Cardiac Glycosides

Question 1

What are the cardiac glycosides?

Answer 1

Class of drugs derived from the digitalis or foxglove plant (‘digitalization”). These compounds include digoxin, digoxigenin, deacetyl glucoside, and venomous glucosinolate K; used in treating heart failure and certain arrhythmias (AFib and flutter)

Practically, digoxin is the main drug in this class and the only one mentioned on BNF.

Question 2

What is the MOA of digoxin?

Answer 2

Increase cardiac contractility (positive inotrope) and
Decrease heart rate (negative chronotropic)

Inhibits NaK ATPase pump to prevent transport of Na out of cells and K into cells
*potential for hyperkalemia ^^
Also increases vagal activity in the heart to slow conduction through the AV node and decrease HR

Question 3

What is digoxin-specific antibody?

Answer 3

Antibody fragments indicated for the treatment of known or strongly suspected life-threatening digoxin toxicity associated with ventricular arrhytmias or brandy-arrhythmias unresponsive to atropine and when measures beyond the withdrawal of digoxin and correction of any electrolyte abnormalities are considered necessary

Question 4

What are the indications of digoxin? (2)

Answer 4

1. HF
2. Persistent and permanent atrial fibrillation and flutter, particularly in patients with a history of HF or structural heart disease (controls ventricular response)

*no longer used in the treatment of persistent tachycardia

Question 5

What is the half-life of digoxin? (Long or short)

Answer 5

Very long (several weeks), therefore drug interactions may occur long after cessation

Question 6

What is the main factor that should be taken into account when determining digoxin dosage?

Answer 6

Renal function

Question 7

When using digoxin to reduce ventricular response in AFib/AFlutter, what is the target HR?

Answer 7

Resting HR should not be allowed to fall persistently below 60 BPM

Question 8

Can digoxin be administered intramuscularly?

Answer 8

Not recommended; oral route is preferred

Question 9

What are the symptoms of digoxin toxicity? (3)

Answer 9

1. GI: Anorexia, nausea, vomiting,
2. Neurological symptoms: confusion, delirium, anxiety, headache, vision changes
3. Life-threatening arrhythmias (due to hyperkalemia induced by digoxin)

**it can sometimes be difficult to distinguish between toxic effects and clinical deterioration because symptoms of both are similar

Question 10

Is regular monitoring of digoxin plasma concentration recommended during maintenance therapy?

Answer 10

Not unless problems are suspected or if there is reduced kidney function

*The plasma concentration alone cannot indicate toxicity reliably, but the likelihood of toxicity increases progressively through the range 1.5 to 3 micrograms/litre; conversely, toxicity can occur even when digoxin concentration is within the ‘therapeutic range’

Question 11

Which electrolyte imbalance predisposes to digoxin toxicity?

Answer 11

Hypokalemia; may be managed by giving a potassium-sparing diuretic or, if necessary, potassium supplementation

This is because digoxin normally binds to the ATPase pump on the same site as potassium. Therefore, when less potassium is present, digoxin can bind more easily, exerting its inhibitory effects to a greater extent (potential for toxicity)

**Vs digoxin may CAUSE hyperkalemia by inhibiting the pump, leading to arrhythmias

Question 12

What is the management of digoxin toxicity? (4)

Answer 12

1. Withdraw digoxin
2. Give atropine (anti-muscarinic effects, increases HR)
3. Correct electrolyte abnormalities
4. Consider digoxin-specific antibody if other measures unsuccessful for treatment of ventricular arrhythmias or bradyarrhythmias

• Serious cases of digoxin toxicity should be discussed with the National Poisons Information Service

Question 13

In which patients should extra caution be used when prescribing digoxin due to increased risk of toxicity? (10)

Answer 13

1. Elderly patients
2. Hypercalcemia
3. Hypokalemia
4. Hypomagnesemia
5. Hypoxia
6. Recent MI
7. Severe respiratory distress
8. Sick sinus syndrome
9. Thyroid disease
10. Reduced kidney function (eGFR < 30mL/min)

Question 14

What are the main contraindications to using digoxin? (6)

Answer 14

1. Second or third degree heart block
2. Constrictive pericarditis (unless to control atrial fibrillation or improve systolic dysfunction—but use with caution)
3. HOCM (unless concomitant atrial fibrillation and heart failure—but use with caution)
4. Myocarditis
5. Supraventricular arrhythmias associated with accessory conduction pathways eg WPW
6. VTach or VF

Question 15

How should digoxin dose be adjusted if administered with amiodarone, dronedarone, or quinidine?

Answer 15

Reduce dose by half

Question 16

For which drugs should digoxin dose be adjusted when administered concurrently? (3)

Answer 16

1. Amiodarone
2. Dronedarone
3. Quinine

*increased risk of toxicity

Question 17

What are the preferred routes of administration for digoxin?

Answer 17

Oral (HF, rapid or maintenance digitalization for Afib and AFlutter)

IV (initially in emergency loading dose for Afib or AFlutter, followed by oral maintenance dosing)

Question 18

What are the common side effects of digoxin? (6)

Answer 18

1. Arrhythmias
2. Cardiac conduction disorders (bradycardia)
3. GI disturbances (diarrhea, nausea, vomiting)
4. Visual changes (xanthopsia, blurry vision)
5. Rash
6. Dizziness

Question 19

Can digoxin be given in pregnancy?

Answer 19

Yes, but dose adjustment may be required

Question 20

When is monitoring of plasma digoxin concentration recommended? (2)

Answer 20

1. In renal impairment
2. Initially at least 6 hours after first dose (but not throughout maintenance therapy unless problem suspected)

**monitor ECG, serum electrolytes, and renal function to prevent electrolyte disturbances associated with digoxin toxicity

Question 21

Which class of drugs commonly used in treatment of HTN and HF should be used with caution when prescribing digoxin?

Answer 21

Diuretics (and any other drugs that may cause hypokalemia)

Question 22

Is a loading dose required when administering digoxin?

Answer 22

Only when a rapid effect is required (either oral or IV)
A common approach is to give 500 mcg (once only) followed by 250-500 mcg 6 hours later depending on response (total of 0.75 to 1mg in divided doses over 24 hours); thereafter, the usual maintenance dose is 125-250 mcg daily

Question 23

What is the best way to monitor effectiveness of digoxin in patients? (2)

Answer 23

Patients symptoms and HR
(Regular plasma drug concentration is NOT recommended unless renal failure or if toxicity is suspected; electrolytes, ECG, and renal function may also be monitored periodically to prevent toxicity)

Question 24

What is the ‘reverse tick’ sign?

Answer 24

ST-segment depression on ECG caused by therapeutic doses of digoxin; this is NOT a sign of toxicity but is an expected effect