Betaxolol in glaucoma treatment

Betaxolol is a selective antagonist of beta-1-adrenergic receptors. This pharmacological property explains its ability to reduce intraocular pressure (IOP). Betoptic and Betoptic S (Alcon) is used in ophthalmology for treatment of glaucoma and ocular hypertension. It has been shown that despite more IOP decrease versus timolol, betaxolol is superior in visual field preservation in glaucoma patients. This effect can not be explained by adrenergic profile of betaxolol. Recent researches have shown that betaxolol improves ocular blood flow in animals and humans. In the same time it is proved to be able to protect ganglion cells from ischemia in different species of animals. Both ocular blood flow improvement and neuroprotective effect are due to the ability of betaxolol to block calcium channels of cell membrane. Such a range of positive effects on eye makes betaxolol the drug of choice for POAG treatment.

Despite ophthalmology progress, glaucoma treatment remains to one of the major problems of this range of medicine. Traditionally main place in glaucoma treatment is occupied with medicamental therapy. Thanks to progress of pharmacology the arsenal of antiglaucoma agents has considerably replenished. However the wide range of preparations frames certain difficulties for the practical doctor: there is all to understand a huge stream of the scientific and advertising information on new medical products. The present review has for an object to summarise results of the most important experimental and clinical researches devoted to a betaxolol - to one of the effective remedies for glaucoma treatment.

The betaxolol has been synthesised for the first time by firm Synthelabo for treatment of cardiovascular diseases. Then it has started to be applied in ophthalmology in the form of ophthalmic drops to treatment of a Primary Open Angle Glaucoma and an ophthalmic hypertensia. The sire of ophthalmologic medicinal forms of a betaxolol under commercial names «Betoptic» and «Betoptic S» is firm Alcon. From the point of view of pharmaceutics, Betoptic and Betoptic S two various medicinal forms represent. Betoptic 0,5 % an aqueous solution of a betaxolol of a hydrochloride are. Betoptic S 0,25 % ophthalmologic suspension of a betaxolol of a hydrochloride are. From the point of view of the practical doctor, these two preparations are interchangeable, as their efficacyy in respect of hypotensive action and other effects are identical. Identical, despite various concentration, efficacyy Betoptic S (0,25 % of suspension) in comparison with Betopticом (0,5 % an aqueous solution) it is caused by application in Betoptic S the special polymerous technologies raising bioavailability of a preparation. Besides it, use of the special polymerous carrier raises comfort of use of a preparation and reduces risk of development of by-effects.

On the pharmacological properties the betaxolol is a selective blocker of b1-adrenoreceptors. It does not possess intrinsic sympathomimetic activity and membrane-stabilising (local anaesthetic) action. As well as other b-blockers, from the ophthalmotonus at the expense of reduction of production of intraocular fluid reduces, however exact mechanisms of this effect are not studied till now definitively. Besides it, some enriching of outflow of a watery moisture though in the majority of researches outflow change appears statistically doubtful is observed. Different explorers specify about identical efficacyy of a betaxolol in respect of ophthalmotonus depression. Irrespective of the medicinal form (Betoptic or Betoptic S), the preparation reduces an ophthalmotonus to necessary level at 85-88 % of patients. Comparing hypotensive action of a betaxolol and Timololum, explorers result varied results. One consider, that it reduces an ophthalmotonus more weakly, than Timololum, others specify in absence of statistically authentic difference in hypotensive action of two preparations. But also those, and others agree in opinion, that the betaxolol surpasses Timololum in the ability to keep visual functions at sick of a glaucoma.

For the first time more expressed, than at Timololum, positive action of a betaxolol on fields of vision at sick of a glaucoma has been noted in the late eighties - the beginning of 90th years when independently from each other there were some works confirming this position. In spite of the fact that schemes of construction of experiment and procedure of processing of the received data in different works is essential differed from each other, authors have received very similar results. So, in work Colignon-Brach comparison of action of a betaxolol and Timololum on an ophthalmotonus and sensitivity of a retina at patients with a Primary Open Angle Glaucoma and an ophthalmic hypertensia within 2 years was spent. The ophthalmotonus was defined by means of Goldman's tonometer, sensitivity of a retina in the central field of vision (30 °) - by means of the automated perimetre Octopus. It has been shown, that despite more weak hypotensive action of a betaxolol in comparison with Timololum, after 12 months of therapy average sensitivity of a retina at patients receiving it has statistically authentically raised, whereas at the patients receiving Timololum, it has decreased. Prolongation of research till four years has shown, that such tendency completely remains: average sensitivity of a retina at the patients receiving a betaxolol, statistically authentically above, than at receiving Timololum.

With research Colignon-Brach results of one more research will well be compounded. In this research comparison of action of a betaxolol and Timololum on an ophthalmotonus and fields of vision at sick of a Primary Open Angle Glaucoma also was spent. Authors specify, that the hypotensive effect of a betaxolol is a little bit less, than at Timololum, but this difference is statistically doubtful. And on the contrary, statistically authentic difference in operation two preparations on average sensitivity of a retina throughout all 4 years of observation was observed. Average sensitivity of a retina in bunch of the patients receiving a betaxolol, was enlarged at the very beginning of observation and remained above initial level to the extremity of research. At the same time in bunch of the patients receiving Timololum, average sensitivity of a retina decreased after 18 months of observation and till the end of research remained below initial level. It is interesting to notice, that in the bunch receiving Timololum, to three patients the trabeculectomy owing to appreciable narrowing of fields of vision against ophthalmotonus indemnification has been executed.

Researches Tasindi, Colignon-Brach, Flammer, Kaiser, etc. force to assume, that despite more weak hypotensive action, a betaxolol Timololum possesses any additional properties which allow it to keep more effectively visual functions, than. However any of the surveyed researches does not give the answer to a question on what it is properties. Work Turacli and et al thereupon is of interest. Authors have compared hypotensive action of a betaxolol, its influence on fields of vision, a blood stream in and. ophthalmica, a. retinalis centralis, aa. ciliares posteriores, measured ultrasonic doppler a method, level of a fibrinogen of a blood plasma and a blood sedimentation rate. Research has taped, that along with enriching of results computer perimetria, under the influence of a betaxolol vascular resistance to a blood flow in а.ophthalmica decreases. These changes have appeared statistically authentic. Vascular resistance in the central artery of a retina and back ciliary arteries (statistically doubtfully) has besides, decreased. Authors do a conclusion, that positive action on fields of vision can be caused vascular effects of a betaxolol. On the pharmacological properties the betaxolol is a selective blocker of b1-adrenoreceptors. It does not possess intrinsic sympathomimetic activity and membrane-stabilising (local anaesthetic) action. As well as other b-blockers, from the ophthalmotonus at the expense of reduction of production of intraocular fluid reduces, however exact mechanisms of this effect are not studied till now definitively. Besides it, some enriching of outflow of a watery moisture though in the majority of researches outflow change appears statistically doubtful is observed. Different explorers specify about identical efficacyy of a betaxolol in respect of ophthalmotonus depression. Irrespective of the medicinal form (Betoptic or Betoptic S), the preparation reduces an ophthalmotonus to necessary level at 85-88 % of patients. Comparing hypotensive action of a betaxolol and Timololum, explorers result varied results. One consider, that it reduces an ophthalmotonus more weakly, than Timololum, others specify in absence of statistically authentic difference in hypotensive action of two preparations. But also those, and others agree in opinion, that the betaxolol surpasses Timololum in the ability to keep visual functions at sick of a glaucoma.

For the first time more expressed, than at Timololum, positive action of a betaxolol on fields of vision at sick of a glaucoma has been noted in the late eighties - the beginning of 90th years when independently from each other there were some works confirming this position. In spite of the fact that schemes of construction of experiment and procedure of processing of the received data in different works is essential differed from each other, authors have received very similar results. So, in work Colignon-Brach comparison of action of a betaxolol and Timololum on an ophthalmotonus and sensitivity of a retina at patients with a Primary Open Angle Glaucoma and an ophthalmic hypertensia within 2 years was spent. The ophthalmotonus was defined by means of Goldman's tonometer, sensitivity of a retina in the central field of vision (30 °) - by means of the automated perimetre Octopus. It has been shown, that despite more weak hypotensive action of a betaxolol in comparison with Timololum, after 12 months of therapy average sensitivity of a retina at patients receiving it has statistically authentically raised, whereas at the patients receiving Timololum, it has decreased. Prolongation of research till four years has shown, that such tendency completely remains: average sensitivity of a retina at the patients receiving a betaxolol, statistically authentically above, than at receiving Timololum.

Data of the literature on vascular effects of a betaxolol enough considerable quantity is saved up. In the present review the most important works will be surveyed only. Betaxolol action on an ophthalmic blood stream and various pots of an eye was studied by various methods: by measurement of a sphygmic ophthalmic blood flow, by means of ultrasonic doppler, in experiments in vitro. Summarising results of these researches, it is possible to draw following conclusions. First, the betaxolol enlarges rate of a linear blood flow in retina and optic disk pots. Secondly, the betaxolol dilates fine arteries and arterioles of a retina and an optic disk of animals and the human. In aggregate it leads to blood flow enriching in a retina and an optic nerve that is rather actual as at sick of a glaucoma microcirculation, as a rule, is broken.

It is impossible to explain vasohypotonic action of a betaxolol if to survey this material only as b-blokator. Moreover, traditional b-blockers cause a vasospasm owing to the not selective action on b2 receptors of pots. This situation well-known in intrinsic medicine, and for not selective b-blokatorov, prescribed per os, a vasospasm is a known by-effect and contraindication for application. The same data are received and in ophthalmology. So, at an instillation in an eye not selective b1,2 adrenoblocker Timololum causes a spastic stricture of arterioles in experiments in vivo. This contradiction easily is authorised data of some the works, showing, that the betaxolol possesses also properties of a blocker of calcium channels. As is known, calcium is necessary for a muscular contraction, including smooth muscles of a vascular side. It is deposited in a sarcoplasmic reticulum and its concentration considerably above arrives in a cell from intercellular space, in which. Discovering or quenching canals on which calcium is included into a cell, it is possible to influence muscular contraction process. Therefore preparations of this bunch, such as, for example, nifedipine, are used for a long time in cardiology for depression of arterial pressure. Ability of a betaxolol to show property of blockers of calcium channels in ophthalmology is shown on pots of a microcirculatory bed of eyes at rats, pigs, large horned livestock and the human. The preparation interferes with an orifice of calcium in a cell and by that breaks muscular contraction process. It, in turn, leads to a vasodilatation and microcirculation enriching in eye tissues. It is important to notice, that the betaxolol has this an effect in the same concentrations in what it is in eyeground tissues at an instilling in therapeutic doses. On the pharmacological properties the betaxolol is a selective blocker of b1-adrenoreceptors. It does not possess intrinsic sympathomimetic activity and membrane-stabilising (local anaesthetic) action. As well as other b-blockers, from the ophthalmotonus at the expense of reduction of production of intraocular fluid reduces, however exact mechanisms of this effect are not studied till now definitively. Besides it, some enriching of outflow of a watery moisture though in the majority of researches outflow change appears statistically doubtful is observed. Different explorers specify about identical efficacyy of a betaxolol in respect of ophthalmotonus depression. Irrespective of the medicinal form (Betoptic or Betoptic S), the preparation reduces an ophthalmotonus to necessary level at 85-88 % of patients. Comparing hypotensive action of a betaxolol and Timololum, explorers result varied results. One consider, that it reduces an ophthalmotonus more weakly, than Timololum, others specify in absence of statistically authentic difference in hypotensive action of two preparations. But also those, and others agree in opinion, that the betaxolol surpasses Timololum in the ability to keep visual functions at sick of a glaucoma.

For the first time more expressed, than at Timololum, positive action of a betaxolol on fields of vision at sick of a glaucoma has been noted in the late eighties - the beginning of 90th years when independently from each other there were some works confirming this position. In spite of the fact that schemes of construction of experiment and procedure of processing of the received data in different works is essential differed from each other, authors have received very similar results. So, in work Colignon-Brach comparison of action of a betaxolol and Timololum on an ophthalmotonus and sensitivity of a retina at patients with a Primary Open Angle Glaucoma and an ophthalmic hypertensia within 2 years was spent. The ophthalmotonus was defined by means of Goldman's tonometer, sensitivity of a retina in the central field of vision (30 °) - by means of the automated perimetre Octopus. It has been shown, that despite more weak hypotensive action of a betaxolol in comparison with Timololum, after 12 months of therapy average sensitivity of a retina at patients receiving it has statistically authentically raised, whereas at the patients receiving Timololum, it has decreased. Prolongation of research till four years has shown, that such tendency completely remains: average sensitivity of a retina at the patients receiving a betaxolol, statistically authentically above, than at receiving Timololum.

Ability of a betaxolol to quench an orifice of calcium in a cell causes one more property of this preparation - its neuroprotection action. A neuroprotection perceive ability of material to protect neurones from influence of disturbing factors. Is conditional it can be parted on direct and indirect (mediated). It is possible to carry any influences which enrich conditions of existence of the excitatory cells To an indirect neuroprotection: ophthalmotonus depression, blood flow enriching and so forth the Big interest is represented by a direct neuroprotection, that is material influence is direct on a neurone. So, in immuno-histological experiments it is shown, that the betaxolol prevents the  destruction of ganglionic cells caused by an ischemia at rats, rabbits and primacies. This effect is caused by betaxolol action on L-type of calcium channels and bound to a metabolism of exciting amino acids, first of all glutamate.

Thus, summarising the given literatures, it is possible to draw following conclusions. Along with hypotensive action the betaxolol (Betoptic and Betoptic S) possesses properties of a blocker of calcium channels. It leads to enriching of microcirculation of a retina and an optic disk. In addition to it, ability to quench an orifice of calcium in a cell causes neuroprotection action of a betaxolol which shows in rising of fastness of ganglionic cells to an ischemia. All listed explains high efficacyy of a betaxolol in conservation of fields of vision at sick of a glaucoma and allows to recommend a betaxolol (Betoptic and Betoptic S) for wide application at patients with a Primary Open Angle Glaucoma, as an agent of a choice among other b-blockers. On the pharmacological properties the betaxolol is a selective blocker of b1-adrenoreceptors. It does not possess intrinsic sympathomimetic activity and membrane-stabilising (local anaesthetic) action. As well as other b-blockers, from the ophthalmotonus at the expense of reduction of production of intraocular fluid reduces, however exact mechanisms of this effect are not studied till now definitively. Besides it, some enriching of outflow of a watery moisture though in the majority of researches outflow change appears statistically doubtful is observed. Different explorers specify about identical efficacyy of a betaxolol in respect of ophthalmotonus depression. Irrespective of the medicinal form (Betoptic or Betoptic S), the preparation reduces an ophthalmotonus to necessary level at 85-88 % of patients. Comparing hypotensive action of a betaxolol and Timololum, explorers result varied results. One consider, that it reduces an ophthalmotonus more weakly, than Timololum, others specify in absence of statistically authentic difference in hypotensive action of two preparations. But also those, and others agree in opinion, that the betaxolol surpasses Timololum in the ability to keep visual functions at sick of a glaucoma.

For the first time more expressed, than at Timololum, positive action of a betaxolol on fields of vision at sick of a glaucoma has been noted in the late eighties - the beginning of 90th years when independently from each other there were some works confirming this position. In spite of the fact that schemes of construction of experiment and procedure of processing of the received data in different works is essential differed from each other, authors have received very similar results. So, in work Colignon-Brach comparison of action of a betaxolol and Timololum on an ophthalmotonus and sensitivity of a retina at patients with a Primary Open Angle Glaucoma and an ophthalmic hypertensia within 2 years was spent. The ophthalmotonus was defined by means of Goldman's tonometer, sensitivity of a retina in the central field of vision (30 °) - by means of the automated perimetre Octopus. It has been shown, that despite more weak hypotensive action of a betaxolol in comparison with Timololum, after 12 months of therapy average sensitivity of a retina at patients receiving it has statistically authentically raised, whereas at the patients receiving Timololum, it has decreased. Prolongation of research till four years has shown, that such tendency completely remains: average sensitivity of a retina at the patients receiving a betaxolol, statistically authentically above, than at receiving Timololum.