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Results for “Timolol”

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At least 343 records · Page 19Linked to original sources

PubMed2002

A comparison of the effects on intraocular pressure of latanoprost 0.005% and the fixed combination of dorzolamide 2% and timolol 0.5% in patients with open-angle glaucoma.

PURPOSE: To compare the effects on intraocular pressure (IOP) of latanoprost 0.005% and the fixed combination of dorzolamide 2% and timolol 0.5%. METHODS: Overall, 226 patients whose IOP was insufficiently controlled by timolol alone were randomized to receive either latanoprost once daily or the fixed combination of dorzolamide plus timolol twice daily. Intraocular pressure was measured at 10:00 am and 5:00 pm at baseline and after 3 months of treatment. RESULTS: Mean IOP was reduced from baseline in both groups (p < 0.001), with a mean +/- SEM reduction of - 4.3 +/- 0.3 mmHg (19%) for the latanoprost treatment group and - 4.0 +/- 0.3 mmHg (17%) for the dorzolamide plus timolol treatment group. The two therapies were similarly effective in lowering IOP levels (mean difference in reduction: - 0.4 +/- 0.4; 95% confidence interval: - 1.1, 0.4). CONCLUSIONS: Monotherapy with latanoprost once daily was as effective in reducing mean IOP as the fixed combination of dorzolamide plus timolol twice daily in patients with IOP insufficiently controlled by timolol alone.

Adult↗

PubMed1985

Antiarrhythmic effects of intravenous timolol in supraventricular arrhythmias.

The antiarrhythmic effect of timolol was investigated in 160 subjects with supraventricular arrhythmias. In our double-blind, randomized, parallel, multiclinic study, subjects received timolol, 1 mg iv, or matching placebo as a starting dose, followed by a second and third dose of 1 mg each (or matching placebo) at 20-min intervals if the arrhythmia did not convert to sinus rhythm. Subjects in whom the sinus rhythm returned or the ventricular rate decreased to less than 100 bpm were transferred to a dosing regimen of timolol in 10-mg tablets twice a day by mouth, 1 hr after the last intravenous dose. Data indicated that the mean decrease in heart rate was 44 bpm after timolol and 7 bpm after placebo. The overall proportion of responders (either conversion to sinus rhythm or a decrease in ventricular rate to less than 100 bpm) was 68% after timolol and 7% after placebo. The proportions of responders after timolol were significantly higher than the proportions after placebo for paroxysmal supraventricular tachycardia (26 of 32 subjects and two of 38 subjects), atrial fibrillation (17 of 29 subjects and three of 32 subjects), and atrial flutter (seven of 11 subjects and one of nine subjects). The most common adverse effects were bradycardia and hypotension.

Adolescent↗

PubMed1992

Differential response of beta-adrenergic receptor-mediated heart rate and aortic blood flow acceleration to timolol.

The apparent affinity of beta-adrenergic receptors for timolol in the sinus node and ventricular myocardium was compared in 11 normal male subjects. Sinus nodal function was assessed by heart rate, and left ventricular systolic function was assessed by Doppler-derived aortic blood flow acceleration. The dose of isoproterenol required for a heart rate or acceleration increase of 35% (I35) was determined before and 2 hours after an oral 10 mg dose of timolol. The apparent affinity constant (ka) for timolol binding to the receptor was calculated from the serum timolol concentration and the ratio of the I35 after timolol/I35 before timolol. The I35 for sinus node and ventricular myocardium were not significantly different from one another. The ka for timolol binding to the sinus node (1.14 x 10(6) mol/L), however, was significantly greater (p less than 0.05) than ka for ventricular myocardium (7.85 x 10(5) mol/L). These findings suggest that beta-adrenergic receptors in the sinus node may have an overall greater affinity for beta-blocking agents than do receptors in the ventricular myocardium.

Adult↗

PubMed1981

Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction.

A multicenter double-blind randomized study was carried out to compare the effect of timolol (10 mg twice daily) with that of placebo in patients surviving acute myocardial infarction. Treatment was started seven to 28 days after infarction in 1884 patients (945 taking timolol, and 939 placebo), who represented 52 per cent of those evaluated for entry; the patients were followed for 12 to 33 months (mean, 17). There were 152 deaths in the placebo group and 98 in the timolol group. When deaths that occurred during treatment or within 28 days of withdrawal were considered, the cumulated sudden-death rate over 33 months was 13.9 per cent in the placebo group and 7.7 per cent in the timolol group--a reduction of 44.6 per cent (P = 0.0001). The cumulated reinfarction rate was 20.1 per cent in the placebo group and 14.4 per cent in the timolol group (P = 0.0006). We conclude that long-term treatment with timolol in patients surviving acute myocardial infarction reduces mortality and the rate of reinfarction.

Acute Disease↗

PubMed1984

Reduction of infarct size with the early use of timolol in acute myocardial infarction.

One hundred forty-four patients admitted to the hospital within four hours after onset of symptoms of myocardial infarction were randomly assigned to either intravenous timolol treatment or to placebo. Timolol was given intravenously for the first 24 hours and orally thereafter for the duration of hospitalization. Infarct evolution was assessed by continuous vectorcardiography and creatine kinase release. The timolol group had reduced myocardial ischemia and infarct size as measured by an accelerated reduction of ST-vector magnitude, a significant reduction of maximal cumulative creatine kinase release (29.5 per cent), and significantly smaller changes in QRS-vector variables (20 to 25 per cent). Furthermore, the predicted creatine kinase release and maximal QRS-vector change for a given initial ST-vector magnitude was significantly reduced in the timolol group. Timolol was also associated with significant reductions in pain and need for analgesics and was well tolerated overall. This study supports the use of intravenous timolol in the early phase of suspected myocardial infarction to limit infarct size.

Administration, Oral↗

PubMed1999

Effects of topical carteolol and timolol on tissue circulation in the iris and choroid.

PURPOSE: To evaluate the effects of topical carteolol or timolol on tissue circulation in the iris and posterior choroid. METHODS: After a topical instillation of 20 microl of 2% carteolol, 0.5% timolol, or physiological saline (for control) into one eye, and physiological saline into the other eye of pentobarbital-anesthetized Dutch pigmented rabbits, normalized blur value; a quantitative index of tissue blood velocity in the iris (NB(iris)) and posterior choroid (NB(cho)) was obtained using the laser-speckle method. Intraocular pressure (IOP), blood pressure and pulse rate were serially monitored for 2 hours after instillation. Using separate groups of rabbits, NB(iris) and IOP were measured before and after 20-day twice-daily unilateral treatment of carteolol or timolol. RESULTS: After a single instillation of carteolol, NB(iris) was significantly greater only in the treated eyes than control eyes (P = 0.0050, repeated measures two-way ANOVA), while NB(cho) showed no significant change. IOP in the treated eyes significantly reduced (P = 0.0005). Bilateral reductions of tissue vascular resistance in the iris were found after carteolol instillation (P = 0.0183 approximately 0.0322). After timolol instillation, serial changes in NB(iris) and NB(cho) in the treated eyes were significantly different from those in control eyes (P = 0.0129, 0.0031), while there were no significant differences at any of time points (Mann-Whitney test); IOP in both eyes was significantly reduced (P = 0.0096 approximately 0.0005); tissue vascular resistance in the iris and posterior choroid showed no significant changes. After 20-day treatment, NB(iris) in the both eyes of carteolol-treated rabbits significantly increased from the baseline (P = 0.0280, 0.0425, Wilcoxon signed rank test) and NB(iris) in timolol-treated eyes significantly decreased (P = 0.0280). CONCLUSIONS: A single instillation of topical carteolol significantly increased the iris tissue blood velocity in the treated eye and reduced the tissue vascular resistance in both eyes. Topical timolol tended to decrease tissue blood velocity in the iris and choroid of the treated eye, but showed no significant effects on tissue vascular resistance in the both tissues.

Administration, Topical↗

PubMed2004

Iontophoretic enhancement of timolol across human dermatomed skin in vitro.

The objective of this study was to assess the in vitro the iontophoretic delivery of Timolol across human dermatomed skin in order to determine whether therapeutic doses of this drug can be delivered. Anodal iontophoresis of Timolol was performed by manipulating the donor vehicle and the current density. It was observed that by reducing simultaneously the competitive ions (NaCl) from 8 to 4 g/l and the pH from 7.4 to 4.7, the iontophoretic flux was significantly increased by a factor of 1.5 (669+/-81 microg/cm h). In order to simulate the situation in a transdermal patch, the iontophoretic delivery of Timolol was also studied after adding an artificial porous membrane placed between the Timolol formulation and the human dermatomed skin. No significant difference was observed in the steady state flux across the skin when an artificial membrane was added. Furthermore, a linear relationship was found between current density and steady state flux. These results indicate that the iontophoretic delivery of Timolol can be accurately controlled by the applied current. Assuming a one to one in vitro/in vivo correlation the Timolol transport in vitro results in therapeutic plasma concentrations in humans with very low current densities limiting possible skin irritation.

Administration, Cutaneous↗

PubMed2001

Enhanced ocular hypotensive response to timolol in rabbits with prior dexamethasone treatment.

The purpose of this study was to determine glucocorticoid modulation of ocular pressure to timolol applied topically to rabbit eyes that were pretreated with dexamethasone. Rabbits were pretreated with five applications of topical 0.007% of dexamethasone (0.01% dexamethasone phosphate) or saline drops, administered at ten min intervals. The eyes were then treated with timolol maleate drops at concentrations of free base of 0.00007%, 0.0007%, 0.007% and 0.07%. An additional group of rabbits received dexamethasone pre-treatment only. Intraocular pressure was measured for the next four hr. Enhanced lowering of intraocular pressure was observed with dexamethasone pretreatment. Rabbits receiving the smaller dose of timolol had the least decrease in pressure. The most significant decreases in pressures occurred at 45 min after the administration of timolol with an average difference of 4.8 mm Hg between the timolol- and dexamethasone/timolol-treated eyes for the three largest concentrations of timolol. This synergism between glucocorticoids and beta-adrenergic blockers in lowering IOP may be potentially useful in the therapy of ocular hypertension and glaucoma.

Administration, Topical↗

PubMed2002

Bioavailability in the human eye of a fixed combination of latanoprost and timolol compared to monotherapy.

The ocular pharmacokinetics of a single topical administration of a fixed combination (FC) of latanoprost 0.005% and timolol 0.5% was compared to the monotherapies of latanoprost and timolol in cataract surgery patients. The absorption rate of latanoprost and timolol into the aqueous humor was similar after administration of the FC compared to the two drugs given separately. The aqueous humor concentration of the acid of latanoprost tended to be higher 1-4 hours after administration of FC compared to latanoprost monotherapy. This resulted in an increased AUC. The Tmax and elimination half-life of both latanoprost and timolol were similar after administration of either FC or the two drugs given as monotherapy. Latanoprost did not have any influence on the ocular pharmacokinetics of timolol. The bioavailability of latanoprost and timolol into human aqueous humor, after FC, was at least as good as for the two drugs administered separately.

Absorption↗

PubMed1988

Timolol binding to bovine ocular melanin in vitro.

The binding characteristics of 3H-timolol to bovine iris melanin were determined by using a ligand binding assay. The association and dissociation kinetics were performed using 100 nM 3H-timolol and 0.5 mg/ml melanin at 37 degrees C. The effects of pH, ethanol, 2.5 microM isoxuprine and 1 microM d- and 1-propranolol on 100 nM 3H-timolol binding were also determined. In saturation experiments 3H-timolol (from 1.25 nM to 5 microM) was equilibrated with 0.5 mg/ml melanin. The binding was saturable with the binding maximum of about 1 microM timolol/g melanin. The binding of 100 nM 3H-timolol to melanin increased up to 5 hours and amounted 24% of the added radioactivity. The best fit of the association constants was obtained by using a two fit model. The association rate constants were 4.92 x 10(5) M-1 min-1 and 5.95 x 10(6) M-1 min-1. The dissociation was rapid in vitro and uniphasic with a dissociation rate constant of 5.08 x 10(-3) min-1. The pH, ethanol and both enantiomers of propranolol did not appreciably alter the timolol binding, while isoxuprine diminished it.

Animals↗

PubMed1993

Preliminary evaluation of a series of amphiphilic timolol prodrugs: possible evidence for transscleral absorption.

A series of amphiphilic esters of timolol malonate (octanoyl, decanoyl, dodecanoyl, myristoyl and palmitoyl timolol) were tested in rabbits for their capacity to antagonise the isoproterenol-induced ocular hypotension, using timolol maleate as reference standard. The most active prodrug, palmitoyl timolol malonate (PTM) was also evaluated for its capacity: (a) to decrease IOP in a model of bethamethasone-induced ocular hypertension, and (b) to permeate "in vitro" through rabbit corneal tissues. PTM, the prodrug with the longest aliphatic chain and therefore the greatest amphiphilic/lipophilic character, showed "in vivo" significant activity differences with respect to timolol maleate: the beta-antagonism was more important at earlier and later experimental times, and the IOP decrease was more marked at longer times. The prodrug, however, showed "in vitro" an inferior corneal permeability when compared with timolol maleate. The significant differences observed for the beta-antagonism of PTM at earlier times of the test might be attributed to transscleral absorption, due to the physicochemical characteristics of the prodrug, while the prolonged action (also observed in the IOP-depression test) might be due to sustained release, resulting from accumulation of the prodrug in the corneal epithelium. The present preliminary results are indicative of the potentiality of amphiphilic properties in a prodrug molecule.

Absorption↗

PubMed1998

The use of stable isotope labeling and liquid chromatography-tandem mass spectrometry techniques to simultaneously determine the oral and ophthalmic bioavailability of timolol in dogs.

Assays have been established for the quantitation of timolol and its 13C3- and 2H9-stable-isotope-labeled analogs in plasma and urine using liquid chromatography with atmospheric-pressure chemical-ionization tandem mass spectrometry. For the analysis of urine, underivatized timolol and its labeled analogs are monitored while timolol in plasma is assayed down to concentrations of 0.2 ng/mL after derivatization with phosgene. The great power of this technique is illustrated by simultaneously assaying three different species of timolol in plasma and urine obtained from dogs receiving simultaneous ophthalmic, oral, and intravenous doses of unlabeled and [2H9]- and [13C3]-labeled timolol. Thus, the ophthalmic and oral bioavailabilities of timolol are measured in a single experiment rather than as a three-phase crossover experiment. This approach yields accurate and precise analytical data, obviates intrasubject variability, and saves both analytical and animal resources.

Administration, Oral↗

PubMed1981

Effect of timolol on blood flow distribution in the myocardium during acute regional ischaemia in cats.

The beta-adrenergic blocking agent timolol was given to cats with acute coronary artery ligation. Regional myocardial tissue flow was measured by the distribution of 15 micrometers labelled microspheres. Timolol reduced heart rate, cardiac contractility and left ventricular systolic pressure, but end-diastolic pressure rose. Ischaemic tissue blood flow remained unchanged following timolol, thus improving the marked imbalance between oxygen demands and delivery. In normal areas of the myocardial tissue flow was reduced, indicating the beta 2-adrenergic blocking effect of timolol. This was also the case for the border area between ischaemic and non-ischaemic tissue, but significantly less flow reduction was found on the endocardial side than on the epicardial side in the border area. Except for this latter observation, timolol does not appear to improve coronary perfusion. The present study, therefore, indicates that beneficial effects of timolol on ischaemic myocardium are mainly related to a reduction of myocardial oxygen demand.

Animals↗

PubMed1985

Timolol maleate and HDL cholesterol after myocardial infarction.

The influence of long-term timolol treatment on plasma lipids was analysed in cohorts of the Norwegian timolol multicentre study. The prognostic importance of high-density lipoprotein (HDL) cholesterol concentration after myocardial infarction was also examined. One year timolol treatment was related to a significant reduction in HDL cholesterol levels, from 1.32 mmol l-1 to 1.26 mmol l-1 (P less than 0.05). After one year the HDL cholesterol levels were significantly lower in the timolol treated patients (1.26 mmol l-1) than in the placebo treated patients (1.32 mmol l-1, P less than 0.01). However, the HDL cholesterol values after myocardial infarction had no prognostic importance, and in the placebo group total mortality was the same in patients with low HDL cholesterol (less than 1.25 mmol l-1) and high HDL cholesterol (greater than or equal to 1.25 mmol l-1), respectively 15.0% and 14.8%. Timolol treatment was related to a reduction in mortality both in patients with low (24%, NS) and with high (43%, P less than 0.05) HDL cholesterol levels. Thus, any deleterious effects of timolol on serum lipids did not attenuate its protective effect on the damaged myocardium.

Cholesterol↗

PubMedDate not supplied

Effects of propranolol and timolol on calcium uptake by sarcoplasmic reticulum vesicles.

The effects of the beta-adrenergic receptor blocking agents propranolol and timolol on the initial calcium uptake velocity of sarcoplasmic reticulum vesicles of rabbit skeletal muscle were studied. Racemic d- and l-propranolol had similar inhibitory effects on initial calcium uptake velocity, which was inhibited 50% by 5--7 X 10(-4) M racemic propranolol. Timolol was a much less potent inhibitor of initial calcim uptake velocity; 50% inhibition occurred at approximately 10(-2) M timolol. Both drugs inhibited maximal calcium uptake velocity; however, KCa (the Ca2+ concentration at which calcium uptake was half-maximal) was modified differently. Propranolol increased KCa, whereas timolol caused the KCa to decrease. Addition of either drug to an ongoing calcium uptake reaction at the time that calcium content became maximal caused renewed calcium uptake. The relative potencies of propranolol and timolol as negative inotropic agents are similar to their potencies as inhibitors of sarcoplasmic reticulum calcium uptake, but dissimilar to their beta-adrenergic receptor blocking potencies. Timolol, which has been reported to have less negative inotropic effect than propranolol, is approximately 5 time more potent than propranolol as a beta-adrenergic receptor blocking agent but 15 times less potent as an inhibitor of sarcoplasmic reticulum calcium uptake. Inhibition of sarcoplasmic reticulum calcium uptake may thus characterize negative inotropic potencies of new beta-adrenergic receptor blocking agents.

Animals↗

PubMed1984

Changes in heart size during long-term timolol treatment after myocardial infarction.

The effect of long-term timolol treatment on heart size after myocardial infarction was evaluated by X-ray in a double-blind study including 241 patients (placebo 126, timolol 115). The follow-up period was 12 months. The timolol-treated patients showed a small but significant increase in heart size from baseline in contrast to a decrease in the placebo group. These differences may be caused by timolol-induced bradycardia and a compensatory increase in end-diastolic volume. The timolol-related increase in heart size was observed only in patients with normal and borderline heart size. In patients with cardiomegaly, the increase in heart size was similar in both groups. After re-infarction, heart size increased in the placebo group and remained unchanged in the timolol group.

Adult↗

PubMed1989

Cardiovascular responses to metipranolol and timolol eyedrops in healthy volunteers.

1. Intraocular pressure and cardiovascular responses to metipranolol 0.1% and 0.3% and timolol 0.25% eyedrops were measured in a balanced single dose placebo-controlled crossover study in eight healthy volunteers aged 34-58 years. 2. Timolol 0.25% and metipranolol 0.3% reduced intraocular pressure throughout the 6 h period of observation to a similar extent. Metipranolol 0.1% was marginally less effective, significantly reducing pressure up to 4 h only. 3. No drug treatment significantly altered resting heart rate or blood pressure. Timolol 0.25% significantly reduced exercise tachycardia (P less than 0.05), an effect which was not shown by metipranolol 0.1 or 0.3%. Exertional pain in the legs occurred more frequently after timolol 0.25% and metipranolol 0.3% than after metipranolol 0.1% or placebo eyedrops. 4. Octan-1-ol/pH 7.4 buffer distribution coefficients at 37 degrees C were found to be: metipranolol 5.19, timolol 0.84, indicating that metipranolol has an approximately 6-fold greater lipid solubility. 5. It is concluded that, by comparison with timolol, metipranolol in eyedrop concentrations up to 0.3%, despite its greater lipid solubility, reaches concentrations in the systemic circulation which are less likely to affect the heart.

Adult↗

PubMedDate not supplied

Effects of topical nipradilol and timolol maleate on intraocular pressure, facility of outflow, arterial blood pressure and pulse rate in dogs.

Nipradilol is an alpha(1), beta-blocker with milder side effects than other beta-blockers used in humans. In this study the effects of nipradilol were compared with those of timolol maleate in dogs. Twelve clinically normal dogs (nine mongrels, two beagles, and one Akita) were used. We applied 0.25% nipradilol or 0.5% timolol maleate drops for a period of 28 days. Intraocular pressure (IOP) was measured before and after administration on the 2nd, 4th, 7th, 14th, 21st and 28th day. Blood pressure, pulse rate and coefficient of aqueous outflow (C-value) were also measured before and after administration on the 7th, 14th, 21st and 28th day. Both nipradilol and timolol maleate significantly lowered IOP from the 2nd day to the end of the study period. Nipradilol lowered IOP to an equivalent degree to timolol maleate. There was no significant change in blood pressure and pulse rate throughout the study period with administration of nipradilol. C-value showed a significant rise from the 14th day with administration of nipradilol, while it did not show any significant change during the study period with administration of timolol maleate. The reduction of IOP by nipradilol was similar to that by an existing beta-adrenergic antagonist, timolol maleate, but nipradilol was associated with fewer systemic side effects in dogs. Nipradilol appears to be a useful drug for treatment of glaucoma in dogs.

Administration, Topical↗