- Clinical science
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.
- 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)
|Drug||Route||Equivalent doses (systemic)||Relative glucocorticoid potency||Relative mineralocorticoid potency||Duration|
|or hydrocortisone||30 mg||1||1||Short: 8–12 hours|
|Cortisone|| ||37.5 mg||0.8||0.8||Short: 8–12 hours|
|Triamcinolone|| ||6 mg||5||0||Intermediate: 12–36 hours|
|Methylprednisolone|| ||6 mg||5||0.5||Intermediate: 12–36 hours|
|Fludrocortisone|| ||0.2 mg||15||150||Intermediate: 24–36 hours|
| || |
|4||0.8||Intermediate: 12–36 hours|
| ||1 mg||30||0||Long: 36–54 hours|
- Other drugs for mainly local administration: beclomethasone: ., budesonide: , clobetasol, and fluticasone
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)
- → Complex effects on leukocyte differentiation and turnover with inhibition of neutrophil apoptosis; and ; → neutrophilic leukocytosis
- → Promotion of apoptosis in eosinophils, monocytes, and lymphocytes
- → ↑ Inhibition of phospholipase A2,; which decreases the production of arachidonic acid derivatives.
- → ↑ Inhibition of transcription factors (e.g., NF-κB) → ↓ expression of pro-inflammatory genes
- → Translocation to the cell nucleus and binding to glucocorticoid responsive elements (GREs) within the promoters of anti-inflammatory genes (e.g., interleukin-10) → ↑ expression of anti-inflammatory genes
- Acute effects (within minutes)
- Mineralocorticoid properties: e.g., reduced sodium excretion, increased potassium excretion
- Antiproliferative: triggers cell apoptosis; , and inhibits fibroblast proliferation
- 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!
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.
|Metabolism, electrolytes and endocrine system|| |
|CNS and psyche|| |
Many of the side effects listed above are also features of iatrogenic !
|Topical glucocorticoids||Inhaled glucocorticoids|
|Local effects|| |
|Eyes|| || |
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!
We list the most important adverse effects. The selection is not exhaustive.
- Adrenocortical insufficiency ()
- Systemic symptomatic treatment
- Local symptomatic treatment: anterior uveitis; , dermatoses, ; , and osteoarthritis or juvenile idiopathic arthritis
- Organ transplant
- Preterm delivery
- General: hypersensitivity
- Intrathecal administration
- Cerebral dexamethasone) (
- Concomitant live or live attenuated virus immunosuppressive doses) (if glucocorticoids are used in
- (IM administration)
- Use in premature infants (formulations containing benzyl alcohol)
- Use with caution during pregnancy and breastfeeding
- Dermatological: bacterial, viral or fungal infection of the mouth or throat (triamcinolone)
- Inhalation: status asthmaticus or acute asthma episode requiring intensive measures (beclomethasone, budesonide)
We list the most important contraindications. The selection is not exhaustive.
- 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
- Tapering to avoid toxicity
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!