Some common naturally occurring steroid hormones are
cortisol (C 21H 30O 5),
corticosterone (C 21H 30O 4),
cortisone (C 21H 28O 5) and
aldosterone (C 21H 28O 5) (cortisone and
aldosterone are
isomers). The main corticosteroids produced by the adrenal cortex are cortisol and aldosterone.[1]
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.[5] Wound healing or ulcer formation may be inhibited by the immunosuppressive effects.
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).[6][7]
Corticosteroids have been widely used in treating people with
traumatic brain injury.[8] 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.[9]
In addition to their corticosteroid activity, some corticosteroids may have some
progestogenic activity and may produce sex-related side effects.[10][11][12][13]
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.[14][15] However, not all asthma patients respond to corticosteroids and large sub groups of asthma patients are corticosteroid resistant.[16]
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.[17][18]
Adverse effects
Use of corticosteroids has numerous side-effects, some of which may be severe:
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.[19]
Neuropsychiatric:
steroid psychosis,[20] and
anxiety,[21]depression. Therapeutic doses may cause a feeling of artificial well-being ("steroid euphoria").[22] 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.[23]
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 (muscle atrophy).[24] Besides muscle atrophy, steroid myopathy includes muscle pains (myalgias), muscle weakness (typically of the proximal muscles), serum creatine kinase normal, EMG myopathic, and some have type II (fast-twitch/glycolytic) fibre atrophy.[25]
Skeletal:
Steroid-induced osteoporosis may be a side-effect of long-term corticosteroid use.[28][29][30] Use of inhaled corticosteroids among children with asthma may result in decreased height.[31]
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 ulceration is relatively poor except for high doses taken for over a month,[32] the majority of doctors as of 2010[update] still believe this is the case, and would consider protective prophylactic measures.[33]
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).[34] 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.[35]
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.[36]
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.[37]
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).[38][39] 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.[40]
In children the short term use of steroids by mouth increases the risk of vomiting, behavioral changes, and sleeping problems.[41]
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".[42][43]
The highlighted steroids are often used in the screening of allergies to topical steroids.[44]
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.[45]
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.[55] Corticosteroids were voted
Allergen of the Year in 2005 by the American Contact Dermatitis Society.[56]
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
oxbile.[57] The low efficiency of converting deoxycholic acid into cortisone led to a cost of US$200 per gram in 1947.
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.[58]
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.[59] 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[when?], falling to $0.46 per gram by 1980.
Percy Julian's research also aided progress in the field.[60] 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.
Etymology
The cortico- part of the name refers to the
adrenal cortex, which makes these steroid hormones. Thus a corticosteroid is a "cortex steroid".
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