Large-scale Digitoxin Intoxication

Lely, A.H.; Enter, C. H. J. Van

doi:10.1136/bmj.3.5725.737

Cited by 93 publications

(11 citation statements)

References 13 publications

(7 reference statements)

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“…After administration of specific Fab fragments, the percentage of extractable radioactivity increased from a control mean of 40% (phase 4) to 92% during the first 6-h period, gradually decreasing to control levels by the time of the 72-to 96-h urine sample. This is consistent with accelerated excretion of native digitoxin and excludes the possibility that 3H excretion was due to 3H (2,39). Due to its prolonged half-life compared with other glycosides (13), digitoxin intoxication poses a special therapeutic problem.…”

Section: Resultssupporting

confidence: 54%

Reversal of Advanced Digitoxin Toxicity and Modification of Pharmacokinetics by Specific Antibodies and Fab Fragments

Ochs¹,

Smith²

1977

J. Clin. Invest.

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A B S T R A C T The effects of Fab fragments of highaffinity specific antibodies have been studied in a canine experimental model of lethal digitoxin toxicity. Selected antiserum from sheep immunized and boosted with a digoxin-serum albumin conjugate contained antibodies that cross-reacted with digitoxin with an average intrinsic association constant of 1.4 x 10"0 M-1 as determined by equilibrium dialysis.Rapid second-order association kinetics (kf = 3.7x 106 M-1 per s) and slow dissociation kinetics (kr = 1.9 X 10-4 per s) were documented for the antibody-digitoxin complex. Eight dogs given 0.5 mg/ kg digitoxin intravenously developed ventricular tachycardia after 23±4 (SEM) min. Control nonspecific Fab fragments were then given. All animals died an average of 101+36 min after digitoxin administration. Another eight dogs given the same digitoxin dose similarly developed ventricular tachycardia after 28+3 min. This group then received a molar equivalent dose of specific Fab fragments intravenously over 3 min, followed by a 30-min infusion of one-third of the initial dose. All dogs survived. Conducted sinus beats reappeared 18+4 min after initial Fab infusion, and stable normal sinus rhythm was present at 54 ± 16 min. Plasma total digitoxin concentrations increased threefold during the hour after initial Fab infusion, while plasma free digitoxin concentration decreased to less than 0.1 ng/ml. Effects on digitoxin pharmacokinetics of these Fab fragments and the antibody population from which they were derived were further investigated in a primate species. Unlike common laboratory animals previously studied, the rhesus monkey was found to have a prolonged elimination half-life, estimated at 135Dr. Ochs was a Fellow of Deutsche Forschungsgemeinschaft.Received for publication 20 January 1977 and in revised form 5 July 1977. and 118 h by radioimmunoassay and [3H]digitoxin measurements, respectively, similar to man and thus providing a clinically relevant experimental model. Intravenous administration of 2 mol of specific Fab fragments per mole of digitoxin 6 h after 0.2 mg of digitoxin produced a rapid 4.3-fold increase in plasma total digitoxin concentration followed by a rapid fall (t1 4 h) accompanied by a 14-fold enhancement of urinary digitoxin excretion over control values during the 6-h period after Fab was given. Analytical studies were consistent with increased excretion of native digitoxin rather than metabolites, and the glycoside was found in equilibrium dialysis studies to be excreted in the urine in Fab-bound form. Administration of 2 mol of specific antibody binding sites per mole of digitoxin as intact IgG caused a greater and more prolonged increase in plasma total digitoxin concentration, peaking 13-fold above control levels. In contrast to the effects of Fab, however, specific IgG reduced the rate of urinary digitoxin excretion substantially below control values. We conclude that Fab fragments of antibodies with high affinity for digitoxin are capable of rapid reversal of advanced, otherwise let...

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Section: Resultssupporting

confidence: 54%

Reversal of Advanced Digitoxin Toxicity and Modification of Pharmacokinetics by Specific Antibodies and Fab Fragments

Ochs¹,

Smith²

1977

J. Clin. Invest.

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“…In patients with persistent inappropriate sinus bradycardia, sinus pauses, or sinus exit block (sick sinus syndrome), digitalis may exacerbate the underlying bradyarrhythmia. 36 However, in most patients with sick sinus syndrome, digitalis does notalter heart rate on ambulatory monitoring, depress the maximal heart rate achieved during exercise, or further depress sinus node recovery time 37 ; therefore, its safety in treating congestive heart failure in such patients remains controversial.…”

Section: Toxicitymentioning

confidence: 99%

Management of atrial fibrillation and flutter

Simpson¹,

Foster²,

Woelfel³

et al. 1986

Postgraduate Medicine

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“…Visual disturbances are the most common symptoms of digitalis toxicity and often the initial signs [72,73,74]. A common ocular complaint is xanthopsia, but blurring, central scotomas, photopsia and altered color perception have also been reported [72,73,75]. …”

Section: Digoxin Retinopathymentioning

confidence: 99%

The Role of Multifocal Electroretinography in the Assessment of Drug-Induced Retinopathy: A Review of the Literature

Dettoraki

Moschos²

2016

Ophthalmic Res

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Multifocal electroretinography (mfERG) is an objective, noninvasive examination for the assessment of visual function. It enables the stimulation of multiple retinal areas simultaneously and recording of each response independently, providing a topographic measure of retinal electrophysiological activity in the central 40-50° of the retina. A clinical application of mfERG represents the assessment of retinal toxicity associated with systemic medications. Drug-induced retinopathy represents a disease that, although not common, requires early recognition: if not detected early, it may progress and cause irreversible retinal dysfunction with subsequent visual impairment. This review aims to evaluate the use of mfERG in the assessment of retinal dysfunction associated with various systemic pharmacological agents based on the currently available literature. The most commonly recognized systemic medications affecting retinal function are included, such as chloroquine and hydroxychloroquine, vigabatrin, deferoxamine, ethambutol, interferon-α, tamoxifen, digoxin, sildenafil, canthaxanthin, amiodarone and nefazodone. The role of mfERG in the early diagnosis of retinal toxicity and the evaluation of disease severity is reviewed, as well as its clinical value in monitoring disease progression or recovery after drug cessation.

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Large-scale Digitoxin Intoxication

Cited by 93 publications

References 13 publications

Reversal of Advanced Digitoxin Toxicity and Modification of Pharmacokinetics by Specific Antibodies and Fab Fragments

Reversal of Advanced Digitoxin Toxicity and Modification of Pharmacokinetics by Specific Antibodies and Fab Fragments

Management of atrial fibrillation and flutter

The Role of Multifocal Electroretinography in the Assessment of Drug-Induced Retinopathy: A Review of the Literature

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