2.1 Positive inotropic drugs
Digoxin (62.5micrograms, 125micrograms and 250 micrograms tablets; 50 micrograms/mL elixir; 250micrograms/mL injection) increases the contractility of the myocardium by direct activity. The primary action is to inhibit ATP, and thus sodium-potassium exchange activity. This results in an increase in the availability of calcium at the time of excitation-contraction coupling. The potency may therefore become considerably enhanced when the extracellular potassium concentration is low.
It is used mainly in patients with rapid atrial fibrillation, but is not useful in the treatment of paroxysmal atrial fibrillation. It is also of some value in the treatment of patients with symptomatic heart failure. Digoxin should not be used in the treatment of patients with pre-excitation syndromes (e.g. Wolff-Parkinson-White) unless specifically prescribed by a specialist. Hypokalaemia predisposes to dangerous arrhythmias and care should be taken to monitor the electrolytes and to prescribe appropriate potassium-sparing diuretics or potassium supplementation if necessary, or consider foods rich in potassium.
Note: doses of the tablet, liquid and IV formulations are not bioequivalent.
Digoxin has a narrow therapeutic window, and is predominantly renally excreted as unchanged drug. Requirements for individual patients will vary, where some will only require a small dose to be therapeutically effective (or potentially to cause toxic effects), another may require a large dose.
Measurements of plasma digoxin concentration are not routinely indicated although can be useful to check on compliance and to confirm toxic levels. In patients with heart failure, titration to the upper therapeutic level optimises the beneficial effects.
Digoxin is a good agent to control the heart rate at rest, but as some of the effects is to enhance vagal tone, it is not so good at controlling the heart rate during exercise when vagal tone is removed.
Digoxin can be used cautiously but safely in combination with other rate limiting drugs including beta blockers, rate limiting calcium channel blockers and amiodarone (but note interactions which can increase digoxin plasma concentration). The combination of more than two rate limiting agents should only be used on specialist advice.
Intravenous digoxin is potentially hazardous and should be reserved for patients with a clear need for urgent digitalisation. The maintenance dose of digoxin should be reduced in the elderly, patients with renal failure, and patients taking potentiating therapy, e.g. amiodarone.
There is a protocol for the administration of IV digoxin available from the Coronary Care Unit, ARI if this is required.
Milrinone (IV injection) is a selective phosphodiesterase inhibitor which is used in emergency situations, usually in ITU or during cardiac surgery, when other inotropes fail.
DigiFab® 40mg/vial digoxin immune Fab, powder for solution for infusion (digoxin immune Fab [ovine]) is used for the treatment of known (or strongly suspected) life-threatening digoxin toxicity associated with ventricular arrhythmias or bradyarrhthmias unresponsive to atropine where measures beyond withdrawal of digoxin and correction of serum electrolyte abnormalities are considered necessary.