Pharmacotherapy of Glaucoma

Schmidl, Doreen; Schmetterer, Leopold; Garhöfer, Gerhard; Popa-Cherecheanu, Alina

doi:10.1089/jop.2014.0067

Cited by 131 publications

(118 citation statements)

References 192 publications

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“…The death of retinal ganglion cells leads to increased IOP which is the most important risk factor for the development of glaucoma and the only risk factor amenable to treatment [15, 138, 139]. Increased IOP can lead to ischemia, mechanical impairment, oxidative stress and optic nerve inflammation [140].…”

Section: Eye Diseases and Local Rasmentioning

confidence: 99%

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Many Faces of Renin-angiotensin System - Focus on Eye

Holappa¹,

Vapaatalo²,

Vaajanen³

2017

TOOPHTJ

125

110

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The renin-angiotensin system (RAS), that is known for its role in the regulation of blood pressure as well as in fluid and electrolyte homeostasis, comprises dozens of angiotensin peptides and peptidases and at least six receptors. Six central components constitute the two main axes of the RAS cascade. Angiotensin (1-7), an angiotensin converting enzyme 2 and Mas receptor axis (ACE2-Ang(1-7)-MasR) counterbalances the harmful effects of the angiotensin II, angiotensin converting enzyme 1 and angiotensin II type 1 receptor axis (ACE1-AngII-AT1R) Whereas systemic RAS is an important factor in blood pressure regulation, tissue-specific regulatory system, responsible for long term regional changes, that has been found in various organs. In other words, RAS is not only endocrine but also complicated autocrine system. The human eye has its own intraocular RAS that is present e.g. in the structures involved in aqueous humor dynamics. Local RAS may thus be a target in the development of new anti-glaucomatous drugs. In this review, we first describe the systemic RAS cascade and then the local ocular RAS especially in the anterior part of the eye.

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Section: Eye Diseases and Local Rasmentioning

confidence: 99%

“…The exact underlying mechanism for glaucoma development is still poorly known which makes it difficult to develop effective therapies for this destructive disease [14, 15]. As of today, the only treatment demonstrated to be effective to reduce disease progress is to lower IOP [16, 17].…”

Section: Introductionmentioning

confidence: 99%

Many Faces of Renin-angiotensin System - Focus on Eye

Holappa¹,

Vapaatalo²,

Vaajanen³

2017

TOOPHTJ

125

110

View full text Add to dashboard Cite

show abstract

“…As a result, all current treatment options for glaucoma are aimed at lowering IOP [1][2][3][4]. Unfortunately, existing medical therapies have mild to severe side effects [2,[5][6][7] and first line treatment options with prostaglandin analogues are ineffective in up to 25% of patients with primary open-angle glaucoma [8]. Therefore, identification of novel ocular hypotensive agents that have minimal side effect profiles will greatly benefit patients and augment the current therapeutic management strategies for the disease.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological and pharmacokinetic profile of the novel ocular hypotensive prodrug CKLP1 in Dutch-belted pigmented rabbits

et al. 2020

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Elevated intraocular pressure is the only treatable risk factor for glaucoma, an eye disease that is the leading cause of irreversible blindness worldwide. We have identified cromakalim prodrug 1 (CKLP1), a novel water-soluble ATP-sensitive potassium channel opener, as a new ocular hypotensive agent. To evaluate the pharmacokinetic and safety profile of CKLP1 and its parent compound levcromakalim, Dutch-belted pigmented rabbits were treated intravenously (0.25 mg/kg) or topically (10 mM; 4.1 mg/ml) with CKLP1. Body fluids (blood, aqueous and vitreous humor) were collected at multiple time points and evaluated for the presence of CKLP1 and levcromakalim using a liquid chromatography-mass spectrometry/ mass spectrometry (LC-MS/MS) based assay. Histology of tissues isolated from Dutchbelted pigmented rabbits treated once daily for 90 days was evaluated in a masked manner by a certified veterinary pathologist. The estimated plasma parameters following intravenous administration of 0.25 mg/kg of CKLP1 showed CKLP1 had a terminal half-life of 61.8 ± 55.2 min, T max of 19.8 ± 23.0 min and C max of 1968.5 ± 831.0 ng/ml. Levcromakalim had a plasma terminal half-life of 85.0 ± 37.0 min, T max of 61.0 ± 32.0 min and C max of 10.6 ± 1.2 ng/ml. Topical CKLP1 treatment in the eye showed low levels (<0.3 ng/mL) of levcromakalim in aqueous and vitreous humor, and trace amounts of CKLP1 and levcromakalim in the plasma. No observable histological changes were noted in selected tissues that were examined following topical application of CKLP1 for 90 consecutive days. These results suggest that CKPL1 is converted to levcromakalim in the eye and likely to some extent in the systemic circulation.

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“…The medical treatment for glaucoma includes prostaglandin analogs, which are approved as the first-line treatment for glaucoma in the European Glaucoma Society guidelines, carbonic anhydrase inhibitors, β-receptor antagonists, adrenergic agonists, and parasympathomimetics 3,4. Prostaglandins are a family of lipid compounds that are derived enzymatically from essential fatty acids, with each containing 20 carbon atoms, including a 5-carbon ring 5.…”

Section: Introductionmentioning

confidence: 99%

Impact of prostaglandin glaucoma drops on platelet-activating factor action: an in vitro study

Moschos

Nitoda

Chatziralli

et al. 2016

DDDT

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AimThe aim of this study was to investigate the effect of different prostaglandin analogs on platelet-activating factor (PAF) levels.MethodsThree prostaglandin analogs were selected: bimatoprost 0.3 mg/mL, latanoprost 50 μg/mL, and tafluprost 15 μg/mL. Each drug sample was tested for its ability to cause platelet aggregation, which was measured as PAF-induced aggregation, before and after the addition of various concentrations of the examined sample, creating a linear curve of percentage inhibition (ranging from 0% to 100%) versus different concentrations of the sample. The concentration of the sample that inhibited 50% PAF-induced aggregation was calculated based on this curve, and this value was defined as IC50. In addition, the effect of eye drops on PAF metabolism was examined, through an in vitro analysis on PAF basic metabolic enzymes (PAF-cholinephosphotransferase, PAF-acetyl-CoA:1-O-alkyl-sn-glycero-3-phosphocholine acetyltransferase, and PAF-acetylhydrolase).ResultsThe IC50 values for Lumigan UD® (bimatoprost 0.3 mg/mL), Monoprost® (latanoprost 50 μg/mL), and Saflutan (tafluprost 15 μg/mL) were 8.7, 0.28, and 1.4 μg/mL, respectively.DiscussionAll three prostaglandin analogs suspended PAF, but bimatoprost induced the most potent inhibition, compared to tafluprost and to the weak effect of latanoprost.

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Pharmacotherapy of Glaucoma

Cited by 131 publications

References 192 publications

Many Faces of Renin-angiotensin System - Focus on Eye

Many Faces of Renin-angiotensin System - Focus on Eye

Pharmacological and pharmacokinetic profile of the novel ocular hypotensive prodrug CKLP1 in Dutch-belted pigmented rabbits

Impact of prostaglandin glaucoma drops on platelet-activating factor action: an in vitro study

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