β1-Adrenergic Receptor Polymorphisms and Clinical Efficacy of Betaxolol Hydrochloride in Normal Volunteers

Schwartz, Stephen G.; Puckett, Brian J.; Allen, Robert C.; Castillo, I.G.; Leffler, Christopher T.

doi:10.1016/j.ophtha.2005.08.014

Cited by 39 publications

(23 citation statements)

References 18 publications

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“…21 Investigating the association between these ADRB1 polymorphisms and clinical efficacy of betaxolol in 48 normal volunteers, Schwartz et al reported a significantly increased IOP response in individuals with the rs1801253 wild type allele, while no association was found between rs1801252 and IOP response. 22 This is in contrast to the results of a retrospective study including 215 glaucoma patients by McCarthy et al who investigated the impact of polymorphisms of ADRB1, ADRB2 and CYP2D6 on the IOP response to topical beta-blockers. They reported no association between IOP response after topical timolol and rs1801252 and rs1801253 genotype.…”

Section: Beta-blockersmentioning

confidence: 72%

Glaucoma Pharmacogenetics

Pharmacogenetics¹,

Faschinger²

2012

European Ophthalmic Review

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The effect of a drug in terms of desired effects and undesired side-effects on an individual basis is still not 100 % predictable. 1 Undoubtedly, this prediction would be a great advantage for patients' safety and societies' economies and therefore, it has been subject to research ever since drugs have been used in a scientific manner. 2 It is well known that an individuals' response to a certain drug is influenced by extrinsic as well as intrinsic factors. 3 Among the extrinsic factors there are lifestyle issues like diet, alcohol consumption or nicotine abuse and geographical factors. Intrinsic factors comprise constant factors like age, sex, ethnic group and, more specifically, the colour of the iris, but also modifiable ones like the body mass index or concomitant systemic or ocular disease.Furthermore, the personal genetic constitution determines at least partially the pharmacokinetics and pharmacodynamics of a drug.Polymorphic receptors or their downstream pathway targets may aggravate or attenuate the effects of a drug, whereas variants of metabolising or activating enzymes can lead to increased or decreased levels of a drug. The aim of pharmacogenetics is to describe these polymorphisms and their impact on an individuals' reaction to a specific drug. As pharmacogenetic research started about 30 years ago, pharmacogenetic data on a range of drugs have now been reported. 4 Today, the Food and Drug Administration (FDA) lists pharmocogenetic biomarkers in drug labels for more than 100 drugs, most of them anticancer or psychiatric drugs. 5 For example, warfarin dose is greatly influenced by the genotype of the metabolising enzyme CYP2C9 and the genotype of the target enzyme vitamin K epoxide reductase (VKORC1), which together account for roughly 40 % of the interindividual variance of warfarin dose. 6 CYP2D6 is necessary for about 25 % of all drugs metabolised in the human liver, including various psychiatric drugs and beta-blockers. 7 Furthermore CYP2D6 is also mandatory for the activation of codeine to morphine and of tamoxifen to its most therapeutically active metabolite endoxifen.Depending on the existence of active, inactive or alleles, with decreased activity, individuals can be grouped in poor, intermediate, extensive or ultrarapid metabolisers. 4 In case of ultrarapid metabolisers (1-2 % of Caucasians) levels of a metabolised drug might be too low for the intended effect, whereas morphine levels after codeine medication might be dangerously high. 8 Clopidogrel is a antiplatelet agent prodrug activated by CYP2C19, which activity -as is the case for CYP2D6 -depends on the genotype. Poor or intermediate metabolisers (2 % and 26 % in Caucasians, respectively) are therefore at increased risk for cardiovascular events or stent thrombosis compared to extensive metabolisers. 9 Interestingly, recent studies provided evidence that the CFH Y402H genotype has significant impact on anti-vascular endothelial growth factor (VEGF) therapy. Patients with the T/T or T/C genotype showed improved visual acuity in 53 % v...

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Section: Beta-blockersmentioning

confidence: 72%

Glaucoma Pharmacogenetics

Pharmacogenetics¹,

Faschinger²

2012

European Ophthalmic Review

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“…Given that IOP fluctuates following a circadian rhythm, which is similar to the change in the activity of the sympathetic nervous system, the relationship between polymorphisms in adrenergic receptor genes and baseline IOP level was examined in two studies. In a US-based study of racially diverse patients, baseline IOP in normal subjects was reported to be significantly higher in Arg389 homozygotes of the 1-adrenergic receptor gene than in Gly389 carriers (Schwartz et al, 2005). In contrast, a study of untreated Japanese NTG patients reported that diurnal mean IOP was significantly higher for Ser49 homozygotes in the 1-adrenergic receptor gene than for Gly49 carriers, while the polymorphism at codon 389 was unrelated to the diurnal IOP level (Gao et al, 2010).…”

Section: Baseline Iopmentioning

confidence: 92%

Pharmacogenomics of Open-Angle Glaucoma

Schwartz¹,

Ayala-Haedo²,

Kishor³

et al. 2008

CPPM

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“…Betaxolol is more protective against cardiorespiratory side effects but less efficacious compared to timolol. In a small pilot study involving 48 healthy volunteers treated with betaxolol hydrochloride 0.5% for 6 weeks, polymorphism at codon 389 (Arg389) of ADRB1 was found to be associated with significant IOP reduction from baseline (Schwartz et al, 2005). In fact, those with Arg389 recorded higher baseline IOP.…”

Section: Genetics and Pharmacogeneticsmentioning

confidence: 99%

Topical Pressure Lowering Drug: Racial Respond Variation and Pharmacogenetics

Liza-Sharmini¹

2011

Glaucoma - Current Clinical and Research Aspects

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β1-Adrenergic Receptor Polymorphisms and Clinical Efficacy of Betaxolol Hydrochloride in Normal Volunteers

Cited by 39 publications

References 18 publications

Glaucoma Pharmacogenetics

Glaucoma Pharmacogenetics

Pharmacogenomics of Open-Angle Glaucoma

Topical Pressure Lowering Drug: Racial Respond Variation and Pharmacogenetics

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