Treatment of central serous chorioretinopathy with beta-blocker metipranolol.

AIM: The purpose of this study was to evaluate the effect of the systemically administered betablocker metipranolol on the course of central serous chorioretinopathy (CSC). METHODS: A prospective double-blind study involving 48 patients with a first attack of CSC not exceeding two weeks and who agreed to the follow-up ophthalmology examinations every week. The group was divided into a metipranolol group (n=23), receiving 10 mg of drug twice per day and a placebo group (n=25). The outcome measure was time in weeks from drug intervention (metipranolol vs. placebo) to reattachment of macula neuroepithelium. RESULTS: There was no statistically significant difference in duration of CSC in patients who used metipranolol and those who used placebo (P=0.341). CONCLUSIONS: In a prospective double-blind study, we found no effect of the betablocker metipranolol on the duration of central serous chorioretinopathy.

Ocular metipranolol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in glaucoma and ocular hypertension.

Metipranolol is a non-selective beta-adrenoceptor blocking agent used for the topical treatment of elevated intraocular pressure in patients with chronic open angle glaucoma or ocular hypertension. In double-blind comparative studies of up to 4 months duration, metipranolol 0.1 to 0.6% produced comparable reductions in intraocular pressure to timolol 0.25 to 0.5% and levobunolol 0.5%, lowering pressure by about 20 to 29% from baseline. Metipranolol has been well tolerated by most patients, producing only minor changes in objective measurements of ophthalmic status and systemic parameters. Similarly, subjective ophthalmic complaints have been minimal although reports of initial stinging or burning upon instillation have occurred. Further published reports, in which larger numbers of patients are treated over extended periods, are needed to confirm the drug's apparent long term comparative efficacy. Studies of ocular metipranolol to date are encouraging, and the drug demonstrates a lasting intraocular pressure reducing effect with good tolerability. Thus, ocular metipranolol provides a viable alternative to ocular timolol and levobunolol in the topical treatment of chronic open angle glaucoma or ocular hypertension.

Intermittent high altitude hypoxia.

The effect of intermittent high altitude (IHA) hypoxia on the myocardium and lesser circulation was investigated in adult male Wistar rats. IHA can induce intermittent pulmonary hypertension and right ventricular hypertrophy in a relatively short time. Even marked pulmonary hypertension, right ventricular hypertrophy, and pulmonary vascular changes can be normalized when rats are removed from the hypoxic atmosphere. At the beginning of the exposure to IHA acute myocardial necrotic changes were found; prolongation of IHA did not lead to further acute lesions. Experimentally induced CO polycythemia leads to mild pulmonary hypertension; IHA-induced pulmonary hypertension may, thus, be partly due to polycythemia. Beta blocking agents are able to decrease chronic hypoxic pulmonary hypertension, hypertensive changes in the pulmonary circulation, the degree of right ventricular hypertrophy, and necrotic myocardial changes.

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.

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.

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.

Amlodipine in patients with stable angina pectoris treated with nitrates and beta-blockers. The influence on exercise tolerance, systolic and diastolic functions of the left ventricle.

The effects of 5 and 10 mg of amlodipine and of placebo were compared in 21 patients with stable angina pectoris and multivessel coronary artery disease. The blind comparison was performed by means of bicycle ergometry and stress echocardiography using esophageal stimulation of the left heart atrium. All patients subsequently received placebo, amlodipine 5 mg and 10 mg for 2 weeks. In bicycle ergometry both doses of amlodipine in comparison with placebo significantly lowered the ST segment depression in lead V5 and prolonged the time to onset of angina. The exercise duration was significantly prolonged only after 10 mg of amlodipine. In stress echocardiography 10 mg of amlodipine significantly improved ejection fraction and reduced wall motion score during stimulation and increased peak velocity of relaxation of left ventricular posterior wall at rest and immediately after stimulation. In the patients with left ventricular end-diastolic pressure < or = 20 mmHg, amlodipine reduced the ratio of peak transmitral flow velocity in atrial contraction to that in early diastole (A/E) at rest and shortened deceleration time at rest and immediately after stimulation. Amlodipine in patients with stable angina pectoris significantly improved the exercise tolerance and the function of the left ventricle in a dose-dependent way. Amlodipine was well tolerated.

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.

[Are metipranolol eyedrops responsible for intraocular side effects?]. / Verursachen Metipranololhaltige Augentropfen intraokulare Nebenwirkungen?

Metipranolol is a beta-blocker that has been used in ophthalmology and in systemic therapy for about 10 years. Reports about reversible uveitis under the product Glauline (metipranolol-containing eye drops) in England were the reason for extensive studies with metipranolol-containing eye drops produced with different methods. Analytical studies concerning the influence of irradiation sterilization on the drug containers, studies on the toxicity of the ophthalmic drug on tissue cultures, and prospective and retrospective clinical studies on 2,800 glaucoma patients were performed. Irradiation sterilization leads to the formation of free radicals on the surface of the containers and, depending on the radiation dose, to a decrease in the pH of the drug solution. In prospective studies involving 1,516 glaucoma patients, no intraocular side effects due to metipranolol-containing eye drops were found. In the retrospective examination including 1,306 glaucoma patients, 19 cases of uveitis were found. Thirteen cases of recurring iritis were diagnosed, which had already been observed before the onset of glaucoma therapy. In 2 cases the iritis led to secondary glaucoma and was treated with metipranolol. In 2 cases glaucoma was treated with pilocarpine (and dipivefrin) and metipranolol concomitantly. One case of rubeosis iridis was incorrectly classified as iritis. One case is possibly related to metipranolol despite the assessment to the contrary by the ophthalmologist in question. Following the results of these studies, an accumulation of cases of uveitis caused by metipranolol can be excluded.

[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.

[Comparison in healthy volunteers of the systemic beta adrenergic receptor blockade by beta blockader eye drops]. / Comparaison chez le volontaire sain du blocage bêta-adrénergique systémique par les collyres bêta-bloquants.

The isoproterenol dose-response curve was used to assess quantitatively the degree of systemic beta-adrenoceptor blockade induced by metipranolol (Bétanol) and betaxolol (Bétoptic) eye drops. The study was carried out in twelve healthy volunteers, aged 22 +/- 1.4 yr. In a randomized double-blind trial, each volunteer received, on separate occasions at least one week apart, one drop in each eye of either placebo (physiological saline) or either of the ophthalmic beta-blockers. The intraocular pressure (Pio), heart rate (fc), arterial systolic (Pasys) and diastolic (Padia) pressures were measured before instillation of the eye drops after 15 to 30 min rest, and 3 h afterwards. The isoproterenol dose-response curve was studied 3 h after instillation of the drops. The CD25 (the amount of isoproterenol needed to increase fc by 25 b.min-1) was obtained by extrapolation on the least square linear regression curve. Both beta-blockers gave a significant fall in Pio compared with placebo, metipranolol more than betaxolol (p less than 0.02). There was also a significantly greater fall in fc with both metipranolol and betaxolol than with placebo. There were no changes in Pasys and Padia. CD25 was significantly increased with both beta-blocker eye drops as compared with placebo (p less than 0.05 for betaxolol; p less than 0.01 for metipranolol), but there was no difference between the two. Systemic absorption after topical application of ocular beta-blockers was thus confirmed for both metipranolol and betaxolol. However, the degree of beta-adrenoceptor blockade was weaker than that observed with other older ocular beta-blockers (timolol and carteolol).(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of long-term administration of metipranolol on passive diastolic properties of the hypertrophic ventricle]. / Vplyv dlhodobého podávania metipranololu na pasívne diastolické vlastnosti hypertrofovanej komory.

In the course of adaptation of the rabbit heart to volume load passive diastolic properties of the hypertrophic ventricle and myocardium were changing significantly. On day 30 following perforation of the aortic valve stiffness of the ventricle was reduced, yet normalized ventricular stiffness and myocardial stiffness were increased. These changes were prevented by beta adrenergic blockade during development of adaptation of the heart to volume load. Although ventricular stiffness was reduced, normalized ventricular stiffness and myocardial stiffness remained at the level of control values. The demonstrated effect of beta adrenergic blockade on passive diastolic properties of the ventricle and myocardium may be of value in preventing heart failure due to chronic hemodynamic load. (Tab.3,Ref.15.).

[Asthma and beta-blocker eye drops (timolol, metipranolol, carteolol). Inhibition of chronotropic effects of isoprenaline]. / Asthme et collyres beta bloqueurs (timolol, métipranolol, cartéolol). Inhibition des effets chronotropes de l'isoprénaline.

Effects of three beta antagonist eye drops are studied in three parallel groups of asthmatic patients. Each ocular topic lowers FEV1 with a maximal effect of -13.4 +/- 2.1% for timolol (n = 15), -17.9 +/- 3.3% for metipranolol (n = 10), and -8.6 +/- 3.0% for carteolol (n = 10). Vital capacity, systolic and diastolic pressure scarcely change, but all three eye drops give a dose dependent sinus bradycardia. Intravenous infusion of isoproterenol (exclusive beta agonist) shows an important inhibition of cardiac receptors by timolol. Doses necessary to increase heart rate of 50% are of 0.242 +/- 0.019 microgram/kg before eye drops are instilled and of 0.647 +/- 0.054 microgram/kg after timolol treatment. This study stresses out the necessity of following recommended doses and respecting carefully classical contra indications of beta blocking agents and specially asthma.

[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.

[Self-care in the prevention of sudden cardiac death]. / Prevence náhlé koronární smrti svépomocí.

In acute myocardial infarction a third up to half of death registered within the first month occur in the first hour of the onset of attack most frequently because of ventricular fibrillation. Immediate self administration of drugs stabilizing electrically the heart may prevent it. On the basis of experiments in dogs and in rats flunitrazepam (Rohypnol tabl. 1 mg), tramadol (Tramal caps. 50 mg) and the beta blocker metipranolol (Trimepranol tabl. 10 mg) were selected for clinical trial on high risk patients. As the chosen combinations of drugs were not yet tested in view of possible interactions, we studied their effect on circulation and cardiovascular reflexes in eight healthy volunteers. When the drugs were absorbed from the mouth mucosa, the decrease in the heart rate during deep breathing was observed already 15 minutes after the intake of drugs. The subjects started to feel relaxed; later on they had pleasant feelings and felt sleepy. There were no undesirable changes in the heart rate or blood pressure. In the three drug combination with metripranolol, the decrease in the heart rate was more marked. The tests in volunteers were without any undesirable effects and both combinations may, therefore, be given to selected high risk subjects, e g. convalescents from myocardial infarction. Randomized trial to prove the preventive effect already started.

[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.

Novel pluronic-chitosan micelle as an ocular delivery system.

Pluronic micelles were prepared for ophthalmic delivery by incorporation of ethyl acetate as a dispersion agent and their surfaces were modified by chitosan to improve their bioavailability. The micelles disperse well in the solution and have a core-shell like structure with a particle size ranging from 93 to 181 nm for drug unloaded, 123-232 nm for drug-loaded, and a zeta potential between 6.1 and 9.2 mV, indicating very suitable use as ophthalmic carrier. The in vitro serum stability tests indicate the particle size of the micelles was very stable during the serum absorption. The turbidity test reveals that the prepared micelles were very stable under phosphate buffered saline environment, which can prevent the blurred vision. The loading efficiency of metipranolol in micelles can be as high as 83%. Finally, the in vitro and in vivo studies indicate the pluronic micelles modified by chitosan have sustained release behavior and good pharmacological response. As the results, the pluroic-chitosan micelles system provides a potential opportunity in decreasing frequency of administration and improving patient compliance for ocular drug delivery.