Dr. Ranjith Kumar C.

DIGOXIN POISONING
Digoxin is a cardiac glycoside extracted from the leaves of Digitalis lanata Digitalis glycosides are present:

o Digitalis purpura (foxglove) o Nerium oleander (oleander) o convallaria majalis (lily of the valley) o Siberian ginseng o some toads' venom (Bufo bufo).
digoxin is used in children :

o for the treatment of heart failure o some supraventricular tachydysrhythmias.

Acute overdose may occur :

o from dosing errors (especially in younger children) o from accidental or intentional medication ingestion o from ingestion of plant material containing digitalis glycosides
Chronic overdose following 3 circumstances:

o alteration of the digoxin dose o alteration in digoxin clearance due to renal impairment o r drug interactions. PATHOPHYSIOLOGY
Digoxin blocks the Na+, K+-ATPase pump to intracellular loss of K+ and gain of Na+ and Ca2+ increasing the Ca2+ available to the contractile myocardium after excitation (positive inotropic effect). The increased intracellular calcium leads to increased myocardial automaticity, subsequent atrial, nodal, and ventricular ectopy with

The impaired Na-K exchange also leads to dangerously high levels of serum potassium

Dr. Ranjith Kumar C.S

Digoxin affects the cardiac autonomic system (vagally mediated mechanism):

o leading to an increased refractory period, o decreased sinus node firing, and slowed conduction through the AV node, o sinus bradycardia, AV block, or even sinus arrest
The overall effect of digoxin overdose is a combination of slowed or blocked conduction and increased ectopy Digoxin has a very narrow therapeutic index The therapeutic plasma concentration is 0.52.0 ng/mL, >2 ng/mL are considered toxic; >6 ng/mL is considered potentially lethal

Clinical and Laboratory Manifestations:

Acute toxic effects usually occur within 6 hr of ingestion Acute toxic effects : gastrointestinal, cardiovascular, and CNS manifestations Nausea and vomiting the presenting symptoms Cardiovascular manifestations:

o bradycardia, heart block, and ventricular dysrhythmias o Bradydysrhythmias are more common in previously healthy hearts o previously diseased hearts usually respond with tachydysrhythmias o Continuous ECG monitoring is crucial for assessing digoxin's effects and guiding therapy o Blood pressure is usually preserved despite significant bradycardia
CNS manifestations include visual changes, headache, fatigue, lethargy, confusion, and hallucinations. Chronic cardiac glycoside toxicity : combination of ventricular dysrhythmias and impaired AV conduction.

Dr. Ranjith Kumar C.S

LAB :

o The serum digoxin level should be assessed at least 6 hr after ingestion and carefully
interpreted in the clinical context because the digoxin level alone is not reflective of the severity of intoxication

o serum potassium level a useful marker of severe toxicity It may be dangerously increased
(a poor prognostic sign)

o hypokalemia ,Hypomagnecenemia,Hypercalcemia enhances digoxin toxicity o Renal function should also be monitored.
Treatment.:

o Initial treatment includes good general supportive care and gastric decontamination with
activated charcoal if the ingestion was recent

o Immediate therapy should aim life-threatening effects of digoxin toxicity, including

mounting hyperkalemia and ventricular dysrhythmias

o Hemodialysis may temporarily attenuate hyperkalemia, but digoxin cannot be eliminated in

this way, due to its high tissue binding

o An antidote : digoxin-specific Fab antibody fragments (Digibind)

binds free digoxin in both the intravascular and the interstitial spaces and facilitates its renal clearance Effects begin within 1 hr of administration Indications:

digoxin-related life-threatening dysrhythmias, K value of >5 mEq/L in the

+

setting of acute digoxin overdose,

significantly altered mental status, renal failure. serum digoxin level of >10 ng/mL, and ingestion of >4 mg in children or >10
mg in adults

Dr. Ranjith Kumar C.S

o In the absence of Digibind, ventricular ectopy should be treated with phenytoin, which
may reverse the digoxin-induced slowed AV conduction and suppress the tachydysrhythmia without diminishing contractility.

o Atropine is the standard therapy for symptomatic bradycardia