噻吗洛尔与普萘洛尔治疗高血压病与心绞痛的疗效比较

劳累性心绞痛38例采用噻吗洛尔2.5-5mg, tid,共4wk;另12例采用普萘洛尔10-20mg, tid,共4wk。结果:前者显效率为79％,显著高于后者42％(P<0.05)。高血压病(Ⅰ,Ⅱ期)37例采用噻吗洛尔治疗,方法同上;另13例采用普萘洛尔20-40mg, tid,疗程亦4wk。结果:2组均有显著降压疗效(P<0.01),噻吗洛尔治疗后1h即获显效,普萘洛尔须24h才获显效。噻吗洛尔7％(5/75)、普萘洛尔4％(1/25)治疗后发生窦性心动过缓,前者被迫停药,后者未停药。     

A comparative study on the effects of apraclonidine and timolol on the ophthalmic blood flow velocity waveforms

Purpose: To evaluate the effects of topical timolol and apraclonidine on retrobulbar blood flow velocity waveforms in a group of healthy volunteers.Methods: Apraclonidine 1% and timolol maleate 0.5% single dose administrations were crossed over double masked in 12 healthy volunteers. The intraocular pressure measurements were followed by Doppler examination of the ophthalmic artery and the central retinal artery.Results: Intraocular pressure was reduced significantly on both treated and fellow eyes after timolol (p = 0.003, p = 0.04 respectively) and after apraclonidine (p = 0.002, p = 0.01 respectively). After apraclonidine administration end diastolic velocity, mean velocity decreased and pulsatility index increased in the ophthalmic artery of both treated and fellow eyes. Resistivity index increased and peak systolic velocity decreased only in the ophthalmic artery of treated eyes. All Doppler indices remained nonsignificant for central retinal artery of both eyes.After timolol administration there were no significant changes of the Doppler indices in the ophthalmic artery and central retinal artery of the treated and fellow eyes.Conclusion: Topical timolol and apraclonidine significantly reduced the intraocular pressure. Single dose administration of apraclonidine 1% increased the vascular impedance distal to the ophthalmic artery. On the other hand, timolol 0.5% had no effect on vascular impedance.     

Binding ofβ-adrenoceptor blocking drugs to human serum albumin,to α1-acid glycoprotein and to human serum

Summary The binding of 8 -adrenergic blocking drugs to human serum albumin, to ₁-acid glycoprotein and to serum from normal volunteers and from patients with rheumatoid arthritis was studied. Protein binding was determined in vitro using equilibrium dialysis of labelled drug at 25° C. Oxprenolol and propranolol were highly bound to serum, alprenolol, pindolol and timolol to a lesser degree, and atenolol, metoprolol and sotalol were negligibly bound. For the five compounds which were appreciably bound, the mean binding was significantly higher in serum from patients with rheumatoid arthritis than in serum from normal volunteers. For those drugs, binding to ₁-acid glycoprotein was higher than to human serum albumin, and binding to a mixture of both proteins approached that to serum from healthy volunteers. For each of these drugs there was a strong correlation between the serum ₁-glycoprotein concentration and the percentage binding.     

高效液相色谱法测定右旋噻吗洛尔及其对映体含量

目的 :建立右旋噻吗洛尔含量测定、有关物质检查及对映体纯度检查方法。方法 :采用高效液相色谱法 ,以DiamonsilTM C18柱测定噻吗洛尔含量及有关物质 ;以CyclobondI 2 0 0 0 TM 柱检查右旋噻吗洛尔对映体纯度。结果 :噻吗洛尔与其中间体及降解产物之间分离良好 ;噻吗洛尔在 0～ 5 0 0mg·L- 1浓度范围内符合线性关系 ,日内、日间测定的相对标准偏差均小于 0 .6 % ;右旋噻吗洛尔与其左旋对映体可完全分离 (Rs>2 .4 )。结论 :建立的方法快速简便、准确可靠 ,可以用于右旋噻吗洛尔的质量控制     

渗透促进剂对马来酸噻吗洛尔角膜透过性的影响

目的：研究渗透促进剂对马来酸噻吗洛尔（TM）角膜透过性的影响。并对其刺激性进行评价。方法：使用双室扩散池方法测定加入6种渗透促进剂后离体兔眼角膜对TM透过量的变化。以角膜水化值和眨眼值频率为指标评价渗透 促进剂的体内外刺激性。结果：0．05％的去氧胆酸钠和1％的泊洛沙姆188分别使TM的表现透过系数增大1．88和1．55倍而未见体内外刺激性。进一步提高泊洛沙姆188浓度抑制药物透过角膜。月桂氮Zhuo酮虽能显著增加TM的透过量却对角膜组织造成损伤。结论：低浓度的去氧胆酸钠和泊洛沙姆188为刺激性小、有效的眼用渗透促进剂。     

The extended ocular hypotensive effect of positive liposomal cholesterol bound timolol maleate in glaucomatous rabbits

Increased intraocular pressure (IOP) is a significant risk factor for the development of glaucoma. Timolol maleate is a beta-adrenergic receptor blocking agent and it is used for the treatment of glaucoma in order to reduce the elevated IOP that is characteristic of this eye disease. Systemic toxicity from topical timolol occurs more frequently than local toxicity and can affect the pulmonary, cardiac and central nervous systems. The objective of the present study, therefore, was to formulate multilamellar vesicles (MLVs) liposomal preparations of timolol maleate using their advantage of being less toxic compared with non-liposome-based drugs to be applied topically and to evaluate the in vivo performance of the prepared liposomes to extend the time of reduced IOP of glaucomatous rabbit's eye measured using a standard Shiotz tonometer. The encapsulation efficiency of MLVs was measured using a spectrophotometric technique. Differential scanning calorimetry (DSC) was used to monitor the effects of timolol maleate in the absence and presence of cholesterol on liposome thermal behaviour. Positively charged MLVs of timolol in the presence of a lower amount of cholesterol (DPPC(7):Chol(2):Timolol(2):SA(1) molar ratio) were found to be superior compared with other formulations in extending the ocular hypotensive effect approximately for 1 week (160 h) which encourages its physiological effectiveness. The increase of the cholesterol molar ratio in the prepared liposomal formulations serves to decrease the permeability of the lipid bilayer that is manifested by a low rate of drug release, an increased percentage of entrapment efficiency and a consequently lower bioavailability.     

Intraocular pressure-lowering effects of commonly used fixed combination drugs with timolol in the management of primary open angle glaucoma

AIM:To evaluate intraocular pressure (IOP)-lowering effect and ocular tolerability of brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies in the management of primary open angle glaucoma.METHODS:Each drug was administered for two months, after which a circadian tonometric curve was recorded using a Goldmann applanation tonometer. Ocular discomfort (conjunctival hyperemia, burning or stinging, foreign body sensation, itching, ocular pain) of each eye was assessed by the subject on a standardized ocular discomfort scale.RESULTS:Among the three study groups, there were no significant differences in the mean baseline IOP measurements, mean 2^nd mo IOP measurements, and mean (%) change of IOPs from baseline. Among the three study groups, there were no significant differences in the mean IOP measurements obtained at circadian tonometric curves at baseline and at two months controls. In sum brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar effects on IOP levels.CONCLUSION:Brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar lowering efficaties on IOP levels whereas there was no any difference between each other.     

拉坦前列腺素对原发性开角型青光眼患者的疗效

目的:研究拉坦前列腺素对原发性开角型青光眼(POAG)患者的治疗效果.方法:POAG患者135例,随机分为观察组(n=70)和对照组(n=65),观察组给予拉坦前列腺素治疗,对照组给予噻吗心安治疗;记录2组患者治疗前后的眼压及波动值、视野缺损及视网膜纤维层(RNFL)厚度及不良反应.结果:两组患者治疗后昼夜平均眼压、眼压波动值及视野缺损范围均较治疗前明显降低,差异有统计学意义(P＜0.05);治疗后观察组昼夜平均眼压、眼压波动值较对照组降低更明显,下方视野、颞侧视野及鼻侧视野缺损范围较对照组明显缩小,上方视盘、下方视盘、颞侧视盘及鼻侧视盘较对照组明显增厚,差异均有统计学意义(P＜0.05);治疗后观察组9例(12.86％)、对照组11例(16.92％)出现不良反应,差异无统计学意义(P＞0.05).结论:拉坦前列腺素治疗原发性开角型青光眼效果优于噻吗心安.     

Topical timolol 0.5% as the primary treatment of ophthalmic pyogenic granuloma: A prospective,single-arm study

Purpose:To study topical timolol (0.5%) as a first-line treatment in ophthalmic pyogenic granuloma (PG) in terms of safety and efficacy.Methods:This was a prospective, interventional, single-arm study conducted at a tertiary eye care hospital in central India. Only new cases of PG were counseled to get enrolled in the study. A total of 40 patients were analyzed in the study. Topical timolol eye drop (0.5%) was started in each patient twice daily for 4–6 weeks duration. The patients were divided into five categories according to the percentage reduction in the size of PG as follows: i) 80–100% reduction - excellent responders, ii) 60–80% – good, iii) 40–60% – satisfactory, iv) 20–40% – poor, and v) <20% – very poor/nonresponder. After 6 months of starting treatment final evaluation was done.Results:The mean age of the patients was 23.5 ± 13.3 years. Etiology of the disease included chalazion (n = 11, 27.5%), trauma (n = 2, 5%), surgery (n = 7, 17.5%), foreign body (n = 2, 5%), and idiopathic (n = 18, 45%). An excellent response was achieved in 31 (77.5%) patients. Twenty-seven (67.5%) patients had complete resolution of lesions within 6 weeks. Recurrence of the lesion was not noticed in any patients.Conclusion:Timolol 0.5% in topical form is a good treatment option for ophthalmic PG in all age groups. The treatment has no adverse effects when given to suitable individuals for a limited period.     

外用噻吗洛尔在皮肤科的临床应用进展

 噻吗洛尔是一种有效的非选择性β受体阻滞剂,可引起血管收缩、促进创面修复。外用噻吗洛尔不仅已成为浅表性婴儿血管瘤的一线治疗方法,近年来还在慢性溃疡和其他血管性皮肤病等方面显示出广阔的应用前景,具有良好的美容效果。本文对其在皮肤科的临床应用进展作一综述,为更多皮肤病的治疗提供新思路与选择。