Influence of alpha-adrenoceptor blockade with thymoxamine on changes in pupil diameter and accommodation produced by tropicamide and ephedrine.

In a study in 12 healthy volunteers, local instillation of thymoxamine eye-drops (0.2%) completely reversed the mydriasis produced by ephedrine (5%) but not that produced by ephedrine (5%) together with tropicamide (0.5%). Small but significant changes in accommodation were found with ephedrine and reversed by thymoxamine, suggesting that they were mediated through alpha-adrenoceptor activity. The thymoxamine eyedrops were well tolerated.     

Influence of Alpha-Adrenoceptor Blockade with Thymoxamine on Changes in Pupil Diameter and Accommodation Produced by Tropicamide and Ephedrine

Summary

In a study in 12 healthy volunteers, local instillation of thymoxamine eye-drops (0.2 %) completely reversed the mydriasis produced by ephedrine (5 %) but not that produced by ephedrine (5%) together with tropicamide (0.5%). Small but significant changes in accommodation were found with ephedrine and reversed by thymoxamine, suggesting that they were mediated through alpha-adrenoceptor activity. The thymoxamine eyedrops were well tolerated.     

糖尿病视网膜病变患者围手术期散瞳策略

目的：探讨糖尿病视网膜病变患者围手术期最佳散瞳方法,以利于玻璃体切割手术顺利进行。方法：回顾性分析我院2007年6月-2011年6月所有糖尿病视网膜病变患者的手术资料,选取术前常规应用复方托吡卡胺滴眼液、术中瞳孔直径≥7mm的患者手术时散瞳药的应用记录,共189例,204眼。术前点复方托吡卡胺滴眼液,每5min1次,共6次。点滴眼液后,0.5h内瞳孔散大（直径≥7mm）者为A组（78眼）;超过0.5h,但瞳孔散大时间在1h以内者为B组（75眼）;瞳孔散大时间大于1h者为C组（51眼）。B、C组于术前一天随机应用硫酸阿托品眼用凝胶或盐酸环喷托酯滴眼液,术前1h频点复方托吡卡胺滴眼液。结果：术中瞳孔直径能维持≥7mm的眼数比例,B、C组应用硫酸阿托品眼用凝胶者与应用盐酸环喷托酯滴眼液者差异均无统计学意义（P〉0.5）。术中有134眼因白内障同时行超声乳化白内障摘除术,其术中瞳孔直径能维持≥7mm的眼数比例,B组应用盐酸环喷托酯滴眼液者瞳孔维持的比例较用硫酸阿托品眼用凝胶者高（P〈0.5）,C组中二者比较差异无统计学意义（P〉0.5）。结论：对于术前单用复方托吡卡胺滴眼液散瞳时间超过0.5h者,术前点硫酸阿托品眼用凝胶或盐酸环喷托酯滴眼液有利于维持术中瞳孔大小,且二者效果差异无统计学意义。     

RP-HPLC法测定复方托吡卡胺滴眼液中盐酸去氧肾上腺素与托吡卡胺两组分含量

目的测定复方托吡卡胺滴眼液中盐酸去氧肾上腺素和托吡卡胺两组分的含量。方法用RP HPLC法,色谱柱:Inertsil C8柱(150 mm×4.6 mm,5μm);流动相:甲醇0.01 mol.L-1辛基磺酸钠溶液(体积比为1∶1,用磷酸调pH=3.00);检测波长:263 nm;柱温:30℃;流速:1 mL.min-1。结果盐酸去氧肾上腺素和托吡卡胺的线性范围分别为50.4~504.0 mg.L-1、48.8~487.6 mg.L-1;r值分别为0.999 7、0.999 8;盐酸去氧肾上腺素平均回收率为100.1%,RSD为0.45%;托吡卡胺平均回收率为99.74%,RSD为0.20%。结论该方法与国家标准相比简单、快捷,回收率和重复性良好,其线性、重复性、回收率均符合《中华人民共和国药典》的有关规定,可作为复方托吡卡胺滴眼液质量评价的方法。     

早产儿用复方托吡卡胺眼水散瞳的研究

目的研究复方托吡卡胺眼水在不同胎龄早产儿散瞳效果,加强其在早产儿眼底病筛查的管理。方法在低胎龄和高胎龄早产儿的左右眼分别滴用2次和3次复方托吡卡胺眼水。按距双眼第一次点眼散瞳时间长短将其随机平均分成A、B、C三组。A组距双眼第一次点眼散瞳时间45min行双眼瞳孔直径测量及眼底检查;B组为60min;C组是90min。结果 A、B组中左、右眼散瞳直径无差异(P>0.05),C组左眼散瞳直径比右眼小(P<0.05)。无论散瞳时间的长短,低胎龄和高胎龄早产儿组的平均瞳孔直径比较无差异(P>0.05)。结论滴2次复方托吡卡胺眼水60min后行眼底检查更安全有效,并且复发托吡卡胺眼水对不同胎龄的早产儿散瞳效果无差异。     

Evaluation of the effect of thymoxamine solution 0.5% on mydriasis induced by ibopamine solution 1%

Summary The effects of thymoxamine 0.5% solution and of a placebo solution (mannitol) on the mydriasis induced by ibopamine 1% solution were evaluated in 8 healthy volunteers and 12 patients with eye diseases.One drop of ibopamine was instilled into each eye and 30 min later 1 drop of thymoxamine was instilled into one eye and 1 drop of placebo into the contralateral eye. Pupillary diameter was measured before and 30 min after the instillation of ibopamine, immediately before the treatment with thymoxamine and placebo and 30, 60 and 90 min after the instillation of thymoxamine or of placebo.Within 30 min of treatment, ibopamine had produced a statistically and clinically significant mydriatic effect. In eyes treated with thymoxamine, prompt reversal of mydriasis was observed, the baseline diameter being observed within 60 min.No difference in the time-course of the mydriatic effect was detected between healthy subjects and patients. The pupillary response to thymoxamine was not influenced by the colour of the iris. The tolerability of ibopamine and of thymoxamine was good. No local or systemic adverse events were seen or reported.     

复方托吡卡胺滴眼液致突发性耳聋

1名60岁女性糖尿病患者，行眼底检查前用复方托吡卡胺滴眼液散瞳，随后出现听力明显下降伴耳呜，检查提示双耳感音神经性耳聋。经高压氧、葛根素治疗后，听力明显恢复。因眼科检查需要，再次用复方托吡卡胺滴眼液，用药后患者又出现听力明显下降，经对症治疗后好转。当患者第4次使用该药后出现耳聋，治疗1月余，听力仍未恢复。     

注射用帕米膦酸二钠致虹膜睫状体炎

1例70岁男性患者,确诊左肺腺癌Ⅳ期,全身骨扫描示多发骨转移,为预防骨转移产生骨痛和高钙血症,给予注射用帕米膦酸二钠静脉滴注.用药第2天,患者出现虹膜睫状体炎,给予普拉洛芬眼液、妥布霉素地塞米松眼液、复方托吡卡胺眼液等治疗,第5天症状好转.     

Aqueous carboxymethyl gum kondagogu as vehicle for ocular delivery

Aqueous solutions of carboxymethyl gum kondagogu (CMGK), an anionic bioadhesive polymer were evaluated as vehicles for ophthalmic delivery using tropicamide as a model drug. Aqueous ophthalmic solution of tropicamide (1 %, w/v) in CMGK (5 %, w/v) dispersions were formulated. The aqueous CMGK vehicle, formulated tropicamide eye drops and commercial tropicamide formulations were assessed comparatively for ex vivo ocular tolerance using hen’s egg chorioallantoic membrane assay. The results indicated ocular tolerability of aqueous CMGK vehicle. The results of comparative ex vivo corneal permeation study of tropicamide from the aqueous CMGK vehicle (5 %, w/v) conducted across isolated goat cornea revealed a no significant difference in the corneal permeation of tropicamide from the CMGK vehicle based formulation as compared to the commercial formulation. Further, the results of in vivo mydriatic response study conducted in rabbits revealed a non significant difference in the mydriatic response of tropicamide from the aqueous CMGK vehicle and commercial formulations. In conclusion, CMGK can be used as an ocularly tolerable polymer for formulating ophthalmic dosage forms.     

不同浓度托吡卡胺治疗学龄儿童假性近视的临床观察

目的评价0．5％托吡卡胺滴眼液治疗学龄儿童假性近视的临床效果和用药后的不良反应情况,指导临床应用。方法应用0．5％托吡卡胺滴眼液,隔晚给药;0．25％托吡卡胺滴眼液每晚给药,对假性近视的学龄儿童（每组100例,200眼）进行治疗。治疗前后,记录裸眼远视力,散瞳后的静态屈光度。结果两组假性近视的学龄儿童,治疗后裸眼远视力均有提高,差异有统计学意义（P〈0．01）;治疗后静态屈光状态呈大部分近视度数降低,差异有统计学意义（P〈0．01）。两组间用药后的不良反应出现的频率,差异有统计学意义（P〈0．01）。结论0．5％托吡卡胺滴眼液,隔晚使用,防治青少年假性近视疗效确切。可减少用药后的不良反应,增加用药顺应性。     

Visual recovery using small dilating eye drops.

It is well established that reduced size dilating eye drops of 1% tropicamide and 10% phenylephrine (micro drops) are effective for clinical purposes. Excellent pupil dilatation (mydriasis) is achieved and pupil constriction does not occur in response to light. In this study, the effect of micro drops of 1% tropicamide on distance and near visual recovery was compared with standard drops in a group of 20 healthy volunteers. For each person studied, one eye was selected at random to be tested first with the standard drop size, and then after a minimum of one week, the same eye was again tested using a drop of the same drug one fifth standard size. An iris photograph, Snellen visual acuity at 6 m, and reading visual acuity was obtained for each test procedure: before drop instillation and at 30 min, 1, 2 and 4 h after drug instillation. Use of the micro drops caused a small but statistically significant improvement in the rate of recovery of distance and near visual acuity. These findings, allied to the known beneficial effects of reduced systemic absorption using micro drops, lend further weight to the argument that mydriasis may be achieved more safely, with fewer side effects, and with earlier return of normal vision when reduced size drops are used. It is hoped that practical micro drop dispensers will be developed.     

复方托吡卡胺滴眼液致心跳呼吸骤停1例

1例48岁女性患者因双眼前闪光感,拟散瞳检查眼底,给予复方托吡卡胺滴眼液滴眼约30分钟后,出现心跳呼吸骤停,可能与药物用法不当及长期使用抗抑郁药有关,经抢救恢复正常。     

Pharmacodynamics of a new ophthalmic mydriatic insert in healthy volunteers: potential alternative as drug delivery system prior to cataract surgery

Cataract surgery requires a satisfactory degree of mydriasis throughout the entire operation. A phase I, open-labelled, randomised, cross-over trial was conducted in 18 healthy volunteers to compare mydriasis obtained with subsequent administration of phenylephrine 10% and tropicamide 0.5% eyedrops or a new insoluble-matrix retropalpebral ophthalmic insert containing 5.38 mg phenylephrine and 0.28 mg tropicamide. Phenylephrine serum concentrations were measured over 6 hr following each treatment administration. Secondary end-points included cardiovascular, general and local tolerance and quantification of bacterial colonisation of the conjunctiva and the cultured insert, respectively. When normalized to the pupil diameter after conventional treatment, the diameter achieved with the insert was 1.13 (95% confidence interval, 0.94-1.48, P=0.38). Moreover, standard eye drops provided faster effective mydriasis than the insert, starting 30 min. as compared to 90 min. upon treatment administration (P<0.01, repeated-measures ANOVA). Phenylephrine concentrations remained almost undetectable for both treatments and no change in heart rate or blood pressure were observed throughout the study. Only three superficial punctuate keratitis were diagnosed with the insert and two with the eye drops. No significant bacterial contamination of conjunctiva swab and cultured insert was observed. The new insoluble-matrix retropalpebral ophthalmic mydriatic insert produced similar but delayed effective and prolonged mydriasis as compared to the standard delivery system. In addition to its potential usefulness in patients undergoing cataract surgery, such new ophthalmic delivery system may be an advantage in children who need to undergo fundus photography due to the single administration and excellent tolerance as well.     

眼用制剂致不良反应208例文献分析

目的：探讨眼用制剂致不良反应（ADR）的特点及一般规律,为临床合理用药提供参考。方法：检索1995年1月-2013年6月国内医药期刊发表的文献,获得眼用制剂致ADR文献137篇,合计208例患者,就其ADR相关情况进行统计分析。结果：临床上眼用制剂致ADR以阿托品滴眼液、复方托吡卡胺滴眼液、氯霉素滴眼液、盐酸丁卡因滴眼液最为常见,妥布霉素地塞米松滴眼液和噻吗洛尔滴眼液致ADR也较多见;在儿童和老年人中发生率较高;多发生在给药后24h内;其临床表现以过敏反应、变态反应和心血管系统反应居多。结论：临床医师、药师应重视眼用制剂致ADR的规律和特点,加强其合理使用和监测,确保用药安全。     

麝香滴眼液对急性角膜炎的抗炎作用研究

目的:探讨麝香滴眼液对急性角膜炎的抗炎作用。方法:建立家兔手术损伤后的急性角膜炎模型,随机分为麝香滴眼液高、中、低剂量治疗组(0.3%、0.15%、0.05%)、0.5%醋酸可的松滴眼液组与生理盐水(0.9%NS)对照组。在用药24、48、72h时通过2%荧光素染色观察角膜上皮生长情况,测定房水中蛋白含量、钙离子(Ca2+)、白介素1-β(IL-1β)浓度,称量角膜重量,取角膜组织进行病理组织学检查,探讨麝香滴眼液对损伤引起的急性角膜炎的抗炎作用。结果:麝香滴眼液各组均能够减轻角膜水肿,抑制中性粒细胞的游走,抑制房水蛋白和IL-1β浓度的升高,改变房水中Ca2+的水平,促进角膜上皮的生长。结论:麝香滴眼液对急性角膜炎有明显的抗炎作用。     

复方牛磺酸滴眼剂抗过敏作用研究

目的：观察复方牛磺酸滴眼剂（ＣＴＵ）抗过敏作用。方法：以卵清蛋白致敏大鼠，两周后用卵清蛋白液滴眼引起眼过敏反应，同时静脉注射偶氮蓝（ＥＢ）染料，给予药物治疗。测定ＥＢ在眼的渗出量以评价眼组织微血管通透性和炎症水平。结果：ＣＴＵ治疗眼ＥＢ渗出量低于生理盐水治疗眼（Ｐ＜０．０１），与可的松治疗眼差异性无显著意义，渗出抑制率为４０．９６％。结论：复方牛磺酸滴眼剂可望开发成一临床治疗眼部过敏的药物     

Pharmaceutical investigation of vancomycin hydrochloride eye drops and their topical application to MRSA eye infection]

Two formulations of 0.5% vancomycin hydrochloride (VM) eye drops (VM-B and VM-C eye drops) were prepared by dissolving commercial VM powder for injection with preserved water B (PWB) containing phosphate buffer and preserved water C (PWC) containing only antimicrobial preservative, respectively. The VM-B eye drops have neutral pH (about 6.3), and the VM-C eye drops acidic pH of about 3.5. The pharmaceutical examination of these eye drops was performed regarding its clinical application to MRSA eye infection. In an irritability test using a rabbit's eye, the average number of winks after instillation of one drop of VM-B eye drops was 0.8 times/min and significantly smaller than that of VM-C eye drops (2.0 times/min). In dark storage at 4 degrees C, no change of VM concentration in both eye drops was observed for 25 weeks after preparation and the mean residual concentrations as determined by the HPLC-UV (240 nm) method were constant over 90% for 8 weeks, of the initial concentration. However, the residual VM concentration of VM-B eye drops under a room condition declined to 58% after 4 weeks and 20% after 8 weeks, and VM in light storage at 40 degrees C was not detectable after 8 weeks. The drug concentration of VM-C eye drops declined to 83% after 4 weeks and 74% after 8 weeks under a room condition, and to 46% after 4 weeks and 20% after 8 weeks under light storage at 40 degrees C. Under these storage conditions, the precipitation of VM related crystals was observed in both the eye drops when the residual percentage of VM was lower than 80%. Judging from HPLC chromatograms of a solution of the precipitated crystals, it was suggested that this crystal was degradation products of VM. The VM-B eye drops was applied to a patient with MRSA eye infection, because other medication was not effective. After continuous instillation of a drop per times every hour to both eyes, MRSA in corneal culture turned out negative after one week, and the clinical condition was remarkably improved. On the basis of the result of eye-irritability, VM-B eye drops with neutral pH was suggested to be superior to acidic VM-C eye drops from a safety point of view. It was also indicated that VM-B eye drops can be effectively used for 8 weeks under dark storage at 4 degrees C for MRSA eye infection, which is a useful piece information for the proper usage of the VM eye drops.     

Epileptic seizures induced by cycloplegic eye drops

Objective: To assess the incidence of seizures induced by cycloplegic ophthalmic drops.

Materials and methods: A survey among members of the American Association for Pediatric Ophthalmology and Strabismus yielded five patients who received cycloplegic eye drops between 1998 and 2010 and who consequently developed a seizure.

Results: The median age of the patients was 5 years (range 3 months to 12 years). Cyclopentolate hydrochloride 1% was the only causative agent. The seizure happened on average 12?min after the instillation of dilating eye drops. Three were generalized convulsions, and two patients had a focal seizure. Past medical history was unremarkable in four cases. In total, 16 previous cases of seizures induced by cycloplegic drugs were identified in reports published between 1890 and 2004, implicating atropine in nine reports, tropicamide and phenylephrine eye drops in one and cyclopentolate in six.

Discussion: A small amount of cyclopentolate drops could induce convulsions in young children after only minutes to less than an hour, while a larger dosage of atropine over the span of several hours could cause this rare and unpredictable complication. Predisposing factors were rare and those developing the seizures were healthy subjects. Generalized seizures were much more frequent than focal convulsions.

Conclusions: Seizures after instillation of cycloplegic drops are extremely rare.     

Pharmacokinetic and pharmacodynamic evaluation of the anti-cataract effect of eye drops containing disulfiram and low-substituted methylcellulose using ICR/f rats as a hereditary cataract model

We attempted to develop anti-cataract eye drops using disulfiram (DSF) and low-substituted methylcellulose (MC), and evaluated their anti-cataract effect in terms of the lens opacification vs. age-profile curves using a one-exponential equation. The eye drops were prepared using 0.5% DSF and 2% MC (DSF eye drops), and ICR/f rats, a recessive-type hereditary cataractous strain, were used as the experimental model. Gelation of DSF eye drops containing MC was first observed at about 35°C, close to body temperature. In in vivo transcorneal penetration experiments using rabbit corneas, only diethyldithiocarbamate (DDC) was detected in the aqueous humor, while DSF was not detected. The DDC penetration level of DSF eye drops containing MC was approximately 1.3-fold higher than that of DSF eye drops. The opacification rate constant (k) of ICR/f rat instilled with DSF eye drops with or without MC was lower, and the initial time of opacification (τ) was longer than those of ICR/f rats instilled with saline. Furthermore, the k of ICR/f rats instilled with DSF eye drops with MC was lower than that of ICR/f rats instilled with DSF eye drops without MC. In conclusion, the analysis of kinetic parameters including k and τ using a one-exponential equation provided useful information for clarifying the anti-cataract effect of eye drops. ICR/f rats instilled with DSF eye drops using a low-substituted MC-based drug delivery system demonstrated a delay in cataract development, probably resulting from an increase in the retention of DSF eye drops on the cornea.     

Novel mucoadhesive polysaccharide isolated from Bletilla striata improves the intraocular penetration and efficacy of levofloxacin in the topical treatment of experimental bacterial keratitis

Objectives The objective of the present study was to evaluate a novel mucoadhesive polymer extracted from Bletilla striata for ocular delivery of 0.5% levofloxacin in rabbits, and to determine its improved efficacy against experimental keratitis. Methods B. striata polysaccharide (BsP) was subjected to cell cytotoxicity and ferning tests. The pharmacokinetics and bioavailability of topically applied 0.5% levofloxacin‐BsP eye drops was investigated and compared with 0.5% levofloxacin eye drops (Cravit). Experimental Staphylococcus aureus keratitis was induced and treated with levofloxacin or levofloxacin‐BsP eye drops. Key findings BsP markedly increased the proliferative capacity of a human corneal endothelial cell line. The ferning test showed that BsP exhibited optimal performance as a tear fluid. The polysaccharides significantly increased intra‐aqueous penetration and corneal accumulation in rabbits. Treatment with levofloxacin‐BsP reduced the number of organisms more significantly than eye drops containing levofloxacin alone. Conclusions BsP appears to be a promising candidate as a vehicle for topical ophthalmic drug delivery, especially for antibiotics.