TDM Digoxin Flashcards
What is the drug class of Digoxin?
Digoxin is a cardiac glycoside which increases the force of myocardial contraction and reduces conductivity within the atrioventricular (AV) node. It is used in the treatment of mild to moderate heart failure and as a rate limiting drug for patients with atrial fibrillation.
Describe the mechanism of action of Digoxin in greater depth.
Digoxin inhibits the Na+/K+ ATPase in cardiac muscle. This pump is responsible for maintaining the negative membrane potential by pumping 3 sodium ions out, for every 2 potassium ions pumped inwards. When inhibited this therefore results in the accumulation of Na+ intracellularly causing depolarisation and leading to an increased calcium concentration within the myocardial cells due to the Na+/Ca2+ exchange system. Increased binding of calcium to troponin-C results in a positive ionotropic effect where the contractility of the heart is increased.
Digoxin also stimulates the parasympathetic nervous system, slowing down the electrical conduction in the AV node thereby reducing heart rate.
Why is TDM used in Digoxin therapy?
Digoxin levels may need to be taken in the following situations as part of therapeutic drug monitoring:
To check compliance - if there is doubt surrounding adherence or clinical outcomes are not what is expected
Multiple drug therapy - if Digoxin is being taken concomitantly with another drug known to interact with it, levels should be monitored closely
Toxicity - if the patient is complaining of symptoms such as nausea, vomiting, blurred vision
Altered disease states - may affect Digoxin levels e.g. in AKI as the drug is renally excreted, reduced renal function may cause levels to rise
Poor response - dose adjustments may needed to be guided by levels if patient is not responding adequately to treatment, or to investigate what is going on
What are the indications of Digoxin?
Atrial fibrillation or flutter (either as a loading dose, rapid digitalisation or as maintained therapy)
- First line drug therapy rate control in those with sedentary lifestyle
Heart failure for those with a sinus rhythm
- Add on therapy
What are the contraindications to Digoxin?
Constrictive pericarditis
Hypertrophic cardiomyopathy
Intermittent complete heart block Myocarditis
Second degree AV block
Supraventricular arrhythmias associated with accessory conducting pathways e.g. Wolff-Parkinson-White syndrome
Ventricular tachycardia or fibrillation
What are the cautions for use of Digoxin?
Recent myocardial infarction - haemodynamically unstable
Severe respiratory disease
Sick sinus syndrome
Thyroid disease - monitor closely, those with hyperthyroidism may be resistant to therapy
What conditions can precipitate Digoxin toxicity?
Hypercalcaemia
Hypokalaemia
Hypomagnesaemia
Hypoxia
Outline some of the key drug interactions with Digoxin.
Digoxin interacts with:
- Beta-adrenoceptor blocking drugs (may increase atrio-ventricular conduction time)
- Drugs causing hypokalaemia may cause increased sensitivity to digoxin
- Calcium, by rapidly I.V., may produce serious arrhythmias in digitalised patients
- Sympathomimetic drugs have direct positive chronotropic effects that can promote cardiac arrhythmias and may also lead to hypokalaemia, which can lead to or worsen cardiac arrhythmias
- P glycoprotein inhibitors, increase Digoxin absorption therefore affecting levels
- Amiodarone increases exposure to Digoxin, a standard reduction of 50% in the maintenance dose of digoxin when initiating amiodarone is appropriate
With which other drugs should Digoxin dose be reduced by 50%?
Dronedarone and quinine
Should Digoxin dose be reduced if a cardiac glycoside has been used recently
?
Yes, the Digoxin dose may need to be reduced if digoxin (or another cardiac glycoside) has been given in the preceding 2 weeks
What is an important consideration when switching Digoxin formulations?
Formulations of Digoxin are not bioequivalent. Tablets have a bioavailability of 0.63; Liquids 0.8; IV 1
Therefore, when switching from intravenous to oral route may need to increase dose by 20–33% to maintain the same plasma-digoxin concentration.
What is bioavailability?
The fraction of the drug that reaches systemic circulation. It relates to the extent rather than rate of absorption
What is the therapeutic range of Digoxin?
0.8-2.0 mcg/L
Patients with CCF lower end of the range is the target whilst those with atrial fibrillation the upper end of the range is the target
When should sampling take place for Digoxin therapy?
For IV therapy: 6-8 hours post-dose (peak level)
For oral therapy: Pre dose (trough level) and at least 8 hours post dose (peak level)
Post dose level times account for drug distribution time which even IV can take 2-4 hours
Describe the distribution of Digoxin.
Digoxin follows a two compartment distribution model meaning that the drug distributes centrally and peripherally but takes time to reach equilibrium which is accounted for in its sampling time of 6-8 hours post-dose. The drug binds mostly to skeletal muscle and myocardial tissue (little binds to adipose tissue).
