Electrophysiologic and Electroretinographic Evidence for Photoreceptor Dysfunction as a Toxic Effect of Digoxin

Madreperla, Steven A.; Johnson, Mary A.; Nakatani, Keigo

doi:10.1001/archopht.1994.01090180105044

Cited by 25 publications

(21 citation statements)

References 8 publications

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“…Digoxin‐induced cone dysfunction has been reported in humans, rats and cats 11,26–32,36 . In this study, ERG examination confirmed that digoxin affects cone function in dogs.…”

Section: Discussionsupporting

confidence: 80%

“…We used digoxin (Digosin, Chugai, Tokyo, Japan), a cardiac glycoside that is used to treat congestive heart failure in small animals 33 . Digoxin‐induced cone dysfuction has been reported in humans and cats 26–32 . Digoxin was administered orally once daily for 14 days at a dose of 0.0125 mg/kg/day, which is within the recommended oral maintenance dosage range for dogs 34…”

Section: Methodsmentioning

confidence: 99%

“…We initially performed ERG using contact electrodes with a built‐in color light source (color LED‐electrode) in normal Beagle dogs. Next, we administered digoxin, which causes disorder of specific cone function in humans or cats, 26–32 and evaluated the effect on discrete cones by ERG using the color LED‐electrode. We herein discuss the clinical application of this method.…”

Section: Introductionmentioning

confidence: 99%

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Detection of cone dysfunction induced by digoxin in dogs by multicolor electroretinography

Maehara

Osawa

Itoh

et al. 2005

Veterinary Ophthalmology

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It is difficult to detect discrete cone function with the present conventional electroretinography (ERG) examination. In this study, we developed contact electrodes with a built-in color (red (644 nm), green (525 nm), or blue (470 nm)) light source (color LED-electrode), and evaluated an experimental model of digoxin in the dog. First, 17 normal Beagle dogs were used to determine which electrode works well for color ERG measurement on dogs. Then, color ERG was performed on seven normal Beagle dogs at various points during a 14-day period of digoxin administration. A single daily dose of 0.0125 mg/kg/day, which is within the recommended oral maintenance dosage range for dogs, was administered orally for 2 weeks. Ophthalmic examination, measurement of plasma concentration of digoxin, and color ERG examination were performed. On first examination, amplitudes of all responses were significantly (P < 0.01) lower with the red, than with the blue and green electrodes during ERG recording. In ERG using the red electrode, the standard deviation was large. According to these preliminary results, the red electrode was not used in the experimental dog model with digoxin. In the digoxin administrated animals, no significant change was observed in the ophthalmic examination findings. The digoxin level increased steadily throughout the dosing period but was always within the therapeutic range for dogs. In rod ERG, no abnormalities were detected with any electrode. In standard combined ERG, decreased amplitude of the a-wave was detected with every electrode. In single flash cone ERG, prolongation of implicit time was detected by color ERG with the blue and green electrodes. In 30-Hz flicker ERG, decreased amplitude was detected only by color ERG with the blue electrode. The decreased amplitude and prolonged implicit time recovered after termination of digoxin administration. Cone dysfunction induced by digoxin in the dog was revealed by multicolor ERG using blue and green LED-electrodes. Multi-color ERG was useful for detecting cone type-specific dysfunction in the dog.

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“…Digoxin‐induced cone dysfunction has been reported in humans, rats and cats 11,26–32,36 . In this study, ERG examination confirmed that digoxin affects cone function in dogs.…”

Section: Discussionsupporting

confidence: 80%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Detection of cone dysfunction induced by digoxin in dogs by multicolor electroretinography

Maehara

Osawa

Itoh

et al. 2005

Veterinary Ophthalmology

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“…There is evidence that the retina is the primary site of drug toxicity. [17][18][19] Several retinal cells express digitalis sensitive isoforms of sodium-potassium ATPase (Na + K + ATPase)-for Figure 1 Histogram showing the total red-green and total tritan error scores for controls and patients receiving digoxin therapy. The differences are statistically significant *p<0.05, **p<0.01 (unpaired t test) Figure 2 Graph compairing serum digoxin levels with combined error scores for red-green (R/G) and tritan tests.…”

Section: Discussionmentioning

confidence: 99%

Acquired colour vision deficiency in patients receiving digoxin maintenance therapy

Lawrenson

Kelly

Lawrenson

et al. 2002

British Journal of Ophthalmology

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Background/aims: Disturbances of colour vision are a frequently reported sign of digoxin toxicity. The aim of this study was to investigate the incidence of acquired colour vision deficiency in elderly hospitalised patients receiving maintenance digoxin therapy. Methods: 30 patients (mean age 81.3 (SD 6.1) years) receiving digoxin were tested using a battery of colour vision tests (Ishihara, AO Hardy Rand Rittler plates, City tritan test, Lanthony tritan album, and the Farnsworth D15). These were compared to an age matched control group. Serum digoxin concentrations were determined from venous blood samples. Results: Slight to moderate red-green impairment was found in approximately 20-30% of patients taking digitalis, and approximately 20% showed a severe tritan deficiency. There was no correlation between colour vision impairment and serum digoxin level. Conclusions: Formal colour vision testing of elderly patients taking digitalis showed a high incidence of colour deficiency, suggesting that impairment of retinal function can occur even at therapeutic drug levels. As a result, colour vision testing in this population would have limited value for the detection of drug toxicity.

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“…The target of voriconazole might be the photopic system based on cones, since this system is responsible for color discrimination and vision at higher light intensities [85]. Furthermore, clinical ERG and in vitro cell studies have shown that digoxin, which also causes visual disturbances similar to those of voriconazole, may lead to rod and cone dysfunction, with cones being affected to a greater extent [86,87].…”

Section: Visual Effectsmentioning

confidence: 99%

Defining Targets for Investigating the Pharmacogenomics of Adverse Drug Reactions to Antifungal Agents

2008

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Adverse drug reactions (ADRs) associated with antifungal therapy are major problems in patients with invasive fungal infections. Whether by clinical history or patterns of genetic variation, the identification of patients at risk for ADRs should result in improved outcomes while minimizing deleterious side effects. A major contributing factor to ADRs with antifungal agents relates to drug distribution, metabolism and excretion. Genetic variation in key genes can alter the structure and expression of genes and gene products (e.g., proteins). Thus far, the effort has focused on identifying polymorphisms with either empirical or predicted in silico functional consequences; the best candidate genes encode phase I and II drug-metabolizing enzymes (e.g., CYP2C19 and N-acetyltransferase), plasma proteins (albumin and lipoproteins) and drug transporters (P-glycoprotein and multidrug resistance proteins), which can affect the disposition of antifungal agents, eventually leading to dose-dependent (type A) toxicity. Less is known regarding the key genes that interact with antifungal agents, resulting in idiosyncratic (type B) ADRs. The possible role of certain gene products and genetic polymorphisms in the toxicities of antifungal agents are discussed in this review. The preliminary data address the following: low-density lipoproteins and cholesteryl ester transfer protein in amphotericin B renal toxicity; toll-like receptor 1 and 2 in amphotericin B infusion-related ADRs; phosphodiesterase 6 in voriconazole visual adverse events; flavin-containing monooxygenase, glutathione transferases and multidrug resistance proteins 1 and 2 in ketoconazole and terbinafine hepatotoxicity; CYP enzymes and P-glycoprotein in drug interactions between azoles and coadministered medications; multidrug resistance proteins 8 and 9 on 5-flucytosine bone marrow toxicity; and mast cell activation in caspofungin histamine release. This will focus on high-priority candidate genes, which could provide a starting point for molecular studies to elucidate the potential mechanisms for understanding toxicity associated with antifungal drugs as well as identifying candidate genes for large population prospective genetic association studies.

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Electrophysiologic and Electroretinographic Evidence for Photoreceptor Dysfunction as a Toxic Effect of Digoxin

Cited by 25 publications

References 8 publications

Detection of cone dysfunction induced by digoxin in dogs by multicolor electroretinography

Detection of cone dysfunction induced by digoxin in dogs by multicolor electroretinography

Acquired colour vision deficiency in patients receiving digoxin maintenance therapy

Defining Targets for Investigating the Pharmacogenomics of Adverse Drug Reactions to Antifungal Agents

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