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1.
Spectrum of digoxin-induced ocular toxicity: a case report and literature review.
Renard, D, Rubli, E, Voide, N, Borruat, FX, Rothuizen, LE
BMC research notes. 2015;:368
Abstract
BACKGROUND Digoxin intoxication results in predominantly digestive, cardiac and neurological symptoms. This case is outstanding in that the intoxication occurred in a nonagenarian and induced severe, extensively documented visual symptoms as well as dysphagia and proprioceptive illusions. Moreover, it went undiagnosed for a whole month despite close medical follow-up, illustrating the difficulty in recognizing drug-induced effects in a polymorbid patient. CASE PRESENTATION Digoxin 0.25 mg qd for atrial fibrillation was prescribed to a 91-year-old woman with an estimated creatinine clearance of 18 ml/min. Over the following 2-3 weeks she developed nausea, vomiting and dysphagia, snowy and blurry vision, photopsia, dyschromatopsia, aggravated pre-existing formed visual hallucinations and proprioceptive illusions. She saw her family doctor twice and visited the eye clinic once until, 1 month after starting digoxin, she was admitted to the emergency room. Intoxication was confirmed by a serum digoxin level of 5.7 ng/ml (reference range 0.8-2 ng/ml). After stopping digoxin, general symptoms resolved in a few days, but visual complaints persisted. Examination by the ophthalmologist revealed decreased visual acuity in both eyes, 4/10 in the right eye (OD) and 5/10 in the left eye (OS), decreased color vision as demonstrated by a score of 1/13 in both eyes (OU) on Ishihara pseudoisochromatic plates, OS cataract, and dry age-related macular degeneration (ARMD). Computerized static perimetry showed non-specific diffuse alterations suggestive of either bilateral retinopathy or optic neuropathy. Full-field electroretinography (ERG) disclosed moderate diffuse rod and cone dysfunction and multifocal ERG revealed central loss of function OU. Visual symptoms progressively improved over the next 2 months, but multifocal ERG did not. The patient was finally discharged home after a 5 week hospital stay. CONCLUSION This case is a reminder of a complication of digoxin treatment to be considered by any treating physician. If digoxin is prescribed in a vulnerable patient, close monitoring is mandatory. In general, when facing a new health problem in a polymorbid patient, it is crucial to elicit a complete history, with all recent drug changes and detailed complaints, and to include a drug adverse reaction in the differential diagnosis.
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2.
Atrial fibrillation (chronic).
Lane, DA, Boos, CJ, Lip, GY
BMJ clinical evidence. 2015
Abstract
INTRODUCTION Atrial fibrillation is a supraventricular tachyarrhythmia characterised by the presence of fast and uncoordinated atrial activation leading to reduced atrial mechanical function. Risk factors for atrial fibrillation include increasing age, male sex, co-existing cardiac and thyroid disease, pyrexial illness, electrolyte imbalance, cancer, and co-existing infection. METHODS AND OUTCOMES We conducted a systematic review and aimed to answer the following clinical question: What are the effects of oral medical treatments to control heart rate in people with chronic (defined as longer than 1 week for this review) non-valvular atrial fibrillation? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS We found four studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta-blockers (rate-limiting, with or without digoxin), calcium-channel blockers (with or without digoxin), and digoxin.
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3.
Digitalis reappraised: Still here today, but gone tomorrow?
Opie, LH
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde. 2014;(2):88-9
Abstract
Digoxin is one of the oldest of drugs acting on the heart and still one of the most frequently used. While in atrial fibrillation digoxin continues to have a valid role in the control of ventricular rate when added to beta-blockers and calcium antagonists, digoxin for heart failure is no longer a supportable option in view of the negative recent meta-analysis.
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4.
Standard nonspecific therapies in the management of pulmonary arterial hypertension.
Sauler, M, Fares, WH, Trow, TK
Clinics in chest medicine. 2013;(4):799-810
Abstract
Recent advances in pulmonary arterial hypertension (PAH) research have created a new era of PAH-specific therapies. Although these therapeutics have revolutionized PAH therapy, their innovation was predated by supportive but nonspecific medical therapies adapted from their use in more common cardiopulmonary diseases. These therapies include oxygen therapy, diuretics, digoxin, anticoagulation, and high-dose calcium channel blockers. Expert opinion continues to support the use of adjunct therapies based on current pathologic understandings of PAH combined with some evidence extrapolated from small studies. This article discusses why these therapies continue to play an important role in the treatment of patients with PAH.
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5.
Chronic atrial fibrillation: a systematic review of medical heart rate control management.
Nikolaidou, T, Channer, KS
Postgraduate medical journal. 2009;(1004):303-12
Abstract
OBJECTIVE Recent guidelines by the National Institute for Health and Clinical Excellence (NICE) and the American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) on rate control management for chronic atrial fibrillation have relegated digoxin to second line treatment, recommending instead the use of beta-blockers or rate limiting calcium antagonists as first line treatment. The objective of this review is to assess the efficacy of these drugs in controlling heart rate, and in improving symptoms and exercise tolerance. DATA SOURCES We electronically searched the Medline, Embase and Cochrane databases, hand searched journals and relevant bibliographies for articles. SELECTION OF STUDIES We included all study designs evaluating or comparing oral digoxin, beta-blockers and calcium antagonists, alone or in combination, for rate control in chronic atrial fibrillation. 46 studies satisfied our inclusion and quality criteria. RESULTS Published studies are small and too heterogeneous to be quantitatively combined. Descriptive synthesis of the data shows little evidence that monotherapy with beta-blockers or calcium antagonists improves symptoms or exercise capacity in patients with chronic atrial fibrillation. Instead it is associated with dose related side effects. CONCLUSION Based on the limited data available, we conclude that the combination of digoxin with either a beta-blocker or calcium antagonist should be first line management in patients with chronic atrial fibrillation.
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6.
Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 2: are calcium channel blockers superior to digoxin for controlling the ventricular rate in patients with acute atrial fibrillation?
Parris, RJ, Clarke, SF
Emergency medicine journal : EMJ. 2009;(12):881-3
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7.
Herbal supplements and therapeutic drug monitoring: focus on digoxin immunoassays and interactions with St. John's wort.
Dasgupta, A
Therapeutic drug monitoring. 2008;(2):212-7
Abstract
Herbal supplements can affect concentrations of therapeutic drugs measured in biological fluids by different mechanisms. Herbal products can either directly interfere with the methodology used in the measurement of drugs or indirectly interfere by altering the pharmacokinetics of coadministered drugs. The active components of Chan Su, Lu-Shen-Wan, Dan Shen, Asian and Siberian ginseng, oleander containing supplements, and Ashwagandha interfere with digoxin measurements by immunoassays, especially the polyclonal antibody-based immunoassays. Herbal supplements are sometimes contaminated with Western drugs causing drug toxicity. A therapeutic drug monitoring (TDM) service is very helpful for diagnosis of drug toxicity in such patients. Herbal products such as St. John's wort, a popular herbal antidepressant, increase the clearance of certain drugs either by increasing the activity of liver or intestinal cytochrome P-450 mixed-function oxidase or through modulation of the P-glycoprotein efflux pump. Significantly reduced concentrations of various therapeutic drugs such as digoxin, theophylline, cyclosporine, tacrolimus, tricyclic antidepressants, warfarin, and protease inhibitors can be observed due to interaction of these drugs with St. John's wort, causing treatment failure. On the other hand, a few drugs such as carbamazepine, mycophenolic acid, and procainamide do not show any interaction with St. John's wort. Understanding the effect of herbal products on TDM methodologies and identification of interactions between herbal products and drugs by TDM are very important clinically.
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8.
Hypothalamic digoxin, cerebral chemical dominance, and regulation of gastrointestinal/hepatic function.
Kurup, RK, Kurup, PA
The International journal of neuroscience. 2003;(1):75-105
Abstract
The role of the isoprenoid pathway in gastrointestinal and hepatic diseases, and its relation to hemispheric dominance, was assessed in this study. The following parameters were measured in patients with (i) acid peptic disease, (ii) ulcerative colitis, (iii) gallstones, (iv) cryptogenic cirrhosis liver, (v) Reye's syndrome, (vi) mesenteric artery occlusion, (vii) irritable bowel syndrome, and (viii) in individuals with right hemispheric, left hemispheric, and bihemispheric dominance: 1. plasma HMG CoA reductase, digoxin, dolichol, ubiquinone, and magnesium levels; 2. tryptophan/tyrosine catabolic patterns; 3. free radical metabolism; 4. glycoconjugate metabolism; and 5. membrane composition. In patients with gastrointestinal and hepatic disease there were elevated digoxin synthesis, increased dolichol, and glycoconjugate levels, and low ubiquinone and elevated free radical levels. The RBC membrane Na(+)-K+ ATPase activity and serum magnesium were decreased. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites in the serum. There was an increase in cholesterol: phospholipid ratio and a reduction in the glycoconjugate level of RBC membrane in these groups of patients. The same biochemical patterns were obtained in individuals with right hemispheric dominance. An upregulated isoprenoid pathway and hyperdigoxinemia is characteristic of gastrointestinal and hepatic disease and in right hemispheric chemical dominance. Right hemispheric chemical dominance is important in deciding the predisposition to gastrointestinal and hepatic disease.
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9.
Myocardial Na,K-ATPase and digoxin therapy in human heart failure.
Kjeldsen, K, Bundgaard, H
Annals of the New York Academy of Sciences. 2003;:702-7
Abstract
The specific binding of digitalis glycosides to the Na,K-ATPase is used as a tool for Na,K-ATPase quantification with high accuracy and precision. In myocardial biopsies from patients with heart failure, total Na,K-ATPase concentration is decreased, and the decrease in Na,K-ATPase concentration correlates with a decrease in heart function. During digitalization, a fraction of remaining pumps are occupied by digoxin. No evidence for an endogenous digitalis-like factor of any clinical importance was obtained. It is recommended that digoxin be administered to heart failure patients who still have dyspnea after institution of mortality-reducing therapy.
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10.
Myocardial Na,K-ATPase: the molecular basis for the hemodynamic effect of digoxin therapy in congestive heart failure.
Kjeldsen, K, Nørgaard, A, Gheorghiade, M
Cardiovascular research. 2002;(4):710-3
Abstract
Congestive heart failure may be deemed the epidemic of cardiology in the 21st century in the industrialized part of the world. Although new therapies improving morbidity and mortality from chronic heart failure have emerged it is likely that there is a growing role for digoxin. Thus, digoxin treatment is known to control symptoms of congestive heart failure when added to standard therapy. In this setting, we review the prevailing knowledge of the Na,K-ATPase, the cellular receptor for the inotropic action of digitalis glycosides, in relation to the hemodynamic effect of digoxin. It is concluded that if improvement of hemodynamics is needed in congestive heart failure, this knowledge should be taken into account and in many cases digoxin should be added to standard therapy. Digoxin is still the only safe inotropic drug for oral use that improves hemodynamics. Digoxin should be used to heart failure patients in sinus rhythm when they after institution of mortality reducing treatment still have heart failure symptoms, and to patients intolerant to heart failure mortality reducing drugs. Digoxin should probably in heart failure patients with sinus rhythm be given in the lowest possible dose that relieves symptoms sufficiently.