Editor, – During December 1999, I witnessed a case that motivated me to read the article 'Digoxin in the 21st century' (Aust Prescr 1999;22:136-7) with accentuated attention. The case was a 56-year-old woman who had suffered from schizophrenia six years ago and had since remained mentally balanced. She has been hypertensive for the past two years and was placed on medications. She had minor congestive heart failure last October (attributed to non-compliance with antihypertensive medications) and was admitted to a rural hospital. After rapid digitalisation she was placed on digoxin (0.125 mg/day) and hydralazine, but when the doctor started noting some neurological imbalance, chlorpromazine was added. On discharge, chlorpromazine and hydralazine were discontinued while digoxin was maintained. Sinepress (dihydroergotoxine 0.6 mg, reserpine 0.1 mg, hydrochlorothiazide 10 mg) was added. However, around the middle of December, she reverted back to a schizophrenic state, for which she is still being treated.
Does Dr Semsarian think that this bout of schizophrenia may have been precipitated by the adverse effects of digoxin ('digitalis delirium', confusion and hallucination) or to digoxin's common drug interactions, say, with the components of the combination antihypertensive drug?
Hypokalaemia induced by potassium-depleting diuretics is known to be the cause of adverse drug interactions between digoxin and such diuretics. The first self-test question (p. 137) may mislead readers to assume that all diuretics can provoke digoxin toxicity. After all, potassium-sparing diuretics such as amiloride may even be beneficial in digoxin therapy.
S. V. Nwafor
Department of Pharmacology and Toxicology
Faculty of Pharmaceutical Sciences
University of Nigeria, Nigeria
Dr C. Semsarian, the author of 'Digoxin in the 21st century', comments:
The issue of determining whether or not a patient's clinical status is due to a drug effect is an important one. Unfortunately, this is often difficult to resolve in the setting of a patient with multiple diseases, taking several medications. The case presented by Dr Nwafor is interesting and could possibly be due to digoxin toxicity. 'Digoxin delirium' is seen rarely now because of more diligent efforts in prescribing correct doses of digoxin for individual patients based on factors such as age, gender and renal function. Furthermore, regular measurements of serum digoxin levels have become routine. The patient mentioned in Dr Nwafor's letter is taking a product containing two drugs, reserpine and hydrochlorothiazide, both of which can increase digoxin toxicity by lowering serum concentrations of potassium.
We have no information on the patient's renal function, therefore the patient should have had an assessment of renal function, and their serum potassium and digoxin concentration measured. If all of these are normal, then it is less likely that digoxin is the cause of this patient's symptoms. If the combination product is to be continued, regular serum potassium measurements are recommended.
The second issue regarding the interaction of digoxin with diuretics is a common issue in clinical practice. Dr Nwafor seems unaware that bothpotassium-depleting (e.g. thiazides and frusemide) andpotassium-sparing diuretics (e.g. spironolactone, which increases digoxin levels by prolonging its half-life) can result in altered digoxin levels. This is clearly shown in Table 3 of my article and the first self-test question aims to reflect this fact. Not allpotassium-sparing diuretics, however, interact with digoxin.