• Clinical science

Glucocorticoids

Abstract

Glucocorticoids are a group of drugs with various anti-inflammatory and immunosuppressant as well as metabolic and endocrine effects. These drugs are structurally and pharmacologically similar to the endogenous hormone cortisol. Glucocorticoids have immediate effects that do not depend on DNA interaction (e.g., vasodilation). However, they exert their main anti-inflammatory and immunosuppressive actions by binding to glucocorticoid receptors, which, in turn, 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 inhalative glucocorticoids. Topical and ophthalmic glucocorticoids are usually contraindicated if there are pre-existing local infections.

Overview

General

  • Glucocorticoids are a type of corticosteroid
  • These are hormones, based on cholesterol, originally derived from the adrenal cortex
  • Synthetic derivatives of cortisol are used in a variety of conditions
  • Routes of administration :
    • Topical (e.g., eyes, skin, mucous membranes)
    • Local injection (i.e., intraarticular)
    • Inhaled
    • Oral
    • Parenteral

Types

Drug Route Equivalent doses (systemic) Relative glucocorticoid potency Relative mineralocorticoid potency Duration
Cortisol or hydrocortisone 30 mg 1 1 Short: 8–12 hours
Cortisone
  • Systemic (IM, PO)
37.5 mg 0.8 0.8 Short: 8–12 hours
Triamcinolone
  • Systemic (IV, IM)
  • Intralesional or intra-articular injection
  • Topical
  • Nasal
  • Ophthalmic
6 mg 5 0 Intermediate: 12–36 hours
Methylprednisolone
  • Systemic (IV, IM, PO)
  • Intra-articular injection
6 mg 5 0.5 Intermediate: 12–36 hours
Fludrocortisone
  • Systemic (PO)
0.2 mg 15 150 Intermediate: 24–36 hours

Prednisolone or

prednisone

  • Systemic (PO)
  • Ophthalmic

7.5 mg

4 0.8 Intermediate: 12–36 hours

Dexamethasone or

betamethasone

  • Systemic (IV, IM, PO)
  • Intralesional, intra-articular or soft tissue injection
1 mg 30 0 Long: 36–54 hours

Do not confuse cortisol and cortisone!

References:[1][2][3][4]

Effects

  1. Anti-inflammatory and immunosuppressive
    • Acute effects (within minutes)
      • Vasodilation and capillary permeability
      • Leukocyte migration to inflammatory foci
    • Long-term effects (within hours) : Glucocorticoids bind to cytoplasmic glucocorticoid receptors (GRs)
  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:[5][6][7][8][9][10][11][12]

Side 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
  • Mood disorders
  • Cognitive disorders
  • Psychosis
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
  • Skin manifestations as in systemic glucocorticoids
  • Allergic dermatitis
Eyes
  • As in systemic glucocorticoids
  • 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:[13][14][15][16][17][18][19][20][21][22]

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

Indications

References:[23][24]

Contraindications

References:[25][26][27]

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

Guidelines & therapy recommendations

  • 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
    • Possible one-time morning dose before 8 am
    • Principally no IM application

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:[28][29][30]