RU2607291C1 - Method of treating primary glaucoma in patients with accompanying arterial hypertension - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, ophthalmology, namely to methods of treating primary glaucoma in patients with accompanying arterial hypertension (AH). Additionally patient with glaucoma is examined by cardiologist and if observing arterial hypertension selective beta adrenergic blocker Betaloc ARC is prescribed as beta blocker from 25 mg to 100 mg 1 time a day, in patient before and one week after each dose blood pressure (BP), heart rate (HR) and intraocular pressure are determined, at BP within age norm, HR no less than 50 beats/min, intraocular pressure of 22 mm Hg and below treatment is considered effective and prescribed dose of beta-blocker is left as it is. If BP is lower than 110/70 mm Hg, HR less than 50 beats/min, intraocular pressure above 22 mm Hg prescribed dose of blocker Betaloc ARC is reduced and in addition installation of eye drops prostaglandin analogues 1 time a day in evening is prescribed; if therapy is ineffective, carbonic anhydrase inhibitors are added in form of eye drops 3 times a day. If BP is above or within age norm, HR no less than 50 beats/min, intraocular pressure above 22 mm Hg combination therapy of primary glaucoma is prescribed, installation of eye drops prostaglandin analogues 1 time a day in evening is added to dose of 100 mg of blocker Betaloc ARC 1 time a day; if therapy is ineffective carbonic anhydrase inhibitors are added in form of eye drops 3 times a day; if treating of ocular hypertension is ineffective surgical management of glaucoma is recommended.

EFFECT: method allows considerably reducing drug load on system of body detoxification, reducing adverse effects of eye drops on tissues of eyeball and unfavorable systemic effect on patient.

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Description

The invention relates to medicine, ophthalmology, and in particular to methods of treating primary glaucoma in patients with concomitant arterial hypertension (AH).

Treatment of patients with primary glaucoma is an urgent task of modern ophthalmology, since glaucoma is a leading cause of low vision, blindness and visual disability in many countries of the world, including Russia (Volkov V.V. Glaucoma is open-angle. - M .: Medical news agency ”, 2008. - 352 p.).

Antihypertensive drugs used to treat glaucoma are divided into drugs of the first and second choice. The first choice drugs include: analogues of prostaglandins (latanoprost, travoprost, bimatoprost), non-selective beta-blocker (timolol maleate). The second choice drugs include: selective beta-blocker betaxolol, alpha-beta-blocker proxodolol, carbonic anhydrase inhibitors (dorzolamide, brinzolomide), selective alpha- _2- adrenergic agonist brimonidine, m-cholinomimetic pilocarpine.

There is a known method of treating glaucoma when they start with monotherapy with a drug of first choice (National Glaucoma Guide (guide) for outpatients) / Edited by EA Yegorov, Yu.S. Astakhov, A.G. Schuko .-- M., 2008 .-- 136 p.). If it is ineffective or poorly tolerated by the patient, this drug is replaced by another from a different pharmacological group. If the first selected drug is well tolerated by the patient and is generally effective, but still not enough to achieve “target pressure”, or disease progression is observed and the level of target ophthalmotonus is subject to revision, then they switch to combination therapy.

However, when using local therapy, there are undesirable effects. When using analogues of prostaglandins (travoprost), hyperemia of the mucous membrane, burning sensation, reversible increase in the growth of eyelashes, hyperemia of the skin of the eyelids are possible. With prolonged treatment for more than 3 months, an increase in pigmentation of the iris is observed. Local undesirable effects when using non-selective beta-blockers include: dry eyes, conjunctival irritation, corneal epithelial edema, pinpoint superficial keratitis, allergic blepharoconjunctivitis. The installation of carbonic anhydrase inhibitors can cause the following undesirable local effects: a burning sensation in the eye immediately after instillation, bitterness in the mouth, acupuncture keratopathy, lacrimation, photophobia, local allergic reactions. In patients with a reduced number of endothelial cells, the risk of developing corneal edema is increased. Perhaps the appearance of pain, redness of the eyes, the development of transient myopia and iridocyclitis.

Closest to the claimed is a method for the treatment of glaucoma, including installations in the conjunctival sac of eye drops of timolol 1 drop 2 times a day (Glaucoma. National Guide / edited by EA Yegorov. - M .: GEOTAR - Media, 2013. p. 441-443).

The disadvantage of this method is that the long-term use of timolol causes dry eye syndrome (SSH), induced by both timolol and preservatives that are part of the drops, which have a toxic effect (Lebedev O.I. et al. Benzalkonium chloride as one of the reasons for the insufficient effectiveness of antiglaucomatous ophthalmosurgery. 2012; 2: 48-50), in 80.1% of cases noted signs of CVH in patients receiving beta-blockers. Preservatives, playing an important role in preventing the breakdown of the active component and maintaining the sterility and stability of the contents of the vial, with prolonged daily use, have a direct and indirect negative effect on the so-called "front surface of the eye", including the conjunctiva, cornea and tear film, which is manifested by subjective and objective signs of CVD.

Considering that primary elderly and senile age suffer mainly from glaucoma, patients of this age category very often have various associated pathologies - arterial hypertension, diabetes mellitus, coronary heart disease, arthrosis, etc. The most common pathology of elderly and senile patients is arterial hypertension, which is recorded in almost 80% of cases in this age group.

A serious problem in gerontological practice is polypathy - many concomitant diseases in various combinations and, accordingly, a large number of drugs that older patients are forced to take.

The objective of the invention is to improve the results of treatment of patients with glaucoma with concomitant arterial hypertension by choosing a drug that acts on both diseases with a decrease in undesirable effects.

The problem is achieved by the method of treatment of primary glaucoma in patients with concomitant arterial hypertension by the appointment of a beta blocker. Additionally, a cardiologist examines a patient with glaucoma and, if arterial hypertension is detected, a selective beta-blocker Betalok ZOK from 25 mg to 100 mg once a day is prescribed as a beta blocker, and the patient's blood pressure is determined before and a week after each dose increase ( Blood pressure), heart rate (HR) and intraocular pressure, with blood pressure within the age norm, heart rate of at least 50 beats / min, intraocular pressure of 22 mm Hg and below, treatment is considered effective and a selected dose of beta-blocker is left. With blood pressure below 110/70 mm Hg, heart rate less than 50 beats / min, intraocular pressure above 22 mm Hg the prescribed dose of Betaloc ZOK is reduced and installations of eye drops of prostaglandin analogues are added 1 time per day in the evening; with ineffective therapy, carbonic anhydrase inhibitors are added in the form of eye drops 3 times a day. With blood pressure above or within the age norm, heart rate of at least 50 beats / min, intraocular pressure above 22 mm Hg prescribe a combination therapy of primary glaucoma, to the dose of Betaloc ZOK 100 mg 1 time per day add installations of eye drops of prostaglandin analogs 1 time per day in the evening; with ineffective therapy, carbonic anhydrase inhibitors are added in the form of eye drops 3 times a day; with ineffective treatment of increased intraocular pressure, surgical treatment of glaucoma is recommended.

The novelty of the invention lies in the treatment of two diseases of various organs and systems (glaucoma and arterial hypertension) with a beta-blocker tablet.

The proposed method allows to obtain a new technical result:

- significantly reduce the drug (toxic) load on the detoxification system of the body, since one drug is used that acts on both diseases;

- reduce the adverse effects of eye drops (the main active substance and preservatives) on the tissues of the eyeball (development of dry eye syndrome, swelling of the corneal epithelium, pinpoint superficial keratitis, allergic blepharoconjunctivitis, etc.);

- reduce the adverse systemic effect of eye drops on the patient (the development of bradycardia, an attack of bronchial asthma, angina pectoris with the appointment of timolol maleate; the development of blepharoconjunctivitis, kerotuveitis, arthralgia and myositis and other inflammatory processes when prescribing installations of prostaglandin analogues).

Unlike conventional tablet dosage forms of selective β ₁ -adrenergic blocking agents (including metoprolol tartrate), when Betalok ZOK is used, a constant concentration of the drug in blood plasma is observed and a stable clinical effect (β ₁ -blockade) is maintained for more than 24 hours. Due to the absence of apparent peak plasma concentrations, clinically Betalok ZOK is characterized by better β ₁ -selectivity compared to conventional tablet forms of β ₁ -adrenergic blockers. In addition, the potential risk of side effects observed at peak plasma concentrations of the drug, such as bradycardia and weakness in the legs when walking, is significantly reduced.

The use of Betalok Zok with arterial hypertension leads to a significant decrease in blood pressure for more than 24 hours both in the supine and standing position, and during exercise. At the beginning of metoprolol therapy, an increase in vascular resistance is noted. However, with prolonged use, a decrease in blood pressure is possible due to a decrease in vascular resistance with a constant cardiac output. In the MERIT-HF (NYHA Class II-IV Survival Chronic Heart Rate Survival Study) and reduced cardiac output fraction (≤0.40), which included 3991 patients) Betalok ZOK showed an increase in survival and a decrease in hospitalization rates. With prolonged treatment, patients achieved an overall improvement in symptoms (NYHA grades). Also, therapy with Betalok ZOK showed an increase in the ejection fraction of the left ventricle, a decrease in the final systolic and final diastolic volumes of the left ventricle. Improving the quality of life during treatment with Betaloc ZOK was observed in patients after myocardial infarction.

The recommended initial dose of Betalok ZOK during the first week is 25 mg once a day. If necessary, the dose can be increased to 100 mg once a day. Betalok ZOK is intended for daily use once a day, it is recommended to take the drug in the morning. Betalok ZOK tablet should be swallowed with a liquid. Tablets (or tablets divided in half) should not be chewed or crushed. Eating does not affect the bioavailability of the drug. When choosing a dose, it is necessary to avoid the development of bradycardia. When using Betalok ZOK, a constant concentration of the drug in the blood plasma is observed and a stable clinical effect (beta-adrenoreceptor blockade) is maintained for more than 24 hours.

Evaluation of the ophthalmic hypotensive effect (IOP control) is carried out simultaneously with the determination of blood pressure (BP), heart rate (HR) a week after each change in the dose of the drug. Further, the multiplicity of control of intraocular pressure (IOP) and visual functions depends on the stage of glaucoma, the level of IOP and other factors.

Indicators of normal blood pressure for different age periods: 16-20 years - 100/70 - 120/80; 20-40 years old - 120/70 - 130/80; 40-60 years - up to 140/90; older than 60 years - up to 150/90 mm Hg (http://kardiologia.policlinica.ru/kar42.html).

The effectiveness of the method is proven in the clinic.

19 patients with primary glaucoma suffering from arterial hypertension were treated. In 11 patients (22 eyes), IOP was compensated only by taking Betalok ZOK at a dose of 25-50 mg. In 3 patients (6 eyes), IOP was compensated by the appointment of Betalok ZOK in a dose of 50-100 mg and Xalatan eye drops 1 time per day in the evening. In 5 patients (9 eyes), the IOP was compensated by the appointment of Betalok ZOK in a dose of 50-100 mg, Xalatan eye drops 1 time a day in the evening and Dorzopt 1 drop 3 times a day.

The method is as follows. An additional examination of a patient with primary glaucoma is carried out by a cardiologist and, if arterial hypertension is detected, a selective beta-blocker Betaloc ZOK from 25 mg to 100 mg once a day is prescribed inside the beta-blocker, and the arterial is determined before and one week after each dose increase pressure (BP), heart rate (HR) and intraocular pressure, with blood pressure within the age norm, heart rate of at least 50 beats / min, intraocular pressure of 22 mm Hg and below, treatment is considered effective and a selected dose of beta-blocker is left.

In cases with a decrease in blood pressure below 110/70 mm Hg, heart rate less than 50 beats / min, but intraocular pressure above 22 mm Hg the prescribed dose of Betaloc ZOK is reduced and installations of eye drops of prostaglandin analogues (xalatan, travatan) are added once a day in the evening; with ineffective therapy, carbonic anhydrase inhibitors (azopt or dorzopt) are added in the form of eye drops 3 times a day.

With blood pressure above or within the age norm, heart rate of at least 50 beats / min, intraocular pressure above 22 mm Hg prescribe a combination therapy of primary glaucoma, to the dose of Betaloc ZOK 100 mg 1 time per day add installations of eye drops of prostaglandin analogs 1 time per day in the evening; with ineffective therapy, carbonic anhydrase inhibitors are added in the form of eye drops 3 times a day; with ineffective treatment, surgical treatment of glaucoma is recommended.

Clinical example 1

Patient A., 71 years old, with a diagnosis of primary open-angle glaucoma Ib of the right eye; Ia of the left eye. Initial cataract of both eyes. Concomitant diagnosis: AH of the II degree, risk 2.

Glaucoma is first identified. Glaucoma has not been treated. To correct blood pressure, Enap was taken at a dose of 5 mg once a day.

OD - Vis = 0.8 n / a IOP = 29 mmHg

OS - Vis = 0.9 n / a IOP = 24 mmHg

Biomicroscopy revealed a slight subatrophy of the irises, pseudoexfoliation on the lens bag. Wedge-shaped opacities in the cortex of the lens. On the fundus - glaucomatous atrophy of the optic nerves.

HELL = 162/75 mmHg, heart rate = 71 bpm.

The patient was examined and consulted by a cardiologist. The replacement of Enap with Betalok ZOK at a dose of 25 mg in the morning was recommended.

Inspected after a week. General condition is satisfactory. HELL = 138/65 mmHg, pulse 60 beats / min.

OD - Vis = 0.8 n / a IOP = 22 mmHg

OS - Vis = 0.9 n / a IOP = 20 mmHg

It is recommended to continue treatment and follow-up observation by a cardiologist and ophthalmologist. The method allowed to reduce IOP by taking Betalok ZOK tablets and not prescribe drugs in the form of eye drops.

Clinical example 2

Patient Ch., 61 years old, with a diagnosis of Primary open-angle glaucoma in both eyes. Ia OD; Ic OS. Concomitant diagnosis: Arterial hypertension of the III degree, risk 2, CHF ₀ . To correct blood pressure, Enap was taken at a dose of 5 mg once a day.

The diagnosis of glaucoma is made for the first time. There was no cure for glaucoma.

OD - Visual acuity of 0.3 s / c + 2.0 = 1.0 IOP = 26 mm Hg

OS - Visual acuity of 0.3 s / c + 2.0 = 1.0 IOP = 34 mm Hg

Biomicroscopy revealed a slight subatrophy of the irises, crystalline lenses. On the fundus - glaucomatous atrophy of the optic nerves.

HELL = 167/90 mm Hg, pulse 74 beats / min.

The patient was examined and consulted by a cardiologist. Betalok ZOK at a dose of 50 mg in the morning was recommended.

1 week after the first visit: OD - IOP = 23 mm Hg, OS - IOP = 28 mm Hg, BP = 150/78 mm Hg, heart rate = 68 beats / min. The cardiologist increased the dose of Betaloc ZOK 100 mg in the morning.

2 weeks after the first visit: OD - IOP = 21 mm Hg, OS - IOP = 24 mm. Hg, BP = 110/60 mm Hg, heart rate = 52 bpm. The cardiologist reduced the dose of Betaloc ZOK to 50 mg in the morning. Xalatan eye drops were added 1 drop 1 time in the evening in both eyes.

After 6 weeks: OD - IOP = 17 mmHg, OS - IOP = 19 mmHg, BP = 118/68 mmHg, heart rate = 62 beats / min. It is recommended to continue treatment and follow-up observation by a cardiologist and ophthalmologist. The method has reduced the number of applied eye drops.

Clinical example 3

Patient P., 56 years old, with a diagnosis of Primary open-angle glaucoma in both eyes. IIb OD; IIIc OS. Concomitant diagnosis: Arterial hypertension of the III degree, risk 2, CHF ₀ . Enap was taken at a dose of 10 mg once a day to correct blood pressure.

The diagnosis of glaucoma is made for the first time. I did not receive treatment for glaucoma.

OD - Visual acuity of 0.3 s / c + 2.0 = 1.0 IOP = 29 mm Hg

OS - Visual acuity of 0.3 s / c + 2.0 = 1.0 IOP = 36 mm Hg

Biomicroscopy revealed a slight subatrophy of the irises, crystalline lenses. On the fundus - glaucomatous atrophy of the optic nerves.

HELL = 167/87 mmHg, heart rate = 74 bpm.

The patient was examined and consulted by a cardiologist. Betalok ZOK at a dose of 25 mg in the morning was recommended.

1 week after the first visit: OD - IOP = 27 mm Hg, OS - IOP = 32 mm Hg, BP = 162/77 mm Hg, heart rate = 72 beats / min. The cardiologist increased the dose of Betaloc ZOK to 50 mg in the morning.

2 weeks after the first visit: OD - IOP = 25 mm Hg, OS - IOP = 28 mm Hg, BP = 148/78 mm Hg, heart rate = 56 bpm. The dose of Betalok ZOK is increased to 100 mg in the morning.

3 weeks after the first visit: OD - IOP = 22 mm Hg, OS - IOP = 24 mm Hg, BP = 132/65 mm Hg, heart rate = 51 bpm. Xalatan eye drops were added 1 drop 1 time in the evening in both eyes.

4 weeks after the first visit: OD - IOP = 20 mmHg, OS - IOP = 23 mmHg, BP = 126/62 mmHg, heart rate = 58 beats / min. Dorzopt eye drops were added to the treatment, 1 drop 3 times a day in both eyes.

5 weeks after the first visit: OD - IOP = 17 mmHg, OS - IOP = 18 mmHg, BP = 125/68 mmHg, heart rate = 56 bpm.

It is recommended to continue treatment and follow-up observation by a cardiologist and ophthalmologist.

Claims (1)

A method of treating primary glaucoma in patients with concomitant arterial hypertension, including the appointment of a beta blocker, characterized in that they additionally examine the patient with a cardiologist and, when arterial hypertension is detected, a selective beta blocker Betalok ZOK from 25 mg to 100 is prescribed inside mg 1 time per day, in a patient one week after each change in the dose of the drug, blood pressure (BP), heart rate (HR) and intraocular pressure (IOP) are determined, then the multiplicity l control of IOP and visual function depends on the stage of glaucoma, the level of IOP and other factors, with blood pressure within the age norm, heart rate of at least 50 beats / min, intraocular pressure of 22 mm Hg and below, treatment is considered effective and a selected dose of beta-blocker is left; with blood pressure below 110/70 mm Hg, heart rate less than 50 beats / min, intraocular pressure above 22 mm Hg the prescribed dose of Betaloc ZOK is reduced and installations of eye drops of prostaglandin analogues are added 1 time per day in the evening; with treatment failure, carbonic anhydrase inhibitors are added in the form of eye drops 3 times a day; with blood pressure above or within the age norm, heart rate of at least 50 beats / min, intraocular pressure above 22 mm Hg prescribe a combination therapy of primary glaucoma, to the dose of Betaloc ZOK 100 mg 1 time per day add installations of eye drops of prostaglandin analogs 1 time per day in the evening; with treatment failure, carbonic anhydrase inhibitors are added in the form of eye drops 3 times a day; with treatment failure, surgical treatment of glaucoma is recommended.