CV - Digoxin

Question 1

Digoxin?

Clinical pharmacology

Common indications

Answer 1

• In atrial fibrillation (AF) and atrial flutter,digoxin is used to reduce the ventricular rate. However, a β-blocker or non-dihydropyridine calcium channel blocker is usually more effective
• In severe heart failure, digoxin is used as a third-line treatment in patients who are already taking an ACE inhibitor, β-blocker and either an aldosterone antagonist or angiotensin receptor blocker. It is used at an earlier stage in patients with co-existing AF.

Question 2

Mechanisms of action?

Answer 2

• Digoxin is negatively chronotropic (it reduces the heart rate) and positively inotropic (it increases the force of contraction).
• In atrial fibrillation and flutter its therapeutic effect arises mainly via an indirect pathway involving increased vagal (parasympathetic) tone.
• This reduces conduction at the atrioventricular (AV) node, preventing some impulses from being transmitted to the ventricles, thereby reducing the ventricular rate.
• In heart failure, it has a direct effect on myocytes through inhibition of Na+/K+-ATPase pumps, causing Na+ to accumulate in the cell.
• As cellular extrusion of Ca2+ requires low intracellular Na+ concentrations, elevation of intracellular Na+causes Ca2+ to accumulate in the cell, increasing contractile force.

Question 3

Important adverse effects?

Answer 3

• Adverse effects of digoxin include bradycardia, gastrointestinal disturbance, rash, dizziness and visual disturbance (blurred or yellow vision).
• Digoxin is proarrhythmic and has a low therapeutic index: that is, the safety margin between the therapeutic and toxic doses is narrow.
• A wide range of arrhythmias can occur in digoxin toxicity and these may be life threatening.

Question 4

Warnings?

Answer 4

• Digoxin may worsen conduction abnormalities, so is contraindicated in second-degree heart block and intermittent complete heart block.
• It should not be used in patients with or at risk of ventricular arrhythmias.
• The dose should be reduced in renal failure, as digoxin is eliminated by the kidneys.
• Certain electrolyte abnormalities increase the risk of digoxin toxicity, including hypokalaemia,
• hypomagnesaemia and hypercalcaemia.
• Potassium disturbance is probably the most important of these, as digoxin competes with potassium to bind the Na+/K+-ATPase pump.
• When serum potassium levels are low, competition is reduced and the effects of digoxin are enhanced.

Question 5

Important interactions?

Answer 5

• Loop and thiazide diuretics can increase the risk of digoxin toxicity by causing hypokalaemia.
• Amiodorone, calcium channelblockers,
• spironolactone and quinine can all increase the plasma concentration of digoxin and therefore risk of toxicity.

Question 6

Practical prescribing

Prescription

Answer 6

• Digoxin is available as an oral or intravenous preparation.
• The effect of IV digoxin is seen at about 30 minutes, compared to about 2 hours following an oral dose. Intravenous administration is therefore usually unnecessary.
• Due to its large volume of distribution, a loading dose is required if a rapid effect is needed.
• A common approach is to give 500 micrograms of digoxin, followed by 250–500 micrograms 6 hours later, depending on response. Thereafter, the usual maintenance dose is 125–250 micrograms daily.
• For hospital inpatients, the loading doses are prescribed in the once-only section of the drug chart, while the maintenance dose is prescribed in the regular section (starting on day 2).
• Be sure to write ‘micrograms’ in full.

Question 7

Monitoring?

Answer 7

• The best guide to the effectiveness of digoxin is the patient’s symptoms and heart rate.
• Check their ECG, electrolytes and renal function periodically, and particularly when these may change (e.g. during acute illnesses or after a change in medication).
• You should note that therapeutic doses of digoxin can cause ST-segment depression (the ‘reverse tick’ sign) on the ECG.
• This is an expected effect and does not signify toxicity. In acute therapy, continuous cardiac monitoring is advisable.
• You do not need to monitor digoxin levels routinely, but it may be helpful to measure these if you suspect toxicity.
• High plasma concentrations of digoxin do not always indicate toxicity, but the likelihood of toxicity increases as digoxin plasma concentrations increase.
• Conversely, toxicity can occur even when digoxin concentration is within the ‘therapeutic range’.