TUGAS BACA DIGOXIN

I GEDE SUMANTRA

Introduction Sources
Found: secondary metabolities in plants and

insects
Foxglove plant (Digitalis purpurea),Strophanthus
gratus, Lily of the Valley, milkweed butterflies
The therapeutic benefits of digitalis were first
described by William Withering in 1785

Pharmacokinetics/dynamics
Half life 36-48 hours in the case of normal renal function

(levels stabilize 7 days after dose change

Large reservoir in skeletal muscle
Clearance is primarily renal, but some hepatic
metabolism as well
Level should be checked at least 8 hours after dose and
may not reflect tissue concentrations if recent dose
change.

Digitalization
1. Check Renal function
2. Lower digoxin dose

Initiated 0,25 md/day

Maintanance 0,125 mg/day
3. Steady state 5-7 days
4. Therapeutic range: 0.5 1.5 ng/mL
>2.0 ng/mL can lead to toxicity (arrhythmias) life-threatening
Digibind: rapidly reduces plasma digoxin levels

 Level increased by several medications

Verapamil, Diltiazem, amiodarone, itraconazole- decreased
clearance
Erythromycin, clarithromycin, tetracycline- decreased gut flora
metabolism
Toxicity can be increased by any medication decreasing serum K
or potentially affecting renal fxn
Increased level (probably >2.5 but possibly less) +

relevant clinical scenario (usually conduction

distrubance) = TOXICITY

Applications
Indicated for treatment of mild to

moderate heart failure

Atrial Fibrilation
Increases left ventricular ejection fraction
and improves heart failure symptoms

Contraindication
Ventricular fibrillation
HCOM
WPW with AF
AV conduction disturbance

Special Consideration
In women, the DIG trial shows only 22% of participants in

whom there was an unexplained increased 23% risk of

all cause mortality.
Two studies show an increased risk of breast cancer
with digoxin use in women. The larger study relates to use
at any time and the other to continuous use for at least 2
years and to invasive cancer

 In elderly Decreased skeletal muscle, lean body mass,

and renal function increase digoxin levels. Digoxin halflife

may be prolonged up to 73 hours, depending on renal
function. The digoxin dose is often lower than 0.125 mg
daily, such as 0.125 mg every second day

Digoxin Toxicity
Incidence decreasing 2610 reported cases in 2006

compared to 10K for Ca channel blocker and 18K

beta blocker toxicity cases
However there were 22 deaths compared to 13
and 4 for CCB and BB during the same year
Increased incidence in elderly as well as

decreased renal fxn

Digoxin Toxicity
Cardiac disturbances
GI symptoms
Anorexia, N/V/D, abdominal pain
CNS effects
Weakness, blurred vision, halos around light

In severe cases can cause hyper K

Can be difficult to detect clinically
In Dig trial incidence of Digoxin toxicity was 11.9% in
Digoxin group and 7.9% in placebo group

Conduction Defects in Digoxin

Toxicity
Slows nodal conduction while increasing

automaticity
More likely in patients w/ CAD, particularly active
ischemia and are potentiated by low Mg, K
Downward slurring of ST
Heart block
Dalis Mustache
VT/VT
-PAT w/ Block
-Bidirectional VT

Treatment
If early after intentional overdose, can give activated

charcoal
Bradycardia
If asymptomatic keep serum K at least 4.0 (or higher)
Potassium will affect affinity for Na/K pump
Symptomatic- Atropine, pacing

 Digibind (Humanized sheep Mab)

Symptomatic bradycardia not responsive to Atropine
Malignant arrhythmia (particularly in the setting of hyperkalemia)
Hyperkalemia
Important to give adequate dose initially as digoxin levels will be
affected for up to 2 weeks
Plasmapheresis will prevent rebound effect
Neither HD nor PD will decrease serum concentation

Prevention
Err on the lower end of dosing, as there is no clear

lower end of efficacy. The DIG trial dose of 0.25mg

daily is probably not appropriate initial dose for
anyone.
Closely monitor drug levels, especially if used with

Amio, non DHP CCB, or macrolides

Be particularly cautious following recent hospital

discharge

TERIMA KASIH