO(2) laser (OtoLAM). RESULTS: Topical tetracaine was used in all 231 ears (100%) undergoing myringotomy without a tube and 150 of 212 ears (71%) undergoing myringotomy with a tube. Tetracaine alone was effective in providing tympanic membrane anesthesia in 95% of myringotomy without a tube (220 ears) and in 93% of myringotomy with a tube (139 ears). There were six complications, including five cases of severe vertigo and one unusual prolonged, transient facial nerve weakness. CONCLUSION: Topical tetracaine is efficacious and safe for use in office myringotomy.     

不同浓度丁卡因或罗哌卡因对大鼠臂丛神经的毒性

目的 探讨不同浓度丁卡因和罗哌卡因对大鼠臂从神经的毒性.方法 成年雄性SD大鼠48只,体重410 ～ 430 g,采用随机数字表法,将其随机分为8组(n=6):生理盐水组(NS组)、0.25％、0.50％、1.00％丁卡因组(T1-3组)、0.25％、0.50％、1.00％、2.00％罗哌卡因组(R1-4组).随机选取一侧腋鞘,NS组注射生理盐水1.0 ml,T1-3组分别注射0.25％、0.50％、1.00％丁卡因0.5 ml,R1-3组分别注射0.25％、0.50％、1.00％罗哌卡因1.0 ml,R4组注射2.00％罗哌卡因0.5 ml.另一侧腋鞘作为对照.于注药后5d时检测臂从神经复合动作电位及其传导速度(NCV),并采用光镜和透射电镜观察臂从神经的病理学结果.结果 与对照侧和NS组比较,T2-3组和R3-4组臂丛神经复合动作电位降低,NCV减慢(P＜0.05);T1组、T2组和T3组臂从神经复合动作电位位依次降低,NCV依次减慢(P＜0.05);与R1-3组比较,R4组臂丛神经复合动作电位降低,NCV减慢(P＜0.05).病理学改变:T2组、T3组和R4组神经束膜明显水肿,髓鞘板层分离、断裂、重度脱髓鞘,轴突萎缩;R3组为“脱髓鞘”现象,髓鞘板层分离、断裂、重度脱髓鞘,轴突萎缩.结论 0.50％、1.00％丁卡因和1.00％、2.00％罗哌卡因可导致大鼠臂从神经产生病理性损伤,且损伤程度与其浓度有关.     

The cardiovascular effects and pharmacokinetics of intranasal tetracaine plus oxymetazoline: Preliminary findings

BackgroundThe authors evaluated the cardiovascular effects and pharmacokinetics of an intranasal 3 percent tetracaine/0.05 percent oxymetazoline spray developed to provide needle-free anesthesia of maxillary teeth.MethodsThe authors administered to 12 participants a proposed maximum recommended dose (MRD) (18 milligrams tetracaine/0.3 mg oxymetazoline) as three bilateral pairs of 0.1-milliliter nasal sprays. They administered two times this dose (36 mg tetracaine/0.6 mg oxymetazoline) as six bilateral pairs one to three weeks later. The authors recorded the patients’ heart rate, blood pressure and oxygen saturation. They drew blood samples at baseline and 15 times during the two hours after drug administration.ResultsPhysiological measures remained fairly stable throughout the two-hour period, with small but significant decreases (P < .05) in heart rate at 40 and 50 minutes for the two-times MRD (6.1 beats/minute) and MRD (7.5 beats/minute) administrations, respectively, and a significant increase in diastolic blood pressure (5.9 millimeters of mercury) for the two-times-MRD administration at 90 minutes. Mean oxygen saturation remained above 99 percent. Tetracaine plasma levels were undetectable in most participants, whereas concentrations of its major metabolite parabutylaminobenzoic acid from the two-times-MRD administration were approximately twice that from the MRD administration. Oxymetazoline concentrations from the two-times-MRD administration were approximately 50 percent greater than those from the MRD administration, with a half-life of 1.72 to 2.32 hours.ConclusionsIntranasal tetracaine/oxymetazoline mist generally was well tolerated in study participants.Clinical ImplicationsThe safety profile and pharmacokinetics of this intranasal formulation indicate that it appears to be generally well tolerated in patients for achieving anesthesia of the maxilla. Additional safety and efficacy data are required, particularly in patients with cardiovascular disease and other comorbidities.     

碱化丁卡因溶液尿道粘膜表面麻醉的临床观察和药代动力学研究

１６例接受膀胱镜检的患者分为临床碱化组和临床对照组；将２０只家兔匀分为动物碱化组和动物对照组。碱化组均给予ｐＨ７．１５的１％丁卡因溶液，对照组给予ｐＨ５．１的１％丁卡因溶液。结果，临床碱化组麻醉效果优于临床对照组（Ｐ＜０．０５）。但临床对照组药液在血液中达峰时间（Ｔｐｅａｋ）快；峰浓度（Ｃｍａｘ）及血药浓度的各个时点均高于临床碱化组（Ｐ均＜０．０１）。两组中分布半衰期，消除半衰期无显著性差异。表现分布容积（Ｖｄ），药时曲线下面积（ＡＵＣ）和清除率（ＣＬ）有显著性差异（Ｐ均＜０．０１）。动物碱化组丁卡因在血中浓度低，而在膀胱组织中浓度高（Ｐ均＜０．０１）。认为碱化丁卡因具有效果好，毒性低和清除快的优点，用于临床尿道粘膜表面麻醉安全有效。     

1％利多卡因复合0．25％丁卡因液与2％利多卡因应用于上腹部手术时硬膜外麻醉的比较

目的：比较1％利多卡因复合0．25％丁卡因液与2％利多卡因硬膜外腔麻醉的效果和不良反应。方法：采用随机双盲研究1％利多卡因复合0．25％丁卡因液进行硬膜外腔注射(实验组)30例，2％利多卡因(对照组)30例，观察指标分为硬膜外腔阻滞麻醉时效评定；阻滞最高节段数；阻滞最低节段数；VAS疼痛评分；肌松质量和镇痛效果的评定。术中不良反应以及生命体征的改变。结果：1％利多卡因复合0．25％丁卡因液在麻醉时效、麻醉效能和麻醉效果上比2％利多卡因硬膜外腔麻醉，作用时间延长，麻醉平面扩大，有统计学意义。而不良反应两组间无统计学意义。结论：1％利多卡因复合0．25％，丁卡因液在麻醉时效、麻醉效能和麻醉效果上优于2％利多卡因硬膜外腔麻醉。     

Tetracaine induces apoptosis through a mitochondrion-dependent pathway in human corneal stromal cells in vitro

Purpose: Tetracaine is a local anesthetic widely used in ocular diagnosis and ophthalmic surgery and may lead to some adverse effects and complications at a clinical dose. To assess the cytotoxicity and molecular toxicity mechanisms of tetracaine, we used human corneal stromal (HCS) cells as an in vitro model to study the effects of tetracaine on HCS cells.

Materials and methods: The cytotoxicity of tetracaine on HCS cells was investigated by examining the changes of cell growth, morphology, viability and cell cycle progressing when HCS cells were treated with tetracaine at concentrations from 10?g/L to 0.078125?g/L. To prove the hypothesis that the cytotoxicity of tetracaine on HCS cells was related with apoptosis induction, we further detected multiple changes in HCS cells, including plasma membrane (PM) permeability, phosphatidylserine (PS) orientation, genomic DNA integrality, and cell ultrastrcuture after treated with tetracaine. Furthermore, the pro-apoptotic signalling pathway induced by tetracaine was explored through detecting the activation of various caspases, the changes of mitochondrial transmembrane potential (MTP), the expression level of Bcl-2 family proteins and the amount of mitochondria-released apoptosis regulating proteins in cytoplasm.

Results: Tetracaine at concentrations above 0.15625?g/L had a dose- and time-dependent cytotoxicity to HCS cells, which resulted cell growth inhibition, proliferation retardation, morphological abnormalities and decreased viability. Meanwhile, we found that the HCS cells treated with tetracaine had typical features associated with apoptosis, including an increase in PM permeability, PS externalization, DNA fragmentation and apoptotic body formation. Tetracaine not only resulted in caspase-3, caspase-8 and caspase-9 activation and disruption of MTP but also downregulated Bcl-2 and Bcl-xL and upregulated Bad and Bax, along with the upregulation of cytoplasmic cytochrome c (Cyt. c) and apoptosis-inducing factor (AIF).

Conclusions: These results suggested that tetracaine-induced apoptosis might be triggered through Fas death receptors and mediated by Bcl-2 family proteins in the mitochondria-dependent pathway. Our findings identified the cytotoxicity and molecular mechanisms of tetracaine, which could provide a reference value for the safety of this medication and prospective therapeutic interventions in eye clinic.     

盐酸丁卡因胶浆用于肛裂术前灌肠的镇痛效果观察

目的:用盐酸丁卡因胶浆作肛裂患者术前清洁灌肠的润滑剂,观察在插管和排便时对肛门疼痛的镇痛效果。方法:将120例肛裂患者随机分为观察组与对照组,观察组采用盐酸丁卡因胶浆作术前清洁灌肠的润滑剂,对照组用外用液体石蜡作润滑剂,两组用物准备、操作步骤、对疼痛的观察和评估方法相同。结果:观察组使用盐酸丁卡因胶浆后,在插管和排便时肛门疼痛的发生率明显减少,疼痛的程度比对照组轻(P<0.05)。结论:盐酸丁卡因胶浆用作肛裂术前清洁灌肠的润滑剂,可减轻患者在插管和排便时的疼痛。     

反相高效液相色谱法测定口腔溃疡涂剂中甲硝唑和盐酸丁卡因的含量

目的：建立以反相高效液相色谱法测定口腔溃疡涂剂中甲硝唑和盐酸丁卡因含量的方法。方法：色谱柱为Thermo ODS hypersilC18（50mm&#215;4．6mm，5μm）；流动相为甲醇-水-乙腈-三乙胺（35：50：15：0．7）（用冰醋酸调pH=6．8）；流速1．0ml&#183;min^-1；检测波长为310nm；柱温20℃。结果：甲硝唑和盐酸丁卡因分别在20．2～161．6μg&#183;ml^-1（r=0．9994）和6．68～53．44μg&#183;ml^-1（r=0．9993）范围内线性关系良好，平均回收率分别为99．89％（RSD0．62％）和99．84％（RSD0．67％）。结论：本法简便、快速、重复性好，可用于口腔溃疡涂剂的质量控制。     

高效液相色谱法测定盐酸丁卡因注射液中盐酸丁卡因的含量及有关物质

目的 建立高效液相色谱法测定盐酸丁卡因注射液中盐酸丁卡因含量及有关物质检查的方法。方法 采用高效液相色谱法,色谱柱为Agilent ZORBAX SB-C₁₈柱(250 mm×4.6 mm,5 μm),流动相A和B为0.05 mol·L-1磷酸二氢钾溶液[用稀磷酸或三乙胺调节pH值至(3.0±0.1)]和甲醇(70∶30),梯度洗脱,流速为1.0 mL·min-1,柱温30 °C,盐酸丁卡因含量测定检测波长310 nm,有关物质检测波长为280 nm,进样量为20 μL。结果 盐酸丁卡因在10.0～100.0 mg·L-1范围内线性良好(r=0.999 9),平均回收率为98.73%,RSD值为0.72%(n=9)。结论 该方法精密度高、准确可靠,可用于盐酸丁卡因注射液质量控制。     

HPLC法测定盐酸丁卡因麻黄碱溶液中盐酸丁卡因的含量

目的建立高效液相色谱法测定盐酸丁卡因麻黄碱溶液中盐酸丁卡因的含量方法。方法采用Agilent ZORBAX SB-C18色谱柱;以0.05mol/L磷酸二氢钾溶液[用稀磷酸或三乙胺调节pH值至(3.0±0.1)]-乙腈(70∶30);检测波长:310nm;流速:1mL/min;进样量:20μL;柱温:30℃。结果盐酸丁卡因在1.02~50.95μg/mL范围内线性良好(r2=1),平均回收率为100.31%,RSD为0.61%(n=9)。结论该方法可有效的测定样品中盐酸丁卡因的含量,精密度高、方法简便准确可靠。