Fludrocortisone

Fludrocortisone has been used in the treatment of cerebral salt-wasting syndrome.^[10] It is used primarily to replace the missing hormone aldosterone in various forms of adrenal insufficiency such as Addison's disease and the classic salt-wasting (21-hydroxylase deficiency) form of congenital adrenal hyperplasia. Due to its effects on increasing Na+ levels, and therefore blood volume, fludrocortisone is the first-line of treatment for orthostatic intolerance, and postural orthostatic tachycardia syndrome (POTS).^[11] It can be used to treat low blood pressure.^[12]

Fludrocortisone is also a confirmation test for diagnosing Conn's syndrome (aldosterone-producing adrenal adenoma), the fludrocortisone suppression test. Loading the patient with fludrocortisone would suppress serum aldosterone level in a normal patient, whereas the level would remain elevated in a Conn's patient. The fludrocortisone suppression test is an alternative to the NaCl challenge (which would use normal saline or salt tablets).^{[medical citation needed]}

Use of fludrocortisone can lead to one or more of the following side effects:^[13]

• Sodium and water retention
• Swelling due to fluid retention (edema)
• High blood pressure (hypertension)
• Headache
• Low blood potassium level (hypokalemia)
• Muscle weakness
• Fatigue
• Increased susceptibility to infection
• Impaired wound healing
• Increased sweating
• Increased hair growth (hirsutism)
• Thinning of skin and stretch marks
• Disturbances of the gut such as indigestion (dyspepsia), distention of the abdomen and ulceration (peptic ulcer)
• Decreased bone density and increased risk of fractures of the bones
• Insomnia
• Depression
• Weight gain
• Raised blood sugar level
• Changes to the menstrual cycle
• Cataracts
• Raised pressure in the eye (glaucoma)
• Increased pressure in the skull (intracranial pressure)

Fludrocortisone is a corticosteroid and acts as a powerful mineralocorticoid, along with some additional but comparatively very weak glucocorticoid activity.^[14] Relative to cortisol, it is said to have 10 times the glucocorticoid potency but 250 to 800 times the mineralocorticoid potency.^[14][15] Fludrocortisone acetate is a prodrug of fludrocortisone, which is the active form of the drug.^[16]

Plasma renin, sodium, and potassium are checked through blood tests to verify that the correct dosage is reached.^{[medical citation needed]}

Fludrocortisone, also known as 9α-fluorocortisol (9α-fluorohydrocortisone) or as 9α-fluoro-11β,17α,21-trihydroxypregn-4-ene-3,20-dione, is a synthetic pregnane steroid and a halogenated derivative of cortisol (11β,17α,21-trihydroxypregn-4-ene-3,20-dione).^[3][4] Specifically, it is a modification of cortisol with a fluorine atom substituted in place of one hydrogen atom at the C9α position.^[3][4] Fluorine is a good bioisostere for hydrogen because it is similar in size, with the major difference being in its electronegativity. The acetate form of fludrocortisone, fludrocortisone acetate, is the C21 acetate ester of fludrocortisone,^[3][4] and is hydrolyzed into fludrocortisone in the body.^[16]

Fludrocortisone was described in the literature in 1953^[17] and was introduced for medical use (as the acetate ester) in 1954.^[15][18] It was the first synthetic corticosteroid to be marketed, and followed the introduction of cortisone in 1948 and hydrocortisone (cortisol) in 1951.^[17][19] Fludrocortisone was also the first fluorine-containing pharmaceutical drug to be marketed.^[20]