Digoxin Toxicity
--What meds can lead to digoxin toxicity?
Abx that inhibit gut flora can reduce the metabolism (erythromycin); meds that dec GI motility can inc absorption; quinidine; verapamil; amiodarone
--In addition to DigiFab, what can we give a digoxin toxic patient if they present < 1 hour from ingestion?
Activated charcoal 50 g PO
--What is DSAF?
Digoxin specific antibody fragment
--Do we obtain digoxin levels after giving DigiFab?
No, wouldn't really be beneficial b/c levels will be falsely high (including DigiFab + digoxin complexes) and few facilities are able to measure free digoxin levels.
--What is the use of hemodialysis in digoxin toxicity?
Not effective
--How is renal fxn a/w digoxin toxicity? How do we measure?
Often precipitates elevated digoxin levels in chronic toxicity; measure with BUN, SCr, urine output (for AKI)
--What is the MoA of digoxin?
Inhibits the Na+/K+ ATPase which increases intracellular Na+/extracellular K+; Compensatory action of Na+/Ca++ Pump increases intracellular Ca++ conc; Increased contractility is desired effect
--How long must we wait to obtain a serum digoxin steady state trough?
6-8 hours after the patient's last dose
--What level of serum potassium is (typically) a major concern in chronic digoxin toxicity?
<3.5 mEq/L
--What level of serum potassium is a major concern in acute digoxin toxicity?
>5 mEq/L
--What is our goal therapeutic window for digoxin in heart failure tx?
0.5-0.8 ng/mL
--What is our goal therapeutic window for digoxin in atrial fibrillation tx?
0.8-1.2 ng/mL
--How do we dose DigiFab for a pt when amount ingested is known, but [dig] is unknown?
1 vial binds 0.5 mg of digoxin --> total body load (TBL) for digoxin = dose in mg * 0.8 --> # vials = TBL/0.5
--How do we dose DigiFab for a pt when acute toxicity when *neither* steady state [digoxin] or amount ingested is known?
10 vials are given, may repeat add'l 10 vials as early as 30 minutes later; small kids may start w/ 5 vials
--How do we dose DigiFab for cardiac glycoside poisoning *other* than digoxin & amount ingested is unknown?
10 vials initially
--Toxicity is commonly a/w serum digoxin levels greater than:
2 ng/mL
--How does DigiFab work?
Antibodies from glycoprotein IgG irreversibly bind and form complexes with digoxin; renal excretion of complex results
--What are the s/sx a/w an acute digoxin OD?
CNS - lethargy, confusion, weakness, AMS CV - arrhythmias, hypotension *GI - N/V, abdom pain* Electrolytes - hyperkalemia
--What are the s/sx a/w a chronic digoxin OD?
CNS - lethargy, confusion, weakness, HA, hallucinations CV - arrhythmias, hypotension GI - N/V/D, abdom pain, weight loss Electrolytes - *hypokalemia, hypomagnesemia* Ocular - yellow halos, blurring
--What is our DSAF agent of choice?
DigiFab (Digibind was d/c)
--How do we dose DigiFab for a pt when steady state conc is known?
Estimate # of vials based on steady state level by using equation ([digoxin]*patient weight)/100
--What should we do if a pt p/w hyperkalemia + bradycardia + on digoxin?
Get a digoxin level! Then interpret the level. Think of this like a triad.
--How do we dose DigiFab for a pt when chronic toxicity with unknown steady state level?
Give a lower empiric dose & only for severe tox, to avoid unmasking dz state; give 2 or *3 vials* here usually and more if needed as early as 30 minutes post-dose
--Why are we concerned with dosing DigiFab for digoxin toxicity in a patient with renal dysfxn?
If we are tx a chronic digoxin OD in that pt, they still need digoxin after tx of the OD. This DigiFab will hang around for a long time (~7-10 days possibly) with kidney dysfxn and will render the subsequent necessary therapeutic digoxin ineffective.
--What are the most common causes of hypokalemia during chronic digoxin toxicity?
Loop diuretics, vomiting, diarrhea
--What are the various causes of digoxin toxicity?
Medications; renal dysfxn; increasing age; severe heart dz, MI; hypothyroidism
--What are some of the ADRs of DigiFab?
Rare anaphylaxis; hypokalemia; *unmasking condition being tx by digoxin (exacerbating CHF d/2 loss of inotropy; rebound into A. fib)*; sheep product hypersens known (ovine, papain, chymopapain, papaya)
--Describe the use of calcium during digoxin toxicity & hyperkalemia.
Recommend *against* its use during digoxin toxicity, it is *contraindicated*; best tx for hyperkalemia is DigiFab
--*What is important to remember, as a pharmacist, when admin DigiFab?*
Reconstitute each vial with 4 mL of NS; then, usually further diluted into ~50 mL NS; admin as IV over 30 minutes; use a 0.22 micrometer filter; may give IV push if cardiac arrest (or impending) or severe dysrhythmia
--What is the *most important marker* for lethality during acute digoxin toxicity? (very important when determining use of antidote)
Serum potassium
--What ECG changes do we see during digoxin toxicity?
T wave changes (flattening or inversion); QT interval shortening; Scooped ST segments with ST depression in the lateral leads
--Clinically, why are we concerned with hypokalemia and hypomagnesemia during chronic digoxin toxicity?
These levels ↑ toxic effects of digoxin for the patient. However... a patient with chronic toxicity doesn't always have hypokalemia, can be high d/2 other dz states.
--How do FDA recommendations for DigiFab differ from clinical practice?
They suggest use when: > 4 ng/mL serum conc in chronic ingestion; K+ > 5.5 mEq/L
--What are the *clinical* indications for DigiFab?
V tach, V fib, asystole, heart block, symptomatic bradycardia; chronic elevation of digoxin conc a/w dysrhythmias, significant GI sx, or AMS; [digoxin] > 10 ng/mL @ 6h post-dose (*based also on s/sx not just dose*); 10 mg ingestion in dig-naive adult; 4 mg ingestion in dig-naive child; if K+ >5 mEq/L
--*What is the equation for dosing DigiFab vials when we know steady-state conc for a chronic digoxin toxicity?*
Vials = (serum conc of dig in ng/mL * weight in kg)/100 Always round up
--*What is the equation for dosing DigiFab vials when we have an acute digoxin toxicity w/ known amount ingested?*
Vials = (total body load in mg * 0.8)/0.5 Always round up
