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[A treatment of mild and moderate hypertension with timolol (author's transl)].

21 patients with essential sustained mild or moderate hypertension were treated with timolol for an average of 6 months at a mean dosage of 3,14 tablets per day. The mean decreases of supine systolic and diastolic blood pressures were respectively of 17,8 and 7,3 mm Hg. The efficacy of timolol was considered excellent or good in 11 cases (52,4 p. cent) and its tolerance perfect in 15 cases (71,4 p. cent). The study was extended in 15 cases with one dose of timolol per day. Effectiveness remained excellent in 12 cases. There was neither orthostatic hypotension nor brady-cardia of less than 55 beats per minute nor water retention. Side effects appeared in 6 cases requiring discontinance of therapy in only one case (exertional dyspnea).

Adult↗

PubMed1990

[Raynaud syndrome following timolol-containing eyedrops].

It has been well known for a long time that beta-adrenoreceptor-blocking substances may cause Raynaud's phenomenon in hands and feet if applied orally or parenterally. Nevertheless, vasospastic phenomenons of the "Raynaud"-type have never before been described following local administration. Now a Raynaud's syndrome found in a 58-year old patient, who had been treated for glaucoma with timolol (Chibro-Timoptol-eyedrops), leaves no doubt that there is a risk of systemic vasospasm in ocular application, too. An exposition test was carried out to prove the connection between the application of timolol eyedrops and Raynaud's syndrome. It did reveal that an initially already marginally prolonged warm-up time after exposition to cold water, as measured in the thermographic test, did relevantly get worse after timolol application. At the same time, no change in arterial systolic finger blood pressure could be demonstrated using Doppler sonography. The induction of Raynaud's syndrome by beta-adrenoreceptor-blocking eyedrops may depend on an individual disposition.

Glaucoma↗

PubMed1990

Timolol reduces IOP in normal NZW rabbits during the dark only.

The role of beta-adrenergic receptors in mediating the circadian rhythm of intraocular pressure was examined by determining the effect on intraocular pressure of timolol applied topically at different times during the circadian cycle to New Zealand White rabbits entrained to alternating 12 hr periods of light and dark. Timolol lowered intraocular pressure when applied during the dark but not during the light phase of the circadian cycle. Timolol did not lower intraocular pressure when applied during the dark to animals after cervical ganglionectomy. These results are consistent with the idea that beta-adrenergic receptors participate in mediating the circadian rhythm of intraocular pressure, and suggest that endogenous agonists released by adrenergic nerves in the eye during the dark stimulate ocular beta-adrenergic receptors to increase intraocular pressure in rabbits.

Administration, Topical↗

PubMed1987

Tolerability of timolol and betaxolol in patients with chronic open-angle glaucoma.

Twenty-four patients with bilateral chronic open-angle glaucoma received three treatments: (1) artificial tears (control) in both eyes, (2) artificial tears in one eye and one drop of timolol (0.05%) in the other, and (3) artificial tears in one eye and one drop of betaxolol (0.05%) in the other. Twelve patients always received the test medication in the left eye and 12 in the right eye. The patients were examined and questioned about ocular symptoms at the time of drug administration and at 1, 5, 30, and 60 minutes. Irritation was noted in five treated eyes after artificial tears, in three after timolol, and in 11 after betaxolol. The incidence of irritation after initial treatment was significantly lower than expected for timolol than for artificial tears or betaxolol (P less than 0.01).

Adrenergic beta-Antagonists↗

PubMed1988

[Asthma and beta-blocker eye drops (timolol, metipranolol, carteolol). Inhibition of chronotropic effects of isoprenaline].

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.

Adult↗

PubMed1988

[Comparative study of levobunolol and timolol in the treatment of chronic open-angle glaucoma and chronic ocular hypertension].

Forty patients with chronic open-angle glaucoma or ocular hypertension participated in this randomized double-masked clinical trial. The patients instilled either 0.5% Levobunolol or 0.5% Timolol into each eye twice daily for three months. Levobunolol produced an overall decrease in mean intraocular pressure of approximately 7 mmHg, while Timolol produced an overall decrease of approximately 5 mmHg but no significant difference has been proved. Intraocular pressure was inadequately controlled in five patients in each treatment group. Both drugs caused heart rate decreases that were judged to be of limited clinical significance. Levobunolol was found to be as safe and effective as Timolol for the treatment of patients with open-angle glaucoma as for those with chronic ocular hypertension.

Adrenergic beta-Antagonists↗

PubMed1987

Timolol promotes reactivation of latent HSV-1 in the mouse iontophoresis model.

The present study examined the effect of topical timolol, a nonspecific beta 1 and beta 2 blocker on reactivation and ocular shedding of latent HSV-1 in an improved mouse iontophoresis model. Latent trigeminal ganglionic infection was established in Balb/C mice following inoculation by corneal scarification with HSV-1 W strain, a clinical isolate, and confirmed by co-cultivation. On day 30, postinfection (pi), the mice were divided into two groups, and treatment begun with coded eye drops (timolol 0.5% or placebo) BID OU for 5 days. On day 31 pi, iontophoresis with 1% 6-hydroxydopamine was performed, and daily treatment with topical epinephrine and 1% prednisolone was administered. Reactivation and recovery of latent HSV-1 was determined by daily ocular swabs, and characteristic HSV-1 cytopathic effect in Vero cells. Results demonstrated that the timolol-treated group had a significantly greater number of positive eyes, multiple shedding episodes, and total shedding days compared to the control group. We conclude that beta blockade promotes recurrent ocular shedding induced by epinephrine in the mouse iontophoresis latency model.

Animals↗

PubMed1978

Timolol. Hypotensive effect, used alone and in combination for treatment of increased intraocular pressure.

In 43 persons with increased intraocular pressure (IOP) Timolol maleate eye drops (0.25% and 0.5%) were used as a single and combined treatment. A significant decrease in IOP was noticed in 34 persons (P less than 0.001) initially. No diminished effect of treatment was apparent after 9 weeks in 34 subjects or after 15 weeks in 23 subjects with Timolol alone. In nine persons with high IOP, Timolol had a significant (P less than 0.001) but insufficient lowering effect. Epinephrine (1%) and acetazolamide appeared to have an additive effect in these cases. No serious local or systemic adverse effects were discovered.

Acetazolamide↗

PubMed1987

Psychiatric side effects from topical ocular timolol, a beta-adrenergic blocker.

Neuropsychiatric side effects have been reported with various systemic betablockers. Data submitted to the National Registry of Drug-Induced Ocular Side Effects appear to indicate similar adverse reactions secondary to topical ophthalmic timolol. One hundred sixty-three of 369 central nervous system cases (44%) reported depression, psychosis, confusion, and hallucinations following topical ophthalmic timolol administration. The psychiatric community should be aware that sudden changes in mental status or onset of common psychiatric conditions, such as depression, may be due to topical ocular timolol. Withdrawal of the drug usually results in disappearance of these effects in 1 to 7 days.

Aged↗

PubMed1987

The effect of timolol on anterior-chamber oxygenation.

The effect of timolol maleate, a nonspecific beta-blocking agent, on anterior-segment oxygenation was studied using oxygen-sensitive microelectrodes inserted into the mid-anterior chamber of 13 cat eyes. The anterior-chamber oxygen tension was monitored continuously for two hours following the topical application of three drops of timolol 0.5%. Although a small, but significant, decline in oxygen tension of 19% was observed over the initial 90 minutes (P less than or equal to .05), the overall 10% decrease at the end of two hours was not considered either clinically or statistically significant when compared with a group of controls. Timolol, since it does not contribute significantly to hypoxia, may therefore be a more prudent choice for lowering intraocular pressure in disorders where hypoxia is believed to play an important role, such as in neovascular glaucoma and sickle-cell hyphema.

Animals↗

PubMed1985

Timolol and guanethidine plus adrenaline in combination in the treatment of chronic open angle glaucoma.

A four month study was conducted in patients with chronic open angle glaucoma to determine whether timolol and guanethidine plus adrenaline have an additive effect in lowering intraocular pressure. Thirty-five patients were assigned to four treatment sequences (timolol 0.25 per cent and 0.5 per cent supplemented with guanethidine 1 per cent plus adrenaline 0.2 per cent (Ganda 1.0/0.2) and vice-versa). There was a significant reduction in intraocular pressure after one month's combined therapy in three of the four treatment groups but this reduction was maintained in only one group (timolol 0.5 per cent with Ganda 1.0/0.2) after four months therapy. The results are discussed with particular reference to adrenergic influences on aqueous humour dynamics.

Aged↗

PubMed1979

Timolol in the treatment of open angle glaucoma.

Timolol maleate is the first beta-adrenergic-blocking drug available in the United States for topical therapy in open angle glaucoma. It may be used alone for initial therapy in selected patients or with other antiglaucoma drugs in patients requiring additional control. It should be tried, before resorting to surgery, when traditional maximal medical therapy has failed or is not tolerated. Timolol has few local side effects, but since it is absorbed, it may produce systemic reactions similar to those induced by orally administered propranolol hydrochloride. Timolol appears to be an important advance in antiglaucoma therapy, although further experience is needed to determine whether its long-term usefulness will be limited by the development of tolerance or the appearance of unexpected side effects.

Administration, Topical↗

PubMed1979

[Timolol maleate. Pharmacology and review of the literature].

The sympathetic system is composed of alpha and beta receptors. Beta blockers block the beta effect competitively. They slow the heart and decrease its contractile strength. They block bronchodilatation and the vasodillation of muscular arteries. Timolol is a non specific beta blocker. It decreases intraocular pressure by reducing aqueous humor formation. It does not change outflow facility. Its action starts twenty minutes after a topical drop, is maximum two to four hours later and lasts 24 hours and more. Timolol o.50% seems equivalent to pilocarpine 4% while Timolol 0.25% seems equivalent to epinephrine 2%. There is a further drop in pressure when added to pilocarpine, diamox as maximum medical treatment. Tables show its advantages, drawback, adverse reactions, and precautions to be taken.

Acetazolamide↗

PubMed1979

Effect of systemic autonomic inhibition on the hemodynamic response to antihypertensive therapy with timolol.

To evaluate the role of systemic autonomic tone in the hemodynamic response to beta-inhibitors, the hemodynamic effects of long-term timolol therapy were studied in hypertensive patients under two sets of conditions: at rest and after pharmacologic systemic autonomic inhibition (SAI). Hemodynamic studies were performed in every subject at the end of a 4-week placebo period and again at the end of a 9-week treatment period. The antihypertensive effect of timolol was associated with decreased cardiac output and unchanged peripheral resistance at rest and with unchanged cardiac output and decreased peripheral resistance after SAI. The hemodynamic response to SAI during the two studies was also markedly different. The findings provide evidence of increased alpha-adrenergic component of systemic autonomic tone during long-term therapy with timolol.

Adult↗

PubMed1979

[A follow-up study on the intraocular pressure response of timolol eye drops (author's transl)].

In 22 open-angle glaucoma patients a total of 39 eyes were treated with Timolol 0.25% twice daily for an average period of 12.6 months. The relative intraocular pressure decrease at the beginning of the study was 47% of the untreated pressure level. This initial response declined to a 23% pressure decrease at the end of the study. In 8 eyes treatment had to be discontinued because of insufficient pressure control and in one patient because of subjective intolerance. In two patients (4 eyes) a complete loss of response of Timolol therapy was observed. The phenomenon of slowly diminishing drug effectiveness was not related to the untreated pressure levels in the patients covered by this study. In 5 eyes there was evidence of a rebound effect after discontinuation of Timolol therapy.

Adult↗

PubMed1980

Pharmacology of ocular drugs. 1. Timolol maleate.

Timolol maleate is a new, potent ocular antihypertensive that has an effect additive with other antiglaucoma medications. It does not cause miosis and is relatively free of ocular complications, although a few have been documented. Timolol does exacerbate asthma and should not be used in patients with a history of this disease. It should be used with caution in cases of significant cardiovascular disease and may produce occasional psychic disturbances. In general, timolol is a potent, effective, and relatively safe drug with few ocular side effects but should be used with appropriate care.

Adrenergic beta-Antagonists↗

PubMed1981

The effect of timolol maleate on the disruption of the blood-aqueous barrier in the rabbit eye.

A disruption of the blood-aqueous barrier in rabbit eyes was elicited by use of topical prostaglandin E2(PGE2), infrared irradiation of the iris, or by subcutaneous alpha-melanocyte-stimulating hormone (alpha-MSH). The aqueous flare provoked was measured quantitatively with a photoelectric instrument. The effect of the (topical) beta-adrenergic antagonist timolol maleate on the breakdown of the blood-aqueous barrier was tested. Timolol applied topically in very large doses had no effect on exogenously administered PGE2. However, even in a very small concentration applied topically, timolol reduced the flare response to both infrared irradiation and alpha-MSH. These results support the theory that the effect of alpha-MSH and infrared irradiation on the blood-aqueous barrier is dependent on intact beta-adrenergic receptor sites.

Administration, Topical↗

PubMed1984

Timolol and a hydrochlorothiazide-amiloride combination in the treatment of essential hypertension in young and middle-aged patients: a comparative study with once-daily administration.

The antihypertensive effects of timolol administered once daily and a combination diuretic were compared in 45 young and middle-aged hypertensive patients. Both treatments significantly reduced lying and standing systolic and diastolic blood pressures as compared to placebo. There were no significant differences between blood pressure reductions after treatment with timolol or with the diuretic. There was a slight negative correlation between the decrease of diastolic blood pressure during timolol treatment and patient age. Serum potassium decreased slightly but significantly during treatment with the diuretic.

Adult↗