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Comparison of the efficacy and safety of dorzolamide 2% when added to brimonidine 0.2% or timolol maleate 0.5% in patients with primary open-angle glaucoma.

OBJECTIVE: To determine the ocular hypotensive efficacy and safety of dorzolamide when added to brimonidine or timolol in patients with uncontrolled primary open-angle glaucoma (POAG). PATIENTS AND METHODS: This is a 1-year prospective open-label clinical trial of 48 consecutive POAG patients with inadequate intraocular pressure (IOP) control while using brimonidine 0.2% (23 patients) and timolol 0.5% (25 patients), 2 times daily. Patients were assigned to receive dorzolamide 2% as adjunctive therapy, added 3 times daily to brimonidine or timolol. IOP was measured on week 2, and months 3, 6, 9, and 12. RESULTS: A significant reduction in IOP from the baseline was observed after dorzolamide use in both groups at visits during that year (P < 0.001). Overall, mean IOP reduction was 5.6 +/- 1.9 mmHg with the brimonidine-dorzolamide combination, and 6.8 +/- 1.7 mmHg with timolol-dorzolamide after 1 year of treatment; the difference was significant (P = 0.029). No statistical differences existed between the groups for adverse events (P < 0.05). CONCLUSION: The addition of dorzolamide to brimonidine or timolol has significant IOP-lowering efficacy during 1 year in patients with POAG whose IOPs were inadequately controlled with brimonidine or timolol alone. The IOP-lowering effect of the timolol-dorzolamide combination at 1 year was more pronounced than brimonidine-dorzolamide. Both combinations were well-tolerated by the patients.

Adult↗

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↗

A placebo-controlled inpatient comparison of fluvoxamine maleate and imipramine in major depression.

Fluvoxamine, a selective serotonin reuptake inhibitor, was investigated in a 6-week double-blind study among severely ill inpatients with DSM-III major depression. All but 1 patient also fulfilled criteria for melancholia. Following a 3-day placebo wash-out patients were randomly assigned to fluvoxamine, imipramine or placebo. Sixty of 81 patients completed at least 2 weeks following wash-out and were evaluated for efficacy. Analysis of covariance (controlling for baseline scores) showed significant (p less than 0.05) differences on CGI severity and BPRS total and a similar trend (p = 0.08) on the Hamilton Depression Scale. Fluvoxamine was superior (p less than or equal to 0.02) to both placebo and imipramine on these measures. Fluvoxamine's most common adverse effects were nausea and agitation. The number of fluvoxamine patients withdrawn for side-effects was less than imipramine and not significantly different than placebo. Fluvoxamine was not associated with significant changes in vital signs, ECG or laboratory tests. The results therefore indicate that fluvoxamine is a safe and highly effective treatment for hospitalized patients with major depression.

Adolescent↗

The effect of lisuride hydrogen maleate in the hyperprolactinaemia-amenorrhoea syndrome: clinical and hormonal responses.

Eleven women with secondary amenorrhoea and hyperprolactinaemia were treated with lisuride, a new semisynthetic ergot derivative. Acute administration of lisuride (100 microgram orally) significantly suppressed serum prolactin (PRL) levels in nine out of eleven subjects. In these nine patients, prolonged treatment with lisuride (50--200 microgram daily) lowered PRL levels into the normal range, menstrual cycles were resumed and eight patients ovulated. Two patients, in whom lisuride failed to lower PRL levels into the normal range, did not resume normal menstruation. These data demonstrate that lisuride may be used clinically to lower PRL levels and to restore cyclic gonadotrophin secretion and ovulation in amenorrhoeic patients with hyperprolactinaemia.

Adult↗

Effect of DL-6-(N-alpha-pipecolinomethyl)-5-hydroxy-indane maleate (PMHI) on the reproductive system of a wild rat, Bandicota bengalensis.

The anti-testicular action of PMHI was investigated in a wild rodent, the bandicoot rat. Bandicoots were given a single subcutaneous injection of this compound at a dose of 150 mg/kg and were killed 2, 10, or 30 days later. PMHI induced marked and rapid testicular regression with complete arrest of spermatogenesis by day 10 such that the seminiferous tubules contained only a ring of Sertoli cells with few spermatogonia. This was also reflected by a severe depletion of the number of sperm in the cauda epididymis. However, by day 30 after PMHI injection, testicular histology indicated restoration of spermatogenesis in parallel with the time schedule of germ cell development. The results indicate that PHMI produces a reversible anti-spermatogenic effect in the bandicoot rat which appears to be time dependent.

Animals↗

Effect of the H1 antihistamine chlorpheniramine maleate on histamine-induced symptoms in the human conjunctiva. Indirect evidence for nervous H1 receptors.

Earlier studies have shown that intranasal chlorpheniramine (0.77%) can inhibit histamine-induced tickling, sneezing, and hypersecretion by a local effect on nerve fibres. The aim of the present study was to examine whether this solution had local anaesthetic of parasympatholytic properties. If neither of these properties are present it suggests that the anti-pruritic effects of the solution are caused by inhibition of H1 receptors, which in turn is indirect evidence for the presence of H1 receptors on nerve fibers. In a double-blind design 15 normal subjects were provoked with histamine in the eye after pretreatment with chlorpheniramine or with a local anaesthetic, oxybuprocain. Both drugs inhibited itching, but the H1 antihistamine was significantly more effective than the local anaesthetic (P less than 0.01). Corneal sensitivity was measured by an esthesiometer, and pupil difference was used as a measure for atropine activity. Chlorpheniramine had neither a local anaesthetic nor a parasympatholytic effect. This study has therefore strengthened the hypothesis that there are nervous H1 receptors in the mucous membranes of the eye and airways and has extended its application in animals to also include man.

Adult↗

A trial of Timoptol (timolol maleate) in a clinical situation.

The results of treatment with Timoptol in 138 cases are reviewed. There was an average lowering of pressure by 6mm Hg in the whole group with an average follow up of 10 weeks (range 2-26 weeks). Most patients had a satisfactory fall only when Timoptol was combined with other treatment, with a fall of 3mm Hg or more in 60% of patients and with pressure controlled to less than 22mm Hg in 48 to 55%. A good response was achieved in all types of chronic open angle glaucoma except in low tension glaucoma. In established glaucoma it seems best to add Timoptol to the existing therapy and then modify treatment as indicated. Serious side effects occurred in five patients; 2 with severe pain, 2 with an attack of angle closure glaucoma, one a general sensitivity reaction and one with temporary central visual loss, but these do not detract from the immense potential of the drug in treatment of glaucoma.

Drug Therapy, Combination↗