DIGITALIS GLYCOSIDES: PROPERTIES Pharmacokinetics and drug selection Absorption: Nearly 10

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DIGITALIS GLYCOSIDES: PROPERTIES Pharmacokinetics and drug selection * Absorption: Nearly 100% of an oral dose of digitoxin and 70-90% of a dose of digoxin will be absorbed. * Elimination: Digitoxin is metabolized in the liver and eventually ex- creted by the kidneys; digoxin is metabolized to a lesser extent and eliminated primarily by the kidneys. Patients with severe heart fail- ure have a prolongation of digoxin half-life. * Accumulation: Because of their long half-lives (see Table 4-1), the cardiac glycosides accumulate in the body when given daily. Thus cau- tion is indicated when increasing dosage since the new steady state will not be achieved for 4-6 days (digoxin) or 3-5 weeks (digitoxin). * Selection of a glycoside: Digoxin is the most suitable drug in 90-95% of patients. It has a reasonably rapid onset of action and a shorter half-life than digitoxin. Digitoxin is sometimes useful in patients with rapidly changing renal function because its half-life is rela- tively insensitive to such changes. It is doubtful that other drugs in this group need ever be used except in rare instances of hyper- sensitivity to the above 2 agents. (PgDn key for references) References: 1. Arnold SB, et al: Long-term digitalis therapy improves left ventricular function in heart failure. NEJM 1980; 303:1443. 2. Cohn JN (editor): New concepts in the mechanisms and treatment of congestive heart failure (Symposium). Am J Cardiol 1985; 55: 1A. 3. Cohn JN, et al: Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative study. NEJM 1986; 314: 1547. 4. Digitalis. (Symposium) J Am Coll Cardiol 1985; 5: 1A. 5. Doherty JE: Clinical use of digitalis glycosides. An update. Cardiol- ogy 1985; 72:225. 6. Franciosa JA, Dunkman WB, Leddy CL: Hemodynamic effects of vasodilators and long-term response in heart failure. J Am Coll Car- diol 1984; 3: 1521. 7. Jaski BE, et al: Positive inotropic and vasodilator actions of mil- rinone in patients with severe congestive heart failure. Dose response relationships and comparison to nitroprusside. J Clin Invest 1085; 75: 643. (PgDn key for more references) 8. Maekawa K, Liang C-S, Hood WB: Comparison of dobutamine and dopamine in acute myocardial infarction. Effects of systemic hemodynamics, plasma catecholamines, blood flows and infarct size. Circulation 1983; 67:750. 9. Smith TW, et al: Digitalis glycosides: Mechanisms and manifestations of toxicity. (in 3 parts) Prog Cardiovasc Dis 1984; 26:413,495; 27:21. (Home key to return to top of file)

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