Digoxin toxicity pharmacokinetics
Initially, digitalis was used to treat dropsy, which is an old term for edema.
Therefore, when initiating treatment, a special dosing regimen involving "loading doses" is used to rapidly increase digoxin plasma levels. Eur J Heart Fail. The therapeutic benefits of digitalis were first described by William Withering in Understanding digoxin use in the elderly patient.
The time to equilibrium can be variable and in the elderly it can be delayed. Digoxin associates with mortality in ESRD. Unfortunately, digoxin is associated with a significant increase in hospitalisations and mortality amongst the elderly [ 10 ].
Emergency hospitalizations for adverse drug events in older Americans. Digoxin is not strongly influenced by first pass metabolism or hepatic metabolism. For water soluble drugs, like digoxin, elimination is solely or primarily via renal excretion [ 8911 ]. Digoxin antibody fragment use should be considered in the context of life-threatening dysrhythmias, a potassium level greater than 5.
Reduced homeostatic capacity and reduced functional reserve have significant pharmacokinetic implications. This partly relates to the wide variety of co-morbid conditions and medications that can interfere with the reliability of the serum measurement of digoxin; factors more prevalent in the elderly.
Volume of distribution Vd.
This calls into question the practice of using digoxin for lowering ventricular rate in patients with atrial fibrillation. Armour D, Cairns C, editors.
By mechanisms that are not fully understood, digitalis compounds also increase vagal efferent activity to the heart. Since many factors may influence the sensitivity of the myocardium to digoxin, measurement of serum digoxin levels in only one, but a useful criterion, when making clinical decisions about adjustment of digoxin dosage. Oral digoxin is available as a solution 0. Finally, the reduction in first pass metabolism and decreased liver capacity to manage toxins contribute to an increase in adverse effects in the elderly.
As a result, there is an increase in intracellular sodium concentration, a reduction in cytoplasmic potassium, and ultimately an increase in cytoplasmic calcium that promotes myocardial contractility. This is particularly important for drugs with a narrow therapeutic index, like digoxin, because it increases the likelihood of serious toxicity [ 11 ].
Practitioners involved in monitoring digoxin use need to maintain a high level of suspicion for digoxin toxicity. This is reflected in some early research in normal young and old populations [ 31 ].
J Am Geriatr Soc. Digoxin blood concentrations should be measured following the first distribution phase—at least 6 hours after the daily dose. Serum digoxin concentrations are a good marker for toxicity but should be interpreted with heavy weighting on clinical judgement because serum concentrations are not always a good indicator of toxicity [ 30 ].