Digoxin pharmacodynamics

Mahgoub AA, El-Medany AH, Abdnlatif AS. A comparison between the effects of diltiazem and isosorbide dinitrate on digoxin pharmacodynamics and kinetics in the treatment of patients with chronic ischemic heart failure. Saudi Med J 2002 23(6) 725-31. 

In general there appears to be no pharmacokinetic interaction between digoxin and beta biockers, although talinolol and carvedilol appear to increase the bioavailability of digoxin. Pharmacodynamic interactions, resulting in additive bradycardia, are possible. A few cases of excessive bradycardia have been reported when propranolol was used to control digitalis-induced arrh i h-mias. 

Age-related variations in central nervous system (CNS) neurotransmitter production and receptor sensitivity are the most likely explanations for the pharmacodynamic differences observed between children and adults following administration of psychotropic medications [39a], Children have lower phenobarbital ratios than adults, and the ratio increases with gestational age [40,41]. Conversely, a lower therapeutic range for children has been identified for cyclosporine, phenytoin, and digoxin [42]. 

Increased age is most likely associated with enhanced susceptibility to digoxin toxicity, possibly due to unknown pharmacodynamic changes, even when plasma concentrations are within therapeutic range (Miura et al. 2000). 

Homestam, B., Jerling, M., Karlsson, M.O., and Held, P. DAAf Trial Group, Intravenously administered digoxin in patients with acute atrial fibrillation a population pharmacokinetic/pharmacodynamic analysis based on the digitalis in acute atrial fibrillation trial, Eur.. Clin. Pharmacol., 58, 747-755, 2003. 

Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharmacodynamic profile of digoxin. 

Sarich TC, Schutzer KM, Wollbratt M, et al. No pharmacokinetic or pharmacodynamic interaction between digoxin and the oral direct thrombin inhibitor ximelagatran in healthy volunteers. J Clin Pharmacol 2004 44 935-941. 

The interaction of zaleplon with digoxin has been investigated in 20 subjects (22). There were one or more adverse effects in 18% of those who took digoxin alone and 35% of those who took digoxin plus zaleplon, but these were all mild and resolved quickly. Zaleplon had no significant effects on selected pharmacokinetic and pharmacodynamic properties of digoxin. 

Sanchez Garcia P, Paty I, Leister CA, Guerra P, Frias J, Garcia Perez LE, Darwish M. Effect of zaleplon on digoxin pharmacokinetics and pharmacodynamics. Am J Health Syst Pharm 2000 57(24) 2267-70. 

DIGOXIN TACROLIMUS Digoxin toxicity (pharmacodynamic) Possibly due to tacrolimus-induced hyperkalaemia and hypomagnesaemia Watch for digoxin toxicity. Monitor potassium and magnesium levels... 

Weiss M, Kang W. Inotropic effect of digoxin in humans Mechanistic pharmacokinetic/pharmacodynamic model based on slow receptor binding. Pharm Res 2004 21 231-6. 

De Vito JM, Friedman B. Evaluation of the pharmacodynamic and pharmacokinetic interaction between calcium antagonists and digoxin. Pharmacotherapy 1986 6(2) 73-82. 

Schwartz JB, Keefe D, Kates RE, Kirsten E, Harrison DC. Acute and chronic pharmacodynamic interaction of verapamil and digoxin in atrial fibrillation. Circulation 1982 65(6) 1163-70. 

Belz GG, Wistuba S, Matthews JH. Digoxin and bepridil pharmacokinetic and pharmacodynamic interactions. Clin Pharmacol Ther 1986 39(1) 65-71. 

In 14 healthy men dofetilide 250 pg bd for 5 days had no effect on the pharmacokinetics of digoxin at a steady-state trough concentration of 1.0 ng/ml (258). However, in a placebo-controUed study in patients with atrial fibrillation or atrial flutter, conversion to sinus rhythm in patients given dofetilide was more likely if they were also given digoxin (259), so there may be a pharmacodynamic interaction. 

Fondaparinux sodium, a selective inhibitor of coagulation factor Xa, is eUminated by the kidneys. In a randomized, crossover study in 24 healthy volunteers the pharmacokinetics and pharmacodynamics of digoxin 0.25 mg/day orally for 7 days were unaffected by fondaparinux sodium 10 mg/day subcutaneously for 7 days (260). 

Peters J, Welker HA, Bullingham R. Pharmacokinetic and pharmacodynamic aspects of concomitant mibefradh-digoxin therapy at therapeutic doses. Eur J Drug Metab Pharmacokinet 1999 24(2) 133-40. 

Zussman BD, Kelly J, Murdoch RD, Clark DJ, Schubert C, Collie H. Cilomilast pharmacokinetic and pharmacodynamic interactions with digoxin. Clin Ther 2001 23(6) 921-31. 

Peelers PA, Crijns HJ, Tamminga WJ, Jonkman JH, Dickinson JP, Necciari J. Clopidogrel, a novel antiplatelet agent, and digoxin absence of pharmacodynamic and pharmacokinetic interaction. Semin Thromb Hemost 1999 25(Suppl 2) 51. ... 

Levy RH, Ragueneau-Majlessi I, Baltes E. Repeated administration of the novel antiepileptic agent levetirace-tam does not alter digoxin pharmacokinetics and pharmacodynamics in healthy volunteers. Epilepsy Res 2001 46(2) 93-9. 

Ragueneau I, Poirier JM, Radembino N, Sao AB, Funck-Brentano C, Jaillon P. Pharmacokinetic and pharmacodynamic drug interactions between digoxin and macrogol 4000, a laxative polymer, in healthy volunteers. Br J Clin Pharmacol 1999 48(3) 453-6. 

Zhou H, Horowitz A, Ledford PC, Hubert M, Appel-Dingemanse S, Osborne S, McLeod JF. The effects of tegaserod (HTF 919) on the pharmacokinetics and pharmacodynamics of digoxin in healthy subjects. J Clin Pharmacol 2001 41(10) 113. 

Spironolactone increases steady-state digoxin concentrations by about 30%, probably by inhibiting the renal tubular secretion of digoxin by P glycoprotein. There may also be a pharmacodynamic interaction with digoxin. The clinical importance of these observations is uncertain (SEDA-9, 209). 

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