Corticosteroid


Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, and also their synthetic analogues. The two main classes of corticosteroids – glucocorticoids and mineralocorticoids – 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, corticosterone, cortisone and aldosterone . The main corticosteroids produced by the adrenal cortex are cortisol and aldosterone.

Etymology

The etymology of the cortico- part of the name refers to the adrenal cortex, which makes these steroid hormones. Thus a corticosteroid is a "cortex steroid".

Classes

Synthetic pharmaceutical drugs with corticosteroid-like effects are used in a variety of conditions, ranging from hematological neoplasms to brain tumors or skin diseases. Dexamethasone and its derivatives are almost pure glucocorticoids, while prednisone and its derivatives have some mineralocorticoid action in addition to the glucocorticoid effect. Fludrocortisone is a synthetic mineralocorticoid. Hydrocortisone 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, eyes, lungs, nose, and bowels. Corticosteroids are also used supportively to prevent nausea, often in combination with 5-HT3 antagonists.
Typical undesired effects of glucocorticoids present quite uniformly as drug-induced Cushing's syndrome. Typical mineralocorticoid side-effects are hypertension, steroid induced diabetes mellitus, psychosis, poor sleep, hypokalemia, hypernatremia without causing peripheral edema, metabolic alkalosis and connective tissue weakness. Wound healing or ulcer formation may be inhibited by the immunosuppressive effects.
A variety of steroid medications, from anti-allergy nasal sprays to topical skin creams, to eye drops, to prednisone have been implicated in the development of central serous retinopathy.
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.

Pharmacology

Corticosteroids act as agonists 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 and TBX21. 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:
  • 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.
  • Neuropsychiatric: steroid psychosis, and anxiety, depression. Therapeutic doses may cause a feeling of artificial well-being. 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. Besides muscle atrophy, steroid myopathy includes muscle pains, muscle weakness, serum creatine kinase normal, EMG myopathic, and some have type II fibre atrophy.
  • 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 ulceration is relatively poor except for high doses taken for over a month, the majority of doctors as of 2010 still believe this is the case, and would consider protective prophylactic measures.
  • 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. 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.
  • Vulnerability to infection: By suppressing immune reactions, 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 in pregnancy.
  • Habituation: Topical steroid addiction or red burning skin has been reported in long-term users of topical steroids. 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'. 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.
  • Dysphonia: Inhaled corticosteroids are used for treatment of asthma as a standard treatment. This can cause local adverse effects like vocal cord dysfunction.