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Corticosteroids are hormone mediators produced by the cortex of adrenal glands that further categorize into glucocorticoids, mineralocorticoids, and androgenic sex hormones. They are used in a plethora of conditions, commonly called steroid-responsive disorders and dermatoses. Corticosteroids constitute a double-edged sword - significant benefit with a low incidence of adverse effects can be expected if used in proper dosage and for a limited duration; however, wrong dose and/or duration and unmindful withdrawal after prolonged administration can have catastrophic effects. Corticosteroids are used across all medical specialties. This activity reviews the must-know properties of this group of drugs, their broad indications and contraindications, ways of administration, adverse event profile, practical aspects of the pharmacokinetics of different molecules, monitoring essentials, approach to maximize the benefit and minimize adverse effects, and clinically relevant drug-interactions pertinent for all specialists whether used in isolation or administered by an interprofessional team.

Objectives:Review the anti-inflammatory, anti-proliferative, and immunosuppressive actions of corticosteroids.Summarize the monitoring required for corticosteroid therapy.Describe the possible adverse effects of corticosteroid therapy.Explain the importance of improving care coordination among the interprofessional team to enhance the delivery of care to patients requiring corticosteroids.Access free multiple choice questions on this topic.

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Corticosteroids are hormone mediators produced by the cortex of adrenal glands that are further categorized into glucocorticoids (major glucocorticoid produced by the body is cortisol), mineralocorticoids (major mineralocorticoid produced in the body is aldosterone), and androgenic sex hormones. Endogenous cortisone was first isolated in 1935 and synthesized in 1944. In 1948, Dr. Philip S Hench published administered cortisone (called Compound E at that time) to a 29-year-old woman who was bed-ridden secondary to active rheumatoid arthritis. The patient was able to walk after three days of treatment. This case was published in 1949, and in 1950, Philip S. Hench, Edward C. Kendall, and Tadeusz Reichstein were awarded the Nobel Prize in Physiology or Medicine "for their discoveries relating to the hormones of the adrenal cortex, their structure, and biological effects."[1]

Glucocorticoids (GCs) are a group of drugs structurally and pharmacologically similar to the endogenous hormone cortisol with various functions like anti-inflammatory, immunosuppressive, anti-proliferative, and vaso-constrictive effects. Their actions are used medically for the treatment of various conditions indicated below. The list of indications of glucocorticoids is extremely long. We have categorized and mentioned the most important and broad-spectrum indications below.

Due to several roles played by corticosteroids in the human body, they see extensive use in medical practice to treat various diseases. As a result, their side-effects have, in turn, become another significant medical issue requiring special attention.

The anti-inflammatory and immunosuppressive effects of glucocorticoids are dose-dependent, with immunosuppressive effects seen mostly at higher doses. The pharmacological anti-inflammatory and immunosuppressive effects of glucocorticoids are extensive and can occur via genomic or non-genomic mechanisms. Most effects of glucocorticoids are via the genomic mechanisms, which takes time, while immediate effects via the non-genomic mechanisms can occur with high doses of glucocorticoids (such as pulse therapy). Clinically, it is not possible to separate these effects.

The immediate effects of high dose-glucocorticoids are mediated via non-genomic mechanisms. At high doses, glucocorticoids bind the membrane-associated glucocorticoid receptors on target cells such as T-lymphocytes, resulting in impairment of receptor signaling and immune response of the T lymphocytes. High-dose glucocorticoids also interact with the cycling of calcium and sodium across the cell membrane resulting in a rapid decrease in inflammation.

By altering the cytokine production via the genomic and non-genomic mechanisms, glucocorticoids lead to suppression of the immune system and decreased inflammation. They target a wide variety of cells, including T-lymphocytes, macrophages, fibroblasts, neutrophils, eosinophils, and basophils. Notably, glucocorticoids have almost no effect on B-cell function and immunoglobulin production. The downstream effects of glucocorticoids are summarized below:

Glucocorticoids exert negative feedback effects on the HPA axis. They directly suppress adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) secretion. Additionally, by suppressing the release of pro-inflammatory cytokines that stimulate ACTH and CRP secretion, glucocorticoids further suppress ACTH and CRH secretion indirectly in inflammatory diseases. Chronic HPA axis suppression by glucocorticoids leads to functional adrenal atrophy (sparing the mineralocorticoid producing outer adrenal cortex that is functionally independent of ACTH). The risk of this functional adrenal atrophy and insufficiency is challenging to predict and varies from patient to patient but is largely dependant on the dose and duration of glucocorticoid therapy. The adrenal function generally recovers by slow tapering of glucocorticoids.

Glucocorticoids bind to mineralocorticoid receptors (MRs) and produce their mineralocorticoid effect (i.e., increasing sodium and decreasing potassium), but only when used at the high dose and for an extended period.

Several preparations of glucocorticoids are available, each with varying efficacy. Dexamethasone and betamethasone are long-acting with the highest glucocorticoid efficacy with a biological half-life of 36 to 54 hours. Cortisone and cortisol are short-acting with a biological half-life of under 12 hours and are not frequently used. Prednisone, prednisolone, methylprednisolone, and triamcinolone are intermediate-acting with a biological half-life of 18 to 36 hours. The glucocorticoid and mineralocorticoid effects of each available preparation vary, with cortisol and cortisone having almost 1 to 1 glucocorticoid and mineralocorticoid effects while all others with almost no mineralocorticoid effects. Equivalent glucocorticoid doses can be calculated for these various preparations. 5 mg of prednisone is equivalent in its glucocorticoid effects to 5 mg of prednisolone, 4 mg of methylprednisolone, 4 mg of triamcinolone, 0.75 mg of dexamethasone, 0.60 mg of betamethasone, 20 mg of cortisol, and 25 mg of cortisone.

Glucocorticoid administration can be via several non-systemic routes, including intra-articular joint injections for joint inflammation, inhalational for asthma, topical for dermatological problems, ocular drops for eye conditions, and intra-nasal for seasonal rhinitis. Clinicians generally avoid intramuscular (IM) glucocorticoids due to the risk of local muscle atrophy due to depot effect, and the only indications for intramuscular glucocorticoids are for IM triamcinolone acetonide for specific inflammatory disorders and IM injection of betamethasone to a pregnant mother less than 37 weeks of gestation to stimulate fetal lung maturity. When appropriate, a non-systemic route is preferable to the systemic route of administration to minimize systemic adverse effects.

Several other factors may influence the adverse effects of glucocorticoids. Older age, comorbid conditions (such as diabetes mellitus), concomitant use of other immunosuppressive agents, severity and nature of the underlying disease, and poor nutritional status can all influence the occurrence and magnitude of side effects.

Glucocorticoids induced Osteoporosis is one of the well-known and devastating adverse effects of long-term use of glucocorticoids. Up to 40% of patients on long-term glucocorticoids develop bone loss leading to fractures.[7] Several mechanisms play a role, including osteoclast activation by promoting RANK-ligand as well as a decrease in function and number of osteoblasts and osteocytes. The trabecular bone is initially affected, with cortical bone loss seen with longer-term use. The loss of trabecular bone can occur within the first 6 to 12 months of therapy.

The impairment of growth in young children and delay in puberty commonly presents in children receiving glucocorticoids for chronic illnesses like nephrotic syndrome and asthma. The effect is most pronounced with daily therapy and less marked with an alternate-day regimen and can also occur with inhaled glucocorticoids. Although growth impairment can be an independent adverse effect of corticosteroid therapy, it can also be a sign of adrenal suppression.

Mineralocorticoid effects, especially as seen with cortisol and cortisone, can lead to fluid retention, edema, weight gain, hypertension, and arrhythmias by increasing renal excretion of potassium, calcium, and phosphate. Hypertension usually occurs with higher doses only.[11] Long-term use of medium-high dose glucocorticoids has implications in premature atherosclerosis in a dose-dependent pattern.[12] 9af72c28ce