可速普特(Cosopt)是0.5%马来酸噻吗洛尔(timolol MALEATE)和2%盐酸多佐胺(dorzolamide HCL)组成的复方制剂,供局部眼用.噻吗洛尔属于非选择性β-受体阻滞剂,通过抑制眼睫状突的β2受体,减少房水生成,降低眼压.而多佐胺属于碳酸酐酶抑制剂(CAI),强效抑制存在于睫状突和视网膜中的碳酸酐酶(CA)-Ⅱ,减少房水生成,有效降低眼内压(IOP).二者合用有相加作用.可速普特主要用于高眼压症,原发性开角型青光眼.全身性不良反应少.

盐酸多佐胺(dorzolamide HCL)
【药理特点】
1、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。
2、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。

TIMOLOL MALEATE(马来酸噻吗洛尔)
【药物相互作用】
1．与肾上腺素合用可引起瞳孔扩大。
2．不主张两种局部p受体阻断剂同时应用。
3．本品与钙通道拮抗剂合用应慎重，囚可引起房室传导阻滞，左心室衰竭及低血压。肘心功能受损的患者，应避免两种药合并使用
4．正在服用儿茶酚胺耗竭药(如利血平)者，使用本品时应严密观察，因可引起低血压和明显的心动过缓。
5．本品与洋地黄类和钙通道拮抗剂合用可进一步延长房室传导时间。
6，本品与奎宁丁合用能引起心率减慢等全身p受休阻断的副作用。可能的原因是奎宁丁可抑制P450酶和CYPZD6对噻吗洛尔的代谢作用。
【药理作用】
药理作用：马来酸噻吗洛尔是一种非选择性p—肾上腺能受体阻滞剂，没有明显的内源性拟交感活性和局麻作用，对心肌无直接抑制作用。本品为马来酸噻吗洛尔滴眼液．对高眼压患者和正常人均有降低眼内压作用、其降低眼内压的确切机理尚不清楚，眼压描记和房水荧光光度研究提示本品的降眼压作用与减少房水生成有关非临床毒理研究：致癌性：动物实验显示长期大量口服马来酸噻吗洛尔可使雄性大鼠肾卜腺嗜铬细胞瘤，雌性小鼠良性及恶性肺部肿瘤，良性子宫息肉及乳腺痛的发生率明显增高。生殖毒性：动物实验显示大剂量门服马来酸噻吗洛尔，对雄、雌性小鼠的生殖功能均无影响。
【孕妇及哺乳期妇女用药】本品对于孕妇的安全性尚未确定。滴眼后可在哺乳期妇女乳汁中测到本品，因对授乳婴儿具有多种潜在不良反应，需根据滴用本品对母亲的重要性决定终止哺乳或终止用药。
【儿童用药】本品对于儿童的安全性和疗效尚未确定。
【药物相互作用】
1.与肾上腺素合用可引起瞳孔扩大。
2.不主张两种局部β受体阻断剂同时应用。
3.本品与钙通道拮抗剂合用应慎重，因可引起房室传导阻滞，左心室衰竭及低血压。对心功能受损的患者，应避免两种药合并使用。
4.正在服用儿茶酚胺耗竭药（如利血平）者，使用本品时应严密观察，因可引起低血压和明显的心动过缓。
5.本品与洋地黄类和钙通道拮抗剂合用可进一步延长房室传导时间。
6.本品与奎宁丁合用能引起心率减慢等全身β受体阻断的副作用。可能的原因是奎宁丁可抑制P450酶和CYPZD6对噻吗洛尔的代谢作用。
【药物过量】过量应用本品可引起类似全身应用β受体阻断剂的副作用，如头晕，头痛，气短，心动过缓，支气管痉挛及心搏停止。
【适应症】
对原发性开角型青光眼具有良好的降低眼内压疗效。对于某些继发性青光眼，高眼压症，部分原发性闭角型青光眼以及其他药物及手术无效的青光眼，加用本品滴眼可进一—步增强降眼压效果。
【禁忌】
1．支气管哮喘者或有支气管哮喘史者，严重慢性阻塞性肺部疾病。
2．窦性心动过缓，II或III度房室传导阻滞，明显心衰，心源性休克。
3．对本品过敏者。
【注意事项】
1．当出现呼吸急促、脉搏明显减慢、过敏等症状时，请立即停止使用本品。
2．使用中若出现脑供血不足症状时应立即停药，
3．心功能损害者，使用本品时应避免服用钙离子拮抗剂．
4．对无心衰史的患者，如出现心衰症状应立即停药。
5.正在服用儿茶酚胺耗竭药(如利血平)者，使用本品时应严密观察。
6．冠状动脉疾患、糖尿病、甲状腺功能亢进和重症肌无力患者，用本品滴眼时需遵医嘱。
7．本品慎用于自发性低血糖患者及接受胰岛素或口服降糖药治疗的患者，因p受体阻滞剂可掩盖低血糖症状。
8．本品不宜单独用于治疗闭角型青光眼。
9．与其他滴眼液联合使用时，请间隔lO分钟以上。
10．定期复查眼压，根据眼压变化调整用药方案
11．用前应摇匀，避免容器尖端接触眼睛，防止滴眼液污染。

【原产地英文商品名】:COSOPT EYE DROPS 10ml/bottle
【原产地英文药品名】:TIMOLOL MALEATE/DORZOLAMIDE HCL
【中文参考商品译名】:可素普特滴眼液 10毫升/瓶
【中文参考药品译名】:马来酸噻吗洛尔/盐酸多佐胺
【生产厂家中文参考译名】:默克
【生产厂家英文名】:Merck & Co., Inc.

欧盟批准复方布林唑胺/噻吗洛尔眼用混悬液上市
欧盟批准爱尔康公司（Alcon ）的10 mg/5 mg/mL复方布林唑胺/噻吗洛尔眼用混悬液（brinzolamide/timolol，Azarga）上市，用于治疗单一用药不能降低眼内压的成人开角性青光眼或眼内压高引起眼内压升高。

两项临床研究显示，本品较Cosopt（复方马来酸噻吗洛尔/盐酸多佐胺滴眼液0.5%/2%）用药舒适且患者耐受性好。在本品与Cosopt对照研究中，79％的青光眼患者更青睐本品。许多医生认为，用药的舒适性可提高青光眼患者用药的持续性，此对防止他们可能失明是关键。

临床研究结果支持了此批准：本品的活性成分以复方制剂给药较单一药物或两药分别给药更有效。研究还显示，本品降低眼内压的疗效在研究中的每一时段测定点均优于单一用药，而安全性两者却相近。此外，逐一对照研究表明，本品降低眼内压的疗效可与Cosopt相媲美。

How does it work?
Cosopt eye drops contain two active ingredients, timolol and dorzolamide. These are both medicines that decrease raised pressure within the eye.

The pressure within the eyeball is normally maintained by a continuous flow of liquid called aqueous humour through the eyeball. Aqueous humour is produced by a part of the eye called the ciliary body. If aqueous humour builds up inside the eyeball, this increases the pressure within the eyeball. This pressure needs to be reduced, as otherwise it can damage the optic nerve and impair vision.

Timolol and dorzolamide work in different ways to reduce the production of aqueous humour and so decrease its build-up inside the eyeball. They both therefore decrease the pressure in the eyeball.

Timolol is a type of medicine called a beta-blocker. These medicines block beta receptors in various parts of the body. Blocking the beta receptors in the eye reduces the amount of aqueous humour that is produced.

Dorzolamide is a type of medicine called a carbonic anhydrase inhibitor. It works by blocking the action of an enzyme in the body called carbonic anhydrase. Carbonic anhydrase is usually responsible for the production of a salt called bicarbonate in the body. Bicarbonate is needed for the production of the aqueous humour. By decreasing the production of bicarbonate, dorzolamide also decreases the production of aqueous humour.

Cosopt eye drops are used to treat glaucoma when treatment with a beta-blocker eye drop on its own has not lowered the pressure in the eye sufficiently.

The eye drops should be put into the affected eye(s) twice a day.

Cosopt eye drops are available in multi-dose bottles or preservative-free single-dose containers.

What is it used for?
Open angle glaucoma.
Pseudo-exfoliative glaucoma.

Warning!
This medicine is not to be taken by mouth.

When using these eye drops you should take care to not touch the dropper tip to any surface, or to your eye, in order to avoid contaminating the eye drops.

Cosopt eye drops in a multi-dose bottle contain the preservative benzalkonium chloride, which can be absorbed by soft contact lenses and cause eye irritation. If you wear soft contact lenses, you should remove them before putting in these eye drops. You should wait at least 15 minutes after using the drops before putting your contact lenses back in.

This medicine may cause temporary blurred vision after you have applied it into the eye(s). If affected, do not drive or operate machinary until this has worn off. You should also take into account that this medicine can sometimes cause other visual disturbances, eg double vision, and dizziness or fatigue, all of which may affect your ability to drive or operate machinary.

Cosopt eye drops are sterile until opened. The multi-dose bottles contain a preservative that helps keep the eye drops sterile. Any medicine remaining in the bottle four weeks after the first opening should be carefully disposed of, as after this time it is likely to be contaminated with germs. You may find it helpful to write the date of first opening on the packet. Dispose of carefully, preferably by returning to your pharmacy. Cosopt single dose containers do not contain a preservative and are for single use only.

They should be disposed of after use, even if there is some solution remaining.
Beta-blockers such as timolol can be absorbed into the bloodstream after being applied into the eye.

They may mask the symptoms of low blood sugar (hypoglycaemia) such as increased heart rate, sweating, tremor and nausea. For this reason, people with diabetes should carefully monitor their blood sugar while using these eye drops.

Beta-blockers such as timolol can increase sensitivity to substances which cause allergy and the seriousness of severe allergic reactions (anaphylaxis). People who experience an anaphylactic reaction while using this medicine may need larger than normal doses of adrenaline to treat the reaction. Seek further medical advice from your doctor if you have a history of allergies.
While using this medicine you should have regular eye examinations.

Use with caution in
History of heart disease.
A severe form of angina pectoris, not caused by exertion (Prinzmetal's angina).
Low blood pressure (hypotension).
Severe disturbance of blood circulation in the extremities, eg Raynaud's disease.
Decreased liver function.
History of allergies.
Psoriasis.
Diabetes mellitus.
Overactive thyroid gland (hyperthyroidism).
Abnormal muscle weakness (myaesthenia gravis).
History of kidney stones (nephrolithiasis)
Chronic defects of the transparent circular part of the front of the eyeball (cornea).
People who have had eye surgery.

Not to be used in
History of asthma.
Severe chronic obstructive pulmonary disease (COPD).
Slow heart rate caused by the pacemaker of the heart (sinus bradycardia).
Serious defect in the heart's electrical message pathways resulting in decreased function of the heart (2nd or 3rd degree heart block).
Uncontrolled heart failure.
Failure of the heart to maintain adequate circulation of blood (cardiogenic shock).
Severely decreased kidney function.
High acid levels in the blood and tissues (acidosis).
Pregnancy.
Breastfeeding.

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding
Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

This medicine can pass into the bloodstream after application into the eye. It should not be used during pregnancy as it may be harmful to a developing baby. Seek further medical advice from your doctor.

This medicine can pass into breast milk after application into the eye. It should not be used by mothers who are breastfeeding. Seek further medical advice from your doctor.

Side effects
Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here does not mean that all people using this medicine will experience that or any side effect.

Eye burning, stinging or itching.
Bitter taste.
Watering eyes.
Blurred vision.
Inflammation or irritation of the eyelids.
Inflammation of the surface of the eye (keratitis).
Headache.
Inflammation of the sinuses (sinusitis).
Disorders of the front layer of the eye (cornea).
Dry eyes.
Nausea.
Visual disturbances.
Feeling weak or fatigued.
Dizziness.
Slow heart rate (bradycardia).
Low blood pressure (hypotension).
Kidney stones.

Breathing difficulties due to a narrowing of the airways (bronchospasm).

The side effects listed above may not include all of the side effects reported by the drug's manufacturer.For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

How can this medicine affect other medicines?
The timolol and dorzolamide in these eye drops can be absorbed into the bloodstream after application to the eye and may therefore interact with other medicines that you are taking. It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while using this one, to ensure that the combination is safe.

If you are using more than one type of eye drop you should administer them at least five minutes apart, to prevent the second drop washing away the first. Use eye gels or ointments last.

There may be an increased risk of a slowed heart rate or drop in blood pressure if these eye drops are used in combination with any of the following medicines:

medicines for an abnormal heartbeat (antiarrhythmics), eg amiodarone, quinidine
beta-blocker medicines taken by mouth, eg atenolol, propranolol
calcium channel blockers such as diltiazem, nifedipine or verapamil
digoxin.

If this medicine is used with clonidine, there is a risk of a rebound increase in blood pressure if the clonidine is stopped suddenly. If the clonidine needs to be stopped, this medicine should be stopped several days before slowly stopping the clonidine.

In people with diabetes, timolol can prolong the lowering of blood sugar (hypoglycaemia) caused by insulin or other antidiabetic medicines. People with diabetes should monitor their blood sugar, as timolol can also mask the signs of hypoglycaemia.

There may be an increased risk of toxicity if these eye drops are used by people taking high-dose salicylates, eg aspirin.

Other medicines containing the same active ingredients
There are currently no other eye drops available in the UK that contain both timolol and dorzolamide.

Timoptol, Timoptol-LA and Nyogel contain just timolol.

Trusopt contains just dorzolamide.