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PubMed1983

Chronic open angle glaucoma treated with Timolol. A four year study.

Many reported series of patients treated with topical Timolol for chronic open angle glaucoma have been changed from other medication after a 'wash-out' period. This four year study reports the ocular hypotensive effect of Timolol in 82 new patients with chronic open angle glaucoma followed for up to 4.5 years. The effects on intraocular pressure, visual acuity, visual field, pupil size, pulse rate, blood pressure and Schirmer's test were recorded and correlated. Corneal sensitivity was also followed in some patients, matched by a series of controls, using the method of Cochet and Bonnet. The results are discussed, and only slight reduction in blood pressure and pulse rate was found, and there was no significant effect on the pupil diameter or Schirmer's test. There was no significant effect on corneal sensitivity. There was only slight tachyphylaxis. Of the 82 patients, 20 patients required extra medical or surgical treatment. 16 patients dropped out through death or failure to attend, and of the remaining 66 patients, 69.7 per cent were controlled by Timolol alone.

Adult↗

PubMed1981

[Beta-blockade with timolol after myocardial infarction (author's transl)].

In a recently published study, timolol lowered the overall mortality by 43% and the reinfarction rate by 37% during an average duration of treatment of 17 months after myocardial infarction. Although the timolol study is the best and most convincing of the post-infarction therapy studies yet presented, some important questions remain unanswered; in particular, the effect of other measures (eg the control of risk factors) is not clear. The future role of timolol will depend on further analysis of the study and on the definition of its significance as part of a comprehensive management plan of post-infarction patients.

Clinical Trials as Topic↗

PubMed1983

Giant vacuoles in the lining endothelium of the human Schlemm's canal after topical timolol maleate.

The outflow system was studied by light microscopy in nine human eyes that were treated with topical timolol maleate (0.5%) prior to enucleation for malignant melanoma of the choroid. The frequency of "giant vacuoles" in the lining endothelium of Schlemm's canal and the diameter of these structures was the same in a control group of eyes as in the timolol-treated series. There was no qualitative difference between the architecture of the meshwork in the control and treated groups. These morphologic findings suggested that timolol had no direct action on the outflow apparatus and did not reflect the intraocular pressure (IOP) lowering effect of the drug. The effects of anesthesia, surgical manipulations, and fixation by immersion may have masked any subtle drug effects.

Aqueous Humor↗

PubMed1983

Ophthalmic timolol treatment causing altered hypoglycemic response in a diabetic patient.

A diabetic patient experienced a dangerous alteration in hypoglycemic symptoms during treatment with ophthalmic timolol maleate. Before and after timolol therapy, hypoglycemic reactions were characterized by sweating, uneasiness, and prompt resolution with glucose treatment. During timolol therapy, reactions were characterized by a changed mental status (including seizures on occasion) and a relative resistance to glucose treatment. Caution must be exercised in the use of even topically applied beta-adrenergic blockers in diabetic patients who are prone to hypoglycemia.

Aged↗

PubMed1978

Absence of an effect of timolol on the pupil.

Timolol, a relatively new beta-adrenergic blocker which has been found to lower the intraocular pressure in man, has not been observed to have any side effects upon the visual system. This study utilized pupillography to determine the effect of conjunctival instillation of 0.5% timolol ophthalmic solution upon pupillary size and reaction. No clinically significant effect was observed, but a statistically significant decrease in the amplitude of redilation of the pupil was found in the eye that received timolol.

Conjunctiva↗

PubMed1981

Potential side effects of timolol therapy in the treatment of glaucoma.

The literature concerning the clinical and pharmacologic studies of systemically administered timolol in 2233 patients was reviewed. Side effects reported were correlated with dosage levels and estimated plasma levels. Most adverse effects occurred with levels much higher than would be expected after the topical use of timolol to control glaucoma. The table of potential complications and adverse effects seen with the use of systemic timolol is meant to focus attention on expected and unexpected side effects. All could occur and should be looked for with the topical use of this drug. The goal of this paper is to define better what physicians should look for in evaluating the clinical safety of this drug and what can be realistically expected to be seen as the use of this drug becomes more widespread.

Clinical Trials as Topic↗

PubMed1981

Antihypertensive effect of oral timolol maleate and hydrochlorothiazide once daily compared with hydrochlorothiazide once daily.

The efficacy and safety of timolol maleate combined with hydrochlorothiazide given once daily compared with hydrochlorothiazide given once daily to patients with hypertension was investigated in a double-blind, randomized study. Patients with uncomplicated, mild to moderate hypertension were admitted to the study. Ten patients received two tablets once daily of timolol maleate 10 mg and hydrochlorothiazide 25 mg (T/H). Nine patients received hydrochlorothiazide 25 mg (HCTZ). Blood pressure and pulse rate measurements and laboratory tests were performed after a six-week placebo baseline period and throughout the 12-week study. Mean supine systolic blood pressure decreased by 21-35 mm Hg for the T/H group and by 10-24 mm Hg for the HCTZ group. Mean supine diastolic blood pressure decreased by 15-22 mm Hg for the T/H group and by 10-13 mm Hg for the HCTZ group. Changes observed in the laboratory variables were not statistically significant between the two treatment groups. One patient in each group had an adverse experience considered unrelated to the drug, and no patient had to discontinue the drug therapy because of an adverse reaction. Although both drug regimens effectively and safely treated uncomplicated mild to moderate hypertension, the timolol maleate and hydrochlorothiazide combination had a greater antihypertensive effect.

Adult↗

PubMed1981

[Comparative clinical study of metoprolol and timolol (author's transl)].

Timolol is a non-specific beta-blocking agent acting on both beta 1 and beta 2 receptors while metoprolol is a specific beta 1 blocking agent. Both timolol and metoprolol decrease intraocular pressure by reducing aqueous humor secretion without increasing facility of outflow. They have both similar short and long term efficacy which does not diminish even after several months of use. Generally, there are adequate to treat glaucoma without perimetric changes, while treatment of glaucoma with functional defects requires their association with miotics. When blocking beta 1 receptors, timolol causes marked constriction of bronchi and peripheral vessels. Hence, it is contraindicated in bronchial asthma and ischemic optic neuropathy. This is not the case with metoprolol, which does not block beta 2 receptors.

Glaucoma↗

PubMed1980

Acute effect of epinephrine on aqueous humor formation in the timolol-treated normal eye as measured by fluorophotometry.

A double-blind, randomized, placebo-control study of the effect of epinephrine on the rate of aqueous formation in eyes pretreated with a beta-adenergic blocking drug was carried out in 25 normal subjects with the use of fluorophotometry. All eyes were pretreated with timolol maleate before epinephrine or placebo was given. The effect of timolol maleate alone was to lower intraocular pressure and to reduce the rate of formation of aqueous humor. In the presence of timolol, aqueous formation was decreased further, approximately 7% more, in the epinephrine treated-eye as compared to the placebo-treated eye. This additional decrease in aqueous formation was statistically significant. No statistically significant difference was found in intraocular pressure or in tonographic C value between the epinephrine-treated and the placebo-treated eye. However, intraocular pressure was so low in both eyes that differences in intraocular pressure were not expected and tonographic tracings were difficult to interpret.

Aqueous Humor↗

PubMed1980

Pulmonary effects of topical timolol.

Timolol, a beta-adrenergic blocking agent, recently became available for the treatment of glaucoma. We report the occurrence of acute bronchospasm in a previously asymptomatic asthmatic patient following topical use of timolol. Therapy with the drug was discontinued, and four weeks later the patient was challenged with two drops of 0.5% timolol. A 25% decrease in forced expiratory volume at one second (FEV1) was demonstrated at one hour. The fall in FEV1 was even greater (47%) when the patient was rechallenged with four drops. We emphasize the need to avoid topical beta-adrenergic blocking agents in asthmatic patients.

Administration, Topical↗

PubMed1980

[Preliminary study of acidification of the pH of the aqueous humor in rats treated with timolol maleate].

The Authors have studied in a homogeneous group of rabbits the variations of intraocular pressure and of aqueous humour pH caused by instillation of timolol maleate at different concentrations. In the animals treated with drug concentration of 0,25% and 0,5% a constant reduction of IOP has been observed in comparison with controls, associated to acidification of aqueous humour: no evidence of this correlation it seems to be at low doses of timolol. Further studies are in course to indicate an eventual action of intermediate substances in the mechanism of IOP depression caused by timolol.

Acid-Base Equilibrium↗

PubMed1994

Effect of timolol vs. acetazolamide on sodium hyaluronate-induced rise in intraocular pressure after cataract surgery.

This prospective study was done to compare the efficacy of timolol and acetazolamide in lowering the intraocular pressure (IOP) secondary to the use of sodium hyaluronate (Healon) in cataract surgery. Fifty patients undergoing extracapsular cataract extraction and implantation of a posterior chamber lens were randomly assigned to one of four treatment groups: no viscoelastic (10 patients), Healon with 0.5% timolol drops postoperatively (12 patients), Healon with acetazolamide postoperatively (16 patients), or Healon only (12 patients). The IOP was measured during the first 24 hours after surgery. Sodium hyaluronate caused a marked increase in IOP in the early (6 to 12 hours) postoperative period. Timolol proved to be more effective than acetazolamide in controlling this pressure increase.

Acetazolamide↗

PubMed1993

Effect of topical 0.5% timolol on tear flow in patients with primary open-angle glaucoma as assessed by fluorophotometry.

The question as to whether or not topical medication with beta blockers causes a decrease in tear production remains unanswered. Earlier studies using filter-paper strip tests have yielded contradictory results. In the present study, computerized objective fluorophotometry was used to assess the effect of topical medication with 0.5% timolol (b.i.d.; OU) on tear volume and tear production in 24 consecutive patients with bilateral primary open-angle glaucoma. Tear-film fluorophotometry was performed before treatment as well as at 7 days, 14 days, and 4-7 months after the onset of treatment. The results showed that by 7 days after the initiation of timolol treatment, both tear volume (-29%, P < 0.01) and tear secretion (-36%, P < 0.01) had decreased significantly. However, at both 14 days and 4-7 months after the onset of treatment, none of the values differed significantly from those obtained before treatment. Thus, topical antiglaucomatous treatment with 0.5% timolol eye drops leads to a transient decrease in tear production. This effect, however, lasts no longer than 14 days after the beginning of treatment.

Administration, Topical↗

PubMed1993

[A case of severe bronchial asthma following first use of timolol ophthalmic solution].

A 65-year-old woman with stable atopic bronchial asthma received a prescription for timolol maleate eye drops (0.25% solution, one drop twice a day to both eyes) for glaucoma. On that evening, ten minutes after administration of the first application of timolol, the patient experienced wheeze and slight difficulty in breathing. Within the next ten minutes, her respiration became obviously asthmatic. Her symptoms progressed rapidly. When she arrived at our hospital, reduced respiratory sounds, cyanosis and disturbance of consciousness were observed. After treatment with aminophylline, hydrocortisone, epinephrine and oxygen inhalation, her symptoms completely recovered. In a provocation test, fifteen minutes after application of timolol, wheeze and dyspnea were induced following an increase in respiratory resistance. After the asthma attack, transient hypoxemia, bradycardia and decrease in blood pressure were also observed.

Aged↗

PubMed1995

Topical timolol and lipid profile.

To evaluate the effects of topical timolol on lipid profile, blood samples from 25 patients (16 males and 9 females) were analysed before topical instillation of 0.5% timolol maleate and thereafter at one month and two months. After two months of therapy, the level of high density lipoprotein (HDL) decreased significantly (p < 0.02). The levels of low density lipoprotein (LDL), very low density lipoprotein (VLDL) and triglyceride increased but the changes were not statistically significant. Since low level of HDL is strongly associated with increased risk of myocardial infarction, our study cautions use of topical timolol in patients with low levels of HDL or with previous history of coronary heart disease.

Administration, Topical↗

PubMed1976

Duration of cardiac effects of timolol and propranolol.

The duration of the cardiac effects of single intravenous doses of the beta-antagonists, timolol and propranolol, was compared in 6 healthy male subjects. Timolol and propranolol were given in doses of 1 mg and 10 mg, respectively, and at specified times after their administration, beta-blockade was assessed by the reduction of maximal exercise-induced tachycardia and by the inhibition of the chronotropic and inotropic effects of isoproterenol. Inotropic effects were measured by changes in the pre-ejection period of left ventricular systole obtained from systolic time intervals. There was no statistically significant difference in the timolol and propranolol time-courses of beta-blockade. The change in exercise-tachycardia was maximal 5 min after beta-antagonist infusion but dissipated rapidly so that no statistically significant change was observed 9 hr later. The chronotropic and inotropic effects of isoproterenol were almost completely antagonized for 11/2 hr after beta-antagonist infusion, and significant beta-blockade could be demonstrated 9 hr later. There was no difference in the time-course of the negative chronotropic and inotropic effects of either beta-antagonist.

Adrenergic beta-Antagonists↗

PubMed1976

Haemodynamic long-term effects of beta-receptor-blocking agents in hypertension: a comparison between alprenolol, atenolol, metoprolol and timolol.

1. Oxygen consumption and central haemodynamics were recorded at rest and during exercise in fifty-one men with essential hypertension (W.H.O. stage I) and repeated after 1 year on a single drug: alprenolol (n equals 10), atenolol (13) metoprolol (12) and timolol (16). 2. Mean arterial pressure was significantly reduced in all groups at rest (11-18%) and during exercise (5-11%). Heart rate was significantly reduced in all groups (20-28%) at rest and (17-26%) during exercise. Owing to increase in supine resting and exercise stroke volume in the alprenolol and atenolol group, cardiac index decreased less than heart rate---in contrast to the timolol group where cardiac index was decreased 26-32%. The calculated post-treatment total peripheral resistance was significantly increased at rest and during exercise in the timolol group. In the other groups the total peripheral resistance was significantly increased at rest when sitting, but not at rest when supine and during exercise. 3. It is concluded that the major haemodynamic changes induced in subjects with moderate and mild essential hypertension by these different beta-receptor blockers are the same, but that minor differences exist with respect to effect upon stroke volume and total peripheral resistance.

Adrenergic beta-Antagonists↗

PubMed1975

Timolol maleate (Blocadren) in the treatment of essential hypertension.

The antihypertensive activity of timolol (Blocadren, FROSST-MSD), a new beta blocking agent, was assessed in a single blind crossover placebo-controlled study in 14 patients with essential hypertension. Ten patients completed the trial. The average standing pressure during the placebos periods was 168/109mmHg and during the periods on treatment with timolol the average standing pressure was 139/92mmHg. All 10 patients showed some hypotensive response. The average daily dosage was 21 mg with a range of 15-30 mg. Four patients achieved optimal levels of blood pressure by the end of one week's therapy with the maximum time required being four weeks. Timolol appears to be an effective antihypertensive agent. Side effects were insignificant.

Adrenergic beta-Antagonists↗