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DIGOXIN
Digoxin is a cardiac
glycoside extracted from foxgloves. It is used in the treatment of
atrial fibrillation with a fast ventricular rate. It is also used in
congestive cardiac failure with sinus rhythm, although for this its use
is controversial.
The plasma digoxin concentration that will result from a given dose of the drug can
be predicted at best with only 34% accuracy, although knowledge of a previous concentration
improves the ability to predict subsequent concentrations. In outpatients taking a fixed daily dosage,
steady state plasma digoxin concentrations vary widely (between 0.5 and 3.5 nmol/l).
This means that if a target plasma digoxin concentration is desirable, measuring the concentration
may be useful in tailoring dosages to individual requirements.
In this chapter we apply to digoxin the criteria (described in the previous chapter on
measuring plasma drug concentrations) which must be fulfilled in part or in full before the
measurement of its plasma concentration can be considered worth while.
Criteria for measurement
Is there difficulty in interpreting clinical evidence of the therapeutic or toxic effects?
In patients with atrial fibrillation the slowing of the ventricular rate is usually
a good guide to the therapeutic effect of digoxin. However, in patients with congestive cardiac
failure with sinus rhythm who are taking digoxin for its positive inotropic effect there is no
easily measurable end point by which to assess the therapeutic response. Furthermore,
digoxin toxicity can be difficult to diagnose because anorexia, nausea and vomiting, mental confusion,
and cardiac arrhythmias may all be signs or symptoms of both congestive cardiac failure and digitalis toxicity.
Thus measuring the plasma digoxin concentration will allow the dosage to be increased within safe limits in order to ensure,
firstly, that an adequate response to treatment is not missed because the dose is suboptimal and,
secondly, that toxicity does not occur because of too large a dose. Of course this assumes that there
is a good relation between the plasma concentration of digoxin and its therapeutic or toxic effects.
Is there a good relation between the plasma concentration and its therapeutic or toxic effects?
In the case of atrial fibrillation there is good evidence that increasing the concentration
of digoxin within the therapeutic range produces an increase in its effect of slowing the ventricular rate.
In patients with heart failure in sinus rhythm a relation between the plasma concentration
of digoxin and its therapeutic effect has not been clearly established. Generally a
satisfactory therapeutic response is most likely to be achieved when plasma digoxin concentrations
are between 1.0 nmol/l and 3.8 nmol/l. These limits are based, at least in part, on observations outside
this range: the risk of digoxin toxicity increases at concentrations above 2.6 nmol/l and is almost
invariable at concentrations greater than 3.8 nmol/l, and it is difficult to detect any effect of
digoxin when the plasma concentration is below 1.0 nmol/l. Within the range 1.0 to 3.8 nmol/l there is some evidence of dose responsiveness.
Although concentration correlates well with some measurable actions of digoxin on the heart,
such as changes in systolic time intervals and changes in the electrocardiographic
configuration (shortened PR interval, prolonged QTc interval, T wave depression and inversion),
these changes are difficult to interpret in terms of the therapeutic outcome.
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