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PubMed2006

Microemulsions with timolol as potential eye drops.

Stable microemulsions oil-in-water (o/w) and water-in-oil (w/o) with timolol were obtained. These formulations were sterilized using two methods: by autoclaving and by sterile filtering according to the Polish Pharmacopeia V. Microemulsions were kept in the temperatures of 25 degrees C and 5 degrees C during three months. The following physical parameters were investigated: density, dynamic viscosity, refractive index, surface tension, pH and osmotic tension. All the microemulsions met the requirements for eye drops.

Adrenergic beta-Antagonists↗
PubMed1991

Pharmacodynamic effects of transdermal bupranolol and timolol in vivo: comparison of microemulsions and matrix patches as vehicle.

Transdermal administration of drugs possesses several advantages in therapy, but is limited by generally poor penetration through the skin. The aim of this study was to assess whether in vivo transdermal absorption could be enhanced by using microemulsions (ME) as vehicles. Water uptake from the occluded skin changes the water-free microemulsion base (MEB) into a ME. The increasing content of water decreases the solubility of apolar drugs. This leads to in situ formation of a super-saturated ME that possesses a particularly high absorption rate due to the enhanced diffusion pressure of the drug. A saturated solution of the model drugs bupranolol (B) and timolol (T) in a water-free microemulsion base was applied to an clipped area of the dorsal skin of rabbits with an occlusive patch. Evaluations were made in comparison to matrix patches (M) containing 1.2 mg/cm2 B or 2.0 mg/cm2 T. The beta-blocker dose applied was 2.0 mg/kg body weight throughout the study. The measured parameter of the pharmacodynamic effect was the maximal heart rate (HR) after an i.v. bolus injection of a standard dose of isoproterenol. Observations were made in different intervals over a 10-h time period after application of the patches. The response to isoproterenol was calculated as beta-blocker effect. Faster increasing effects and higher maxima for both drugs was found after application in MEB compared to M. After administration of B and T in MEB the effects were found to be identical, with a maximum (85-90%) after 2 h. Application in M showed B to be less effective (34%, 10h no plateau) than T (74%, 10h). Therefore microemulsions represent an improved vehicle for transdermal administration of test drugs.

Administration, Cutaneous↗
PubMedDate not supplied

[Value of the timolol-hydrochlorothiazide-amiloride hydrochloride combination in the mass treatment of arterial hypertension. Results of a multinational study].

In a 10-week double-blind study, 283 hypertensive patients were treated with a beta-blocker (timolol) alone, a combination of two diuretics (hydrochlorothiazide + amiloride) or a combination of both types of treatment. The results on blood pressure figures were very much in favor of the combination therapy as compared to monotherapy. In a second step, the trial was unblinded and all patients continued with the beta-blocker/diuretic combination for a total of 24 weeks. The medium-term results confirmed those obtained during the double-blind study with regard to the effectiveness and good tolerance of the combination treatment.

Amiloride↗
PubMedDate not supplied

[Pharmacological basis for a fixed association of hydrochlorothiazide, amiloride hydrochloride, and timolol maleate (author's transl)].

The treatment of hypertension requires in many cases a therapeutic combination. This survey, carried out in 96 cases, shows the interest of a fixed combination including a thiazide diuretic (hydrochlorothiazide), a potassium sparing (chlorhydrate of amiloride) and a beta-blocking agent (timolol maleate) as compared to therapy with a beta-blocking agent or diuretic alone. This combination, logical from a pharmacological view point, has proved significantly more effective (81% of patients were normalized) and as well tolerated (none additional side effect) as each of its components. As it simplifies prescription by reducing the number of tablets, it appears a considerable contribution to hypertension therapy.

Amiloride↗
PubMed1989

Trifluridine decreases ocular HSV-1 recovery, but not herpetic lesions after timolol iontophoresis.

To determine the effect of a topically applied antiviral agent on shedding of herpes simplex virus type 1 (HSV-1) into the tear film and corneal epithelial lesions, ten rabbits latently infected with HSV-1 were subjected to transcorneal iontophoresis of 0.01% timolol once a day for 3 consecutive days to induce viral shedding and lesions. Iontophoretic induction was performed similarly in five uninfected rabbits as controls. Half of the infected rabbits and all of the uninfected controls received topical 1.0% trifluridine five time a day for 9 days, beginning the day after the first iontophoresis. All eyes were examined daily for 10 days by slit-lamp biomicroscopy and tear film samples collected on swabs were analyzed for virus. In the infected rabbits, the eyes treated with trifluridine had significantly fewer swabs positive for HSV-1 than the untreated eyes (P less than 0.001); however, there was no significant difference in the numbers of lesions in the treated and untreated eyes. The uninfected controls had no positive swabs and developed no lesions. These results suggest that topical treatment with trifluridine may reduce recovery of HSV-1 from the tear film, but does not affect the incidence of iontophoretically induced corneal epithelial lesions.

Animals↗
PubMed1979

[Efficacy and safety of long-term maintenance treatment with timolol ophthalmic solution in chronic open-angle glaucoma (author's transl)].

Timoptol Ophthalmic Solution (timolol maleate, MSD) is a topical beta-adrenergic receptor blokking agent which lowers elevated intraocular pressure when applied once or twice daily. It represents a major advance in topical therapy for glaucoma and elevated intraocular pressure. It is more effective in reducing elevated intraocular pressure and produces fewer side effects than pilocarpine and epinephrine. It does not alter pupil size or affect visual acuity. Timoptol maintained satisfactory reductions in intraocular pressure in long-term maintenance studies treating over 100 patients for up to 16 months. The drug was well tolerated and without serious adverse effects. In general, reductions in intraocular pressure for non-white patients (predominantly Blacks) were similar to the Whites.

Aphakia, Postcataract↗
PubMed1985

Potential systemic and ocular side effects associated with topical administration of timolol maleate.

A review of current literary sources disclosed a host of adverse reactions which may potentially be associated with the topical administration of timolol maleate. Systemic complications included a variety of cardiovascular, respiratory, central nervous system, gastrointestinal, and dermatologic reactions. Numerous ocular side effects were also reported including superficial punctate keratitis, ocular pain or discomfort, corneal anesthesia, and vague visual disturbances.

Eye↗
PubMed1985

Timolol and pilocarpine are hypotensive in light-induced avian glaucoma.

Two antiglaucoma drugs were tested on Hubbard chicks with light-induced avian glaucoma (LIAG). This animal model for open-angle glaucoma was further assessed by a novel method for monitoring aqueous inflow and outflow simultaneously. When the chicks were 8 to 9 weeks of age the preglaucomatous eyes were significantly enlarged (p less than 0.001), weighing a mean of 3.37 g, compared with 2.59 g for a group of normal eyes, but the intraocular pressure (IOP) was slightly lower in the former (13.79 v. 16.46 mm Hg; p less than 0.05). At this age the aqueous outflow was markedly reduced (to 0.70 v. 2.47 microL/min; p less than 0.05), but no change in aqueous inflow could be demonstrated. By 18 to 20 weeks the glaucomatous eyes were further enlarged (mean weight 4.67 v. 3.76 g; p less than 0.001) and hypertensive (mean IOP 29.85 v. 22.27 mm Hg; p less than 0.05). Timolol elicited a 29% to 33% reduction in the IOP at 8 to 9 weeks in both groups of eyes. At 18 to 20 weeks it reduced the IOP of the glaucomatous eyes to normal values but caused a less marked reduction in the normal eyes. Pilocarpine elicited an initial sharp rise in the IOP but was ultimately hypotensive, causing about a 33% decrease from the preinfusion IOP, in both young and adult birds.

Animals↗
PubMed1979

Effects of timolol and Daranide on elevated intraocular pressure after aphakic keratoplasty.

In a randomized, blind clinical study, we tested the effect of timolol and Daranide against placebo medications among patients who had intraocular pressures greater than 30 mm Hg on the first postoperative day after aphakic keratoplasty. The study failed to show any significant difference in the pressure course. We concluded that because this type of severe secondary glaucoma is extremely difficult to treat, it should be prevented by using a donor cornea larger in size than the recipient bed.

Adult↗
PubMed1983

Timolol maleate: side effects on healthy nonglaucomatous volunteers.

As the number of military pilots over the age of 40 increases, open-angle glaucoma becomes an important aeromedical problem. Epinephrine ophthalmic solution is the only antiglaucomatotic agent in use among flying personnel. Timolol maleate, a new antiglaucomatotic agent, is a nonselective beta-blocker. This drug has a potent hypotensive effect on intraocular pressure with a minimal effect on visual functions. Our data show that it significantly decreases the pulse rate and may eventually be a basis for cardiac dysrythmias.

Adrenergic beta-Antagonists↗
PubMed1983

[Comparative studies of initial pressure reduction using 0.3% metipranolol and 0.25% timolol in eyes with wide-angle glaucoma].

In a short-term study the pressure-lowering effects of Metipranolol 0.3% and Timolol 0.25% were compared in eyes with open-angle glaucoma by means of one-drop curves, diurnal pressure curves and tonography. It appears that these two drugs may be regarded as equal in respect of extent and duration of action. Aqueous humor outflow was facilitated slightly by both drugs, although increase was only statistically significant with Metipranolol.

Adult↗
PubMed1984

Effects of timolol on blood pressure, systemic hemodynamics, plasma renin activity, and glomerular filtration rate in patients with essential hypertension.

Timolol, a non-cardioselective beta-blocking agent, was administered orally after 2 weeks of placebo to 14 patients with essential hypertension for 8 weeks following 1-4 weeks of dose-ranging period. Patients were first hospitalized and submitted to a diagnostic workup. They were placed on a diet containing 100 mEq of Na+ and 65 mEq of K+; this regimen was also prescribed during outpatient treatment. The changes in blood pressure, systemic hemodynamics, plasma renin activity, urine aldosterone, and glomerular filtration rate were evaluated. A significant and stable decrease in systolic and diastolic blood pressure associated with a fall in cardiac output (-21%), heart rate (-17%), plasma renin activity, and urine aldosterone were observed. The blood pressure lowering effect was unrelated to the decrease in cardiac output and plasma renin activity. Glomerular filtration rate was unchanged. No important side effects were observed during the treatment.

Adult↗
PubMed1984

Comparison of a fixed ratio combination of hydrochlorothiazide, amiloride and timolol ('Moducren') given once versus twice daily in mild to moderate hypertension.

An open, multi-centre study was carried out in general practice to compare the efficacy and tolerance of antihypertensive therapy with once-daily and twice-daily dosage of a fixed ratio combination of hydrochlorothiazide (25 mg), amiloride (2.5 mg) and timolol (10 mg). A total of 604 patients with mild to moderate hypertension were treated over a period of 12 weeks with either 1 to 2 tablets once-daily (294 patients) or 1/2 to 1 tablet twice-daily (310 patients). The results showed that there was a significant reduction in systolic and diastolic blood pressures in both groups after only 2-weeks' therapy and the overall reduction after 12 weeks was 31/19 mmHg, with 57% of patients being adequately controlled on the equivalent of 1 tablet per day, whether taken once daily or in divided doses. Forty-six (8%) patients withdrew from the study because of drug-related symptoms, mainly central nervous system in origin. Overall, treatment with either regimen was considered suitable and acceptable by over 80% of patients and doctors.

Adult↗
PubMed1983

[Therapy of hypertension with timolol, hydrochlorothiazide and amiloride].

The effectiveness of fixed combination tablets of timolol 10 mg. hydrochlorothiazide 25 mg and amiloride 2.5 mg (Moducrin) once daily in the control of blood pressure has been assessed in fully ambulant hypertensives by the technique of continuous intra-arterial recording. Highly significant blood pressure reduction (p less than 0.001) was obtained consistently throughout the whole day, confirming the potency and usefulness of the preparation for those patients who need more than one drug to control their blood pressure. 2. Blood pressure responses to both isometric and dynamic forms of exercise were also significantly lowered by combination therapy. 3. The addition of a diuretic to a beta-adrenoceptor blocker appears to be an advantage if the aim of treatment in hypertension is 24 h blood pressure control.

Amiloride↗
PubMed1980

Combination of timolol maleate, hydrochlorothiazide and amiloride hydrochloride in the treatment of hypertension: A multicentre trial.

The effect of a single dose of timolol, hydrochlorothiazide and amiloride in fixed combination (Moducren; MSD) in patients with mild to moderate essential hypertension was tested in an open study during 1978. Ninety-one and a half per cent of the patients studied responded with a fall in diastolic blood pressure of 20 mmHg or more. In 72% a single daily tablet of the combined preparation was sufficient to achieve and maintain control. Patient compliance was excellent and adverse reactions were generally of a minor nature.

Adult↗
PubMed1980

Evaluation of a fixed combination of timolol maleate, hydrochlorothiazide and amiloride hydrochloride in the treatment of hypertension: A long-term multicentre trial.

The effect of a single daily dose of timolol, hydrochlorothiazide and amiloride hydrochloride in fixed combination (Moducren; MDS) in patients with mild to moderate essential hypertension was tested during 1978 in an open study covering 10 weeks per patient. This was subsequently extended to cover a total of 50 weeks per patient, and the results are compared. Of the patients studied during phase 1, 91,5% responded with a fall in diastolic blood pressure of 10 mmHg or more. This figure decreased to 87,5% during phase 2, but none the less remained satisfactory. A single daily dose of one tablet or less of the trial preparation proved effective in the majority of patients (75%). Adverse effects were infrequent and usually of a minor nature.

Adult↗
PubMed1981

Timolol. Canadian multicenter study.

This collaborative study involves 39 investigators and shows the effects of timolol maleate when used short-term on large numbers of patients (418). Intraocular pressure response is excellent. Statistical analyses of pressure response are done using random sampling. Patient complaints were monitored during the study and present interesting findings. Very few adverse reactions were reported.

Blood Pressure↗