Spironolactone

Question 1

Drug class?

Answer 1

Potassium Sparing Diuretic

Question 2

How does it work?

Answer 2

Act on the aldosterone-responsive segments of distal nephron, where K+ homeostasis is controlled. Aldosterone stimulates Na+ reabsorption, generating a negative potential in the lumen, which drives K+ and H+ ions into the lumen (and hence their excretion. PSDs reduce Na+ reabsorption by either antagonizing aldosterone (spironolactone) or blocking Na+ channels (amiloride, triamterene). Causes the electrical potential across the tubular epithelium to fall, reducing the driving force for K+ secretion. May cause severe hyperkalaemia, especially in patients with severe real impairment. Also likely to occur if patients taking ACE-i, because these drugs reduce aldosterone secretion and therefore, K+ secretion.

Question 3

Indications?

Answer 3

Oedema and ascites in liver cirrhosis, malignant ascites, nephrotic syndrome, oedema in congestive heart failure, moderate to severe heart failure, resistant hypertension, treatment of primary hyperaldosteronism (Conn’s syndrome).

Question 4

Contra-indications?

Answer 4

Hyperkalaemia, anuria, Addison’s disease.

Question 5

Side-effects?

Answer 5

GI disturbances, hepatotoxicity, malaise, confusion, drowsiness, dizziness, gynaecomastia, benign breast tumour, breast pain, menstrual disturbances, changes in libido, hypertrichosis, electrolyte disturbances including hyperkalaemia, hyponatraemia, acute renal failure, hyperuricaemia, leucopenia, agranulocytosis, thrombocytopenia, leg cramps, alopecia, rash, Stevens-Johnson syndrome.

Question 6

Possible interactions?

Answer 6

• Concomitant use of drugs known to cause hyperkalaemia with spironolactone may result in severe hyperkalaemia.
• Spironolactone has been reported to increase serum digoxin concentration and to interfere with certain serum digoxin assays.
• Potentiation of the effect of antihypertensive drugs occurs. Since ACE inhibitors decrease aldosterone production they should not routinely be used with Aldactone, particularly in patients with marked renal impairment.
• Non-steroidal anti-inflammatory drugs may attenuate the natriuretic efficacy of diuretics due to inhibition of intrarenal synthesis of prostaglandins.
• Spironolactone reduces vascular responsiveness to noradrenaline. Caution should be exercised in the management of patients subjected to regional or general anaesthesia while they are being treated with spironolactone.

Question 7

Elimination?

Answer 7

Spironolactone is excreted in the urine and faeces in the form of metabolites.
The renal action of a single dose of spironolactone reaches its peak after 7 hours, and activity persists for at least 24 hours.