Fludrocortisone

Class Mineralocorticoid
Chemistry

Steroid

Routes of administration

Oral

Absorption

70-100% oral bioavailability, but very variable

Solubility

pKa=12.55; poor water solubility; highly lipid soluble

Distribution

VOD=1.2L/kg; 70-80% protein-bound

Metabolism

Metabolised extensively in the liver

Elimination

Inactive metabolites are eliminated in the urine

Time course of action

Half-life is 18- 36 hours.

Target receptor

Glucocorticoid receptor, which is a cytoplasmic and nuclear receptor, that regulates gene transcription and protein synthesis (but some actions are also attributed to membrane-bound receptors and nongenomic pathways)

Mechanism of action

A combination of genomic effects and nongenomic effects, where some (medium and long term) activity is mediated by the regulation of protein synthesis, and some more immediate effects are mediated by the interference in cell membrane function, intracellular second messenger systems and membrane-bound mineralocorticoid receptors. Most of the major effects are due to the increased expression of aldosterone-sensitive ENaC channels on the surface of distal nephron tubular cells, resulting in sodium reabsorption and potassium loss.

Clinical effects

- Hypernaremia, hypokalemia, water retention
- gradual myocardial remodelling
- Hypertension, increased cardiac output due to increased preload

Literature reference

Rahman et al, 2022

CICM details of understanding Not specifically listed in the CICM syllabus
Mentioned around Deranged Physiology
Related SAQs