Corticosteroids are a class of that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, and mineralocorticoids, are involved in a wide range of physiology processes, including stress response, immune system, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.
Some common naturally occurring steroid hormones are cortisol (), corticosterone (), cortisone () and aldosterone () (cortisone and aldosterone are isomers). The main corticosteroids produced by the adrenal cortex are cortisol and aldosterone.
The etymology of the part of the name refers to the adrenal cortex, which makes these steroid hormones. Thus a corticosteroid is a "cortex steroid".
Classes
Medical uses
Synthetic pharmaceutical drugs with corticosteroid-like effects are used in a variety of conditions, ranging from hematological neoplasms
to
or
.
Dexamethasone and its derivatives are almost pure glucocorticoids, while
prednisone and its derivatives have some mineralocorticoid action in addition to the glucocorticoid effect.
Fludrocortisone (Florinef) is a synthetic mineralocorticoid.
Hydrocortisone (cortisol) is typically used for replacement therapy,
e.g. for adrenal insufficiency and congenital adrenal hyperplasia.
Medical conditions treated with systemic corticosteroids:
Topical formulations are also available for the skin disease, eyes (uveitis), lungs (asthma), nose (rhinitis), and bowels. Corticosteroids are also used supportively to prevent nausea, often in combination with 5-HT3 antagonists (e.g., ondansetron).
Typical undesired effects of glucocorticoids present quite uniformly as drug-induced Cushing's syndrome. Typical mineralocorticoid side-effects are hypertension (abnormally high blood pressure), steroid induced diabetes mellitus, psychosis, poor sleep, hypokalemia (low potassium levels in the blood), hypernatremia (high sodium levels in the blood) without causing peripheral edema, metabolic alkalosis and connective tissue weakness.
A variety of steroid medications, from anti-allergy nasal sprays (Nasonex, Flonase) to topical skin creams, to eye drops (Tobradex), to prednisone have been implicated in the development of central serous retinopathy (CSR).
Corticosteroids have been widely used in treating people with traumatic brain injury.
Pharmacology
Corticosteroids act as
of the glucocorticoid receptor and/or the mineralocorticoid receptor.
In addition to their corticosteroid activity, some corticosteroids may have some progestogenic activity and may produce sex-related side effects.
Pharmacogenetics
Asthma
Patients' response to inhaled corticosteroids has some basis in genetic variations. Two genes of interest are CHRH1 (corticotropin-releasing hormone receptor 1) and TBX21 (transcription factor T-bet). Both genes display some degree of polymorphic variation in humans, which may explain how some patients respond better to inhaled corticosteroid therapy than others.
However, not all asthma patients respond to corticosteroids and large sub groups of asthma patients are corticosteroid resistant.
A study funded by the Patient-Centered Outcomes Research Institute of children and teens with mild persistent asthma found that using the control inhaler as needed worked the same as daily use in improving asthma control, number of asthma flares, how well the lungs work, and quality of life. Children and teens using the inhaler as needed used about one-fourth the amount of corticosteroid medicine as children and teens using it daily.
Adverse effects
Use of corticosteroids has numerous side-effects, some of which may be severe:
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Severe amoebic colitis: Fulminant amoebic colitis is associated with high case fatality and can occur in patients infected with the parasite Entamoeba histolytica after exposure to corticosteroid medications.
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Neuropsychiatric: steroid psychosis,
[Benjamin H. Flores and Heather Kenna Gumina. The Neuropsychiatric Sequelae of Steroid Treatment. URL:http://www.dianafoundation.com/articles/df_04_article_01_steroids_pg01.html]
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Cardiovascular: Corticosteroids can cause sodium retention through a direct action on the kidney, in a manner analogous to the mineralocorticoid aldosterone. This can result in fluid retention and hypertension.
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Metabolic: Corticosteroids cause a movement of body fat to the face and torso, resulting in "moon face", "buffalo hump", and "pot belly" or "beer belly", and cause movement of body fat away from the limbs. This has been termed corticosteroid-induced lipodystrophy. Due to the diversion of amino-acids to glucose, they are considered anti-anabolic, and long term therapy can cause muscle wasting (muscle atrophy).
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Endocrine: By increasing the production of glucose from amino-acid breakdown and opposing the action of insulin, corticosteroids can cause hyperglycemia,
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Skeletal: Steroid-induced osteoporosis may be a side-effect of long-term corticosteroid use.
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Gastro-intestinal: While cases of colitis have been reported, corticosteroids are often prescribed when the colitis, although due to suppression of the immune response to pathogens, should be considered only after ruling out infection or microbe/fungal overgrowth in the gastrointestinal tract. While the evidence for corticosteroids causing is relatively poor except for high doses taken for over a month,
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Eyes: chronic use may predispose to cataract and glaucoma. Clinical and experimental evidence indicates that corticosteroids can cause permanent eye damage by inducing central serous retinopathy (CSR, also known as central serous chorioretinopathy, CSC).
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Vulnerability to infection: By suppressing immune reactions (which is one of the main reasons for their use in allergies), steroids may cause infections to flare up, notably candidiasis.
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Pregnancy: Corticosteroids have a low but significant teratogenic effect, causing a few birth defects per 1,000 pregnant women treated. Corticosteroids are therefore contraindicated in pregnancy.
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Habituation: Topical steroid addiction (TSA) or red burning skin has been reported in long-term users of topical steroids (users who applied topical steroids to their skin over a period of weeks, months, or years).
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In children the short term use of steroids by mouth increases the risk of vomiting, behavioral changes, and sleeping problems.
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Dysphonia: Inhaled corticosteroids are used for treatment of asthma as a standard treatment. This can cause local adverse effects like vocal cord dysfunction.
Biosynthesis
The corticosteroids are synthesized from
cholesterol within the
adrenal cortex.
Most steroidogenic reactions are catalysed by
of the cytochrome P450 family. They are located within the
mitochondria and require
adrenodoxin as a cofactor (except 21-hydroxylase and 17α-hydroxylase).
Aldosterone and corticosterone share the first part of their biosynthetic pathway. The last part is mediated either by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). These enzymes are nearly identical (they share 11β-hydroxylation and 18-hydroxylation functions), but aldosterone synthase is also able to perform an 18-oxidation. Moreover, aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex; 11β-hydroxylase is found in the zona fasciculata and zona glomerulosa.
Classification
By chemical structure
In general, corticosteroids are grouped into four classes, based on chemical structure. Allergic reactions to one member of a class typically indicate an intolerance of all members of the class. This is known as the "Coopman classification".
The highlighted steroids are often used in the screening of allergies to topical steroids.
Group A – Hydrocortisone type
Hydrocortisone, hydrocortisone acetate, cortisone acetate, tixocortol pivalate,
prednisolone, methylprednisolone, and
prednisone.
Group B – Acetonides (and related substances)
Amcinonide,
budesonide,
desonide, fluocinolone acetonide,
fluocinonide,
halcinonide, triamcinolone acetonide, and
Deflazacort (O-isopropylidene derivative)
Group C – Betamethasone type
Beclometasone,
betamethasone,
dexamethasone,
fluocortolone,
halometasone, and
mometasone.
Group D – Esters
Group D1 – Halogenated (less labile)
Alclometasone dipropionate, betamethasone dipropionate, betamethasone valerate, clobetasol propionate, clobetasone butyrate, fluprednidene acetate, and mometasone furoate.
Group D2 – Labile prodrug esters
Ciclesonide, cortisone acetate, hydrocortisone aceponate, hydrocortisone acetate, hydrocortisone buteprate, hydrocortisone butyrate, hydrocortisone valerate,
prednicarbate, and tixocortol pivalate.
By route of administration
Topical steroids
For use topically on the skin, eye, and
.
Topical corticosteroids are divided in potency classes I to IV in most countries (A to D in Japan). Seven categories are used in the United States to determine the level of potency of any given topical corticosteroid.
Inhaled steroids
For nasal mucosa, sinuses, bronchi, and lungs.
This group includes:
There also exist certain combination preparations such as Advair Diskus in the United States, containing fluticasone propionate and salmeterol (a long-acting bronchodilator), and Symbicort, containing budesonide and formoterol fumarate dihydrate (another long-acting bronchodilator).[ They are both approved for use in children over 12 years old.
]
Oral forms
Such as prednisone, prednisolone, methylprednisolone, or dexamethasone.
Systemic forms
Available in injectables for intravenous and parenteral routes.
History
+ Introduction of early corticosteroids |
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| 1948 |
| 1951 |
1954 |
| 1955 |
1955 |
| 1956 |
| 1956 |
| 1958 |
| 1958 |
| 1958 |
| 1959 |
1969 |
Tadeusz Reichstein, Edward Calvin Kendall, and Philip Showalter Hench were awarded the Nobel Prize for Physiology and Medicine in 1950 for their work on hormones of the adrenal cortex, which culminated in the isolation of cortisone.
Initially hailed as a miracle cure and liberally prescribed during the 1950s, steroid treatment brought about adverse events of such a magnitude that the next major category of anti-inflammatory drugs, the nonsteroidal anti-inflammatory drugs (NSAIDs), was so named in order to demarcate from the opprobrium.
Lewis Sarett of Merck & Co. was the first to synthesize cortisone, using a 36-step process that started with deoxycholic acid, which was extracted from ox bile.
In 1952, D.H. Peterson and H.C. Murray of Upjohn developed a process that used Rhizopus mold to oxidize progesterone into a compound that was readily converted to cortisone.
Corticosteroids were voted Allergen of the Year in 2005 by the American Contact Dermatitis Society.
See also
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List of corticosteroids
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List of corticosteroid cyclic ketals
-
List of corticosteroid esters
-
List of steroid abbreviations
