Page 98 - Small Animal Internal Medicine, 6th Edition

70 PART I Cardiovascular System Disorders

elixir produces approximately 50% higher serum concentra- Digoxin toxicity causes GI, myocardial, and sometimes
tions than the tablet form of digoxin. For the rare feline case central nervous system (CNS) signs. GI toxicity can develop
VetBooks.ir where digoxin might be helpful, dosing every 48 hours pro- before signs of myocardial toxicity. Signs include anorexia,
depression, vomiting, borborygmi, and diarrhea. Some of
duces effective serum concentrations, with steady state
achieved in about 10 days. Digoxin elimination is primarily
chemoreceptors in the area postrema of the medulla. CNS
by glomerular filtration and renal secretion in dogs, although these GI signs result from the direct effects of digoxin on
approximately 15% is metabolized by the liver. Renal and signs include depression and disorientation.
hepatic elimination appear equally important in cats. Myocardial toxicity can cause ventricular or supraven-
Serum digoxin concentration (and risk of toxicity) tricular tachyarrhythmias, sinus arrest, Mobitz type I second-
increases with renal failure because of reduced clearance and degree AV block, and junctional rhythms. Myocardial
volume of distribution. However, there is no consistent cor- toxicity can occur before any other signs and can lead to
relation between the degree of azotemia and the serum collapse and death, especially in animals with myocardial
digoxin concentration in dogs. Lower doses and close moni- failure. Therefore PR interval prolongation on the electrocar-
toring of serum digoxin concentration are recommended in diogram (ECG) or signs of GI toxicity should not be used to
animals with renal disease. guide progressive dosing of digoxin. Digoxin can stimulate
Digoxin dose and serum concentration are only weakly spontaneous automaticity of myocardial cells by inducing
correlated in dogs with heart failure. Because much of the and potentiating late afterdepolarizations; cellular stretch,
drug is bound to skeletal muscle, animals with reduced calcium overloading, and hypokalemia enhance this effect.
muscle mass or cachexia as well as those with compro- Toxic concentrations enhance automaticity by increasing
mised renal function easily can become toxic at usual sympathetic tone to the heart, whereas the parasympathetic
calculated doses. Digoxin has poor lipid solubility. Initial effects of slowed conduction and altered refractory period
dosing should be based on the patient’s estimated lean body facilitate development of reentrant arrhythmias. In patients
weight, especially in obese animals. Management of digoxin taking digoxin, toxicity should be suspected when ventricu-
toxicity is outlined later. Conservative dosing and moni- lar arrhythmias or tachyarrhythmias with impaired conduc-
toring of serum digoxin concentrations are important to tion appear.
prevent toxicity. Therapy for digoxin toxicity depends on its manifesta-
Serum concentration measurement is recommended at 7 tions. GI signs usually respond to drug withdrawal and cor-
days (or 10 days for cats) after beginning digoxin therapy. rection of fluid or electrolyte abnormalities. AV conduction
Digoxin serum concentration also should be measured after disturbances resolve after drug withdrawal, although anti-
a dosage change, or whenever potential signs of toxicity cholinergic therapy may be necessary. Lidocaine is used to
occur. Samples should be drawn 8 (to 10) hours post-dose. treat digoxin-induced ventricular tachyarrhythmias because
The target serum concentration range is 0.8 to 1.5 ng/mL. If it can suppress arrhythmias caused by re-entry and late
the serum concentration is less than 0.8 ng/mL, the digoxin afterdepolarizations, with little effect on sinus rate and AV
dose could be increased by 25% to 30%, and the serum con- conduction. A β-blocker might help control ventricular
centration remeasured the following week. If serum concen- tachyarrhythmias not responsive to lidocaine alone, but this
trations cannot be measured and toxicity is suspected, the is not used if AV conduction block is present. Phenytoin
drug should be discontinued. If necessary, the drug can be (diphenylhydantoin) is a rarely used alternative antiarrhyth-
reinstituted at half of the original dose after a couple days. mic agent for dogs with digoxin-induced ventricular tachyar-
rhythmias if lidocaine is ineffective (see Chapter 4, p. 82).
Digoxin Toxicity If the serum potassium concentration is less than 4 mEq/L,
Azotemia and hypokalemia both predispose to digoxin IV potassium supplementation is helpful (see p. 83). Magne-
toxicity. Therefore it is important to monitor renal func- sium supplementation also can help in suppressing arrhyth-
tion and serum electrolyte concentrations during digoxin mias; MgSO 4 has been used at 25 to 40 mg/kg via slow IV
therapy. Hypokalemia predisposes the patient to myocardial bolus, followed by infusion of the same dose over 12 to 24
toxicity by allowing increased digoxin binding to membrane hours. Fluid therapy to correct dehydration and maximize
+
+
Na , K -ATPase; conversely, hyperkalemia displaces digitalis renal function should be used only with caution and at con-
from those binding sites. Hypercalcemia and hypernatre- servative volumes in patients with heart failure. Quinidine
mia potentiate both the inotropic and the toxic effects of should not be used because it increases digoxin serum con-
the drug. Hyperthyroidism can potentiate the myocardial centration. Oral administration of the steroid-binding resin
effects of the drug. Hypoxia sensitizes the myocardium to cholestyramine is useful only soon after accidental digoxin
the toxic effects of digoxin. Certain drugs can affect serum overdose because this drug undergoes minimal enterohe-
digoxin concentrations when administered concurrently, patic circulation. A preparation of digoxin-specific antigen-
including amiodarone, quinidine, and verapamil. Diltiazem, binding fragments (digoxin-immune Fab) derived from
prazosin, spironolactone, and triamterene possibly increase ovine antidigoxin antibodies occasionally has been used for
serum digoxin concentration. Drugs affecting hepatic digoxin overdose; the Fab fragment–digoxin complex inac-
microsomal enzymes may also have effects on digoxin tivates digoxin’s effects and is subsequently excreted by the
metabolism. kidney.