Fludrocortisone

Fludrocortisone, sold under the brand name Florinef among others, is a corticosteroid used to treat congenital adrenal hyperplasia, postural hypotension, and adrenal insufficiency.<ref name="Elks2014">Template:Cite book</ref><ref name="IndexNominum2000">Template:Cite book</ref><ref name=AHFS2016/> In adrenal insufficiency, it is generally taken together with hydrocortisone.<ref name=AHFS2016/> Fludrocortisone is taken by mouth<ref name=AHFS2016>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and is most commonly used in its acetate form.<ref name=DayFurst2010>Template:Cite book</ref>

Common side effects of fludrocortisone include high blood pressure, swelling, heart failure, and low blood potassium.<ref name="AHFS2016" /> Other serious side effects can include low immune-system function, cataracts, muscle weakness, and mood changes.<ref name=AHFS2016/> Whether use of fludrocortisone during pregnancy is safe for the fetus is unknown.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Fludrocortisone is mostly a mineralocorticoid, but it also has glucocorticoid effects.<ref name=AHFS2016/>

Fludrocortisone was patented in 1953.<ref name=Fis2006>Template:Cite book</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO21st">Template:Cite book</ref>

Medical uses

Fludrocortisone has been used in the treatment of cerebral salt-wasting syndrome.<ref name="pmid17101713">Template:Cite journal</ref> 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).<ref>Template:Cite journal</ref> It can be used to treat low blood pressure.<ref>Template:Cite journal</ref>

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).Template:Medcn

Side effects

Use of fludrocortisone can lead to one or more of the following side effects:<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

• 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)

Pharmacology

Template:See also Fludrocortisone is a corticosteroid and acts as a powerful mineralocorticoid, along with some additional but comparatively very weak glucocorticoid activity.<ref name="pmid25905379">Template:Cite book</ref> Relative to cortisol, it is said to have 10 times the glucocorticoid potency but 250 to 800 times the mineralocorticoid potency.<ref name="pmid25905379" /><ref name="LemkeWilliams2008" /> Fludrocortisone acetate is a prodrug of fludrocortisone, which is the active form of the drug.<ref name="pmid27416887">Template:Cite journal</ref>

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

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).<ref name="Elks2014" /><ref name="IndexNominum2000" /> Specifically, it is a modification of cortisol with a fluorine atom substituted in place of one hydrogen atom at the C9α position.<ref name="Elks2014" /><ref name="IndexNominum2000" /> 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,<ref name="Elks2014" /><ref name="IndexNominum2000" /> and is hydrolyzed into fludrocortisone in the body.<ref name="pmid27416887" />

History

Fludrocortisone was described in the literature in 1953<ref name="pmid13875857">Template:Cite journal</ref> and was introduced for medical use (as the acetate ester) in 1954.<ref name="LemkeWilliams2008">Template:Cite book</ref><ref name="Publishing2013">Template:Cite book</ref> It was the first synthetic corticosteroid to be marketed, and followed the introduction of cortisone in 1948 and hydrocortisone (cortisol) in 1951.<ref name="pmid13875857" /><ref name="pmid16178782">Template:Cite journal</ref> Fludrocortisone was also the first fluorine-containing pharmaceutical drug to be marketed.<ref name="pmid24776946">Template:Cite journal</ref>

Society and culture

Generic name

Fludrocortisone is the generic name of fludrocortisone and its Template:Abbrlink, Template:Abbrlink, Template:Abbrlink, Template:Abbrlink, and Template:Abbrlink, whereas fludrocortisone acetate is the generic name of fludrocortisone acetate and its Template:Abbrlink, Template:Abbrlink, and Template:Abbrlink.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="Drugs.com">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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.<ref name="IndexNominum2000" /><ref name="Drugs.com" />

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.<ref name="IndexNominum2000" /><ref name="Drugs.com" />