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Digoxin


Definition


  • Digoxin is an analogue of digitoxin.
  • A cardiac glycoside derived from Digitalis lanata consisting of a steroid nucleus and a lactone coupled with sugar moieties.
  • Other name: Lanoxin.
  • Normal therapeutic range: 0.8 " “2.0 ng/mL (1.2 " “2.6 nmol/L).

Use


  • Treatment of CHF and atrial fibrillation/flutter

Interpretation


  • Toxic range: >2.5 ng/mL, but 10% of patients may show toxicity at <2 ng/mL.
  • Toxicity may be observed at a lower serum concentration in presence of hypokalemia, hypercalcemia, hypomagnesemia, hypoxia, and heart disease.
  • Increased with coadministration of
    • Quinidine
    • Verapamil
    • Amiodarone
    • Indomethacin
    • Cyclosporin A

Limitations


  • Draw blood 6 " “8 hours (or 8 " “24 hours) after last oral dose after steady state has been achieved in 1 " “2 weeks.
  • Pediatric toxic concentration may be higher; therapeutic index is very low (i.e., small difference between therapeutic and toxic blood concentration). However, approximately 10% of patients have serum concentration of 2 " “4 ng/mL without evidence of toxicity. On a dose of 0.25 mg/day, mean serum concentration is 1.2 ‚ ± 0.4 ng/mL; on a dose of 0.5 mg/day, mean serum concentration is 1.5 ‚ ± 0.4 ng/mL. A Digitalis leaf dose of 0.1 g/day produces the same serum concentration as 0.1 mg/day of crystalline digitoxin. There is ECG evidence of toxicity in one third to two thirds of patients, with no symptoms or signs.
  • False low results may be due to spironolactone.
  • Endogenous digoxin-like substances may produce positive test results in persons who have not received the drug, especially in
    • Uremia.
    • Severe agonal states and postmortem " ”therefore, a high postmortem concentration may not have been high before death and a normal postmortem concentration suggests that the antemortem concentration was not toxic.
  • Because most methods measure both endogenous digoxin-like substances and inactive metabolites of digoxin, therapeutic monitoring should mostly be used to assess patient compliance and to confirm drug toxicity.
  • Tests: bioassay, Na+/K+-ATPase receptor assay, colorimetry, fluorometry, HPLC, GC, enzyme assay, immunoassay, and LC/MS.
  • Immunoassay is the most widely used methodology: RIA, FPIA, EIA, and chemiluminescence.
    • Confounders in analysis-low concentrations, steroid-like nucleus, endogenous digoxin-like immunoreactive factors (observed in patients with renal failure, liver disease, MI, newborns, pregnancy, hypertension, strenuous exercise, volume expansion), digoxin metabolites, presence of antidote (Fab).
    • Immunoassays exhibit <5% cross-reactivity with digitoxin and digoxigenin, and 80 " “100% with the metabolites digoxigenin bis- and monodigitoxoside.
    • Hb, lipid, and bilirubin do not typically interfere.
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