Problem 9: Digoxin Toxicity Flashcards
Explain the possible reasons why the patient felt nauseous. Describe how this could be managed pharmacologically.
Total hip replacement surgery; post operative nausea and vomiting (PONV)
Alternatively could be caused by the high digoxin level. Opioids and digoxin can both contribute to PONV via stimulation of the CTZ.
The choice of prophylactic agent should be based on level of risk, efficacy of agents available, their side effect profiles and the cost of prophylaxis versus the cost of treating vomiting. Patients at moderate risk should be considered for monotherapy, whereas high-risk patients can require several prophylactic agents with different pharmacological actions.
There are four main classes of drugs used in the management of PONV: anticholinergics, antihistamines, D2 antagonists and 5HT3 antagonists.
Anti-emetics can be used short-term for PONV
- anticholinergics (such as hyoscine hydrobrominde or scopolamine)
- antihistamines (promethazine or cyclizine) block H1 and muscarinic receptors in VC)
- dopamine antagonists of D2 receptors in CTZ (benzamides i.e. metoclopramide and domperidone, phenthiazides and butyrophenones)
Metoclopramide; blocks the D2 receptors in the CTZ and has been shown to be relatively ineffective and also crosses the BBB so has been associated with extrapyramidal side effects.
Domperidone ; central dopamine antagonist but does exhibit 5HT3 antagonist effects also. Does not cross the BBB so is preferred for nausea in PD. Less likely to cause effects such as dystonic reactions and sedation.
5HT3 antagonists have proven efficacy and limited side effects; ondansetron, dolasetron etc specifically block 5HT3 peripherally in gut and centrally in the CTZ.
Dexamethasone is the steroid most commonly used for PONV in combination with another agent.
Risks with PONV anti-emetics; like all drugs, antiemetics carry some risk for adverse
effects, which range in severity from mild headache to possibly
more meaningful QTc prolongations that may rarely
be associated with cardiac arrest
Patient safety warnings re ondansetron prolongation of QTc interval and cardiac arrythmias. Domperidone is the same and should be used at smallest effective dose for shortest amount of time. Contraindicated in other medication that can prolong QT interval or CYP3A4 inhibitors.
Explain the rationale for taking the digoxin level
Digoxin has a narrow therapeutic window so level taken to check level is not sub-therapeutic or toxic.
Also checked for digoxin toxicity that could be causing the nausea and vomiting.
Hypokalaemia predisposes a patient to digoxin toxicity (digoxin toxicity depends on the level in the blood but also the sensitivity of myocardium that it is treating).
Describe the signs and symptoms of digoxin toxicity
Digoxin level alone cannot diagnose toxicity but levels from 1.5-3micrograms/litre is a likely range for digoxin toxicity.
Digoxin toxicity causes an imbalance of electrolytes such as hypokalaemia (less potassium ions competing with digoxin and Na+/K+/ATPase channel enhances digoxin effects due to more binding. Hypercalcemia enhances the effect of digoxin induced intracellular calcium. Calcium overload leads to arrhythmia.
Signs: nausea, vomiting, blurred vision or confusion. Arrythmias
Discuss if the dose of digoxin was appropriate for the patient
125 micrograms OD - 250 micrograms OD is a maintenance dose for AF in patients.
Maintenance dose:
is peak body stores x (% daily loss ÷ 100)
Where: peak body stores = loading dose; % daily loss = 14 + creatinine clearance (Ccr)/5.
Does warn to reduce dose in the elderly.
Explain how low potassium increases the risk of digoxin toxicity
Hypokalaemia (less potassium ions competing with digoxin and Na+/K+/ATPase channel enhances digoxin effects due to more binding.
Describe how digoxin toxicity should be managed in this case
Omit next dose, reduce regular maintenance dose
Restore electrolyte balance through oral potassium (IV potassium could be used with close monitoring of blood vessels)
In an emergency then Digifab pr Digoxin antibody fragments should be administered.
Will Anna require Digifab?
No
Provide a rationale for when you would advise digoxin levels to be repeated?
The elimination half-life of digoxin is about 40 hours in patients with normal renal function
