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→Introduction
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.
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==Introduction==
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==
As with most drugs, steroids may be administered in a variety of ways. Topical steroids are appropriate for used in the eyes and ears, and on the skin. The structure of the drug can affect how useful it is topically; the C17 aliphatic side chain can influence topical absorption, and acetonide esters (e.g. betamethasone-17-valerate) are well absorbed from the skin but have little systemic access. Steroids are well absorbed orally, and may also be used parenterally, by inhalation and intra-articularly.
As with most drugs, steroids may be administered in a variety of ways. Topical steroids are appropriate for used in the eyes and ears, and on the skin. The structure of the drug can affect how useful it is topically; the C17 aliphatic side chain can influence topical absorption, and acetonide esters (e.g. betamethasone-17-valerate) are well absorbed from the skin but have little systemic access. Steroids are well absorbed orally, and may also be used parenterally, by inhalation and intra-articularly.
==Side Effects and Contraindications==
==Side Effects and Contraindications==
Side effects of steroids include:
* [[:Category:Gastric Ulceration|Gastric ulceration]]. This is potentiated by [[NSAIDs|NSAIDs]] and therefore concurrent use of these drugs is contraindicated.
* Muscle atrophy
* Cutaneous atrophy
* Hyperglycaemia
* 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.
* [[Adrenal Glands - Anatomy & Physiology#Mineralocorticoids|Mineralocorticoid]] activity, resulting in sodium and water retention and loss of potassium.
* Polyuria and polydipsia
* Increased susceptibility to infection, due to immuno-suppressive effects.
* Laminitis in horses
* Corneal ulceration
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 [[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==
The activity and duration of action of some steroid drugs is summarised in the table below.
<center>
<center>
|12-36
|12-36
|- style="background:#F0F8FF; color:black"
|- style="background:#F0F8FF; color:black"
|<font color=#0C1A5D>'''Triamcinolone''' </font>
|5
|None
|24-48
|-
|<font color=#0C1A5D>'''Dexamethasone''' </font>
|<font color=#0C1A5D>'''Dexamethasone''' </font>
|30
|30
|Minimal
|Minimal
|24-28
|24-28
|-
|- style="background:#F0F8FF; color:black"
|<font color=#0C1A5D>'''Betamethasone''' </font>
|<font color=#0C1A5D>'''Betamethasone''' </font>
|30
|30
|Minimal
|Minimal
|24-48
|24-48
|- style="background:#F0F8FF; color:black"
|-
|<font color=#0C1A5D>'''Fludrocortisone''' </font>
|<font color=#0C1A5D>'''Fludrocortisone''' </font>
|15
|15
|}
|}
</center>
</center>
Short acting (less than 24 hours) drugs include:
* Prednisolone
* Prednisone
* Methylprednisolone
Long acting (greater than 24 hours) drugs include:
* Dexamethasone
* Betamethasone
* Triamcinolone
There is a mnemonic to help you remember the actions and potency of the steroid drugs:
* '''H'''elp (hydrocortisone)
* '''P'''ain (prednisolone)
* '''M'''anagement (methylprednisolone);
* '''T'''reat (triamcinolone)
* '''B'''ad (betamethasone)
* '''D'''ermatitis (dexamethasone)
Potency of the drug increases as you go down the list. "Helping pain management" relates to a mainly anti-inflammatory action; "treating bad dermatitis" relates to a mainly immuno-suppressive effect.
Methylprednisolone acetate and triamcinolone acetonide are suitable for intra-articular used. Methylprednisolone acetate is rapidly metabolised to methylprednisolone. Although levels within the joint are maintained for up to 39 days, by 24 hours there is a very low serum concentration of the drug. This steroid has adverse affects on articular cartilage. Triamcinolone acetonide levels in the plasma are higher and maintained for longer, but the drug is undetectable in the joint two weeks post-treatment. It does not have effects on bone remodelling or fragility.
==Clinical Uses==
==Clinical Uses==
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 [[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 in the treatment of neoplasia. They are usually used as part of a chemotherapeutic protocol in conjunction with additional chemotherapeutic agents, but also help in the management of secondary complications such as paraneoplastic hypercalcaemia.
As above, some steroids can be used intra-articularly.
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===
* Drugs with minimal mineralocorticoid activity are preferred. This is so that ion and fluid balance is not adversely affected.
* Treatment with steroids is merely palliative. Although it relieves the symptoms, it does not resolve the underlying cause of disease.
* If antimicrobial drugs are used in conjuction with steroids, these should be bactericidal rather than bacteristatic. This is because steroids have an immuno-suppressive effect and so more effective anti-microbials are required.
* Treatment should be withdrawn gradually to reduce the risk of a crisis occuring (see [[#Side Effects and Contraindications|Side Effects and Contraindications]]).
* Long acting compunds carry a greater risk of toxicity.