英文药名: Trusopt(Dorzolamide Ophthalmic Solution)

中文药名: 舒净露（多佐胺滴眼液） 

品牌药生产厂家: Merck Frosst

作用机制

本品是碳酸酐酶抑制剂(Carbonic Anhydrase Inhibitor，CAI)。碳酸酐酶(carbonic anhydrase，CA)是催化CO2＋H2O=H+＋HCO3-化学反应的酶HCO3-和Na+结合形成碳酸氢钠，碳酸氢钠增多，可使睫状血管系统的渗透压增加，从而吸收水分增多，眼压增高。CA有7种类型，与眼有关的同工酶是CA-I，CA-II和CA-Ⅳ，人体的CA-I，CA-Ⅳ存在于角膜内皮、晶状体中，CA-II存在于睫状突和视网膜中。CA的活性可被CAI抑制。多佐胺是一种CAI，强效抑制CA-Ⅱ，可作用于眼部的CA位点，使HCO3-生成减少，房水内渗透压下降，房水生成减少，眼压下降。多佐胺还可使眼内血管扩张，对眼灌注有积极的影响。 
药代动力学

按常规用法，即本品每8h l滴(30μl)，或每日总剂量4mg，8d后红细胞内的药物浓度可达20～25umol/L，与CA-II在红细胞中的浓度相似。该浓度可持续18个月。其血浆浓度为0.034umol/L，或为红细胞浓度的1/700。红细胞中也含有少量的N-去乙基代谢物(5umol/L)，该代谢物可抑制CA-I的作用。在最初用药的8d内，尿中测不到药物及其代谢物的浓度，待稳态后，肾排泄1.3mg/d，代谢物中包括20%N-去乙基多佐胺。 
本品通过角膜和基质吸收后，在睫状突抑制碳酸酐酶，使房水的产生减少而发挥作用。应用1000ng/mL多佐胺，在人房水中的达峰时间约为2h；用药后4～6h的平均浓度约为700ng/ml；12h后约200ng/mL，平均吸收半衰期为1.2h，消除半衰期为3.0h。 
进入血循环后，本品主要作用于红细胞上的碳酸酐酶，其缓慢代谢产物N-去乙基多佐胺，也依次储存在红细胞中。本品及其代谢物均通过肾脏代谢，代谢缓慢(t1/2＞4月)。局部用药避免了全身的不良反应。 
本品经肝细胞色素P450代谢为N-去乙基多佐胺，后者亦是人碳酸酐酶(CA)-I、II和Ⅳ抑制剂，其抑制CA-I作用较母体化合物更强，但抗CA-II作用较弱，这与它们对两种异构酶的亲和力大小不同相关。本品与血浆蛋白适度结合，未结合部分占68%～76%，游离浓度在0.15-15umo/L。 
临床应用

青光眼是一类眼内压(intraocular pressure，IOP)过高，引起视神经损害的眼病。虽然仅仅眼压上升不能作为青光眼的诊断根据，但是眼压上升，是造成各种类型青光眼的危险因素，所以青光眼的治疗目标首先是使眼压下降。多佐胺(Dorzolamide，商品名：Trusopt，默克公司)是第一个获得FDA批准局部眼用碳酸酐酶抑制剂(carbonic anhydrase inhibitor，CAI)，有较强的降IOP的作用。1994年在美国上市。 
1、开角型青光眼 
本品可降低开角型青光眼(POAG)的眼压或治疗高眼压症(OHT)，每日2～3次，连续使用12周，可使患者眼压下降18%～26%，降眼压效果与0.5%倍他洛尔(betaxol01)相当。 
Portellos等在随机对照研究中，让病人分别接受乙酰唑胺和本品治疗，2组疗程分别为2个月和1个月。结果乙酰唑胺组眼压降低(35.7±15.6)%，盐酸多佐胺组眼压降低(27.4±17.1)%，P>0.05，表明，局部应用本品与口服碳酸酐酶抑制剂乙酰唑胺作用相当。 
Hutzelmann等随机研究了患者在使用噻吗洛尔的基础上，分别加用乙酰唑胺和本品的疗效，均治疗12周，也得出类似结论，且盐酸多佐胺组表现出良好的耐受性。Sall在高眼压症和开角型青光眼的治疗中比较了2%多佐胺3次/d和1%布林佐胺(brinzolamide)2次/d及3次/d的临床疗效。3组眼压分别下降(16.9±20.1)%，(13.2±16.7)%和(16.9±19.1)%，经统计学处理3组眼压改变无显著性差异。 
Silver在572例开角型青光眼和高眼压症病人的治疗中采用类似的临床方案并得出相同的结论，说明本品与1%布林佐胺有着相同的临床疗效。一项随机双盲对照试验比较了本品、0.2%溴莫尼定(brimonidine)以及0.005%拉坦前列素(latanoprost)治疗原发性开角型青光眼一年后的疗效和安全性，结果表明，3种药物均有明显的降低眼压的作用(P<0.001)，不良反应相类似。 
2、夜间降眼压作用 
Orzalesi-N临床研究显示本品夜间降眼压幅度明显高于噻吗洛尔，稍低于拉坦前列素滴眼液。 
3、改善视野 
Bernd AS等研究显示，青光眼患者接受本品治疗9个月后，不仅眼压下降，平均光敏度增加18%。提示本品长期应用可改善视野。 
一项最新的研究比较了本品、噻吗洛尔和拉坦前列素对新诊断POAG病人微循环的效果，用药4周，眼压显著下降(P<0.001)，但盐酸多佐胺组明显缩短动静脉通过时间(AVPS)(P=0.009)，而噻吗洛尔和拉坦前列素组没有明显的改变。光敏度试验显示盐酸多佐胺组比噻吗洛尔组有明显的提高(P=0.007)。 
4、剥脱综合征继发性青光眼治疗的辅助用药临床上，剥脱综合征相关的青光眼与原发性开角型青光眼相比病情更为严重，此时对药物治疗抵抗力更强。一项对剥脱综合征相关的高眼压病人为期6个月的研究，比较了单用本品3次/d和单用0.5%噻吗洛尔2次/d的作用。结果显示，盐酸多佐胺组和噻吗洛尔组对继发性青光眼病人有类似降低IOP的作用。 
5、眼外科术后高眼压 
本品可有效预防白内障囊外摘除术后和经睫状体扁平部玻璃体切除，联合长效气体填充术后的眼压增高。本品尤适用于伴黄斑囊样水肿的青光眼患者，有研究表明，本品可减轻黄斑水肿，并提高视力。

TRUSOPT

(DORZOLAMIDE)

CARBONIC ANHYDRASE INHIBITOR

DIRECTIONS:

Once the drops are in, lie back with your eyes closed for at least three minutes. Using your thumb and first finger, lightly push in on your nose where the two eye lids come together (See: Proper eye drop insertion). This will give you the maximum pressure lowering effect on your eyes with minimum side effects. 

HOW IT WORKS:

Trusopt is a carbonic anhydrase inhibitor (CAI). Carbonic anhydrase is an enzyme that is used by the body to produce aqueous (one of the fluids inside the eye). By inhibiting this enzyme the body produces less aqueous and therefore the pressure in the eye is reduced by 15 to 20 percent.  For many years there has been a search for an eye drop form of oral carbonic anhydrase inhibitors like Acetzolamide or diamox. This has now been achieved in the form of dorzolamide. Dorzolamide has proved a satisfactory eye pressure lowering drop by reducing the production of aqueous fluid.  It is used twice daily in combination with a beta blocking drop, or three times daily on its own.

ADVERSE REACTIONS:

Although Trusopt is sulfa-based, it probably does not share "sulfa allergy" with sulfonamide antibacterials because of a significantly different chemical structure. No measurable amount of the drug is found in the blood plasma, so there is little or no impact on the kidney. One quarter of patients notice stinging and a bitter taste in their throat when taking Trusopt. Gentle eyelid closure and punctual pressure for three minutes after instillation tends to eliminate or minimize this (see instructions for: Proper eye drop insertion). Other side effects may include dry mouth, fatigue, headache, increased eye redness, stinging, burning and blurred vision. If headaches do occurs they tend to go away within a short period of time.

ADVANTAGES:

Trusopt has good pressure lowering ability. It causes little if any discomfort to the eyes or vision in most patients.

Breast-feeding/ Pregnant:

Trusopt passes into breast milk and may reduce the milk supply. The British National Formulary states "the amount is too small to be harmful to the baby" however, the manufacture of Dorzolamide (Trusopt) advises against use in pregnancy or during breast feeding. The use of these drugs must be discussed with your doctor’s. Examples of these drugs are: Diamox Tablets, Diamox SR Capsules, Daranide Tablets, Trusopt and Azopt Eye Drops.