Digoxin toxicity is caused by all except:
a. Hyperkalemia protects against the digoxin toxicity by reducing the binding.
b. Decrease in magnesium, and increase in calcium can precipitate toxicity of digoxin.
c. Thiazides are most common drugs that can precipitate toxicity of digoxin as they can reduce potassium and magnesium and increase levels of calcium.
Precautions and Contraindications
a. Hypokalemia: enhances digitalis toxicity by increasing it’s binding to Na+K+ ATPase.
b. Elderly, renal or severe hepatic disease: patients are more sensitive.
c. Myocardial infarction: severe arrhythmias are more likely. Digitalis should be used after MI only when heart failure is accompanied with AF and rapid ventricular rate.
d. Thyrotoxicosis: reduces responsiveness to digitalis, but these patients are more prone to develop digitalis arrhythmias.
e. Myxedema: these patients eliminate digoxin more slowly; cumulative toxicity can occur.
f. Ventricular tachycardia: digitalis is contraindicated-may precipitate ventricular fibrillation.
g. Partial A- V block: may be converted to complete A-V block.
h. Acute myocarditis:Diphtheria, acute rheumatic carditis, toxic carditis-inotropic response is poor, more prone to arrhythmias.
i. Wolff-Parkinson- White syndrome: Digitalis is contraindicated-decreases the ERP of bypass tract in 1/3 patients. In them rapid atrial impulses may be transmitted to ventricles → VF may occur. Digitalis can increase the chances of reentry by slowing conduction in the normal A-V bundle and accelerating it in the aberrant pathway.
a. Diuretics: cause hypokalemia, which can precipitate digitalis arrhythmias; potassium supplements may be given prophylactically.
b. Calcium: synergism with digitalis → precipitates toxicity.
c. Quinidine: reduces binding of digoxin to tissue proteins as well as its renal and biliary clearance by inhibiting efflux transporter P-glycoprotein → plasma concentration is doubled → toxicity can occur. Verapamil, diltiazem, captopril and amiodarone: increase plasma concentration of digoxin to variable extents.
d. Adrenergic drugs: can induce arrhythmias in digitalized patients; both increase ectopic automaticity.
e. Digoxin absorption can be reduced by metoclopramide (gastrointestinal hurrying) and sucralfate, which adsorbs digoxin. Antacids, neomycin, sulfasalazine also can reduce digoxin absorption; stagger their administration. Atropinic drugs and tricyclic antidepressants increase absorption, by delaying gastric emptying. Erythromycin, omeprazole and tetracycline increase bioavailability of digoxin.
f. Propranolol, verapamil, diltiazem and disopyramide: may additively depress A-V conduction and oppose positive inotropic action.
g. Phenobarbitone and other enzyme inducers expedite digitoxin metabolism and decrease its t1/2; No effect on digoxin t1/2 as it is not metabolized significantly.
h. Succinylcholine: causes arrhythmias in digitalized patients.