digoxin

introduction:

digoxin is a cardiac glycoside used in the treatment of most types of cardiac failure and supraventricular dysrhythmias.

aim for max 0.75-1.5mg ((10 to 12 mcg/kg lean body weight) total load dose in 1st 24hrs
load dose should be reduced to total 0.75mg if patient has a condition which makes them sensitive to digoxin such as:
load dose should also be halved in those with chronic renal impairment and digoxin Rx is generally avoided in those with ESRF or on dialysis
load dose should also be halved in those who weigh < 45kg
IV 0.25-0.5mg over several minutes every 6hrs, or,
oral 0.25-0.5mg every 6hrs

oral 0.125-0.25mg daily until steady state in 7-10 days then adjust to maintenance dosing
use lower doses in renal impairment or low body weight

65 - 75% of oral digoxin is absorbed;
Absorption may be reduced by neomycin, some resins, antidiarrhoeal agents containing pectin and kaolin, and non-absorbable antacids.
Absorption is close to complete within two hours.
25% is protein bound in blood stream.
High volume of distribution, i.e. only 1% of body stores is found in plasma:
- 3.5-6.0L/kg in premature infants
- 8.0-16.3L/kg in infants 2-24 months
- 5-7.5L/kg in adults
Concentration in cardiac muscle is 30 x plasma concentration.
Is not significantly metabolised.
85% excreted in urine.
T 1/2 = 30 hours if normal renal function.
T 1/2 may be decreased (e.g. 13 hours) in overdose.
Drugs such as quinidine can double the serum digoxin levels.

(i) elevation of intracellular Na concentration which competes with calcium for efflux at internal membranes, thus, less calcium is transported out of the cell and more is available to activate contractile sites, thereby increasing contractility;
(ii) in high concentrations, reduces the resting potential and augments rate of diastolic depolarisation, and thus, increases rhythmicity and ectopic impulse activity;
(iii) the lowering of resting potential is associated with a reduced rate of rise of the action potential causing slower conduction velocity, and thus is conducive to causing re-entry;
(iv) in extreme digoxin toxicity, the increased efflux of K from cells is sufficient to cause significant hyperkalaemia;
see also sodium and the Na/K ATPase

prolongation of the functional refractory period of AV node, atrial and ventricular muscle;
slowing of sinus rate;

peripheral venous and arterial vasoconstriction;
reflex peripheral vasodilatation in CCF due to withdrawal of sympathetic constrictor action;