| Class | Mineralocorticoid receptor antagonist |
|---|---|
| Chemistry |
Steroid lactone |
| Routes of administration |
Oral only |
| Absorption |
95% bioavailability, when taken with food |
| Solubility |
pKa 18.01; practically insoluble in water |
| Distribution |
VOD= about 2L/kg; 90% protein bound |
| Metabolism |
100% of spironolactone is metabolised in the liver - some of the metabolites are active and have long half-lives |
| Elimination |
Elimination of inactive metabolites is renal. Half-life of spironolactone itself is only 2-3hours, whereas the metabolites have half-lives of 10-12 hrs |
| Time course of action |
Some effect is seen withn 3-4 hours, but the maximum effect takes up to 2 days to develop |
| Target receptor |
Aldosterone receptors everywhere (particularly inthe collecting duct and distal convoluted tubule) |
| Mechanism of action |
By decreasing the reabsorption of sodium via the ENaC channel, aldosterone receptor antagonists increase the loss of sodium. The increased sodium concentration in the lumen of the collecting duct creates a positive charge which repels potassium ions and therefore leads to potassium retention. |
| Clinical effects |
Decreased blood pressure and circulating volume, hyponatremia, hyperkalemia, metabolic acidosis (Type 4 RTA), hirsuitism and gynaecomastia (by cross-reactivity with other steroid receptors, eg. sex hormones) |
| Literature reference |
FDA PI data sheet |
| CICM details of understanding | Not specifically listed in the CICM syllabus |
| Mentioned around Deranged Physiology | |
| Related SAQs |