Changes

Steroids are 21-carbon, 4-ring molecules, with biologically active steroids have a double covalent bond between carbon atoms 4 and 5, and a ketone group at C3. The body endogenously produces steroids which are essential for life; they regulate a variety of functions under normal physiological conditions and have important roles in response to stress. These steroids are  produced in the [[Adrenal Glands - Anatomy & Physiology#Adrenal Glands|adrenal cortex]] and are therefore known as "corticosteroids". The corticosteroids can be further divided to [[Adrenal Glands - Anatomy & Physiology#Mineralocorticoids|mineralocorticoids]] and [[Adrenal Glands - Anatomy & Physiology#Glucocorticoids|glucocorticoids]] which are synthesised in different areas of the cortex. [[Adrenal Glands - Anatomy & Physiology#Mineralocorticoids|mineralocorticoids]] (such as aldosterone) are produced in the [[Adrenal Glands - Anatomy & Physiology#Adrenal Glands|zona glomerulosa]]; [[Adrenal Glands - Anatomy & Physiology#Glucocorticoids|glucocorticoids]] include cortisol (from the [[Adrenal Glands - Anatomy & Physiology#Adrenal Glands|zona fasiculata]]) and corticosterone (from the [[Adrenal Glands - Anatomy & Physiology#Adrenal Glands|zona reticularis]]). Corticosteroids are synthesised from plasma cholesterol which is stored in the adrenal gland and assimilated to corticosteroids as they are required. Endogenous glucocorticoid levels are regulated by the [[Adrenal Glands - Anatomy & Physiology#Glucocorticoids|hypothalamus-pituitary adrenal axis]], whereas the [[Important Hormonal Regulators of the Kidney - Anatomy & Physiology#The Renin Angiotensin Aldosterone System (RAAS)|renin angiotensin aldosterone system]] controls [[Adrenal Glands - Anatomy & Physiology#Mineralocorticoids|mineralocorticoid]] levels.

 

 

Steroids are a diverse class of molecules, all of which have a 21-carbon, 4-ring skeleton. Biologically active steroids have a double covalent bond between carbon atoms 4 and 5, and a ketone group at C3. The body endogenously produces steroids which are essential for life; they regulate a variety of functions under normal physiological conditions and have important roles in response to stress. These steroids are  produced in the [[Adrenal Glands - Anatomy & Physiology#Adrenal Glands|adrenal cortex]] and are therefore known as "corticosteroids". The corticosteroids can be further divided to [[Adrenal Glands - Anatomy & Physiology#Mineralocorticoids|mineralocorticoids]] and [[Adrenal Glands - Anatomy & Physiology#Glucocorticoids|glucocorticoids]] which are synthesised in different areas of the cortex. [[Adrenal Glands - Anatomy & Physiology#Mineralocorticoids|mineralocorticoids]] (such as aldosterone) are produced in the [[Adrenal Glands - Anatomy & Physiology#Adrenal Glands|zona glomerulosa]]; [[Adrenal Glands - Anatomy & Physiology#Glucocorticoids|glucocorticoids]] include cortisol (from the [[Adrenal Glands - Anatomy & Physiology#Adrenal Glands|zona fasiculata]]) and corticosterone (from the [[Adrenal Glands - Anatomy & Physiology#Adrenal Glands|zona reticularis]]). Corticosteroids are synthesised from plasma cholesterol which is stored in the adrenal gland and assimilated to corticosteroids as they are required. Endogenous glucocorticoid levels are regulated by the [[Adrenal Glands - Anatomy & Physiology#Glucocorticoids|hypothalamus-pituitary adrenal axis]], whereas the [[Renin Angiotensin Aldosterone System|renin angiotensin aldosterone system]] controls [[Adrenal Glands - Anatomy & Physiology#Mineralocorticoids|mineralocorticoid]] levels.

==Mechanism of Action==

==Mechanism of Action==

==Actions==

==Actions==

Both endogenous and exogenous steroids have a variety of actions. Some of these, such as [[Steroids#Anti-Inflammatory Effects|anti-inflammatory effects]], are only seen at pharamacological concentrations.

Both endogenous and exogenous steroids have a variety of actions. Some of these, such as [[Steroids#Anti-Inflammatory Effects|anti-inflammatory effects]], are only seen at pharmacological concentrations.

Alterations in steroid dose can influence the action they have. This is particulatly relevant to anti-inflammatory and immuno-suppressive effects.

Alterations in steroid dose can influence the action they have. This is particulatly relevant to anti-inflammatory and immuno-suppressive effects.

===Metabolic Effects===

===Metabolic Effects===

The metabolic effects of steroids are mainly catabolic and primarily effect carbohydrate and protein metabolism. They include:

The metabolic effects of steroids are mainly catabolic and primarily affect carbohydrate and protein metabolism. They include:

* Increasing gluconeogenesis, meaning amino acids and lactate are converted to glucose.

* Increasing gluconeogenesis, meaning amino acids and lactate are converted to glucose.

* '''Blood vessels''', to decrease vasodilation and fluid exudation.

* '''Blood vessels''', to decrease vasodilation and fluid exudation.

* '''Inflammatory mediators''', by:

* '''Inflammatory mediators''', by:

** Inhibiting cyclo-oygenase, leading to a decrease in prostanoid levels.

** Inhibiting cyclo-oxygenase, leading to a decrease in prostanoid levels.

** Inhibiting phosphlipase-A2, reducing conversion of phospholipid to arachidonate and therfore mediator production.

** Inhibiting phospholipase-A2, reducing conversion of phospholipid to arachidonate and therefore mediator production.

** Decreasing generation of inflammatory cytokines.

** Decreasing generation of inflammatory cytokines.

** Decreasing histamine release.

** Decreasing histamine release.

===Immuno-Suppressive Effects===

===Immuno-Suppressive Effects===

Low doses of steroid inhibit the cellular response, decreasing lymphocytes, eosinophils, monocytes and basophils. However, neutrophil numbers are increased. High steroid doses inhibit the humoral response.

Low doses of steroid inhibit the cellular response, decreasing lymphocytes, eosinophils, [[Monocytes]] and basophils. However, neutrophil numbers are increased. High steroid doses inhibit the humoral response.

==Pharmacokinetic Considerations==

==Pharmacokinetic Considerations==

Side effects of steroids include:

Side effects of steroids include:

* Gastric ulceration. This is potentiated by [[NSAIDs|NSAIDs]] and therefore concurrent use of these drugs is contraindicated.

* [[:Category:Gastric Ulceration|Gastric ulceration]]. This is potentiated by [[NSAIDs|NSAIDs]] and therefore concurrent use of these drugs is contraindicated.

* Muscle atrophy

* Muscle atrophy

* Cutaneous atrophy

* Cutaneous atrophy

* Hyperglycaemia

* Hyperglycaemia

* Osteoporotic effects. These occur sicne steroids decrease absroption and increase excreting of calcium. They also increase parathyroid hormone activity, leading to decreases in osteoblastic activity and increases in activity of osteoclasts. Degeneration of epiphyseal cartilage can also occur in young animals.

* Osteoporotic effects. These occur since steroids decrease absorption and increase excretion of calcium. They also increase parathyroid hormone activity, leading to decreases in osteoblastic activity and increases in activity of osteoclasts. Degeneration of epiphyseal cartilage can also occur in young animals.

* Mineralocorticoid activity, resulting in sodium and water retention and loss of potassium.

* [[Adrenal Glands - Anatomy & Physiology#Mineralocorticoids|Mineralocorticoid]] activity, resulting in sodium and water retention and loss of potassium.

* Polyuria and polydipsia

* Polyuria and polydipsia

* Increased susceptibility to infection, due to immuno-suppressive effects.

* Increased susceptibility to infection, due to immuno-suppressive effects.

Suppression of the hypothalamus-pituitary axis can occur. Exogenous steroids extert negative feedback in the same way that endogenous steroids do. This leads to suppression of ACTH formation and storage and may cause atrophy of the pituitary gland. Sudden termination of treatment with exogenous steroids can therefore lead to failure of production of endogenous steroids, causing a crisis. This means that gradual dose reduction is of paramount importance. One method of achieving this is by alternate day thereapy, where a short-acting glucocorticoid in a short-acting formulation us used every other day at times to conincide with peak endogenous steroid levels.

Suppression of the hypothalamus-pituitary axis can occur. Exogenous steroids extert negative feedback in the same way that endogenous steroids do. This leads to suppression of ACTH formation and storage and may cause atrophy of the pituitary gland. Sudden termination of treatment with exogenous steroids can therefore lead to failure of production of endogenous steroids, causing a crisis. This means that gradual dose reduction is of paramount importance. One method of achieving this is by alternate day thereapy, where a short-acting glucocorticoid in a short-acting formulation us used every other day at times to conincide with peak endogenous steroid levels.

Another serious side effect of steroid administration is iatrogenic Cushing's disease (hyperadrenocorticism). This can result from prolonged glucocorticoid treatement, and signs can include polydipsia, polyuria, polyphagia, elevation of liver enzyme levels and a pot-belly.

Another serious side effect of steroid administration is iatrogenic [[Hyperadrenocorticism|Cushing's disease]] (hyperadrenocorticism). This can result from prolonged glucocorticoid treatement, and signs can include polydipsia, polyuria, polyphagia, elevation of liver enzyme levels and a pot-belly.

==Drugs in This Group==

==Drugs in This Group==

Steroids can be used as treatment in a wide variety of clinical scenarios. For example, one major use of steroids is against inflammatory disease. Both acute inflammatory disease (such as allergic reactions) and chronic conditions (such as osteoarthritis) may benefit from the administration of steroids.

Steroids can be used as treatment in a wide variety of clinical scenarios. For example, one major use of steroids is against inflammatory disease. Both acute inflammatory disease (such as allergic reactions) and chronic conditions (such as osteoarthritis) may benefit from the administration of steroids.

Immune-mediated disorders can also be treated with steroids. Initially, high doses are used which are gradually decreased until an effective maintenance dose for that individual is reached. In protocols such as this, steroids may be used in conjunction with other immuno-supressive drugs. Examples of diseases that may be treated this way are [[Autoimmune diseases - WikiClinical#1. Immune Mediated Haemolytic Anaemia (IMHA)|immune-mediated haemolytic anaemia]], [[Muscles Developmental - Pathology#Myasthenia gravis (MG)|myasthenia gravis]] and immune-mediated skin disease.

Immune-mediated disorders can also be treated with steroids. Initially, high doses are used which are gradually decreased until an effective maintenance dose for that individual is reached. In protocols such as this, steroids may be used in conjunction with other immuno-supressive drugs. Examples of diseases that may be treated this way are [[Immune Mediated Haemolytic Anaemia|immune-mediated haemolytic anaemia]], [[Myasthenia Gravis|myasthenia gravis]] and immune-mediated skin disease.

Steroids can be used to treat shock. The timing of treatment is important in this instance, and a high dose of a short-acting glucocorticoid is usually used.  Cerebral oedema can also be treated with steroids.

Steroids can be used to treat shock. The timing of treatment is important in this instance, and a high dose of a short-acting glucocorticoid is usually used.  Cerebral oedema can also be treated with steroids.

As above, some steroids can be used intra-articularly.

As above, some steroids can be used intra-articularly.

Steroids with mineralocorticoid activity are used to treat [[Hypoadrenocorticism - Addison's Disease|Addison's Disease]]. The condition is treated acutely using hydrocortisone, with fludrocortisone being used for long-term management.

Steroids with mineralocorticoid activity are used to treat [[Hypoadrenocorticism|Addison's Disease]]. The condition is treated acutely using hydrocortisone, with fludrocortisone being used for long-term management.

===Principles of Therapy===

===Principles of Therapy===