Background: The therapeutic properties of cardiac
glycosides (eg, digoxin, a product of the foxglove plant) have been known since
the days of the Roman Empire.
Digoxin's inotropic
effect results from the inhibition of the sodium-potassium adenosine
triphosphatase (NA+/K+ ATPase) pump. The subsequent rise
in intracellular calcium (Ca++) and sodium (NA+) coupled
with the loss of intracellular potassium (K+) increases the force of
myocardial muscle contraction (contractility), resulting in a net positive
inotropic effect.
Digoxin also increases
the automaticity of Purkinje fibers but slows conduction through the
atrioventricular (AV) node. Cardiac dysrhythmias associated with an increase in
automaticity and a decrease in conduction may result.
The relationship between
digoxin toxicity and the serum digoxin level is complex; clinical toxicity
results from the interactions between digitalis, various electrolyte
abnormalities, and their combined effect on the Na+/K+
ATPase pump
History:
Constitutional
symptoms (eg, weakness, fatigue)
Cardiovascular
Palpitations
Syncope
Dyspnea
Central
nervous system
Confusion
and somnolence
Dizziness
without vertigo
Agitation,
delirium, and hallucinations
Headache
Paresthesias
and neuropathic pain
Seizures
(extremely rare)
Ocular
Disturbances
of color vision with a tendency to yellow-green coloring
Blurred
vision and diplopia
Halos
and scotomas
Photophobia
Gastrointestinal
Nausea,
vomiting, anorexia, and diarrhea
Abdominal
pain (uncommon)
Physical: Hemodynamic instability is related directly to the presence
of a dysrhythmia or acute congestive heart failure (CHF).
Cardiovascular
findings on physical examination relate to the severity of CHF, dysrhythmias,
or hemodynamic instability.
Digoxin
toxicity may cause any dysrhythmia. Classically, dysrhythmias that are
associated with increased automaticity and decreased AV conduction occur
(ie, paroxysmal atrial tachycardia with 2:1 block, accelerated junctional
rhythm, or bidirectional ventricular tachycardia [torsade de pointes]).
Premature
ventricular contractions (PVCs) are the most common dysrhythmia. Bigeminy
or trigeminy occurs frequently.
Sinus
bradycardia and other bradyarrhythmias are very common. Slow atrial
fibrillation with very little variation in the ventricular rate
(regularization of the R-R interval) may occur.
First-
and second-degree AV block, complete AV dissociation, and third-degree
heart block are also very common.
Rapid
atrial fibrillation or atrial flutter is rare.
Ventricular
tachycardia is an especially serious finding.
Cardiac
arrest from asystole or ventricular fibrillation is usually fatal.
Gastrointestinal
symptoms are common, but the abdominal examination is usually nonspecific.
Neurological
findings are related to changes in sensorium or mental status.
Lateralizing findings usually indicate another disease process.
Visual
changes occur, but the pupils are spared, and objective findings are few.
Drug-induced
fever does not occur.
Causes:
Deteriorating
renal function, dehydration, electrolyte disturbances, or drug
interactions usually precipitates chronic toxicity.
Acute
overdose or accidental exposure to plants containing cardiac glycosides
may cause acute toxicity.
Hypokalemia,
hypernatremia, or hypomagnesemia increases the toxic cardiovascular
effects of digoxin because of their depressive effects on the NA+/K+
ATPase pump.
Digoxin
toxicity does not cause hypokalemia, but hypokalemia can worsen digoxin
toxicity.
Hyperkalemia
is the usual electrolyte abnormality precipitated by digoxin toxicity,
primarily in the acute setting. Hyperkalemia may be associated with acute
renal failure that subsequently precipitates digoxin toxicity. Chronic
digoxin toxicity does not usually cause hyperkalemia.
Acidosis
depresses the Na+/K+ ATPase pump and may cause
digoxin toxicity.
Myocardial
ischemia suppresses the Na+/K+ ATPase pump and
independently alters myocardial automaticity. Digoxin toxicity is more
likely in this setting.
Hypothyroid
patients are prone to digoxin toxicity secondary to decreased renal
excretion and a smaller volume of distribution.
Bioavailability
varies depending on the drug formulation.
Toxicity
may occur by increasing bioavailability.
Certain
antibiotics that suppress intestinal flora may increase absorption of
digoxin.
