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A better understanding of corticosteroids and their risks

Allergy, Eczema, Eyes, Asthma, General | June 20, 2014 | Author: The Super Pharmacist

Inflammation, corticosteroids, prednisone

A better understanding of corticosteroids and their risks

Corticosteroids are both natural molecules that act as hormones in the body, and artificially produced chemical variations on the basic corticosterone structure. Corticosterone is the essential form on which the other biological corticosteroids are based, which is in turn synthesised in the body from cholesterol molecules.

The function of most corticosteroids is to regulate physiological responses.

These include:

  • Immune system function
  • Stress processing
  • Metabolism
  • Homeostasis
  • Emotions and other neurological functions

There are two main types of corticosteroid; mineralocorticoids and glucocorticoids.

Glucocorticoids are mostly involved in the regulation of major nutrient (i.e. protein, carbohydrate and fat) metabolism, inflammation and immune cell control.
Mineralocorticoids mainly control salt balance in the kidneys, thus contributing to the overall health and function of the body.
Both types also play a role in cognitive and other neurological responses to stress.

Corticosteroids and Their Uses

The most well-known natural corticosteroids are cortisone, corticosterone and aldosterone.

Aldosterone (a mineralocorticoid) and cortisone (a glucocorticoid) are both variations on the chemical structure of corticosterone.

Synthetic corticosteroid-based drugs include dexamethasone, a glucocorticoid, and fludrocortisone, a mineralocorticoid. Some synthetic molecules are purely one main type or another, such as cortisol (hydrocortisone). Others, such as prednisone, have properties of both mineralocorticoids and glucocorticoids. As the release of both types of corticosteroid is controlled by the hypothalmic-pituitary-adrenal (HPA) axis of the central nervous system, they may also be recommended to treat disorders in which this is damaged. These include Addison's disease and adrenal hyperplasia.

They are also used in the treatment of many disorders and diseases in which corticosteroid deficiency or activity may play a role. These may include illnesses associated with the release of inflammatory molecules, such as:

  • Arthritis
  • Systemic lupus erythematosus
  • Crohn's disease
  • Sarcoidosis

As inflammation is also associated with pain, corticosteroids are also used in the treatment of many painful conditions. An effective method of corticosteroid therapy is direct injection into the vicinity of nerves responsible for perception of this pain by the brain. Corticosteroids are often applied to nerves travelling to and from the spine in this manner. These procedures are called epidural steroid injections, and are effective in treating chronic pain associated with conditions such as arthritis, hip fracture, whiplash and cancer.

Corticosteroids may also be injected directly into joints, to inhibit inflammation and thus relieve pain, particularly in cases of hip and knee pain.

These molecules can also treat breathing disorders, which are also often associated with inflammation. This is done by the formulation of corticosteroids (e.g. budesonide, flunisolide, triamcinolone and the fluticasones) into inhalable preparations, which are delivered with either nasal sprays or inhalers. Conditions associated with these include asthma, bronchitis and chronic obstructive pulmonary disorder.

How do corticosteroids work?

Glucocorticoids bind to the glucocorticoid receptor (GR), which is found in a huge variety of cell types - i.e. cells of virtually every organ and system in the body. When the corticosteroid molecule binds, it and the receptor form a single entity that migrates into the nucleus (or central 'control' area) of the cell. The nucleus contains the DNA of the cell. The receptor-corticosteroid complex binds to this and either activates or inhibits the expression of certain genes, which cause the cell (and possibly other similar cells around it) to change in behavior. Ultimately, this results in the discernible effects as outlined above.

Mineralocorticoids also bind to their corresponding receptor, which are located mainly in the renal, pulmonary and nervous systems. This results in gene expression changes in a similar way to glucocorticoid action. Mineralocorticoid receptor binding may also cause changes in the salt balance of tissues - i.e. sodium and/or potassium is taken up or expelled - which can result in water loss or retention, e.g. in the course of renal function. As mentioned above, some corticosteroids are compatible with both the mineralocorticoid and glucocorticoid receptors. The extent to which a molecule may bind and activate either, is known as potency. Each corticosteroid may have a particular degree of glucocorticoid potency, mineralocorticoid potency, or of both.

Risks and side-effects of Corticosteroids

Corticosteroids are associated with a range of severe side-effects, particularly in cases of long-term use. A recent study indicated that up to 6% of patients taking corticosteroids experience these events. As both glucocorticoids and mineralocorticoids play important roles in psychiatric responses to stress, and in other aspects of neurology such as cognition, altered levels of these can result in behavioral and emotional reactions. These include an increased propensity for negative affect-related disorders such as depression. Conversely, corticosteroid therapy may elicit feelings of euphoria, excessive energy and exaggerated well-being. There is also an increased risk of psychosis associated with corticosteroid intake.

  • Fat distribution. Corticosteroids may also be associated with a migration of fat away from the extremities and into the facial area or torso instead.
     
  • Mucscle loss. They can also cause a decrease in muscle tissue, which is ironic as they are used in treating the symptoms of wasting diseases such as Duchenne's muscular dystrophy.
     
  • Osteoporosis. They also increase the risk of osteoporosis (brittle bones) in the later life of some patients.
     
  • Hypertension. Corticosteroids is associated with an increased risk of hypertension (high blood pressure).
    This may be due to the aldosterone-like effects of some mineralocorticoids on salt balance in the body.
     
  • Diabetes. Synthetic corticosteroid therapy may disrupt the glucose metabolism regulation of their natural analogs. This may result in a heightened probability of type 2 diabetes or insulin resistance. This may have a similar effect on sex hormones (which are themselves steroid derivatives), which may have a knock-on effect, resulting in conditions such as hypogonadism and menstrual cycle abnormalities.
     
  • Gastic ulcers. Corticosteroids can cause gastrointestinal side-effects, such as gastric ulcers and bleeding. As they tend to inhibit or otherwise negatively regulate the immune system, patients on corticosteroid therapy may be immunocompromised and thus more susceptible to infection.
     
  • Cataract/retinal damage. Intake or administration via eyedrops (for conditions such as uveitis or eye infection) of these drugs can increase the probability of cataract development or retinal damage.
     
  • Risk to foetus. Corticosteroids intake while pregnant is associated with teratogenicity, or fetal abnormalities.

Withdrawal of Corticosteroids 

The risks associated with corticosteroids should include issues involving abrupt discontinuation of corticosteroid therapy. Short-notice withdrawal from inhaled formulations for pulmonary conditions can result in the resurgence and/or worsening of original symptoms, decrease in lung capacity and sleep disturbance (i.e. due to breathing difficulties).

Withdrawal of artificial glucocorticoids (for conditions related to immune system dysfunction) can result in the symptoms of adrenal insufficiency, particularly in elderly patients. Corticosteroid reductions may also result in the increased risk of bone density loss.

Use of corticosteroids in children

Corticosteroids are commonly used in children, particularly for respiratory conditions. The most common use involves specified time use of less than 7 days. When these medications are used ongoing, the risks of corticosteroid therapy may also be magnified in pediatric patients. The most prominent of these are adverse behavioral, cognitive and emotional effects.

There are also concerns about links to reduced growth rates and bone development with childhood corticosteroid intake. Recent research indicates that this may be due to changes in the HPA axis activity in these patients, and also to possible deficits in bone growth while taking corticosteroids.

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