4％毛果芸香碱凝胶单次应用治疗青光眼的临床观察

目的：比较４％毛果芸香碱凝胶（ｐｉｌｏｅａｒｐｉｎｅ ｇｅｌ,ＰＧ）和１％毛果芸香碱溶液（ｐｉｌｏｅａｒｐｉｎｅ ｓｏｌｕｔｉｏｎ,ＰＳ）的降眼压效果及安全性。方法：２０例（４０只眼）高眼压症及早期原发性开角型青光眼患者,采用自身对照,分别比较ＰＧ（每晚一次）和ＰＳ（每天４次）对日间多次眼压的降眼压效应,分别比较二者连续４周用药对某一时点（１０ＡＭ）的眼压、瞳孔及屈光度的影响,以及眼部副作用。结果     

毛果芸香碱凝胶的研究

与毛果芸香碱眼水比较，毛果芸香碱凝胶经动物实验证实其眼内房水及睫状体药物浓度较高，持续时间较长，ＰＧ对瞳孔的作用时间与其粘度和浓度有关，对角膜上皮可造成损害；临床研究表明：ＰＧ每晚一次维持１８－２４小时，药效与ＰＳ每日４次相当。     

0．004％曲伏前列腺素滴眼液和2％毛果芸香碱滴眼液联合应用对正常兔降眼压效果的评价

背景拟胆碱能药物和前列腺素类似物分别用于治疗原发性闭角型青光眼和开角型青光眼的临床效果已被证实,临床上二者常联合用药治疗青光眼,但理论上二者对睫状肌的作用机制是相背离的,因此有必要对二者联合用药的效果和作用机制进行进一步探讨。目的观察联合应用质量分数0．004％曲伏前列腺素和质量分数2％毛果芸香碱的降眼压效果。方法将正常无色素兔30只以随机数字表法随机分为毛果芸香碱组、曲伏前列腺素组和联合用药组3个组,每只兔任意选择一侧眼作为实验眼,分别每日3次点用2％毛果芸香碱滴眼液或每晚1次0．004％曲伏前列腺素滴眼液,联合用药组按上述用法同时点用上述两种药物;对侧眼点用生理盐水为对照眼。各组动物于用药前1d 8：00时以Perkins手持式压平眼压计测量双眼眼压作为基线眼压,并分别于用药后第1、2、4、8、14和24天的8：00时测量双眼眼压,以点眼前后眼压的变化作为主要观测指标。结果毛果芸香碱组、曲伏前列腺素组和联合用药组点眼后1d的眼压均明显低于基线眼压,而对照眼点眼前后眼压无明显变化;各实验眼治疗后各时间点间眼压无明显变化。毛果芸香碱组、曲伏前列腺素组和联合用药组实验眼眼压在点眼前与对照眼相比无明显差异,但点眼后均明显低于对照眼,差异均有统计学意义（P〈0．05）。与各组基线眼压比较,毛果芸香碱组、曲伏前列腺素组和联合用药组的实验眼眼压分别降低了17．5％～22．0％、23．8％～26．4％和27．6％～32．0％。对正常眼来说,联合用药组降眼压作用最强,其次依次为曲伏前列腺素和毛果芸香碱。结论联合用药的降眼压效果比单独点用毛果芸香碱和曲伏前列腺素的效果要好,但小于单独滴用毛果芸香碱和曲伏前列腺素的降眼压幅度之和。     

丁公藤碱Ⅱ——降眼压和缩瞳作用的研究

采用Goldmann压平眼压计、红外线瞳孔计与双盲法研究了丁公藤碱Ⅱ(以下简称碱Ⅱ)的降眼压和缩瞳作用,共观察原发性开角型青光眼72例144眼。结果表明:碱Ⅱ在降眼压方面有明显的剂量反应关系,0.01％、0.05％碱Ⅱ的降眼压幅度与1％毛果芸香碱相似,0.25％碱Ⅱ比1％毛果芸香碱强,碱Ⅱ在缩瞳方面则有一定的剂量反应关系,三种浓度碱Ⅱ的缩瞳作用与1％毛果芸香碱相似。连续滴药一个月,0.05％碱Ⅱ和1％毛果芸香碱的眼压下降率相接近,均可显著改善房水流畅系数,副作用不明显。此外,尚采用放射免疫法测定碱Ⅱ对兔眼房水中c-AMP和c-GMP含量的影响。结果表明0.01％碱Ⅱ在缩瞳、降眼压的同时,伴有c-GMP的升高,但不影响c-AMP的含量。作者就碱Ⅱ的M-胆碱能受体作用机制进行了讨论。     

单次滴用2%毛果芸香碱眼液致速发全身严重反应一例

毛果芸香碱是节后胆碱能药物，具有缩瞳和降眼压作用，主要用于青光眼的治疗。我院于2003年收治1例因用2％毛果芸香碱眼液滴眼后，致速发全身不良反应患者，现报告如下。     

双眼急性闭角型青光眼合并前房大量渗出一例

双眼急性闭角型青光眼合并前房大量渗出一例周继红王丽华卢艳患者男，６７岁，于１９９６年３月初观戏３小时后，自觉鼻根部酸胀不适，视物不清，当即到外院就诊，双眼眼压６．２５ｋＰａ（１ｋＰａ＝７．５ｍｍＨｇ），拟诊为青光眼，给予１％毛果芸香碱等降眼压药治疗，...     

前房内应用毛果芸香碱对角膜内皮细胞的影响

对白内障囊外摘除后房型人工晶体植入术中前房内用０．１％毛果芸香碱缩瞳的２３只眼，术后３～６个月使用非接触型内皮显微镜观察内皮细胞变化，内皮损失率为１７．３５％。术中不用毛果芸香碱缩瞳的对照组２８只眼术后内皮损失率为１６．４３％，两组经卡方检验Ｐ＞０．０５，差异无显著性。我们认为在后房型人工晶体植入术中，前房内应用０．１％毛果芸香碱缩瞳是安全、可靠的。     

青光眼药物治疗的新趋势-合理联合用药

合理联合用药是青光眼药物治疗的新趋势.本文介绍拉坦前列素分别与噻吗心安、毛果芸香碱、碳酸酐酶抑制剂、双三甲基乙酰肾上腺索、喘灵,噻吗心安与杜塞酰胺以及毛果芸香碱与噻吗心安联合降眼压作用的研究进展.     

联合毛果芸香碱滴眼液治疗眼外伤房角后退继发性青光眼

目的探讨联合毛果芸香碱滴眼液治疗外伤引起房角后退继发性青光眼的临床疗效。方法回顾性分析山东省眼科医院2007年8至2012年7收治12例(12只眼)眼外伤房角后退继发性青光眼患者的临床资料,患者均有眼球钝挫伤史且超生生物显微镜(UBM)和前房角镜检查可见外伤眼有不同程度的房角后退,入院眼压为(48.50±3.10)mm Hg,瞳孔直径为(5.15±0.70)mm。治疗:积极治疗原发性损伤,控制炎症,口服及静脉给予降眼压药物联合局部应用0.5%马来酸噻吗洛尔滴眼液、1%布林佐胺滴眼液、酒石酸溴莫尼定滴眼液降眼压治疗3～5 d,眼压不再下降,记录眼压为(35.00±3.55)mm Hg,此时加用0.5%毛果芸香碱滴眼液每日4次。详细记录患者治疗转归,观察眼压变化。结果加用毛果芸香碱眼滴眼液24 h后眼压为(21.90±3.87)mm Hg,平均下降(13.10±1.10)mm Hg。治疗前后瞳孔直径缩小(2.10±0.31)mm。4例患者最终逐渐减量药物致停,眼压正常;8例患者眼压降低后行小梁切除术控制眼压。结论毛果芸香碱滴眼液可以应用于眼外伤房角后退继发性青光眼患者,在减轻炎症的的基础上,联合应用毛果芸香碱滴眼液能够有效的降低眼压。     

角膜胶原膜载释毛果芸香碱的研究

目的研究自制的胶原膜以不同方式载释毛果芸香碱的功能。方法将新西兰白兔４０只（８０只眼）随机分为胶原膜浸药组、胶原膜载药后滴药组及合成胶原药膜组，测定用药后０．５、１、３及６小时前房水中毛果芸香碱浓度及缩瞳效应。结果胶原膜三种不同载药方式均能在短时间内达到较高房水药物浓度并持续６小时以上，起到“临时药库”作用。胶原膜载释毛果芸香碱的房水药物代谢过程符合一级动力学模式，并由缩瞳效应得到进一步证实。结论国产胶原膜具有良好的载释药物功能。     

Effect of pilocarpine 4% in combination with latanoprost 0.005% or 8-iso prostaglandin E2 0.1% on intraocular pressure in laser-induced glaucomatous monkey eyes.

PURPOSE: To compare the effect of pilocarpine, an agent that reduces uveoscleral outflow, on the ocular hypotensive efficacy of latanoprost and 8-iso prostaglandin E2 (PGE2). METHODS: Each of the two treatment groups was composed of the same eight monkeys with unilateral laser-induced glaucoma. Intraocular pressure (IOP) was measured hourly for 6 hours beginning at 9:00 AM on the baseline day (Thursday before treatment week) and on treatment days 1, 3, and 5 (Monday, Wednesday, and Friday). On all five treatment days, one drop of pilocarpine 4% was administered at 9:00 AM and 3:00 PM and one drop of latanoprost 0.005% or 25 microL of 8-iso PGE2 0.1% was administered at 10:00 AM and 4:00 PM. RESULTS: One hour after pilocarpine instillation on day 1, the reduction of IOP was similar (P > 0.90) in both treatment groups, 7.6 +/- 1.1 mm Hg (mean +/- standard error of the mean ) in the latanoprost group and 7.4 +/- 0.8 mm Hg in the 8-iso PGE2 group. However, the IOP effects of the two treatment groups became significantly different (P < 0.05) beginning 2 hours after dosing with latanoprost or 8-iso PGE, on day 1. A difference (P < 0.05) between the two groups persisted at all subsequent measurements. The reduction of IOP lessened with repeated dosing in the latanoprost and 8-iso PGE2 groups. Three hours after dosing with pilocarpine and two hours after dosing with the prostanoids, the IOP reduction was 8.3 +/- 0.9 mm Hg in the latanoprost group and 9.9 +/- 0.6 mm Hg in the 8-iso PGE2 group on day 1, and 2.1 +/- 1.0 mm Hg in the latanoprost group and 7.3 +/- 0.9 mm Hg in the 8-iso PGE1 group on day 5. CONCLUSIONS: The smaller reductions in IOP with pilocarpine and latanoprost than with pilocarpine and 8-iso PGE2 show that pilocarpine blocks much more of the ocular hypotensive effect of latanoprost than of 8-iso PGE2. The results also indicate that pilocarpine and latanoprost are mutually antagonistic. Enhancement of uveoscleral outflow appears to account for most of the ocular hypotensive effect of latanoprost and for much less of the ocular hypotensive effect of 8-iso prostaglandin E2.     

The long-term hypotensive effect of timolol maleate compared with the effect of pilocarpine in simple and capsular glaucoma.

The long-term intraocular pressure (IOP) lowering effect of a beta-adrenergic blocking agent, timolol maleate, in topical administration was compared with the effect of pilocarpine on simple and capsular glaucoma by means of diurnal pressure curves during a six-month follow-up. In simple glaucoma timolol was more effective than pilocarpine in lowering IOP. In the follow-up a significant but not marked increase of the IOP was observed. In capsular glaucoma timolol was not effective enough, but when it was co-administered with miotics the IOP lowering effect was better than with either substance alone. Timolol induced no accomodative myopia, miosis, reduction of tear flow or other side effects. It increased the outflow facility in simple glaucoma but not in capsular glaucoma. During the trial, the anterior chamber depth increased while the corneal thickness remained unchanged. Four out of the six eyes included in a previous report of secondary glaucoma due to chronic uveitis are still, after one year of therapy, controlled with timolol.     

Use of latanoprost to reduce acute intraocular pressure rise following neodymium: Yag laser iridotomy

PURPOSE: To evaluate the efficacy of latanoprost in reducing acute intraocular pressure (IOP) elevation after neodymium:Yag laser iridotomy (LI). METHODS: Primary angle-closure glaucoma (PACG) eyes were randomized to receive premedication with latanoprost and pilocarpine or with pilocarpine only before LI. Postoperative IOP changes were compared with Wilcoxon signed-ranks test using the fellow eyes of 47 patients who had one eye in each group. RESULTS: Postoperative pressure spikes were significantly lower (p = 0.010) in the latanoprost group (4.1 +/- 5.0 mmHg) than in the control group (6.7 +/- 7.0 mmHg). Mean elevation of IOP was less in the latanoprost group than in the control group at 1 hour (2.5 +/- 4.8 versus 4.1 +/- 4.7 mmHg, p = 0.013) and 2 hours (0.8 +/- 5.6 versus 4.4 +/- 8.1 mmHg, p = 0.003) postoperatively. Eleven eyes in the latanoprost group (23.4%) and 20 eyes in the control group (42.6%) developed a rise in IOP > or = 6 mmHg (p = 0.048). CONCLUSION: Latanoprost may reduce the pressure rise following LI in PACG eyes, but its application is limited by a late onset of effect.     

Piloplex, a new long-acting pilocarpine polymer salt. A: Long-term study.

Thirty eyes of 15 patients with open-angle glaucoma were followed up for a period of up to 1 year while being treated with Piloplex eye drops containg a new long-acting pilocarpine polymer salt. Average morning intraocular pressure (IOP) values during treatment with pilocarpine hydrochloride administered 4 times daily was 20.5 mmHg. Average morning IOP values during Piloplex medication administered only twice daily were 19.8 to 18.2 mmHg (range of averages on 14 sessions). These findings indicate the lower average pressure during Piloplex medication and show its prolonged hypotensive effect. Both medications contained an equivalent total daily amount of pilocarpine. Throughout the 1-year study period no adverse side effects were reported, and only 1 patient complained of local sensitivity reaction. Visual disturbances characteristic of pilocarpine eye drops were reduced from 3 times a day on pilocarpine hydrochloride 4 times daily to once a day on Piloplex twice daily.     

Pilocarpine concentrations in aqueous humor following single drop application. I. Effect of soft contact lenses

Following single drop instillation of pilocarpine, drug levels in individual aqueous humor samples of rabbits were determined by high-performance liquid chromatography and correlated with changes in pupillary diameter and intraocular pressure (IOP). Application of higher concentrations of pilocarpine resulted in higher drug levels but these differences were neither statistically significant nor consistently proportional to the strength applied. Maximum miosis occurred between 30 and 60 minutes and the maximum fall in IOP occurred between 1 and 2 hours. The influence of contact lenses with varying water content and thickness upon intraocular penetration of pilocarpine was studied. Contact lenses did not affect 30-minute concentrations of pilocarpine in aqueous humor. Although two-hour levels were significantly lower with contact lenses, miosis and IOP at these time periods were comparable with and without lenses. Neither water content nor thickness appreciably influenced miosis and IOP.     

Effect of CS-088, an angiotensin AT1 receptor antagonist, on intraocular pressure in glaucomatous monkey eyes

To evaluate the effect of CS-088, an angiotensin AT1 receptor antagonist, on intraocular pressure (IOP) in monkey eyes with unilateral laser-induced glaucoma. A multiple-dose study was performed in 8 glaucomatous monkey eyes. One 50 microl drop of CS-088, 2% or 4%, was topically applied to the glaucomatous eye at 9:30 a.m. and 3:30 p.m. for 5 consecutive days. IOP was measured hourly for 6 hours beginning at 9:30 a.m. for one baseline day, one vehicle-treated day, and daily for 5 days of treatment with CS-088. The washout period between the two drug concentrations was at least 2 weeks. Twice daily administration of 2 % CS-088 for 5 days did not reduce the IOP until the third dose on day 2 of the treatment regimen. A significant (p<0.02) reduction in IOP began 1 hour after the third dose, and lasted for 3 hours. The maximum reduction in IOP was 5.3+/- 0.8 (mean+/-SEM) mmHg (15%) (p<0.001), with the longest duration of IOP reduction of at least 6 hours after dosing on day 5. The 4% dose of CS-088 reduced (p<0.05) IOP from 1 to 5 hours after the first dose. The maximum reduction in IOP was 6.9+/-1.0 mmHg (20%), with the longest duration of IOP reduction of at least 18 hours after administration on day 5. Both 2% and 4% CS-088 showed enhancement of the ocular hypotensive effect with repeated dosing. 4% CS-088 produced greater (p<0.05) IOP reduction with longer duration of action than 2%. Topically applied CS-088, a new antagonist drug at the angiotensin AT1 receptor, reduced IOP in glaucomatous monkey eyes in a dose-dependent manner.     

Effect of changing from concomitant timolol pilocarpine to bimatoprost monotherapy on ocular blood flow and IOP in primary chronic angle closure glaucoma.

The aim of the present prospective masked study was to assess the effect of bimatoprost monotherapy on ocular blood flow and intraocular pressure (IOP) in eyes of primary chronic angle closure glaucoma patients already on concomitant timolol and pilocarpine. Thirty two patients of bilateral primary chronic angle closure glaucoma (PCACG) on topical timolol 0.5% twice a day and pilocarpine 2% three times daily were switched over to bimatoprost 0.03% once daily in both eyes. Intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) were recorded before and after starting bimatoprost and were followed up every four weeks for three months. Bimatoprost had statistically significant (p < 0.05) mean IOP reduction from 19.3 +/- 6.6 to 13.5 +/- 4.5 mmHg (30.5%) and there was improvement from 858 +/- 260 to 1261 +/- 321 microL/min (46.8%) in mean pulsatile ocular blood flow (p < 0.05). Conjunctival hyperemia (32%) was the most common adverse effect of bimatoprost. Bimatoprost 0.03% monotherapy improved ocular blood flow and provided a better diurnal IOP control than concomitant timolol-pilocarpine in eyes with primary chronic angle closure glaucoma and was found to be well tolerated.     

Topical atenolol versus pilocarpine: a double-blind study of the effect on ocular tension.

Topical atenolol (a beta1-adrenoceptive antagonist), pilocarpine, and placebo were tested in a randomised double-blind crossover trial of 8 patients with ocular hypertenion. Atenolol (2% 3 times a day) caused a fall in intraocular pressure (IOP) comparable to that achieved by topical application of pilocarpine (2% 3 times a day). The decrease in IOP by each compound was demonstrable on the second day of application and was significantly (P is less than 0.05) reduced on the seventh and 14th days of treatment. The combination of 2% pilocarpine and 2% atenolol administered 15 minutes apart (3 times a day) lowered the IOP significantly from the second day of treatment, and this reduction persisted throughout the trial period of 14 days. This combined of treatment, treatment lowered the IOP more than either substance alone. However, this further decrease was statistically significant only on the 14th day of treatment (atenolol versus atenolol + pilocarpine, P is less than 0.05). No change of the episcleral venous pressure was observed after 14 days' treatment with either atenolol or pilocarpine alone, or combined.