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Fludrocortisone

Clinical data
Trade names	Astonin, Astonin-H, others
Other names	StC-1400; 9α-Fluorohydrocortisone; 9α-Fluorocortisol; 9α-Fluoro-17α-hydroxycorticosterone; 9α-Fluoro-11β,17α,21-trihydroxypregn-4-ene-3,20-dione
AHFS/Drugs.com	Monograph
Pregnancy category	C
Routes of administration	By mouth
Drug class	Corticosteroid; glucocorticoid; mineralocorticoid
ATC code	H02AA02 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Protein binding	High
Metabolism	Liver
Elimination half-life	3.5 hours
Identifiers
IUPAC name (8S,9R,10S,11S,13S,14S,17R)-9-fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopentaphenanthren-3-one
CAS Number	127-31-1 Acetate: U0476M545B
PubChem CID	31378
PubChem SID	46508616
IUPHAR/BPS	2873
DrugBank	DB00687
ChemSpider	29111
UNII	U0476M545B
KEGG	D07967
ChEBI	CHEBI:50885
ChEMBL	ChEMBL1201388
PDB ligand	ZK5 (PDBe, RCSB PDB)
CompTox Dashboard (EPA)	DTXSID7023061
ECHA InfoCard	100.004.395
Chemical and physical data
Formula	C21H29FO5
Molar mass	380.456 g·mol
3D model (JSmol)	Interactive image
SMILES O=C(CO)3(O)2(C(O)4(F)1(/C(=C\C(=O)CC1)CC42CC3)C)C
InChI InChI=1S/C21H29FO5/c1-18-7-5-13(24)9-12(18)3-4-15-14-6-8-20(27,17(26)11-23)19(14,2)10-16(25)21(15,18)22/h9,14-16,23,25,27H,3-8,10-11H2,1-2H3/t14-,15-,16-,18-,19-,20-,21-/m0/s1 Key:AAXVEMMRQDVLJB-BULBTXNYSA-N
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Fludrocortisone acetate

Clinical data
Trade names	Cortineff, Florinef, Florinefe, Fludrocortison, others
Other names	Fluorohydrocortisone acetate; 9α-Fluorohydrocortisone 21-acetate; 9α-Fluoro-17α-hydroxycorticosterone 21-acetate; 9α-Fluoro-11β,17α,21-trihydroxypregn-4-ene-3,20-dione 21-acetate
Routes of administration	By mouth
Drug class	Corticosteroid; glucocorticoid; mineralocorticoid
Pharmacokinetic data
Metabolism	Liver
Identifiers
IUPAC name phenanthren-17-yl]-2-oxoethyl] acetate
CAS Number	514-36-3
PubChem CID	225609
ChemSpider	196144
UNII	V47IF0PVH4
KEGG	D00986
ChEBI	CHEBI:5102
ChEMBL	ChEMBL1201010
CompTox Dashboard (EPA)	DTXSID7023061
ECHA InfoCard	100.004.395
Chemical and physical data
Formula	C23H31FO6
Molar mass	422.493 g·mol
3D model (JSmol)	Interactive image
Melting point	260 to 262 °C (500 to 504 °F) (dec.)
SMILES CC(=O)OCC(=O)1(CC21(C(3(2CCC4=CC(=O)CC43C)F)O)C)O
InChI InChI=1S/C23H31FO6/c1-13(25)30-12-19(28)22(29)9-7-16-17-5-4-14-10-15(26)6-8-20(14,2)23(17,24)18(27)11-21(16,22)3/h10,16-18,27,29H,4-9,11-12H2,1-3H3/t16-,17-,18-,20-,21-,22-,23-/m0/s1 Key:SYWHXTATXSMDSB-GSLJADNHSA-N

Fludrocortisone, sold under the brand name Florinef, among others, is a corticosteroid used to treat adrenogenital syndrome, postural hypotension, and adrenal insufficiency. In adrenal insufficiency, it is generally taken together with hydrocortisone. Fludrocortisone is taken by mouth and is most commonly used in its acetate form.

Common side effects of fludrocortisone include high blood pressure, swelling, heart failure, and low blood potassium. Other serious side effects can include low immune-system function, cataracts, muscle weakness, and mood changes. Whether use of fludrocortisone during pregnancy is safe for the fetus is unknown. Fludrocortisone is mostly a mineralocorticoid, but it also has glucocorticoid effects.

Fludrocortisone was patented in 1953. It is on the World Health Organization's List of Essential Medicines.

Medical uses

Fludrocortisone has been used in the treatment of cerebral salt-wasting syndrome. 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). It can be used to treat low blood pressure.

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).

Side effects

Use of fludrocortisone can lead to one or more of the following side effects:

• 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
• Difficulty in sleeping (insomnia)
• Depression
• Weight gain
• Raised blood sugar level
• Changes to the menstrual cycle
• Partial loss of vision due to opacity in the lens of the eye (cataracts)
• Raised pressure in the eye (glaucoma)
• Increased pressure in the skull (intracranial pressure)

Pharmacology

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

Plasma renin, sodium, and potassium are checked through blood tests to verify that the correct dosage is reached.

Chemistry

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). Specifically, it is a modification of cortisol with a fluorine atom substituted in place of one hydrogen atom at the C9α position. 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, and is hydrolyzed into fludrocortisone in the body.

History

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

Society and culture

Generic name

Fludrocortisone is the generic name of fludrocortisone and its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, BANTooltip British Approved Name, DCFTooltip Dénomination Commune Française, and DCITTooltip Denominazione Comune Italiana, whereas fludrocortisone acetate is the generic name of fludrocortisone acetate and its USPTooltip United States Pharmacopeia, BANMTooltip British Approved Name and JANTooltip Japanese Accepted Name.

Brand names

Fludrocortisone is marketed mainly under the brand names Astonin and Astonin-H, whereas the more widely used fludrocortisone acetate is sold mainly as Florinef, but also under several other brand names including Cortineff, Florinefe, and Fludrocortison.

Availability

Fludrocortisone is marketed in Austria, Croatia, Denmark, Germany, Luxembourg, Romania, and Spain, whereas fludrocortisone acetate is more widely available throughout the world and is marketed in the United States, Canada, the United Kingdom, various other European countries, Australia, Japan, China, Brazil, and many other countries.

References

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External links

• "Fludrocortisone". Drug Information Portal. U.S. National Library of Medicine.

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