fludrocortisone

Fludrocortisone has been used in the treatment of cerebral salt-wasting syndrome.{{cite journal | vauthors = Taplin CE, Cowell CT, Silink M, Ambler GR | title = Fludrocortisone therapy in cerebral salt wasting | journal = Pediatrics | volume = 118 | issue = 6 | pages = e1904–e1908 | date = December 2006 | pmid = 17101713 | doi = 10.1542/peds.2006-0702 | s2cid = 28871495 }} 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).{{cite journal | vauthors = Freitas J, Santos R, Azevedo E, Costa O, Carvalho M, de Freitas AF | title = Clinical improvement in patients with orthostatic intolerance after treatment with bisoprolol and fludrocortisone | journal = Clinical Autonomic Research | volume = 10 | issue = 5 | pages = 293–299 | date = October 2000 | pmid = 11198485 | doi = 10.1007/BF02281112 | s2cid = 20843222 }} It can be used to treat low blood pressure.{{cite journal | vauthors = Veazie S, Peterson K, Ansari Y, Chung KA, Gibbons CH, Raj SR, Helfand M | title = Fludrocortisone for orthostatic hypotension | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 5 | pages = CD012868 | date = May 2021 | doi = 10.1002/14651858.CD012868.pub2 | pmid = 34000076 | pmc = 8128337 }}

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).{{medcn|date=August 2020}}

Use of fludrocortisone can lead to one or more of the following side effects:{{Cite web |title=Fludrocortisone Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD |url=https://www.webmd.com/drugs/2/drug-6802/fludrocortisone-oral/details |access-date=2023-09-05 |website=www.webmd.com |language=en}}

• 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)

{{see also|Glucocorticoid#Pharmacology}}

Fludrocortisone is a corticosteroid and acts as a powerful mineralocorticoid, along with some additional but comparatively very weak glucocorticoid activity.{{cite book | vauthors = De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Chrousos, Pavlaki AN, Magiakou MA | display-authors = 6 | chapter = Glucocorticoid Therapy and Adrenal Suppression | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK279156/ | year = 2000 | pmid = 25905379 | veditors = Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP | display-editors = 6 | title = Endotext [Internet]. | location = South Dartmouth (MA) | publisher = MDText.com, Inc. }} 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.{{cite journal | vauthors = Polito A, Hamitouche N, Ribot M, Polito A, Laviolle B, Bellissant E, Annane D, Alvarez JC | display-authors = 6 | title = Pharmacokinetics of oral fludrocortisone in septic shock | journal = British Journal of Clinical Pharmacology | volume = 82 | issue = 6 | pages = 1509–1516 | date = December 2016 | pmid = 27416887 | pmc = 5099539 | doi = 10.1111/bcp.13065 }}

Plasma renin, sodium, and potassium are checked through blood tests to verify that the correct dosage is reached.{{medcn|date=August 2020}}

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.

Fludrocortisone was described in the literature in 1953{{cite journal | vauthors = Calvert DN | title = Anti-inflammatory steroids | journal = Wisconsin Medical Journal | volume = 61 | pages = 403–404 | date = August 1962 | pmid = 13875857 }} and was introduced for medical use (as the acetate ester) in 1954.{{cite book| vauthors = Lemke TL, Williams DA |title=Foye's Principles of Medicinal Chemistry|url=https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA890|year=2008|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-6879-5|pages=890–|url-status=live|archive-url=https://web.archive.org/web/20171105200659/https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA890|archive-date=2017-11-05}}{{cite book|author=William Andrew Publishing|title=Pharmaceutical Manufacturing Encyclopedia, 3rd Edition|url=https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA1642|date=22 October 2013|publisher=Elsevier|isbn=978-0-8155-1856-3|pages=1642–|url-status=live|archive-url=https://web.archive.org/web/20171105200659/https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA1642|archive-date=5 November 2017}} It was the first synthetic corticosteroid to be marketed, and followed the introduction of cortisone in 1948 and hydrocortisone (cortisol) in 1951.{{cite journal | vauthors = Khan MO, Park KK, Lee HJ | title = Antedrugs: an approach to safer drugs | journal = Current Medicinal Chemistry | volume = 12 | issue = 19 | pages = 2227–2239 | year = 2005 | pmid = 16178782 | doi = 10.2174/0929867054864840 }} Fludrocortisone was also the first fluorine-containing pharmaceutical drug to be marketed.{{cite journal | vauthors = Walker MC, Chang MC | title = Natural and engineered biosynthesis of fluorinated natural products | journal = Chemical Society Reviews | volume = 43 | issue = 18 | pages = 6527–6536 | date = September 2014 | pmid = 24776946 | doi = 10.1039/c4cs00027g | s2cid = 205904152 }}

Fludrocortisone is the generic name of fludrocortisone and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|BAN|British Approved Name}}, {{abbrlink|DCF|Dénomination Commune Française}}, and {{abbrlink|DCIT|Denominazione Comune Italiana}}, whereas fludrocortisone acetate is the generic name of fludrocortisone acetate and its {{abbrlink|USP|United States Pharmacopeia}}, {{abbrlink|BANM|British Approved Name}}, and {{abbrlink|JAN|Japanese Accepted Name}}.{{cite web |url=https://www.drugs.com/international/fludrocortisone.html |title=Fludrocortisone Uses, Side Effects & Warnings |access-date=2017-07-16 |url-status=live |archive-url=https://web.archive.org/web/20150513235052/http://www.drugs.com/international/fludrocortisone.html |archive-date=2015-05-13 }}

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.

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.

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{{Glucocorticoids and antiglucocorticoids}}

{{Mineralocorticoids and antimineralocorticoids}}

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{{Mineralocorticoid receptor modulators}}

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