Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0595921 (intraocular pressure)
 11,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Latanoprost, a prostaglandin analogue, was given topically to 20 patients with normal pressure glaucoma in a double masked randomized study. Either latanoprost 0.006% or placebo (vehicle) was administered twice a day for 14 days. Latanoprost caused a statistically significant (p < 0.001) reduction in intraocular pressure from a diurnal baseline level of 16.8 to 14.3 mmHg, as measured on day 14. Latanoprost was well tolerated.
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PMID:The short-time effect of latanoprost on the intraocular pressure in normal pressure glaucoma. 749 34

The long term effects of two dose regimens of latanoprost (PhXA41) administered to eyes concomitantly treated with timolol which had not adequately been controlled by timolol alone were compared. A total of 50 patients, 17 with primary open angle glaucoma and 33 with capsular glaucoma, were recruited from five clinics. All had glaucomatous visual field defects and an intraocular pressure (IOP) of at least 22 mm Hg despite treatment with 0.5% timolol twice daily. Patients were randomised to two treatment groups. In one group 0.006% latanoprost was given twice daily, in the other group placebo was given at 8 am and latanoprost at 8 pm for 3 months, with concomitant timolol treatment in both groups. Average daytime IOP (mean (SD)) at baseline (on timolol alone) and after 4 and 12 weeks' treatment was 24.8 (3.6), 16.8 (4.3), and 15.7 (2.4) mm Hg respectively with once daily application of latanoprost and 24.9 (2.9), 18.1 (3.0), and 18.0 (3.6) mm Hg respectively with latanoprost twice daily. No clinically significant side effects were observed during treatment. Latanoprost causes a marked and sustained IOP reduction in eyes which are also being treated with timolol. Latanoprost given once daily is at least as effective and probably superior to a twice daily dose regimen.
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PMID:Latanoprost administered once daily caused a maintained reduction of intraocular pressure in glaucoma patients treated concomitantly with timolol. 788 Jul 88

Latanoprost is an ester prodrug analogue of prostaglandin F2 alpha which effectively reduces intraocular pressure (IOP) by increasing uveoscleral outflow rather than altering conventional trabeculo-canalicular) aqueous outflow. The IOP-lowering effect of latanoprost lasts for 20 to 24 hours after a single dose, which allows a single daily dosage regimen. Data from 4 randomised double-masked multicentre studies indicate that a once daily dose of topical latanoprost 0.005% is as effective as timolol 0.5% twice daily in the treatment of patients with primary open-angle glaucoma or ocular hypertension. A number of studies also demonstrate that latanoprost enhances IOP-lowering effects when applied in combination with other antiglaucoma agents. Latanoprost is well tolerated with no, or barely detectable, conjunctival hyperaemia, and, unlike timolol, is not associated with systemic adverse effects. However, 3 to 10% of patients treated with latanoprost 0.005% have shown increased iris pigmentation after 3 to 4.5 months' treatment. In summary, the available data show that latanoprost is a potent IOP-lowering agent with a number of positive features including a single daily dosage regimen, a novel mechanism of action that enhances the IOP-lowering effect of contemporary agents, and a lack of systemic adverse effects. These properties suitably poise latanoprost for a prominent position in the management of patients with primary open-angle glaucoma and ocular hypertension.
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PMID:Latanoprost. A review of its pharmacological properties, clinical efficacy and tolerability in the management of primary open-angle glaucoma and ocular hypertension. 892 63

Several prostaglandins (PGs), their prodrugs, and their analogues have been shown to reduce intraocular pressure (IOP) in normotensive volunteers and in patients with elevated IOP. Initial clinical trials demonstrated efficacy with most of these agents, but a PGE2 analogue, PGD2, and BW245C (an analogue selective for the DP-receptor) cause an initial rise in IOP with a minimal subsequent reduction. Although PGF2 alpha tromethamine salt, PGF2 alpha-isopropyl ester (PGF2 alpha-IE), and 15-propionate-PGF2 alpha-IE are all very effective in reducing IOP, they produce unacceptable side effects, including conjunctival hyperemia and ocular irritation. Isopropyl unoprostone, a 22-carbon chain PGF2 alpha metabolite, produces a 10-25% reduction in IOP lasting approximately 2-5 hours, is well tolerated, and is commercially available for use in Japan. 17-phenyl substituted PGF2 alpha-IE analogues, such as PhXA34 or latanoprost, effectively reduce IOP by 30-40% for at least 24 hours, and are very well tolerated with minimal conjunctival hyperemia and without irritation. Latanoprost is the more potent 15R-epimer of PhXA34, and has become a useful agent in glaucoma therapy.
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PMID:Initial clinical studies with prostaglandins and their analogues. 915 78

Latanoprost, a prostaglandin F2 alpha analogue prodrug, has been shown to be an effective ocular hypotensive agent when used alone on ocular hypertensive or open angle glaucoma patients. In various studies, the ocular hypotensive effects of latanoprost have also been evaluated when used in addition to, or in combination with, other ocular hypotensive agents. Latanoprost produces an additional reduction of intraocular pressure (IOP) when used in combination with timolol, pilocarpine, acetazolamide and dipivefrin. These represent four different classes of glaucoma drugs-beta-adrenergic antagonists, cholinergic agonists, carbonic anhydrase inhibitors, and adrenergic agonists-all of which reduce the IOP by different mechanisms (reduction of aqueous humor production, increased outflow facility, or by a mixed effect on aqueous humor dynamics). All the available evidence shows that latanoprost produces a clinically significant additive ocular hypotensive effect when used in combination with any currently available ocular hypotensive agent.
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PMID:The additive intraocular pressure-lowering effect of latanoprost in combined therapy with other ocular hypotensive agents. 915 83

Three large, masked, multicenter studies are reviewed comparing the safety and efficacy of 0.005% latanoprost eyedrops given once daily to 0.5% timolol eyedrops given twice daily for six months in patients with elevated intraocular pressure (IOP). A total of 829 patients were recruited from centers in Scandinavia, the United Kingdom (UK) and the United States of America (USA). In addition, data are reviewed from the first 198 of these patients to complete an additional six months of latanoprost treatment in an openlabel study. In all centers, both latanoprost and timolol were very effective in reducing the diurnal IOP. In the UK, both drugs reduced the IOP by 34%. In the USA, latanoprost was more effective than timolol, reducing IOP by 27% compared to 20%. In Scandinavia, latanoprost was given for three months in the evening and for three months in the morning while timolol was given twice daily for six months. Latanoprost given in the evening reduced IOP (35% reduction) significantly (p < 0.001) more than latanoprost given in the morning (31% reduction) and timolol given twice daily (27% reduction). Darkening of the iris color occurred in 7% of eyes treated with latanoprost for six months. A clinical evaluation of eyes with increased pigmentation, as well as preclinical studies; suggest that this side effect is a cosmetic problem in patients treated unilaterally. Other side effects were slight and not clinically significant. After one year of treatment with latanoprost in 198 patients, the IOP reduction of 32% was maintained. There was no loss of efficacy and no significant increase in the incidence of side effects or adverse events other than iris color darkening, which occurred or was suspected in 12%. These results demonstrate that latanoprost is a valuable drug for the treatment of chronic open angle glaucoma.
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PMID:Phase III latanoprost studies in Scandinavia, the United Kingdom and the United States. 915 85

1. Latanoprost is not preferred for use in inflammatory glaucoma. 2. Brimonidine acts by reducing the aqueous inflow and promotes uveoscleral outflow. 3. Dorzolamide causes a moderate reduction of intraocular pressure, but is relatively safe.
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PMID:New topical medications in the treatment of glaucoma. 946 Apr 17

An ideal glaucoma drug reduces intraocular pressure profoundly and long-lastingly without known major side effects. Latanoprost, a new prostaglandin F2 alpha-analogue, indeed has these properties. However, we need long-term experience to exclude major, clinically relevant side effects. The influence of latanoprost on ocular circulation also needs further evaluation. Nevertheless, the clinician does have a new and very potent drug to reduce intraocular pressure. Literature search by Medline.
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PMID:[Latanoprost--a new prostaglandin F2 alpha analog in therapy of glaucoma--an overview]. 954 88

Latanoprost (PhXA41, Xalatan) and isopropyl unoprostone (UF-021, unoprostone, Rescula) two new prostanoid derivatives, have been shown to reduce intraocular pressure (IOP) significantly in patients with glaucoma or ocular hypertension. This study was designed to compare the ocular hypotensive effects of latanoprost and unoprostone in cynomologus monkeys with glaucoma and characterizes the prostanoid's mechanisms of action in normal cynomolgus monkey eyes. Intraocular pressure was measured daily at 0, 0.5, and 1 hour and hourly for 5 additional hours during 1 baseline day, 1 vehicle-treated day, and 5 days of therapy with either 0.005% latanoprost or 0.12% unoprostone applied twice daily, at 9:30 AM and 3:30 PM, to the glaucomatous eye of eight monkeys with unilateral laser-induced glaucoma. Outflow facility was measured in six normal monkeys 3 hours prior to dosing and 1 hour after unilateral dosing with either drug. Aqueous humor flow rates were measured in six normal monkeys hourly for 4 hours on 1 baseline day and on 1 treatment day beginning 1 hour after administration of either drug to one eye. Intraocular pressure was significantly (P < 0.005) reduced after the first application for 4 hours with latanoprost and for 2 hours with unoprostone, up to 5.4 +/- 0.8 mm Hg (mean +/- SEM) (latanoprost) and 3.8 +/- 0.5 mm Hg (unoprostone). Intraocular pressure was significantly (P < 0.005) reduced for at least 18 hours following each PM dose of latanoprost. Intraocular pressure was not reduced (P > .05) 18 hours after each PM dose of unoprostone. An enhancement of the ocular hypotensive effect was observed from day 1 to day 5 with repeated dosing of either drug. Latanoprost produced a greater magnitude of IOP reduction for a longer duration of time than unoprostone after each application. Neither drug altered outflow facility or aqueous humor flow rates. Latanoprost and unoprostone appear to reduce IOP in monkeys by enhancing uveoscleral outflow. Latanoprost appears to be more efficacious and potent than unoprostone in reducing IOP in glaucomatous monkey eyes.
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PMID:A comparative study of latanoprost (Xalatan) and isopropyl unoprostone (Rescula) in normal and glaucomatous monkey eyes. 958 40

We investigated the effects of the protein tyrosine kinase inhibitors, genistein, tyrphostin 47, and herbimycin on prostaglandin F2alpha- and carbachol-induced inositol-1,4,5-trisphosphate (IP3) production, [Ca2+]i mobilization and contraction in cat iris sphincter smooth muscle. Prostaglandin F2alpha and carbachol induced contraction in a concentration-dependent manner with EC50 values of 0.92 x 10(-9) and 1.75 x 10(-8) M, respectively. The protein tyrosine kinase inhibitors blocked the stimulatory effects of prostaglandin F2alpha, but not those evoked by carbachol, on IP3 accumulation, [Ca2+]i mobilization and contraction, suggesting involvement of protein tyrosine kinase activity in the physiological actions of the prostaglandin. Daidzein and tyrphostin A, inactive negative control compounds for genistein and tyrphostin 47, respectively, were without effect. Latanoprost, a prostaglandin F2alpha analog used as an antiglaucoma drug, induced contraction and this effect was blocked by genistein. Genistein (10 microM) markedly reduced (by 67%) prostaglandin F2alpha-stimulated increase in [Ca2+]i but had little effect on that of carbachol in cat iris sphincter smooth muscle cells. Vanadate, a potent inhibitor of protein tyrosine phosphatase, induced a slow gradual muscle contraction in a concentration-dependent manner with an EC50 of 82 microM and increased IP3 generation in a concentration-dependent manner with an EC50 of 90 microM. The effects of vanadate were abolished by genistein (10 microM). Wortmannin, a myosin light chain kinase inhibitor, reduced prostaglandin F2alpha- and carbachol-induced contraction, suggesting that the involvement of protein tyrosine kinase activity may lie upstream of the increases in [Ca2+]i evoked by prostaglandin F2alpha. Further studies aimed at elucidating the role of protein tyrosine kinase activity in the coupling mechanism between prostaglandin F2alpha receptor activation and increases in intracellular Ca2+ mobilization and identifying the tyrosine-phosphorylated substrates will provide important information about the role of protein tyrosine kinase in the mechanism of smooth muscle contraction, as well as about the mechanism of the intraocular pressure lowering effect of the prostaglandin in glaucoma patients.
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PMID:Tyrosine kinase inhibitors suppress prostaglandin F2alpha-induced phosphoinositide hydrolysis, Ca2+ elevation and contraction in iris sphincter smooth muscle. 985 85


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