Fludrocortisone Acetate

Fludrocortisone is a synthetic mineralocorticoid used in conjunction with hydrocortisone to replace missing endogenous corticosteroids in patients with adrenal insufficiency. It is functionally similar to aldosterone, the body's primary endogenous mineralocorticoid, and is structurally analogous to cortisol, differing only by a fluorine atom at the 9-position of the steroid structure - this fluorination is thought to be crucial to fludrocortisone's significant mineralocorticoid potency.

Fludrocortisone is a mineralocorticoid used to treat adrenocortical insufficiency and salt-losing adrenogenital syndrome.

Fludrocortisone is indicated as partial replacement therapy for primary or secondary adrenocortical insufficiency in Addison's disease. It is also indicated for the treatment of salt-losing androgenital syndrome.

• Otitis Externa
• Otitis Media (OM)
• Primary adrenocortical insufficiency
• Secondary adrenocortical insufficiency
• Salt-losing Androgenital syndrome

Fludrocortisone is a synthetic mineralocorticoid used to replace endogenous aldosterone in conditions resulting in missing or inadequate endogenous synthesis. It acts on the kidneys to increase both sodium reabsorption and potassium excretion. As its effects are exerted at the transcriptional level, a single dose of fludrocortisone may work over the course of 1-2 days despite a relatively short plasma half-life. Like other systemic corticosteroids, fludrocortisone may mask signs of infection by depressing the normal immune response - infections occurring during fludrocortisone therapy should be promptly treated with appropriate antimicrobial therapy.

The main endogenous mineralocorticoid, aldosterone, is produced in the zona glomerulosa of the adrenal cortex - it acts on mineralocorticoid receptors in the kidneys to increase sodium reabsorption and potassium excretion, which in turn helps to regulate plasma electrolyte composition and blood pressure. In conditions of adrenal insufficiency, such as Addison’s disease, aldosterone is not produced (or is produced in insufficient quantities) and must be replaced by exogenous mineralocorticoids such as fludrocortisone.

Fludrocortisone binding to mineralocorticoid receptors causes alterations to DNA transcription and translation of proteins that result in an increased density of sodium channels on the apical side of renal tubule cells and an increased density of Na^{+ These increases in receptor density result in increased plasma sodium concentrations, and thus increased blood pressure, as well as a decreased plasma potassium concentration. Fludrocortisone may also exert a direct effect on plasma sodium levels via action at the Na+}

Fludrocortisone also acts on glucocorticoid receptors, albeit with a much lower affinity - the glucocorticoid potency of fludrocortisone is approximately 5-10 times that of endogenous cortisol, whereas its mineralocorticoid potency is 200-400 times greater.

Absorption of fludrocortisone following oral administration is rapid and complete. Pharmacokinetic studies have estimated the C_max to be 0.0012 to 0.20 μg/L with a T_max between 0.5 and 2 hours. The AUC_0-∞ of fludrocortisone after oral administration has been variably estimated to be between 1.22 to 3.07 μg.h/L.

The apparent volume of distribution of fludrocortisone is 80-85 L. Distribution into CSF appears minimal - the observed ratio of CSF drug concentration versus plasma drug concentration is 1:6.

Fludrocortisone is 70-80% protein bound in plasma, mostly to albumin and corticosteroid-binding globulin.

Approximately 80% of an administered dose of fludrocortisone shows up in the urine, with the other 20% likely eliminated via fecal or biliary route.

The plasma half-life of fludrocortisone has been variably reported to be between 1-3.5 hours, though prescribing information gives an approximate half-life of 18-36 hours.

Population pharmacokinetics have estimated the plasma clearance of fludrocortisone to be 40.8 L/h.

The oral LD₅₀ of fludrocortisone in rats is >1g/kg. Acute overdosage of fludrocortisone is likely to result in symptoms consistent with its adverse effect profile. Patients receiving a single large dose should be treated with plenty of water by mouth and should undergo monitoring of serum electrolytes, particularly potassium and sodium, and be treated appropriately for any developing imbalances.

• Limit salt intake. Excessive intake of salt can result in hypertension and edema.