Pharmacokinetics and Pharmacodynamics Review of Digoxin

Abstract 2. Overview of Digoxin 3. Physicochemical properties of digoxin 4. Pharmacodynamics of digoxin: 4. Mechanism of action 4. Pharmacogenetics 7. Dosing strategies 8. Conclusion 9. References Key words Digoxin, pharmacokinetics, pharmacodynamics, congestive heart failure, antiarrhythmic, physicochemical properties, oral antiarrhythmic. Abstract Digoxin is scarcely used in the management of chronic heart failure (CHF) and also as an oral antiarrhythmic drug. S. in for having been used by a nurse to kill several patients. Due to its very narrow therapeutic index Digoxin tablets by the name Curaco got recalled from the market following its variability in size. Digoxin is used in the management of heart conditions including arrhythmias such as atrial flutter, atrial fibrillations and congestive heart failure (Turakhia et al. There are two dosage forms of digoxin: parenteral where the injection is by the venous system.

Mechanism of action. The mechanism of action of digoxin is so explicit and involves the interference of ion flow in the muscle. The two important ions involved are Na+ and Ca2+. The inotropic effects of digoxin are due to its ability to inhibit the Na+, K+ ATPase that is predominant in the cardiac muscles. The Na+, K+ ATPase pump is vital in the muscle cells are in causes out flux of potassium following depolarization to initiate the repolarization phase hence the relaxation of the myocardium. Digoxin is widely employed in the management of heart conditions. In heart failure, digoxin has positive inotropic effects hence increasing the volume of ejection from the heart at systole. Digoxin however causes a decrease in pulmonary congestion as well as the preload to the heart.

As an antiarrhythmic drug, digoxin has Para sympathomimetic effect that results to a decrease in the conduction of impulses across the atrioventricular node. There is also a decrease in the ventricular rate in atrial flutter as well as in atrial fibrillation. mg/ml. the therapeutic level of digoxin is 0. ng/ml. toxicity results plasma levels above 2. ng/ml (Murphy, 2012). Absorption occurs mainly in the proximal part of the small intestine (Murphy. Distribution. Digoxin distributes extensively to the cardiac tissues with a distribution half-life of about 36 hours. It has a very large volume of distribution attributed to its wide distribution into tissues with a high affinity for the skeletal and cardiac muscles. it has a serum binding capacity of 20 to 30 % it possess a two- compartment pharmacokinetic model of distribution.

Digoxin has complex kinetics in that it follows two body compartmentalization. In the first phase digoxin undergoes zero order kinetics where its elimination is independent of the serum concentration. At low serum concentration, digoxin appears to follow first order kinetics where the rate of elimination is depended on serum concentration. It is critical as in involves the P-glycoprotein. This forms the basis for the uncalled drug-drug interactions that are exhibited when digoxin is co-administered with other drugs. There is need for dose reduction in geriatrics to avoid toxicity. With age it’s also critical to consider the heart contractility is also decreased and there could be further myocardial hypertrophy. Monitor dosage to avoid overstimulation of weak heart (Murphy. Renal failure: dose reduction for digoxin is mandatory with renal failure since the kidneys serve to excrete the drug in its unchanged form (Murphy.

Drug interactions Digoxin is substrate for renal tubular secretion by the P-glycoprotein (Pgp). Further studies on the genetic involvement with regards to digoxin need to be carried out. The overall individual variability in the biotransformation of digoxin is influenced by two factors: the intragastric pH which influences cleavage of the sugar moiety and variation in the levels of hepatic UDP- glucoronyl transferase that is specific to the conjugation of digitalis compounds (Murphy, 2012). Dosing strategies of digoxin 7. Dose prediction method. Digoxin has a very narrow therapeutic index thus the loading dose and the maintenance dose must be adequately calculated (Kosoglou et al. tablets = 0. Dosage prediction by digoxin renal clearance estimation. It is very vital to determine the creatinine clearance Creatinine clearance is estimated using the Koda-Kimb (Frost et al.

Cl = ((A * CrCl) + B) * C Where A= 0. for patients with acute renal failure, otherwise = 1 B = 23 for patients with acute renal failure, otherwise = 40 C = correction factor for interacting drug (quinidine = 0. P. Santangeli, P. Winkelmayer, W. C. Xu, X. Hartmann, B. Czock, D. Review on pharmacokinetics and pharmacodynamics and the aging kidney. Clinical Journal of the American Society of Nephrology, 5(2), 314-327. Macheras, P. Lip, G. Y. Kotecha, D. Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data. bmj, 351, h4451. Lee, L. S. Schuster, A. Lacerta, F. The effect of Apixiban on the pharmacokinetics of digoxin and atenolol in healthy subjects. International journal of cardiology, 224, 191-198. Kosoglou, T. Zhu, Y. Statkevich, P. Xuan, F.