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Glucocorticoids

Last updated: November 26, 2020

Summary

Synthetic glucocorticoids are a group of drugs with anti-inflammatory, immunosuppressant, metabolic, and endocrine effects. These drugs are structurally and functionally similar to the endogenous glucocorticoid hormone cortisol. Glucocorticoids have immediate effects (e.g., vasodilation) that do not depend on DNA interaction. However, they exert their main antiinflammatory and immunosuppressive actions by binding to glucocorticoid receptors, which causes complex changes in gene transcription. These genomic effects only begin to manifest after several hours. Similarly, glucocorticoids bind to mineralocorticoid receptors, but, for most glucocorticoid drugs, high doses are required for a significant mineralocorticoid effect. Systemic glucocorticoids are used for hormone replacement therapy (e.g., in Addison disease), for acute or chronic inflammatory diseases (e.g., rheumatoid arthritis), and for immunosuppression (e.g., after organ transplants). Local glucocorticoids are used to treat conditions like dermatoses, asthma, and anterior uveitis. Side effects include metabolic and endocrine disturbances, weight gain, skin reactions, hypertension, and psychiatric disorders. Contraindications for systemic glucocorticoids include systemic fungal infections and, in the case of dexamethasone, cerebral malaria. Status asthmaticus is a contraindication for inhaled glucocorticoids. Topical and ophthalmic glucocorticoids are usually contraindicated if there are preexisting local infections.

This article describes the pharmacology of synthetic glucocorticoids in detail; accordingly, glucocorticoids refer here to the drug class rather than the endogenous hormone.

Definition

Overview

Relative potency of systemic corticosteroids [1][3]
Duration of action

Drug

Common routes
of administration
Equivalent
doses
Relative
glucocorticoid
potency
Relative
mineralocorticoid
potency
Systemic glucocorticoids
Short-acting
(8–12 hours)
Hydrocortisone
  • Oral
  • Injectable
  • Topical
  • 20 mg
  • 1
  • 1
Cortisone
  • Oral
  • Injectable
  • 25 mg
  • 0.8
  • 0.8
Intermediate-acting
(12–36 hours)

Prednisolone

  • 5 mg
  • 4
  • 0.8
Prednisone
Methylprednisolone
  • Oral
  • Injectable
  • 4 mg
  • 5
  • 0.5
Triamcinolone
  • Injectable [5][6][7]
  • Topical
  • 4 mg
  • 5
  • 0
Long-acting
36–72 hours

Dexamethasone

  • Oral
  • Injectable
  • Topical
  • 0.75 mg
  • 30
  • 0
Betamethasone
  • Oral
  • Injectable
  • Topical
  • 0.6 mg
  • 30
  • 0
Systemic mineralocorticoid

Intermediate-acting
12–36 hours

Fludrocortisone
  • Oral
  • 0.1 mg
  • 10–15
  • 125–150

Fludrocortisone is not used for glucocorticoid activity but as a mineralocorticoid substitute in the management of adrenal insufficiency. [3][8]

Pharmacodynamics

  1. Anti-inflammatory and immunosuppressive
  2. Mineralocorticoid properties: e.g., reduced sodium excretion, increased potassium excretion
  3. Antiproliferative: triggers cell apoptosis; , and inhibits fibroblast proliferation
  4. Anabolic-androgenic effects with steroid abuse : increase in muscle mass and strength

Both acute and long-term effects lead to inhibition of inflammatory processes and to immunosuppression!

References:[9][10][11][12][13][14][15][16]

Adverse effects

Systemic glucocorticoids

Glucocorticoid toxicity depends on the dose that is administered over a certain period of time. Therefore even low doses can have toxic effects if administered long-term. If glucocorticoids are administered once or only briefly (e.g., for treatment of anaphylactic shock), there are usually no significant side effects even in high doses.

Skin
Cardiovascular system
Metabolism, electrolytes and endocrine system
CNS and psyche
Eyes
Other

Many of the side effects listed above are also features of iatrogenic Cushing's syndrome!

Local glucocorticoids

Topical glucocorticoids Inhaled glucocorticoids
Local effects
Eyes
  • Ocular reactions
Other

-

Local side-effects of inhaled glucocorticoids can be avoided by reducing the dose to the lowest effective amount, rinsing with mouthwash after each puff, improving the inhalation technique and compliance, and keeping vaccinations up to date!

References:[17][18][19][20][21][22][23][24][25][26]

We list the most important adverse effects. The selection is not exhaustive.

Indications

References:[27][28]

Contraindications

References:[29][30][31]

We list the most important contraindications. The selection is not exhaustive.

Additional considerations

  • Systemic administration
    • Tapering to avoid toxicity
      • Short-term administration (≤ 3 weeks): no tapering necessary
      • Long-term administration (> 3 weeks): tapering regimen based on patient age and condition and on duration/dose of prior glucocorticoid administration → e.g., tapering over 2 months
    • Sudden discontinuation after chronic use should be avoided because of the risk of adrenal insufficiency (adrenal crisis) secondary to long-term hypothalamic-pituitary-adrenal axis suppression.
    • IM application
      • Indications include antenatal induction of fetal lung maturity and adrenal crisis
      • For other conditions, IM application is generally avoided as it can result in localized atrophies and disturbances in the endogenous release of glucocorticoids

If the Cushing threshold is exceeded over a longer period of treatment, the glucocorticoid dose should be gradually decreased to minimize the risk of adrenocortical insufficiency.

An intratendinous injection carries the risk of bacterial spread and iatrogenic bacterial arthritis.

References:[2][32][33]

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References

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