TDM Digoxin

PH3110 Unit 4

What are the two clinical uses of Digoxin?

• atrial flutter/ fibrillation

• heart failure

What class of drug is digoxin?

cardiac glycoside

What are the two main effects of digoxin on the heart?

• slows heart rate

• increases force of contraction

What happens to the heart rhythm in AF?

• irregular and chaotic electrical activity

• SA node loses control

What are the two pharmacological strategies in AF?

• rate control

• rhythm control

How does atrial flutter differ from atrial fibrillation?

flutter - fast but irregular

AF - irregular rhythm

Why is digoxin not first line treatment for rate control? Following this, what patients should it be used in?

Works better at rest than at exercise

Should be used in sedentary patients with AF

Why is digoxin used in AF?

Rate control

Why is digoxin used in heart failure?

Increases cardiac contractility and helps control rate

What is the mechanism of action of digoxin?

Inhibits Na+/K+ ATPase to increase intracellular calcium to cause stronger cardiac contraction (positive inotropy)

How does Digoxin control heart rate in AF?

Increases parasympathomimetic tone to slow AF node conduction

Why is digoxin ineffective in exercise?

Sympathetic activity overrides vagal effects to cause reduced AV node slowing

What part of the heart does digoxin act on to control rate?

AVN

Name a toxicity risk of digoxin

Arrythmias

What are the common symptoms of digoxin toxicity?

• nausea

• vomiting

• visual disturbances

• abdominal pain

• diarrhoea

What electrolyte imbalance increases the risk of digoxin toxicity? Why?

Hypokalaemia - less potassium competes with digoxin so increased binding to Na+/K+ATPase

Hypercalcaemia - more calcium influx so increased digoxin effect

What must be monitored before and during digoxin toxicity?

• renal function

• electrolytes

• heart rate

What is the target blood plasma levels for digoxin in AF?

0.5 - 2mcg/L

How is digoxin eliminated?

75% by the kidneys

What is the two compartment model in terms of digoxin?

The two compartments display the fact that one compartment of organs reach equilibrium quite fast and the other compartment (peripheral) will reach equilibrium at a lower rate. In the example of digoxin, it reaches the myocardium at a slower rate than other organs. This means that prior to equilibrium, the drug levels in the heart do not reflect drug levels in the plasma.

Why does 50% equilibration not equal 50% of the concentration that moves into the peripheral compartment?

Because some drug is eliminated before equilibrium is reached

How does hypo/hyperthyroidism effect plasma digoxin concentrations? WHY?

• lower in hyperthyroidism

• higher in hypothyroidism

Due to

Altered response of the heart due to thyroid hormone levels

Altered eGFR rates affecting clearance

Altered volume of distribution

What types of drugs can interact with Digoxin?

Inhibitors of Pgp

When should digoxin levels be taken for:

1. IV dose?

2. PO dose?

1. 4-6 hours after

2. 6-8 hours after (most optimal is 12-24 hours post dose)