TDM of Digoxin Flashcards
Digoxin
-cardiac glycosides
-inc force of contraction
-reduce HR at rest and slow down AVN conduction
-Neuromodulator: sensitizationof baroceptor reflex function
inhibit reabsorption and suppression on renin release
Digoxin use
-treat HFrEF and Afib w rapid ventricular responses
Digoxin absorption
-small intestine
-P-gp
-no significant first pass metabolism
-good bioavailability
Digoxin Distribution
-large, highly variable Vd
-tissue binding related to body distribution of Na+/K+ ATPase
-distributes mainly into skeletal muscle with little distribution into fat
Conditions known to affect digoxin distribution
-electrolyte disturbances
-thyroid disorders
-exercise
-renal disease (dec 4.5L/kg)
Digoxin distribution
-mainly bound to albumin
-initial distrivution phase apparent after oral and IV dosing
-3-6 hour duration
-delayed onset of action until concentrations of digoxin can accumulate in the effect site
-blood sampling for determine concentration should not occur during this phase
Digoxin metabolism
-hydrolysis
-formation of dihydro metabolite by intestinal bacteria
-in selected pt, abx may enhance digoxin bioavailability by eliminating intestinal flora that metabolize digoxin
Hepatic Metabolism of digoxin
-minimal
Digoxin excretion
-approx 65-75% of total Cl is renal Cl
-renal Cl net secretion
-relationship between ClCr and Cldig
-P-gp
Digoxin inotropic response
-clinically difficult to assess
-assess of HF signs and symptoms
-in research, systolic time intervals (STI’s, QS2I)
-over the first 6-8h after a dose there is NO relationship between the plasma digoxin concentration and inotropic response
-curves become parallel 12-24h
Therapeutic Drug Monitoring
-NTI
-clinical response measures
-Afib
-heart failure reduced ejection fraction
Recommended Digoxin Concentrations
-Heart Failure
<1 ng/mL
-0.5-0.9 ng/mL
-< 1.2 ng/mL
-based on several post-hoc analyses from large clinical trails in HF
