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Showing posts with label Corticosteroids. Show all posts
Showing posts with label Corticosteroids. Show all posts
Glucocorticoids
By Piscean | Saturday, January 21, 2012 | Posted in , , , , | With 0 comments
Glucocorticoids
Most glucocorticoids are synthetic analogues of hormones secreted by the adrenal cortex. They exert anti-inflammatory, metabolic, and immunosuppressant effects. Drugs in this class include:
  • beclomethasone
  • betamethasone
  • cortisone
  • dexamethasone
  • hydrocortisone
  • methylprednisolone
  • prednisolone
  • prednisone
  • triamcinolone.
Pharmacokinetics
Glucocorticoids are well absorbed when administered orally. After I.M. administration, they’re absorbed completely.
Distribution
Glucocorticoids are bound to plasma proteins and distributed through the blood.
Metabolism and excretion
Glucocorticoids are metabolized in the liver and excreted by the kidneys.
Pharmacodynamics
Glucocorticoids suppress hypersensitivity and immune responses through a process that isn’t entirely understood. Researchers believe that glucocorticoids inhibit immune responses by:
  • suppressing or preventing cell-mediated immune reactions
  • reducing levels of leukocytes, monocytes, and eosinophils
  • decreasing the binding of immunoglobulins to cell surface receptors
  • inhibiting interleukin synthesis.

Taking the red (and more) out
Glucocorticoids suppress the redness, edema, heat, and tenderness associated with the inflammatory response. They start on the cellular level by stabilizing the lysosomal membrane (a structure
within the cell that contains digestive enzymes) so that it doesn’t release its store of hydrolytic enzymes into the cells.
Now I get it!
How methylprednisolone works
Tissue trauma normally leads to tissue irritation, edema, inflammation, and production of scar tissue. Methylprednisolone counteracts the initial effects of tissue trauma, promoting healing.

No leaks, no drips
As corticosteroids, glucocorticoids prevent the leakage of plasma from capillaries, suppress the migration of polymorphonuclear leukocytes (cells that kill and digest microorganisms), and inhibit phagocytosis (ingestion and destruction).
To ensure a job well done, glucocorticoids decrease antibody formation in injured or infected tissues and disrupt histamine synthesis, fibroblast development, collagen deposition, capillary dilation, and capillary permeability.

Warning!
Adverse reactions to cortico-steroids
Corticosteroids affect almost all body systems. Their widespread adverse effects include:
  • insomnia
  • increased sodium and water retention
  • increased potassium excretion
  • suppressed immune and inflammatory responses
  • osteoporosis
  • intestinal perforation
  • peptic ulcers
  • impaired wound healing.
Diabetes and more
Endocrine system reactions may include:
  • diabetes mellitus
  • hyperlipidemia
  • adrenal atrophy
  • hypothalamic-pituitary axis suppression
  • cushingoid signs and symptoms (such as buffalo hump, moon face, and elevated blood glucose levels).
Pharmacotherapeutics
Besides their use as replacement therapy for patients with adrenocortical insufficiency, glucocorticoids are prescribed for immunosuppression and reduction of inflammation and for their effects on the blood and lymphatic systems.
Drug interactions
Many drugs interact with corticosteroids:
  • Aminoglutethimide, barbiturates, phenytoin, and rifampin may reduce the effects of corticosteroids.
  • Their potassium-wasting effects may be enhanced by amphotericin B, chlorthalidone, ethacrynic acid, furosemide, and thiazide diuretics.
  • Erythromycin and troleandomycin may increase their effects by reducing their metabolism.
  • They reduce the serum concentration and effects of salicylates.
  • The risk of peptic ulcers associated with nonsteroidal anti-inflammatory drugs and salicylates increases when these agents are taken with corticosteroids.
  • The response to vaccines and toxoids may be reduced in a patient taking corticosteroids.
  • Estrogen and hormonal contraceptives that contain estrogen increase the effects of corticosteroids.
  • The effects of antidiabetic drugs may be reduced, resulting in increased blood glucose levels
Corticosteroids
By Piscean | Wednesday, November 2, 2011 | Posted in , , | With 0 comments

Corticosteroids
Any of a group of steroid hormones produced in the adrenal cortex or made synthetically. There are two kinds: glucocorticoids and mineralocorticoids. They have various metabolic functions and some are used to treat inflammation
Explanation:
Glucocorticoids have multiple effects, and are used for a large number of conditions. They affect glucose utilization, fat metabolism, and bone development, and are potent anti-inflammatory agents. They may be used for replacement of natural hormones in patients with pituitary deficiency (Addison's disease), as well as for a wide number of other conditions including, but not limited to, arthritis, asthma, anemia, various cancers, and skin inflammations. Additional uses include inhibition of nausea and vomiting after chemotherapy, treatment of septic shock, treatment of spinal cord injuries, and treatment of hirisutism (excessive hair growth). The choice of drug will vary with the condition. Cortisone and hydrocortisone, which have both glucocorticoid and mineralocorticoid effects, are the drugs of choice for replacement therapy of natural hormone deficiency. Synthetic compounds, which have greater anti-inflammatory effects and less effect on salt and water balance, are usually preferred for other purposes. These compounds include dexamethasone, which is almost exclusively glucocorticoid in its actions, as well as prednisone, prednisolone, betamethasone, trimacinolone, and others. Glucocorticoids are formulated in oral dosage forms, topical creams and ointments, oral and nasal inhalations, rectal foams, and ear and eye drops.
 
Mineralocorticoids control the retention of sodium in the kidneys. In mineralocorticoid deficiency, there is excessive loss of sodium through the kidneys, with resulting water loss. Fludrocortisone (Florinef) is the only drug available for treatment of mineralocorticoid deficiency, and is available only in an oral dosage form.
Corticotropin (ACTH, adrenocorticotropic hormone) stimulates the pituitary gland to release cortisone. A deficiency of corticotropic hormone will have the same effects as a deficiency of cortisone. The hormone, which is available under the brand names Acthar and Actrel, is used for diagnostic testing, to determine the cause of a glucocorticoid deficiency, but is rarely used for replacement therapy since direct administration of glucocorticoids may be easier and offers better control over dosages.
 
In this topic:
Clinical pharmacology
Adverse effects of corticosteroids
Approximate relative potency and half-lives of oral corticosteroids (Table 5.34)
Classification of potencies of topical corticosteroids (Table 4.9)
Dosing
Use in dentistry
Use in dermatology
Use in endocrinology
Use in inflammatory bowel disease
Use in pain management
Use in respiratory diseases
Use in rheumatology
Corticosteroids: use in rheumatology
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Corticosteroids: use in rheumatology
In rheumatology, corticosteroids are important drugs for both their anti-inflammatory and immunosuppressant actions. The main drugs in use are oral prednisone or prednisolone, intravenous methylprednisolone, and intra-articular betamethasone, triamcinolone, and methylprednisolone. They have a rapid onset of action and are useful for controlling severe joint inflammation in early disease, or during flares.
Strategies for minimising the adverse effects of corticosteroids are discussed in Adverse effects of corticosteroids. These strategies are particularly relevant to rheumatology where in many conditions, such as connective tissue diseases, inflammatory arthritis and myopathies, long-term corticosteroid use, often in higher doses than in other chronic disease states, may be necessary.
Corticosteroids: use in respiratory diseases
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Corticosteroids: use in respiratory diseases

introduction
Corticosteroids are widely used in the treatment of asthma and other respiratory diseases to reduce bronchial inflammation and hyper-responsiveness. They are thought to reduce the synthesis and secretion of a variety of inflammatory mediators (such as prostaglandins and leukotrienes) and cytokines, which are implicated in the pathogenic process underlying asthma.
Corticosteroids are used in the management of acute severe asthma, as well as in the preventive management of asthma. The most commonly used oral corticosteroid is prednisolone. Commonly used parenteral corticosteroid preparations are hydrocortisone, dexamethasone and methylprednisolone.

Use of inhaled corticosteroids in respiratory diseases
Inhaled corticosteroids currently marketed in Australia include beclomethasone dipropionate, budesonide and fluticasone propionate. Inhaled corticosteroids are used as preventive therapy in asthma and are known as ‘preventers’. They have a delayed onset of clinical effect and should be used regularly. They are not sufficiently potent and do not have a sufficiently rapid effect to be of use in acute severe asthma.
Adverse effects, interactions and precautions: Inhaled corticosteroids do not generally produce systemic adverse effects until large doses are administered. Systemic effects are dependent on a complex interplay between:

potency of the corticosteroid
absorption of the drug deposited in the airway, which is related to formulation (suspension, solution, dry powder) and delivery device used (MDI with or without spacer, powder inhaler)
absorption of drug deposited in the pharynx and swallowed, and first-pass hepatic metabolism (to a minor degree). 
The dose at which systemic effects are observed is product-specific and may be patient-specific. Using the currently available devices, estimated dose equivalent ratios of inhaled corticosteroids are 1:2:1 for beclomethasone, budesonide and fluticasone respectively. In adults, doses at which systemic adverse effects may become manifest are those greater than 1000 to 1500 micrograms daily of budesonide or 500 to 750 micrograms daily of beclomethasone or fluticasone. In children, doses at which systemic adverse effects may become manifest are those greater than 800 micrograms daily of budesonide or 400 micrograms daily of beclomethasone or fluticasone. Systemic adverse effects occur at lower doses in some patients, and the possibility of cataracts should be considered, particularly in those receiving therapy of extended duration. The dose at which the hypothalamic-pituitary-adrenal (HPA) axis is suppressed has not yet been established for any corticosteroid, so the lowest effective dose should always be recommended.
The effect of inhaled corticosteroids on long-term growth in children is unclear. Most studies have focused on short-term growth velocity and have failed to show any reduction in final height. In fact, children with severe asthma may have improved growth velocity after starting inhaled corticosteroids, perhaps by eliminating the growth-suppressive effects of poorly-controlled asthma.

In low doses adverse effects are uncommon, but include hoarse voice and oral and oesophageal Candida albicans infection (candidiasis/thrush). To minimise oropharyngeal thrush and absorption of inhaled corticosteroids, patients should be advised to rinse their throat and mouth with water and spit out after inhalation. Patients using an MDI should also be advised to use a spacer. Dry powder devices are an appropriate alternative to MDI plus spacer delivery.
Corticosteroid nasal sprays may cause sneezing, nasal irritation and nosebleeds.


Use of oral corticosteroids in respiratory diseases
Prednis(ol)one is frequently given as a short course lasting several days to weeks with the aim of disease control without exposing the patient to the corticosteroid for a long enough period for significant adverse effects to develop or for significant adrenal suppression to occur. After long-term use (more than 2 weeks), dose reduction must be slow to enable the hypothalamic-adrenal feedback system to re-equilibrate

Use of parenteral corticosteroids in respiratory diseases
Dexamethasone and hydrocortisone are used intravenously for the acute treatment of asthma. The exact time course of action is not well established, but response takes at least some hours to develop.
Approximate dose equivalents of oral and parenteral corticosteroids are:
Oral prednisolone or prednisone
IV dexamethasone
IV hydrocortisone
25 mg
4 mg
100 mg
Evidence suggests that moderate- to high-dose oral corticosteroids may be as effective as parenteral corticosteroid treatment for the management of acute asthma.

Very few acute adverse effects are seen, but psychoses, mood changes, hypokalaemia and hyperglycaemia can occur.

Use of nebulised corticosteroids in respiratory diseases
Budesonide is available for nebulisation via high-flow nebuliser. This form of treatment should be reserved for severe chronic asthma in patients who are unable to use other forms of inhaled therapy.
Some patients develop a rash on the face following nebulised treatment. It is important to protect the eyes and face from the effects of drug deposition.





Corticosteroids: use in pain management and palliative care
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Corticosteroids: use in pain management and palliative care
Corticosteroids have an established role as adjuvants in pain management, particularly for pain due to inflammation and oedema. They can be administered both locally (eg intralesional, intra-articular) and systemically.

Corticosteroids are important agents for relief of pain associated with space-occupying lesions, not only in the brain, spinal cord and nerves, but also in the liver and soft tissues. They are used where there may be inflammation and oedema in confined spaces (eg in intracerebral, pelvic, retroperitoneal and spinal malignant disease). They are often used as an interim measure while awaiting more definitive therapies (eg radiotherapy).
Corticosteroids usually given by the oral route for treatment of pain include dexamethasone, prednisolone and prednisone. They can be given as a single daily dose (in the morning) because they have long biological half-lives. For parenteral administration, dexamethasone can be given subcutaneously, preferably as a single morning dose or divided doses (in the morning and at midday) rather than as a continuous infusion. Intra-articular or intralesional injection of long-acting or depot corticosteroid, using local anaesthetic without adrenaline, is a potential method of pain relief in musculoskeletal disorders.

In palliative care, high doses of corticosteroids are associated with many adverse effects including loss of control of diabetes, dysphoric reactions and delirium, and proximal myopathy. The incidence of psychosis rises to 25% after 2 weeks use, and can occur when the dose is being adjusted rapidly—either up or down. Dexamethasone is not associated with significant fluid retention. The ceiling dose for dexamethasone is suggested to be 8 mg daily, with higher doses (eg 16 mg) for short periods only if there is a good reason. Children appear to be more sensitive to the adverse effects of corticosteroids.
Corticosteroids: use in inflammatory bowel disease
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Corticosteroids: use in inflammatory bowel disease
Corticosteroids are used principally to induce remission in both Crohn’s disease and ulcerative colitis. Depending on the clinical circumstances, they are given parenterally, orally or rectally.
Prednisolone or prednisone can be used orally.

Budesonide, given orally in a controlled ileal release formulation, is used to induce remission in Crohn’s disease. It acts locally on the mucosa of the terminal ileum and right side of the colon. Budesonide passes via the portal venous circulation to the liver where it undergoes extensive first-pass metabolism. Systemic and cosmetic adverse effects are less prominent although there may still be suppression of the hypothalamic-pituitary-adrenal axis.

Rectal formulations are used in inflammatory bowel disease. The choice of which rectal formulation to use is determined by the site of inflammation. For very distal anorectal disease, suppositories may be used. Foam preparations are often better tolerated than enemas but only reach the sigmoid colon. Enemas can reach as far as the splenic flexure.


Corticosteroids: use in endocrinology
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Corticosteroids: use in endocrinology
The naturally occurring adrenocortical steroids (hydrocortisone, cortisone) have both anti-inflammatory (glucocorticoid) and salt-retaining (mineralocorticoid) properties. They are used as replacement therapy in adrenocortical deficiency states.
Synthetic corticosteroid compounds (eg prednis(ol)one, methylprednisolone) are mainly used for their anti-inflammatory properties. Dexamethasone, methylprednisolone and betamethasone are synthetic compounds with marked glucocorticoid activity and an absence of significant salt-retaining activity. These agents are used for their potent anti-inflammatory effects.
Fludrocortisone has been developed to maximise mineralocorticoid activity. As part of replacement therapy for adrenal insufficiency or congenital adrenal hyperplasia, it allows lower dosage of hydrocortisone or cortisone acetate, with reduction of glucocorticoid adverse effects. Excessive dosage can cause fluid retention and hypertension.
Corticosteroids: use in dermatology
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Corticosteroids: use in dermatology

Introduction
Corticosteroids have anti-inflammatory and immunosuppressant effects that are useful in a number of skin disorders. Modification of the naturally occurring hydrocortisone molecule has produced a large number of drugs with varying anti-inflammatory potency, for topical or systemic use.

Topical corticosteroids
The potency of topically applied corticosteroids is assayed by the degree of vasoconstriction they produce when applied under an occlusive dressing. This depends on the concentration used, the intrinsic activity of the compound and its ability to penetrate the barrier of the epidermis, which may be influenced by the vehicle in which it is applied. The assay permits topical corticosteroid preparations to be arranged in groups with similar potency. Such a ranking corresponds approximately with clinical effectiveness 
Adverse effects of topical corticosteroids may be due to local effects on the skin or mucosa at the site of application or to systemic effects following absorption of the drug Potential local effects include:
  • loss of dermal collagen, leading to skin atrophy, formation of striae, fragility and easy bruising
  • telangiectasia (development of prominent blood vessels)
  • promotion of infection
  • idiosyncratic reactions (eg allergic contact dermatitis, perioral dermatitis)
  • purpura (in the elderly).
  • The intensity of adverse effects is proportional to the therapeutic effect and thus increases with the potency of the preparation.
  • Suggested potencies and preparations for long-term use of topical corticosteroids for chronic dermatoses are:
  • face and flexures—hydrocortisone 1%
  • trunk—betamethasone valerate 0.02%, triamcinolone acetonide 0.02%
  • elbows/knees and palms/soles—betamethasone dipropionate 0.05%, mometasone furoate 0.1%, methylprednisolone aceponate 0.1%.
Penetration of corticosteroid to the dermis is greater on the face, the scrotum, and where conditions mimic application under occlusion such as flexures and intertriginous areas. The use of the more potent corticosteroids on these sites therefore carries greater risk of local damage and they should be used with caution. The only corticosteroids that are safe to use on these sites are hydrocortisone and desonide. In certain circumstances, more potent corticosteroids (eg methylprednisolone aceponate) may be used intermittently on these sensitive areas for up to two weeks; however, the greater the potency the greater the risk of local adverse effects—particularly perioral dermatitis. If improvement does not occur after two weeks, do not persevere with treatment—reconsider the diagnosis and seek expert advice.

With greater potency, there is also an increased risk of rebound on withdrawal.
Absorption of the more potent agents applied to large areas may cause suppression of the hypothalamic pituitary axis and other complications usually associated with systemic corticosteroid administration
Practical issues to consider when prescribing topical corticosteroids are discussed in the Pertinent practical points chapter.
For important issues to consider when using topical corticosteroids in children, 

Systemic corticosteroids
Oral corticosteroids are often used in serious skin diseases or when topical corticosteroids are ineffective. Prednisolone and prednisone are the most commonly used oral corticosteroids in dermatology. The major limiting factor in the use of oral corticosteroids is the development of extensive, dose-related adverse effects.
Corticosteroids: use in dentistry
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Corticosteroids: use in dentistry
Corticosteroids are useful drugs for the management of many dental and oral inflammatory conditions. Their use must be based on a complete medical and medication history plus an accurate diagnosis of the dental or oral condition, as they should not be used when an infection is present or is likely to occur. Corticosteroids can be used intradentally (within a tooth), topically or systemically. The most effective route of administration should be chosen; this usually means using a locally delivered form of the drug rather than a systemically delivered form wherever possible. Thus, intradental or topical corticosteroids are preferred as they place the drug at the site of required action, which results in more rapid onset of action and less chance of systemic effects.
Dosing of Corticosteroids
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Dosing of Corticosteroids

General considerations
Consideration of the patient’s weight and age, as well as the severity of the disease being treated, should guide the dosage regimen for systemic corticosteroids. In general, the lowest dose possible to achieve the desired clinical response should be used. Low doses are used to produce an anti-inflammatory effect, while high doses are needed to produce immunosuppression. Prednis(ol)one is generally given as a single daily dose in the morning to mimic the natural cortisol peak. Dosing in the evening often results in sleep disturbances.
A patient taking corticosteroids should have their corticosteroids increased before surgery. Addisonian (adrenal) crisis can present 6 to 12 hours after surgical stress in a patient taking corticosteroids who has not had them increased before the surgery.

Dose reduction (tapering)
The hypothalamic-pituitary axis is suppressed by glucocorticoid therapy. The dose, duration of treatment, and individual patient characteristics affect the onset and extent of this effect. However, treatment with prednis(ol)one at doses greater than 5 mg for longer than 2 weeks can be considered sufficient to cause adrenal suppression. Therefore tapering of the glucocorticoid dose is required to avoid both adrenal insufficiency and the rebound in symptoms that may occur with sudden cessation. The rate of reduction is dependent on the dose level, duration of treatment, and underlying disease state.
Classification of potencies of topical corticosteroids (Table 4.9)
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Classification of potencies of topical corticosteroids (Table 4.9)
Mild

desonide
0.05%
hydrocortisone
0.5, 1%

hydrocortisone acetate
0.5, 1%

Moderate

betamethasone valerate
0.02%, 0.05%

triamcinolone acetonide
0.02%
Potent

betamethasone dipropionate
0.05%

betamethasone valerate
0.1%

methylprednisolone aceponate
0.1%

mometasone furoate
0.1%

triamcinolone acetonide
0.1%

Very potent

betamethasone dipropionate
0.05% in optimised vehicle


Approximate relative potency and half-lives of oral corticosteroids (Table 5.34)
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Approximate relative potency and half-lives of oral corticosteroids (Table 5.34)
Corticosteroid
Relative glucocorticoid potency
Equivalent dose for glucocorticoid effect
Plasma half-life
Estimated biological half-life
hydrocortisone
1
20 mg
90 minutes
8 to 12 hours

cortisone acetate
0.8
25 mg
30 minutes
8 to 12 hours

dexamethasone
25
750 micrograms
200 minutes
36 to 54 hours

fludrocortisone
10
2 mg [NB1]
[NB3]
18 to 36 hours

prednisone
3.5
5 mg
60 minutes [NB2]
18 to 36 hours
prednisolone
4
5 mg
200 minutes
18 to 36 hours
methylprednisolone
5
4 mg
180 minutes
12 to 36 hours

NB1: see chapter 14, 'Adrenal cortex', in Williams RH, Larsen PR, Kronenberg HM, Melmed S, Polonsky KS, Wilson JD, Foster DW, eds. Williams Textbook of Endocrinology. 10th ed. W B Saunders; 2002.
NB2: preconversion half-life to prednisolone
NB3: consistent information not available
Adverse effects of corticosteroids
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Introduction
Systemic corticosteroid treatment inevitably results in adverse effects if the dose and/or duration of treatment are sufficient, because most are dose-related biological effects of the hormone. A summary of the major adverse effects of systemic corticosteroid treatment is given in Table 6.1. More information about some of these effects and strategies for minimising them are discussed below.

Corticosteroids injected into joints or soft tissues are commonly associated with mild, transient adverse effects 

Corticosteroids applied topically can also cause adverse effects 
Important complications of corticosteroids (Table 6.1)
Glucocorticoid Mineralocorticoid
avascular necrosis of the femoral and humeral head
dermatological effects (eg skin atrophy, purpura and ecchymoses, striae, hirsutism)
gastrointestinal effects (eg dyspepsia, risk factor for peptic ulceration, gastrointestinal bleeding)
growth retardation
immunosuppression, risk of infections
metabolic effects (eg diabetes, hypertriglyceridaemia)
myopathy
ocular effects, particularly increased intraocular pressure and cataracts
osteoporosis
pituitary-adrenal suppression 
psychological disturbances (eg euphoria, depression, paranoid psychosis)
weight gain and redistribution of fat
hypertension
hypokalaemic alkalosis
sodium-retaining effects

Avascular necrosis
Avascular or ischaemic necrosis can affect a variety of bones, but most commonly involves the proximal femur. It is an infrequent and idiosyncratic adverse effect of corticosteroid treatment, and occurs more commonly following exposure to doses in excess of 20 mg/day prednis(ol)one. The time between corticosteroid exposure and the development of avascular necrosis is variable, and can be up to many years, which makes diagnosis difficult. Both the pathogenesis and treatment of this condition remain controversial.
Avascular necrosis should be considered in the differential diagnosis of hip and groin pain especially in patients who have been on high-dose and/or long-term corticosteroids at any time.

Bone density loss
Osteoporosis is a risk for patients on continuous glucocorticoid therapy in doses greater than the equivalent of prednisolone 5 to 7.5 mg per day. The risk of osteoporosis becomes greater at higher glucocorticoid doses. Loss of bone mineral density occurs rapidly after corticosteroids are commenced and may exacerbate the osteoporosis associated with some rheumatological diseases, such as ankylosing spondylitis, and inflammatory bowel disease .

If corticosteroid therapy is expected to last for longer than a month, strategies to minimise bone density loss should begin as soon as treatment with corticosteroids starts.

The key issues are:
  • weight-bearing exercise where possible
  • adequate calcium intake
  • measurement and addition of vitamin D if indicated
  • monitoring bone densitometry from initiation of long-term glucocorticoid therapy
  • bisphosphonate therapy as indicated.
For further discussion and detail,


Hyperglycaemia
Hyperglycaemia frequently accompanies treatment with high-dose corticosteroids. While oral hypoglycaemic agents can often control this, insulin may be necessary. Regimens using intermediate-acting insulin at lunchtime may be most successful in controlling the hyperglycaemia, which is commonly worse in the evening.
Blood glucose levels should be closely monitored in diabetic patients on long-term corticosteroid therapy.
Infections

High-dose corticosteroids increase the risk of contracting many types of infection, and may mask the early symptoms of infection, resulting in later diagnosis, delay in treatment, and more severe clinical consequences. Reactivation of Mycobacterium tuberculosis (TB) infection occurs with such frequency that prior to commencing immunosuppressive treatment with corticosteroids, screening for active or latent TB should be considered . Prophylaxis for Pneumocystis jiroveci (carinii) infection should be considered in patients who are at risk and on high-dose oral corticosteroids long term 

Use of steroid-sparing drugs
Drugs from other classes may be used to allow a reduction of the corticosteroid dose. For example, in rheumatology, use of disease-modifying antirheumatic drugs (DMARDs) and NSAIDs often allows a lower corticosteroid dose to be used.
Corticosteroids: clinical pharmacology
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Corticosteroids: clinical pharmacology
The naturally occurring adrenocortical steroids (hydrocortisone, cortisone) have both anti-inflammatory (glucocorticoid) and salt-retaining (mineralocorticoid) properties. They are used as replacement therapy in adrenocortical deficiency states.
Synthetic corticosteroid compounds (eg prednisolone) are mainly used for their anti-inflammatory properties. Dexamethasone, methylprednisolone and betamethasone are synthetic compounds with marked glucocorticoid activity and an absence of significant salt-retaining activity. These agents are used for their potent anti-inflammatory effects.

Fludrocortisone has been developed to maximise mineralocorticoid activity.

Orally administered corticosteroids are well absorbed; however, cortisone and prednisone are prodrugs that require hepatic activation. They therefore may not be efficacious in patients with liver impairment. Prednisone is a prodrug of prednisolone. It is converted rapidly to prednisolone if liver function is normal. Unless liver function is severely impaired, prednisone and prednisolone are considered to be clinically equivalent and can be used interchangeably. In these guidelines, whenever prednisolone is recommended, an equal dose of prednisone can be substituted. Prednis(ol)one refers to either prednisolone or prednisone.
Corticosteroids have biological half-lives that are 2 to 36 times longer than their plasma half-lives because of their complex mechanism of action. The onset of biological effects lags behind peak plasma levels.

See Use in dermatology for information on the use of topical corticosteroids.
The major limiting factor in the use of corticosteroids is the development of extensive, dose-related adverse effects 

Corticosteroids: dosing
By Piscean | Sunday, September 18, 2011 | Posted in , , | With 0 comments

Corticosteroids: dosing
General considerations
Consideration of the patient’s weight and age, as well as the severity of the disease being treated, should guide the dosage regimen for systemic corticosteroids. In general, the lowest dose possible to achieve the desired clinical response should be used. Low doses are used to produce an anti-inflammatory effect, while high doses are needed to produce immunosuppression. Prednis(ol)one is generally given as a single daily dose in the morning to mimic the natural cortisol peak. Dosing in the evening often results in sleep disturbances.
A patient taking corticosteroids should have their corticosteroids increased before surgery. Addisonian (adrenal) crisis can present 6 to 12 hours after surgical stress in a patient taking corticosteroids who has not had them increased before the surgery.
Dose reduction (tapering)
The hypothalamic-pituitary axis is suppressed by glucocorticoid therapy. The dose, duration of treatment, and individual patient characteristics affect the onset and extent of this effect. However, treatment with prednis(ol)one at doses greater than 5 mg for longer than 2 weeks can be considered sufficient to cause adrenal suppression. Therefore tapering of the glucocorticoid dose is required to avoid both adrenal insufficiency and the rebound in symptoms that may occur with sudden cessation. The rate of reduction is dependent on the dose level, duration of treatment, and underlying disease state.