Download Digitalis (cardiac glycoside) poisoning

Digitalis (cardiac glycoside) poisoning
PHARMACOLOGY AND CELLULAR TOXICOLOGY
 Cardiac glycosides reversibly inhibit the sodium-potassium-ATPase, causing an increase in intracellular sodium
and a decrease in intracellular potassium.
 The increase in intracellular sodium prevents the sodium-calcium antiporter from expelling calcium from the
myocyte, which increases intracellular calcium. The net increase in intracellular calcium augments inotropy.
 Cardiac glycosides also increase vagal tone which results in decreased conduction through the sinoatrial and
atrioventricular nodes.
Bioavailability (percent)
Plasma binding (percent)
VD (L/kg)
Half life (hours)
70
25
5.6 L/kg
50
CLINICAL FEATURES AND DIAGNOSIS
 With an acute ingestion, the patient may remain asymptomatic for several hours, then develop significant
gastrointestinal symptoms such as anorexia, nausea, vomiting, and abdominal pain.
 Neurologic manifestations such as confusion and weakness, independent of hemodynamic parameters, are
common.
 Chronic toxicity is often more difficult to diagnose, as symptom onset tends to be more insidious and may occur
over a period ranging from days to months. Gastrointestinal symptoms, such as anorexia, nausea, and vomiting,
can occur, but may be less pronounced. Neurologic manifestations, such as lethargy, fatigue, delirium, confusion,
disorientation, and weakness, may be prominent in chronic toxicity. Visual changes may include alterations in
color vision, the development of scotomas, or blindness. Often patients are brought to medical attention by
family members who note a change in mental status since their last visit, which may have been days, weeks, or
even months prior.
History
 Determine the agent, amount taken, time of ingestion, and any co-ingestants whenever possible.
 Dig levels should be measured 6/24 post ingestion due to absorption
 Concomitant illness - dehydration or acute renal insufficiency
 Medication history to determine if any recent additions or dosing changes were made. Verapamil, amiodarone,
and quinidine, can increase serum digitalis concentrations.
Physical examination
 After initial evaluation of the patient's airway and breathing, the clinician should assess the patient's vital signs.
Bradycardia is frequently encountered in digitalis toxicity.
 Look for evidence of hypoperfusion and end organ dysfunction. Pay particular attention to mentation and
neurologic status, keeping in mind that such effects are often due to direct toxicity but may be secondary to
cerebral hypoperfusion.
 Look for symptoms and signs suggestive of acute mesenteric ischemia, which is a rare complication.
Ix
Electrolytes
 Inhibition of the sodium-potassium-ATPase, in both heart and skeletal muscle, leads to an increase in extracellular
potassium. Thus, hyperkalemia is a major manifestation of acute digitalis toxicity, and an important predictor of
mortality
 In the setting of chronic toxicity, hypokalemia is of greater concern. Several electrolyte abnormalities, including
hypokalemia, hypomagnesemia, and hypercalcemia, increase patient susceptibility to the toxic effects of digoxin
[15]. Loop diuretics to treat heart failure are the most common cause of hypokalemia in these patients, but other
causes of hypokalemia (eg, diarrhea or vomiting) do occur.
 Renal dysfunction is also commonly encountered in the setting of chronic digoxin toxicity and is often what
precipitates the rise in the digoxin level.
Dig level
The serum digoxin concentration does not necessarily correlate with toxicity.
ECG
 Premature ventricular contractions are the most common
 Others include bradycardia, atrial tachyarrhythmias with AV block, ventricular bigeminy, junctional rhythms, various
degrees of AV nodal blockade, ventricular tachycardia, and ventricular fibrillation.
 Ventricular arrhythmias are reportedly more common in chronic toxicity and in patients with chronic heart disease
 The so-called "digitalis effect" on the electrocardiogram consists of T wave changes (flattening or inversion), QT
interval shortening, scooped ST segments with ST depression in the lateral leads, and increased amplitude of the U
waves. It is often seen with chronic digoxin use and does not correlate well with toxicity
Management
Fab fragments be given to patients with digitalis toxicity and any of the following:
 Life-threatening arrhythmia (eg, ventricular tachycardia; ventricular fibrillation; asystole; complete heart block;
Mobitz II heart block; symptomatic bradycardia)
 Evidence of end-organ dysfunction (eg, renal failure, altered mental status)
 Hyperkalemia (serum potassium >5 to 5.5 meq/L [>5 to 5.5 mmol/L])
GI decontamination — The administration of activated charcoal (AC) or cholestyramine for gastrointestinal
decontamination should be viewed as adjunctive and not primary therapy in patients with digitalis poisoning.
Electrolyte management – tolerate mild hyperK+ and replace K+/Mg2+ as needed
Fluid resuscitate as needed
Extracorporeal removal - Because of digoxin's large volume of distribution and molecular weight, extracorporeal
removal is not beneficial.