Fludrocortisone

Fludrocortisone

Systematic (IUPAC) name
9-fluoro-11,17-dihydroxy-17- (2-hydroxyacetyl)- 10,13-dimethyl- 1,2,6,7,8,9,10,11,12, 13,14,15,16,17- tetradecahydrocyclopenta[a]phenanthren-3-one
Clinical data
AHFS/Drugs.com	monograph
Pregnancy cat.	C
Legal status	?
Routes	oral
Pharmacokinetic data
Protein binding	High
Metabolism	Hepatic
Half-life	3.5 hours
Identifiers
CAS number	127-31-1 Y
ATC code	H02AA02
PubChem	CID 31378
IUPHAR ligand	2873
DrugBank	DB00687
ChemSpider	29111 Y
UNII	U0476M545B Y
KEGG	D07967 Y
ChEBI	CHEBI:50885 Y
ChEMBL	CHEMBL1201388 N
Chemical data
Formula	C21H29FO5
Mol. mass	380.45 g/mol
SMILES O=C(CO)[C@]3(O)[C@]2(C[C@H](O)[C@]4(F)[C@@]1(/C(=C\C(=O)CC1)CC[C@H]4[C@@H]2CC3)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 Y Key:AAXVEMMRQDVLJB-BULBTXNYSA-N Y
N (what is this?)  (verify)

Fludrocortisone (also called 9α-fluorocortisol or 9α-fluorohydrocortisone) is a synthetic corticosteroid with moderate glucocorticoid potency and much greater mineralocorticoid potency. The brand name in the U.S. and Canada is Florinef.

Uses

Fludrocortisone has been used in the treatment of cerebral salt wasting. 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. Fludrocortisone is the first line of treatment for orthostatic intolerance and Postural Tachycardia Syndrome as well.^{[citation needed]}

Fludrocortisone is also a confirmation test for diagnosing Conns 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 will not be altered in a Conns patient. Its effects on increasing Na+ levels, and therefore blood volume, make it useful as an off label treatment for postural orthostatic tachycardia syndrome (POTS)

Dosing

Fludrocortisone is available in 0.1 mg tablets. Typical daily doses for mineralocorticoid replacement are between 0.05 mg - 0.2 mg. Renin plasma, sodium, and potassium is checked through blood tests in order to verify that the correct dosage is reached.

Chemical properties

Chemically, fludrocortisone is identical to cortisol except for the substitution of fluorine in place of one hydrogen. Fluorine is a good bioisostere for hydrogen because it is similar in size. The major difference is in its electronegativity.

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)