Re: Florinef post #2 (a bit more technical)

[Guest guest]

Suzi,

Thank you, thank you, thank you. Great info.

Frannie

Florinef post #2 (a bit more technical)

Description: Fludrocortisone is an oral synthetic adrenocortical steroid. It is

derived from the substitution of a 9alpha-fluoride on the B ring of

hydrocortisone. Fluorination at this position gives rise to potent

mineralocorticoid activity. Pharmacologic actions are similar to those of

aldosterone, an endogenous mineralocorticoid. The sodium-retaining activity of

fludrocortisone is extremely high compared with other adrenocorticoids such as

hydrocortisone. Although fludrocortisone has significant glucocorticoid

activity, it has no appreciable glucocorticoid effects at usual therapeutic

doses. Fludrocortisone is used as mineralocorticoid replacement therapy in

patients with adrenocortical insufficiency and salt-losing adrenogenital

syndrome. Fludrocortisone was approved by the FDA in 1954. The first generic

fludrocortisone tablet was FDA-approved in March 2002.

Mechanism of Action: Endogenous corticosteroids are secreted by the adrenal

cortex; their effects are believed to be due to modification of enzymatic

activity rather than to a direct hormone-induced action. Fludrocortisone mimics

the actions of aldosterone, an endogenous mineralocorticoid. Mineralocorticoids

facilitate sodium resorption and promote hydrogen ion and potassium excretion at

the level of the distal renal tubule. Small oral doses produce marked sodium

retention and increased urinary potassium excretion with a resultant rise in

blood pressure which is apparently due to increased angiotensin activity and

fluid retention. Larger doses can inhibit endogenous adrenal cortical secretion,

thymic activity, and pituitary corticotropin excretion; promote the deposition

of liver glycogen; and, if protein intake is inadequate, induce negative

nitrogen balance.

Pharmacokinetics: Fludrocortisone is administered orally and is absorbed rapidly

from the GI tract. Peak plasma concentrations are reached within 1.5 hours. The

circulating drug binds extensively to the plasma proteins albumin and

transcortin, and only the unbound portion of a dose is active Systemic

fludrocortisone is quickly distributed into the kidneys, intestines, skin,

liver, and muscle. Fludrocortisone distributes into breast milk and crosses the

placenta. Fludrocortisone is metabolized by the liver to inactive metabolites.

These inactive metabolites, as well as a small portion of unchanged drug, are

excreted in the urine. The biological half-life of fludrocortisone is 18—36

hours.