Corticosteroids are a class of steroid hormone
s that are produced in the adrenal cortex
, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoid
s and mineralocorticoid
s, are involved in a wide range of physiological
processes, including stress response
, immune response
, and regulation of inflammation
, carbohydrate metabolism
, protein catabolism
, blood electrolyte
levels, and behavior.
Some common naturally occurring steroid hormones are cortisol
() and aldosterone
(). (Note that cortisone and aldosterone are isomers
.) The main corticosteroids produced by the adrenal cortex are cortisol and aldosterone.
s such as cortisol
affect carbohydrate, fat, and protein metabolism, and have anti-inflammatory
, and vasoconstrictive
Anti-inflammatory effects are mediated by blocking the action of inflammatory mediators
) and inducing anti-inflammatory mediators (transactivation
Immunosuppressive effects are mediated by suppressing delayed hypersensitivity reactions
by direct action on T-lymphocytes
Anti-proliferative effects are mediated by inhibition of DNA synthesis
and epidermal cell
Vasoconstrictive effects are mediated by inhibiting the action of inflammatory mediators such as histidine
s such as aldosterone
are primarily involved in the regulation of electrolyte
and water balance by modulating ion transport
in the epithelial cells
of the renal tubules
of the kidney
Synthetic pharmaceutical drug
s with corticosteroid-like effects are used in a variety of conditions, ranging from brain tumor
s to skin disease
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:
** Chronic obstructive pulmonary disease
** Allergic rhinitis
** Atopic dermatitis
** Food allergies
** Drug allergies
** Nasal polyp
** Hypersensitivity pneumonitis
** Eosinophilic pneumonia
** Some other types of pneumonia
(in addition to the traditional antibiotic
** Interstitial lung disease
** Pemphigus vulgaris
** Contact dermatitis
(usually at physiologic doses)
** Addison's disease
** Adrenal insufficiency
** Congenital adrenal hyperplasia
** Ulcerative colitis
** Crohn's disease
** Autoimmune hepatitis
** Hemolytic anemia
** Idiopathic thrombocytopenic purpura
** Rheumatoid arthritis
** Systemic lupus erythematosus
** Polymyalgia rheumatica
** Optic neuritis
* Other conditions
** Multiple sclerosis
** Organ transplantation
** Nephrotic syndrome
** Chronic hepatitis
** Cerebral edema
** IgG4-related disease
** Prostate cancer
** Lichen planus
Topical formulations are also available for the skin
, 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. Wound healing or ulcer formation may be inhibited by the immunosuppressive effects.
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). This should be borne in mind when treating patients with optic neuritis
. There is experimental and clinical evidence that, at least in optic neuritis
speed of treatment initiation is important.
A variety of steroid medications, from anti-allergy nasal sprays (Nasonex
) to topical skin creams, to eye drops (Tobradex
), to prednisone have been implicated in the development of CSR.
Corticosteroids have been widely used in treating people with traumatic brain injury
. A systematic review
identified 20 randomised controlled trials and included 12,303 participants, then compared patients who received corticosteroids with patients who received no treatment. The authors recommended people with traumatic head injury should not be routinely treated with corticosteroids.
Corticosteroids act as agonist
s of the glucocorticoid receptor
and/or the mineralocorticoid receptor
In addition to their corticosteroid activity, some corticosteroids may have some progestogen
ic activity and may produce sex-related side effects.
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.
Use of corticosteroids has numerous side-effects, some of which may be severe:
* Severe amebic colitis: Fulminant amebic colitis is associated with high case fatality and can occur in patients infected with the parasite ''Entamoeba histolytica
'' after exposure to corticosteroid medications.
* Neuropsychiatric: steroid psychosis
. Therapeutic doses may cause a feeling of artificial well-being ("steroid euphoria"). The neuropsychiatric effects are partly mediated by sensitization of the body to the actions of adrenaline. Therapeutically, the bulk of corticosteroid dose is given in the morning to mimic the body's diurnal rhythm; if given at night, the feeling of being energized will interfere with sleep. An extensive review is provided by Flores and Gumina.
* 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
* 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.
* Endocrine: By increasing the production of glucose from amino-acid breakdown and opposing the action of insulin, corticosteroids can cause hyperglycemia
, insulin resistance
and diabetes mellitus
* Skeletal: Steroid-induced osteoporosis
may be a side-effect of long-term corticosteroid use. Use of inhaled corticosteroids among children with asthma may result in decreased height.
* 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 peptic ulcer
ation is relatively poor except for high doses taken for over a month,
the majority of doctors still believe this is the case, and would consider protective prophylactic measures.
* Eyes: chronic use may predispose to cataract
* 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
* Pregnancy: Corticosteroids have a low but significant teratogenic
effect, causing a few birth defects per 1,000 pregnant women treated. Corticosteroids are therefore contraindicated
* 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). TSA is characterised by uncontrollable, spreading dermatitis and worsening skin inflammation which requires a stronger topical steroid to get the same result as the first prescription. When topical steroid medication is lost, the skin experiences redness, burning, itching, hot skin, swelling, and/or oozing for a length of time. This is also called 'red skin syndrome' or 'topical steroid withdrawal' (TSW). After the withdrawal period is over the atopic dermatitis can cease or is less severe than it was before.
* In children the short term use of steroids by mouth increases the risk of vomiting, behavioral changes, and sleeping problems.
, including corticosteroid biosynthesis.
The corticosteroids are synthesized from cholesterol
within the adrenal cortex
Most steroidogenic reactions are catalysed by enzyme
s of the cytochrome P450
family. They are located within the mitochondria
and require adrenodoxin
as a cofactor (except 21-hydroxylase
share the first part of their biosynthetic pathway. The last part is mediated either by the aldosterone synthase
) or by the 11β-hydroxylase
). 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 of corticosteroids
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 acetate
, Cortisone acetate
, tixocortol pivalate
Group B – Acetonides (and related substances)
, fluocinolone acetonide
, and triamcinolone acetonide
Group C – Betamethasone type
, and mometasone
Group D – Esters
– Halogenated (less labile)
, betamethasone dipropionate
, betamethasone valerate
, clobetasol propionate
, clobetasone butyrate
, fluprednidene acetate
, and mometasone furoate
– Labile prodrug esters
, cortisone acetate
, hydrocortisone aceponate
, hydrocortisone acetate
, hydrocortisone buteprate
, hydrocortisone butyrate
, hydrocortisone valerate
, and tixocortol pivalate
By route of administration
For use topically on the skin, eye, and mucous membrane
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.
For nasal mucosa, sinuses, bronchi, and lungs.
This group includes:
* Fluticasone furoate
* Fluticasone propionate] [
* Triamcinolone acetonide] [
* Beclomethasone dipropionate] [
* Budesonide] [
* Mometasone furoate
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.
Such as prednisone, prednisolone, methylprednisolone, or dexamethasone.
Available in injectables for intravenous and parenteral routes.
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.
Corticosteroids were voted Allergen of the Year in 2005 by the American Contact Dermatitis Society.
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. The low efficiency of converting deoxycholic acid into cortisone led to a cost of US$200 per gram. Russell Marker, at Syntex, discovered a much cheaper and more convenient starting material, diosgenin from wild Mexican yams. His conversion of diosgenin into progesterone by a four-step process now known as Marker degradation was an important step in mass production of all steroidal hormones, including cortisone and chemicals used in hormonal contraception.
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. The ability to cheaply synthesize large quantities of cortisone from the diosgenin in yams resulted in a rapid drop in price to US$6 per gram, falling to $0.46 per gram by 1980. Percy Julian's research also aided progress in the field. [Julian, Percy L., Cole, John Wayne, Meyer, Edwin W., and Karpel, William J. (1956) "Preparation of Cortisone". U. S. Patent 2,752,339] The exact nature of cortisone's anti-inflammatory action remained a mystery for years after, however, until the leukocyte adhesion cascade and the role of phospholipase A2 in the production of prostaglandins and leukotrienes was fully understood in the early 1980s.
The ''cortico-'' part of the name refers to the adrenal cortex, which makes these steroid hormones. Thus a corticosteroid is a "cortex steroid".
* List of corticosteroids
* List of corticosteroid cyclic ketals
* List of corticosteroid esters
* List of steroid abbreviations
Category:World Anti-Doping Agency prohibited substances