Fludrocortisone
Encyclopedia
Fludrocortisone is a synthetic corticosteroid
with moderate glucocorticoid
potency and much greater mineralocorticoid
potency. The brand name in the U.S. and Canada is Florinef.
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
as well.
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. It's effects on increasing Na+ levels, and therefore blood volume, make it useful as an off label treatment for postural orthostatic tachycardia syndrome (POTS)
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
.
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
with moderate glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
potency and much greater mineralocorticoid
Mineralocorticoid
Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...
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 aldosteroneAldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...
in various forms of adrenal insufficiency
Adrenal insufficiency
Adrenal insufficiency is a condition in which the adrenal glands, located above the kidneys, do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production which regulates sodium, potassium and water retention...
such as Addison's disease
Addison's disease
Addison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...
and the classic salt wasting (21-hydroxylase deficiency) form of congenital adrenal hyperplasia
Congenital adrenal hyperplasia
Congenital adrenal hyperplasia refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands ....
. Fludrocortisone is the first line of treatment for orthostatic intolerance
Orthostatic intolerance
Orthostatic intolerance is a subcategory of dysautonomia, a disorder of the autonomic nervous system occurring when an individual stands up....
as well.
Fludrocortisone is also a confirmation test for diagnosing Conns Syndrome
Conns Syndrome
Conn's syndrome is an Aldosterone-Producing Adenoma . Conn's syndrome is named after Jerome W. Conn , the American endocrinologist who first described the condition at the University of Michigan in 1955.-Causes:...
(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. It's 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 cortisolCortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
except for the substitution of fluorine in place of one hydrogen. Fluorine is a good bioisostere
Bioisostere
In medicinal chemistry, bioisosteres are substituents or groups with similar physical or chemical properties which produce broadly similar biological properties to a chemical compound. In drug design, the purpose of exchanging one bioisostere for another is to enhance the desired biological or...
for hydrogen because it is similar in size. The major difference is in its electronegativity
Electronegativity
Electronegativity, symbol χ , is a chemical property that describes the tendency of an atom or a functional group to attract electrons towards itself. An atom's electronegativity is affected by both its atomic number and the distance that its valence electrons reside from the charged nucleus...
.
Side effects
- Sodium and water retention
- Swelling due to fluid retention (edemaEdemaEdema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
) - High blood pressure (hypertensionHypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
) - Headache
- Low blood potassium level (hypokalemiaHypokalemiaHypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...
) - Muscle weakness
- Fatigue
- Increased susceptibility to infection
- Impaired wound healing
- Increased sweating
- Increased hair growth (hirsutismHirsutismHirsutism or frazonism is the excessive hairiness on women in those parts of the body where terminal hair does not normally occur or is minimal - for example, a beard or chest hair. It refers to a male pattern of body hair and it is therefore primarily of cosmetic and psychological concern...
) - Thinning of skin and stretch marks
- Disturbances of the gut such as indigestion (dyspepsiaDyspepsiaDyspepsia , also known as upset stomach or indigestion, refers to a condition of impaired digestion. It is a medical condition characterized by chronic or recurrent pain in the upper abdomen, upper abdominal fullness and feeling full earlier than expected when eating...
), distention of the abdomen and ulceration (peptic ulcerPeptic ulcerA peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...
) - Decreased bone density and increased risk of fractures of the bones
- Difficulty in sleeping (insomniaInsomniaInsomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
) - 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 (glaucomaGlaucomaGlaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
) - Increased pressure in the skull (intracranial pressureIntracranial pressureIntracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...
)