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DIGITALIS GLYCOSIDES: ADVERSE EFFECTS AND TOXICITY Contraindications and Warnings: * Arrhythmias: digitalis should not be used in patients with ventricular tachycardia or runs of complex ventricular premature depolarizations unless there is strong reason to believe that the arrhythmia results from a digitalis-correctable decrease in cardiac function. * Potassium depletion: digitalis arrhythmias are much more common in patients with low serum potassium (less than 3mEq). * Cardioversion: cardioversion tends to exacerbate arrhythmias caused by digitalis. Antiarrhythmic drugs may be preferred to cardioversion if the digitalized patient is stable. However, the presence of nontoxic levels of digitalis is not a contraindication to the use of cardiover- sion. * High output failure (warning): congestive heart failure caused by thyrotoxicosis, beri-beri, arteriovenous shunts, and a few other con- ditions are associated with a higher than normal cardiac output and respond poorly to digitalis glycosides. (PgDn key for more text) Adverse Reactions and Overdosage Toxicity: Digitalis toxicity is an important cause of morbidity and mortality. Some of the more common signs include: * GI: Anorexia, nausea, vomiting, diarrhea are common. * CV: Any arrhythmia is possible, including premature depolarizations, atrial fibrillation, AV nodal tachycardia, bigeminy, ventricular tachycardia, and ventricular fibrillation. Ventricular fibrillation or arrest are the most common causes of death due to digitalis over- dosage. * CNS: Confusion, visual disturbances, hallucinations, and occasionally convulsions. * Endocrine-Metabolic: Gynecomastia and galactorrhea. * Electrolyte: In acute massive overdose, hyperkalemia may be severe and contribute to cardiac arrhythmias and arrest. (PgDn key for more text) * Treatment: digitalis toxicity is relatively common and the cardiac arrhythmias require prompt correction. The following steps are ap- propriate if a digitalis-induced arrhythmia is present: Mild to moderate intoxication: - Stop digitalis therapy. - Correct serum potassium levels if below 3.5 mEq/L. - Administer atropine for severe PR prolongation on the ECG; place a transvenous pacing catheter in the right ventricle if AV block is al- ready present and worsening. - Give lidocaine 1mg/Kg over 5 min, then infuse at 15-50 mcg/Kg/min to maintain normal rhythm. OR: - Give phenytoin, 100mg IV slowly every 5 minutes until control of the arrhythmia or until phenytoin toxicity appears (nystagmus, vertigo, ataxia, nausea). Most digitalis-induced ventricular arrhythmias respond to 200-400mg total dose of phenytoin. - If the above steps are unsuccessful, administer digoxin FAB fragment antibodies. (PgDn key for more text) Severe intoxication, eg suicidal overdose: - For detoxification, gastric lavage with activated charcoal or steroid-binding resins (eg, cholestyramine) may be effective. Conven- tional hemodialysis is not effective. - Give atropine and place a pacing catheter in the right ventricle. - Monitor serum electrolytes and be prepared to reduce serum potassium if necessary. (Severe digitalis intoxication is associated with marked loss of intracellular K+ from all tissues and a potentially catastrophic rise of serum potassium.) - Do not administer antiarrhythmic drugs unless increased excitability is clearly dominant in the pattern of toxicity. Severe intoxication is more often associated with depressed conduction and pacemaker activity (in contrast to moderate overdosage). - Administer FAB fragment digoxin antibodies as soon as it appears that the above measures will be inadequate, or if the serum K+ is increas- ing and rises above 7 mEq/L, or if heart rate falls below the minimum necessary for adequate cardiac output and cannot be maintained by pacing. These antibodies are very effective in digoxin poisoning and moderately effective in digitoxin intoxication as well. (PgDn key for more text) Interactions * Positive inotropic and chronotropic agents: digitalis is additive with cardiac stimulants such as sympathomimetics, methylxanthines, and bipyridines. Additivity includes both therapeutic and toxic effects. * Serum electrolytes: calcium facilitates and potassium inhibits the arrhythmogenic action of digitalis. A patient with hypercalcemia and/or hypokalemia is at high risk for a digitalis arrhythmia. * Thyroid and antithyroid drugs: changes in thyroid activity change digitalis requirement: hypothyroid patients are more sensitive, while hyperthyroid patients show less response to glycosides. * Pharmacokinetic: Digitoxin half-life is decreased by inducers of hepatic drug metabolizing enzymes. Digoxin clearance and volume of distribution are decreased by quinidine and, to a lesser extent, by verapamil and amiodarone.


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