Table of Contents · 11 sections
In a nutshell. Glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressive drugs. The mechanism is predominantly genomic (via transcription factors NF-κB, AP-1). Equivalent dose: prednisolone 5 mg = methylprednisolone 4 mg = dexamethasone 0.75 mg = hydrocortisone 20 mg. Therapy >2 weeks should be tapered gradually due to the risk of adrenal insufficiency.
1. What are glucocorticoids
Glucocorticoids are steroid hormones synthesized in the zona fasciculata of the adrenal cortex, as well as their synthetic analogues. The natural human hormone is cortisol (hydrocortisone as a drug). Synthetic GCs — prednisolone, methylprednisolone, dexamethasone, betamethasone, triamcinolone — were created to enhance anti-inflammatory effects while reducing mineralocorticoid activity (sodium and water retention).
Regulation: the hypothalamus releases corticotropin-releasing hormone (CRH) → anterior pituitary releases ACTH → adrenal cortex secretes cortisol. A negative feedback loop exists: high cortisol levels suppress both the hypothalamus and the pituitary gland. This forms the basis of secondary adrenal insufficiency upon discontinuation of long-term GC therapy.
2. Mechanism of action
Genomic mechanism (primary, develops in 30 min – several hours):
- GC crosses the cell membrane (lipophilic molecule).
- Binds to the cytoplasmic GR (glucocorticoid receptor), releasing the HSP90 chaperone.
- The GC-GR complex is transported to the nucleus.
- Binds to GRE (glucocorticoid response element) on DNA → activation of anti-inflammatory gene transcription (lipocortin-1, IκB, MKP-1) and suppression of NF-κB / AP-1 — key inflammatory factors.
Non-genomic mechanism (minutes, at high doses): interaction with membrane receptors and membrane lipids — utilized in methylprednisolone pulse therapy.
Key effects
- Anti-inflammatory: ↓ expression of COX-2, phospholipase A2, cytokines (IL-1, IL-6, TNF-α).
- Immunosuppressive: ↓ T-lymphocyte activation, lymphocyte apoptosis, ↓ neutrophil migration.
- Metabolic: ↑ gluconeogenesis, ↑ muscle proteolysis, fat redistribution.
- Mineralocorticoid (pronounced in hydrocortisone): retention of Na⁺ and H₂O, loss of K⁺.
3. Duration-of-action classification
| Group | Drugs | Biological T½, h | Min.-cort. act. |
|---|---|---|---|
| Short-acting | Hydrocortisone, cortisone | 8–12 | ++ |
| Intermediate-acting | Prednisolone, methylprednisolone, triamcinolone | 18–36 | + (methylprednisolone has 0) |
| Long-acting | Dexamethasone, betamethasone | 36–54 | 0 |
The longer the biological half-life, the stronger the suppression of the hypothalamic-pituitary-adrenal (HPA) axis.
4. Equivalent dose table — must memorize
| Drug | Equiv. dose (mg) | Anti-inflamm. act. | Min.-cort. act. |
|---|---|---|---|
| Hydrocortisone | 20 | 1 | 1 |
| Prednisolone | 5 | 4 | 0,8 |
| Methylprednisolone | 4 | 5 | 0,5 |
| Triamcinolone | 4 | 5 | 0 |
| Dexamethasone | 0,75 | 25–30 | 0 |
| Betamethasone | 0,6 | 25–30 | 0 |
Mnemonic: 20–5–4–0.75 (hydrocortisone → prednisolone → methylprednisolone → dexamethasone). All yield ≈ equal anti-inflammatory efficacy.
5. Indications for systemic therapy
- Replacement therapy for adrenal insufficiency (Addison's disease, hypopituitarism).
- Rheumatic diseases: SLE, active RA, vasculitis, polymyositis.
- Severe allergic reactions, anaphylaxis (as an adjunct to epinephrine).
- Bronchial asthma (systemic — during exacerbations; inhaled — maintenance).
- Hematology: autoimmune thrombocytopenia, hemolytic anemia, lymphomas (in CHOP regimens).
- Cerebral edema (dexamethasone in tumors, bacterial meningitis).
- Immunosuppression in organ transplantation.
- Prevention of neonatal respiratory distress syndrome (betamethasone administered to pregnant women at risk of preterm labor at 24–34 weeks).
6. Dosing regimens
- Low doses: <7.5 mg prednisolone/day — physiological replacement.
- Medium doses: 7.5–30 mg/day — baseline in rheumatology.
- High doses: 30–100 mg/day — flares, vasculitis.
- Pulse therapy: methylprednisolone 500–1000 mg IV for 3 consecutive days — for severe SLE flares, MS, graft rejection.
Administration once daily in the morning (7–9 AM) is more physiological — it mimics the cortisol circadian rhythm and causes less HPA-axis suppression.
7. Side Effects
GCs are a classic example of drugs with numerous side effects frequently tested on exams. The clinical presentation of long-term therapy resembles Cushing's syndrome (exogenous):
| System | Side effects |
|---|---|
| Metabolism | Steroid diabetes, fat redistribution (moon facies, buffalo hump, thin extremities), hyperlipidemia |
| CVS | Hypertension, fluid retention (with hydrocortisone) |
| Musculoskeletal | Osteoporosis, aseptic necrosis of the femoral head, myopathy, growth retardation in children |
| GI tract | "Steroid" ulcers, pancreatitis |
| Skin | Striae, ecchymoses, atrophy, hirsutism, acne, delayed healing |
| CNS | Insomnia, euphoria, psychosis, depression upon withdrawal |
| Eyes | Posterior subcapsular cataracts, glaucoma |
| Immune system | Activation of latent infections (TB, herpes), opportunistic infections |
| Endocrine | Suppression of the HPA axis, secondary adrenal insufficiency |
8. Withdrawal Rules
If GCs were taken for >2–3 weeks at a dose of ≥ 7.5 mg/day of prednisone, abrupt withdrawal is dangerous due to acute adrenal insufficiency (adrenal crisis: hypotension, nausea, vomiting, weakness, shock).
Tapering schedule (example):
- Decrease by 5–10 mg of prednisone every 1–2 weeks down to a dose of 20 mg/day.
- Then by 2.5 mg every 1–2 weeks down to 10 mg/day.
- Then by 1 mg every 2–4 weeks until complete discontinuation.
During stress (surgery, infection) in a patient on long-term GC therapy — temporarily increase the dose or switch to parenteral hydrocortisone 100 mg IV every 6–8 hours.
9. Contraindications and Precautions
- There are no absolute contraindications in life-threatening conditions.
- Relative: active bacterial, fungal, viral infections (including herpes); GI ulcer; diabetes mellitus; severe hypertension; osteoporosis; history of psychosis; pregnancy (except betamethasone for RDS prevention).
- Before long-term therapy — densitometry, glucose, lipid profile, tuberculosis screening.
- During therapy — calcium 1000–1500 mg/day + vitamin D 800–1000 IU/day, bisphosphonates as indicated.
10. Interactions
- NSAIDs — ↑ risk of GI ulcers (synergy).
- Thiazides, loop diuretics — increased hypokalemia.
- CYP3A4 inducers (rifampicin, phenytoin, carbamazepine) — accelerate GC metabolism, reduce effect.
- CYP3A4 inhibitors (ketoconazole, clarithromycin) — enhance effect and side effects.
- Live vaccines — contraindicated during immunosuppressive doses.
11. FAQ
Which GC is considered the "gold standard" in rheumatology?
Prednisone — due to convenient dosing, favorable pharmacokinetics, and a balance of activity.
Why is dexamethasone specifically used for cerebral edema?
It has zero mineralocorticoid activity (does not retain water) and maximum anti-inflammatory activity. Prednisone retains sodium, which worsens edema.
What is "pulse therapy" and when is it indicated?
Intravenous administration of 500–1000 mg of methylprednisolone for 3 consecutive days. Indications: severe lupus nephritis, MS flare, acute transplant rejection, severe vasculitis.
Can GCs be stopped abruptly after a 5-day course?
Yes. Short courses (up to 2 weeks) do not significantly suppress the HPA axis — they can be stopped without tapering.
Why do GCs cause hyperglycemia?
They stimulate hepatic gluconeogenesis, decrease glucose uptake by peripheral tissues, and increase insulin resistance. "Steroid diabetes" develops.
See also: Antiarrhythmics (Vaughan-Williams) · NSAIDs · Antibiotics · CYP450 Interactions · Pharmacology Catalog · Clinical Scales