Bronchial and cardiovascular effects of ocular topical B-antagonists in asthmatic subjects: comparison of timolol, carteolol, and metipranolol.

B antagonists eye drops are most effective for the treatment of chronic open angle glaucoma. By this way of administration they have a very good systemic bioavailability. Bronchial, and cardiovascular effects of three of these topicals: timolol, carteolol and metipranolol have been evaluated in three parallel groups of asthmatic patients. The three topics induce bronchoconstriction without significant difference between them, and lower heart rate (sometimes very intensely) whatever the B antagonist studied. From these data, it is recommended to practitioners to follow carefully the rules of administration of B blockers, even in eye drops.

Topical ophthalmic beta-adrenergic blockade for the treatment of glaucoma and ocular hypertension.

Since the late 1970s, topical beta-adrenergic blockers have been the drugs of choice in treating ocular hypertension and associated glaucoma. The currently available drugs are timolol, betaxolol, levobunolol, metipranolol, and carteolol. All reduce intraocular pressure by decreasing the production of aqueous humor. Although these drugs are applied locally in the eye, they may enter the general circulation and reach concentrations high enough to cause systemic effects, including alterations in heart rate and rhythm, bronchoconstriction, dyslipidemia, and central nervous system abnormalities. Interactions with other drugs may also occur. Ocular beta- blockers differ in beta 1-selectivity (betaxolol is beta 1-selective, whereas the other drugs are nonselective) and in intrinsic sympathomimetic activity (ISA) or partial agonist properties (only carteolol possesses ISA). These differences give betaxolol and carteolol potential advantages in minimizing certain side effects. The advantage of betaxolol vis-à-vis systemic side effects is more clearly established than that of carteolol. Further systematic study is needed to determine what advantages, if any, are conferred by the presence of ISA.

Metipranolol-associated nongranulomatous anterior uveitis.

PURPOSE: To describe the findings in a patient with a nongranulomatous anterior uveitis, presumed to be induced by metipranolol. METHOD: A 69-year-old woman developed bilateral, nongranulomatous, anterior uveitis while undergoing treatment with metipranolol 0.3% for primary open-angle glaucoma. Four months after resolution of the initial episode, the patient was challenged with metipranolol 0.3% in the right eye. RESULT: On reinstituting metipranolol 0.3%, the patient once again developed a unilateral, nongranulomatous, anterior uveitis in the challenged eye. CONCLUSION: Metipranolol 0.3% eyedrops, used to treat primary open-angle glaucoma, appear to cause a nongranulomatous anterior uveitis.

A clinical trial of metipranolol, a noncardioselective beta-adrenergic antagonist, in ocular hypertension.

In randomized, double-masked fashion, 24 volunteers with ocular hypertension received 0.3% or 0.6% metipranolol, a noncardioselective beta blocker; or placebo twice daily to both eyes for six weeks. Intraocular pressure (mean +/- SEM) was reduced (P = .01) in the metipranolol-treated patients (baseline measurement, 25.9 +/- 0.5 mm Hg to 18.1 +/- 1.2 mm Hg at six weeks, 0.6% concentration; baseline measurement, 27.1 +/- 0.4 mm Hg to 21.6 +/- 1.5 mm Hg at six weeks, 0.3% concentration). Intraocular pressure was not markedly changed in placebo-treated patients. Outflow facility was unaltered two hours after instillation of metipranolol at study week 2 compared to baseline measurement. Aqueous humor flow rates were reduced (P = .02) 20% after 0.6% or 0.3% metipranolol instillation and were unchanged after placebo administration compared to baseline measurement. Mean systolic blood pressure, diastolic blood pressure, and pulse rate were not markedly altered. Metipranolol reduces intraocular pressure by suppressing aqueous humor flow rates.

A blind randomised cross-over trial comparing metipranolol 0.3% with timolol 0.25% in open-angle glaucoma: a pilot study.

A blind randomised cross-over study was conducted on 10 patients (20 eyes) to compare the effect in patients with open-angle glaucoma of metipranolol 0.3% with that of timolol 0.25% on intraocular pressure following one month's topical instillation with each preparation alone. There was no statistically significant difference in intraocular pressure reduction between these two preparations, and the ocular tolerance of both was good. There was no significant difference in the blood pressure, pulse, or pupil diameters of patients receiving either preparation.

Levobunolol and metipranolol: comparative ocular hypotensive efficacy, safety, and comfort.

Topical levobunolol 0.5% was compared with topical metipranolol 0.6% for efficacy, safety, and comfort in 46 patients with open angle glaucoma or ocular hypertension. The study was of parallel design, randomised, double-masked, and of three months' duration. After a washout interval the study medications were instilled twice daily in both eyes. The overall mean decrease in intraocular pressure (IOP) was approximately 7 mmHg in both groups. More than 90% of patients in both groups successfully completed the study. Both agents caused slight decreases in heart rate and blood pressure. More complaints of burning and stinging were reported in the metipranolol group than in the levobunolol group. This three-month, 46-patient study showed levobunolol 0.5% and metipranolol 0.6% to be similarly effective ocular hypotensive agents.

Ocular beta-blockers in glaucoma management. Clinical pharmacological aspects.

Topical beta-blockers reduce the intraocular pressure (IOP) by blockade of sympathetic nerve endings in the ciliary epithelium causing a fall in aqueous humour production. Two types of topical beta-blockers are available for use in glaucoma: nonselective, which block both beta 1- and beta 2-adrenoceptors; and cardioselective, which block only beta 1-receptors. Of the beta-Blockers commercially available, timolol, levobunolol, metipranolol and carteolol are nonselective, and betaxolol is cardioselective. Twice-daily timolol is probably the most effective agent in lowering IOP, although levobunolol is equally effective and can be used once daily with little difference in effect. Carteolol is used twice daily and any theoretical advantage in diminished side effects conferred by its partial beta-agonist activity compared with timolol has not been fully substantiated. Metipranolol is effective twice daily and does not have partial beta-agonist activity. Betaxolol has an effect comparable to timolol in lowering IOP, but is less effective in some patients. beta-Blockers can be used with other antiglaucoma medications, but their combined action with epinephrine (adrenaline) is suspect, particularly in the case of the nonselective beta-blockers, and the effect should be assessed in patients on an individual basis. Local stinging can be a problem in some patients with betaxolol. The most serious side effects of beta-blockers are the exacerbation of chronic obstructive airways disease with nonselective agents and the precipitation of bronchospasm in some patients. Betaxolol seems relatively free of adverse respiratory effects, although this may be dose-related and extreme caution should still be exercised in patients with any history of respiratory illness. Because of the lower risk of precipitating side effects, betaxolol is probably the beta-blocker of first choice for use in glaucoma; timolol or levobunolol are reserved for patients who do not respond satisfactorily to betaxolol and are quite free of respiratory disease.

Reduction of intraocular pressure in a glaucoma patient undergoing hormone replacement therapy.

OBJECTIVES: To show the reducing effect of estrogens and progestins on the elevated intraocular pressure (IOP) in the case of a 56-year-old woman showing typical climacteric complaints, who was admitted to the menopause outpatient unit. She also suffered from a primary open-angle glaucoma treated with betaophtiole eye drops with intraocular pressures of 16-20 mmHg under this local therapy. METHODS: IOP patterns were monitored by means of standardised daily pressure profiles four times a day before as well as 4 and 12 weeks after the beginning of hormone replacement therapy (HRT). The local glaucoma therapy remained unchanged. RESULTS: During HRT, IOP levels were reduced from 16-20 mmHg before therapy to 12-15 mmHg at week 4 and to 13-15 mmHg at week 12 after the beginning of HRT. CONCLUSION: The finding of a close chronological relationship between the onset of menopause and the development of a glaucoma is a potentially new indication for HRT.

Comparison of the effects of 0.5% timolol maleate, 2% carteolol hydrochloride, and 0.3% metipranolol on intraocular pressure and perimetry findings and evaluation of their ocular and systemic effects.

PURPOSE: To compare the effects of 0.5% timolol maleate, 2% carteolol, and 0.3% metipranolol on intraocular pressure (IOP) in 45 patients with primary open-angle glaucoma (POAG) and ocular hypertension. A secondary goal of this study was to evaluate the ocular and systemic side effects of these medications. METHODS: Measurements of IOP were taken at baseline (pretreatment) and 2, 6, and 12 hours after instillation on treatment days 15, 30, 60, and 90. Mean sensitivity (MS) and mean defect (MD) values of perimetry before and after treatment and the effects of the three beta blockers on serum lipid profiles were determined. Ocular and systemic side effects were recorded. RESULTS: The most prominent IOP lowering effect was noted with metipranolol at 2 and 6 hours on day 15, and with timolol maleate at 12 hours on day 15 and at all hours of the subsequent days on which measurements were taken. Timolol maleate produced a significant decrease in IOP at 12 hours on day 15 compared with carteolol. There was not a statistically significant difference between the MS and MD values on perimetry before and after treatment for any treatment. There was a statistically significant decrease in levels of total cholesterol and high-density lipoprotein (HDL) cholesterol and a significant increase in triglyceride levels; these changes were observed for all treatments. CONCLUSION: The effects of the three medications were not statistically different from each other in terms of IOP reduction and visual field changes. Careful monitoring of blood lipid levels is necessary with long-term treatment with beta blockers, because these agents reduced serum levels of HDL and total cholesterol while increasing triglycerides. Such changes in lipid levels could lead to increased incidence of complications, particularly in patients with atherosclerosis or coronary heart disease.

Metipranolol associated granulomatous anterior uveitis: not so uncommon as thought.

Two case reports of bilateral granulomatous anterior uveitis are described in patients with open angle glaucoma treated with metripranolol 0.6% eye drops. Several cases have been described in the United Kingdom and recently in the United States. In my opinion this reaction is not so uncommon as thought. Possible causes of this phenomenon are proposed keeping in mind that a hypotensive drug can cause intra ocular pressure rise. The incidence of similar cases seems to increase.

[Mid-term results of a double-blind study comparing metipranolol to timolol in the treatment of primary open-angle glaucoma]. / Résultats d'une étude à moyen terme à double insu comparant le métipranolol au timolol dans le traitement du glaucome primitif à angle ouvert.

A study on 26 patients with chronic angle glaucoma was completed after 17 weeks. The IOP was satisfactorily stabilized on patients treated with Metipranolol drops. In the Timolol group, the IOP rose again after the 9th week and, at the completion of the study, the difference between the averages of the two groups is significant. No systemic effect was noted as well in the Metipranolol group as in the Timolol group.

[Metipranolol 0.1%: effect of a single dose on the nycthemeral pressure curve in an eye with chronic primary open-angle glaucoma]. / Métipranolol 0.1%: l'effet d'une dose unique sur la courbe tensionnelle nycthémérale d'un oeil porteur d'un glaucome chronique primitif à angle ouvert.

A double blind randomised study was made to compare the efficiency in decreasing intra ocular pressure of Metipranolol 0.1% or 0.3% versus placebo in three groups of 15 patients with chronic open angle glaucoma with or without visual field defects. The results demonstrate that Metipranolol 0.1% significantly lowers the intra ocular pressure in comparison with placebo. But this lowering is less that the one with 0.3% and is markedly reduced after 9 hours. The action of Metipranolol 0.3% is more durable and is still observed at 24 hours with a drop of nearly 20% in comparison with the initial intra ocular pressure. In the three groups, no significant variation of pulse and arterial pressure could be noticed during this 24 hours study.

[Free oxygen radicals in patients with hypertension]. / Volné kyslíkové radikály u nemocných s hypertenzí.

The objective of the investigation was to test the impact of hypertension on the formation of free oxygen radicals which participate in the development of atherosclerosis. Using the method of luminol-dependent chemiluminescence, the authors assessed the spontaneous and stimulated production of free oxygen radicals in phagocytic cells of complete blood in a group of healthy subjects, in not treated essential hypertension (EH), essential hypertension treated with metipranolol (Trimepranol Spofa) and EH treated with diltiazem (Blokalcin Lachema). A statistically significant increase of spontaneous and activated production of free oxygen radicals was found in the group of EH treated with diltiazem. Differences between the group of healthy subjects, untreated EH and hypertension treated with metipranolol were not statistically significant.

[The effect of therapy with adrenergic beta receptor blockers on myocardial beta adrenergic receptors in children with tetralogy of Fallot]. / Vliv lécby beta-adrenergními blokátory na beta-adrenergní receptory v myokardu detí s Fallotovou tetralogií.

Seventeen children with tetralogy of Fallot undergoing cardiac surgery were investigated for alteration in myocardial beta-adrenergic receptors (BAR) in dependence on the previous chronic administration with the beta-adrenergic blocker metipranolol. Binding parameters, Bmax (maximal binding capacity) and Kd (dissociation constant), in right ventricular tissue were assessed in direct saturation binding studies using 125I-pindolol. It can be concluded that a) chronic administration of metipranolol to nine patients in usual doses did not change either Bmax or Kd of BAR in the samples of right ventricle, and b) twelve hours interval between last dose of metipranolol and removal of tissue samples is sufficiently long to enable normalization of possible changes in the sensitivity of BAR. This finding is supported by the pot-operative course and the response to dopamine which did not differ in patients treated and untreated with metipranolol in the preoperative period. Thus, our results suggest that there is no apprehension of chronic application of beta-blockers in patients with tetralogy of Fallot which would negatively influence the response to dopamine during the operation and in the postoperative period.

[Metoprolol and metipranolol in the treatment of hypertension-- comparison of the effects of a single dose and administration for 1 month]. / Metoprolol a metipranolol v lécbe hypertenze--srovnání úcinku jednorázové dávky a jednomesícního podávání.

In six subjects the hypotensive action of metoprolol (Betaloc, Egis) after a dose of 166.7 +/- 47.1 mg and metipranolol (Trimepranol, Spofa) 21.7 +/- 3.7 mg was investigated. Betaloc influences after one month's administration the systolic blood pressure more effectively in a recumbent position and upright position and the diastolic pressure in a sitting position and after walking. The authors investigated also indicators of the circulation, blood sugar values, values of immunoreactive insulin, aldosterone and plasma renin activity after a single dose of 10 mg Trimepranol or 100 mg Betaloc. Betaloc caused a significant drop of the systolic blood pressure already after 15 minutes, Trimepranol after 30 minutes, in both instances the maximum effect was recorded after 45 minutes and persisted throughout the six-hour investigation. The diastolic blood pressure and heart rate were influenced only little. The blood sugar levels after Betaloc rose significantly during the first hour, after both drugs during the third hour. No correlation was found between changes of the blood sugar level and immunoreactive insulin levels. No differences were revealed as regards the effect on plasma renin activity and aldosterone levels.

[Echocardiographic control of treatment of mild hypertension with trimepranol]. / Echokardiografická kontrola lécby mírné hypertenze trimepranolem.

Forty men with hypertension, diastolic BP lower than 14.66 kPa, were treated for six months with Trimepranol, 10 mg three times per day, with echocardiographic checking of changes of the cardiac minute output and the peripheral vascular resistance at rest and during an isometric load. In patients with a low baseline vascular resistance (group A, n = 20) a substantially better therapeutic effect was recorded than in patients with a markedly elevated peripheral resistance (group B, n = 11). Trimepranol is indicated in patients with a higher heart rate at rest and with a significant increase of the latter during isometric loading tests.

[Comparison of the effects of diltiazem and isradipine in adrenergic beta receptor blockade in patients with stable angina pectoris]. / Srovnání úcinku diltiazemu a isradipinu pri blokáde beta-receptoru sympatiku u nemocných se stabilní anginou pectoris.

In 20 patients with stable angina II-III according to NYHA by means of ergometry the effect of short-term administration of dilthiazem (90 mg in three doses), placebo and isradipine (5 mg in three doses) in block of beta-receptors of the sympathetic nerve (metipranolol 3 x 10 mg/day) was compared. As compared with placebo, dilthiazem and isradipine retarded significantly the development of stenocardia, reduced the S-T depression in lead V5 and increased the total work output during ergometry. Based on the results of this and previous work (9) it may be stated that concurrent administration of metipranolol reduced the frequency of side-effects of isradipine and prevented the reflex rise of the heart rate following its short-terms administration. The authors conclude that starting treatment of stable angina with isradipine is safer and more effective in combination with metipranolol than when monotherapy is used. Dilthiazem must be administered with metipranolol carefully with regard to possible development of severe bradycardia and its suitable dose should be established by titration.

[Effect of prolonged administration of beta-blockers on the hemodynamics of patients who have sustained a myocardial infarct]. / Vliianie dlitel'nogo priema beta-blokatorov na gemodinamiku u bol'nykh, perenesshikh infarkt miokarda.

The effect of prolonged treatment with the beta-blocker trimepranol on left-ventricular function was assessed in patients who survived myocardial infarction. Pulmonary arterial catheterization with a floating catheter was used for hemodynamic investigation. Hemodynamic parameters were compared in the treated (20 patients) and control (20 patients matched for age and infarction site) groups. The treated patients showed a reduction in heart rate and cardiac output at rest, as well as stress-induced elevation of the pulmonary arterial pressure and peripheral resistance. Patients with pulmonary hypertension often demonstrated changes of the pressure curve in the pulmonary artery as a possible manifestation of stress-induced mitral regurgitation. Prolonged treatment with trimepranol is associated with increased incidence of pulmonary hypertension in myocardial infarction survivers. The clinical significance of this observation is yet to be established by further studies. Stress-induced mitral regurgitation associated with a mitral subvalvular dysfunction may occasionally be the cause of elevated pulmonary blood pressure.

[Comparative characteristics of various anti-arrhythmia agents used under clinical conditions]. / Sravnitel'naia kharakteristika riada protivoaritmicheskikh sredstv, primeniaemykh v klinike.

Comparative clinical and experimental study of the efficacy of the currently used anti-arrhythmic agents was conducted on 610 patients (828 cases) with various disorders of the cardiac rhythm. The modern classification of these agents is given. The indications and contra-indications for the prescription of the drugs, the optimum doses, and the routes of administration are discussed. Differentiated therapy in various disorders of the cardiac rhythm is recommended.