Molecular Mechanism of Action
Like other glucocorticoids, prednisolone acts intracellularly by interfering with genetic processes. Its action unfolds in several steps:
- Penetration through the cell membrane into the cell.
- Binding to a specific intracellular (cytosolic) receptor.
- Translocation of the resulting hormone-receptor complex into the cell nucleus.
- Interaction with gene promoters, leading to the regulation of DNA transcription.
The immunosuppressive effect is achieved by inhibiting the transcription of genes encoding major histocompatibility complex (MHC) proteins. The drug suppresses the synthesis of pro-inflammatory cytokines and inhibits T-lymphocyte proliferation. In addition, it causes marked suppression of lymphoid tissue proliferation.
Pharmacological Effects and Pharmacokinetics
Prednisolone belongs to agents with intermediate-duration resorptive (systemic) action. It has a high penetrating capacity across histohematic barriers, including the skin and mucous membranes.
Compared to natural hydrocortisone, prednisolone has:
- Glucocorticoid activity that is more pronounced.
- Mineralocorticoid activity that is less pronounced (it causes less sodium and water retention in the body).
The drug exerts a pronounced dose-dependent effect on metabolism. This effect is predominantly catabolic in direction. The main target tissues for prednisolone are lymphoid, adipose, and connective tissue, as well as muscles and skin.
Indications for Use
Historically, glucocorticoids were the first drugs used to suppress immunity in organ transplantation. Today, prednisolone maintains its status as a benchmark immunosuppressant.
In Oncohematology: Used in leukemias and lymphomas. The therapeutic dynamics are characterized by a rapid onset of remission, though relapse is inevitable over time, and drug efficacy decreases after several courses.
- Included in treatment regimens for acute lymphoblastic leukemia (often combined with vincristine and the enzyme L-asparaginase).
- Used in combination chemotherapy regimens (with cyclophosphamide, doxorubicin, and vincristine) combined with the targeted drug rituximab.
Adjuvant Use in Oncology: Prescribed to manage tumor-related complications and chemotherapy side effects, such as:
- Nausea and vomiting;
- Increased intracranial pressure;
- Hypercalcemia;
- Hemolysis.
In Transplantology and Immunology: Used to treat autoimmune diseases and prevent transplant rejection. It is also used as mandatory premedication (along with diphenhydramine and paracetamol) before the administration of muromonab-CD3 to prevent a severe "cytokine release syndrome" (cytokine storm).
In Pulmonology: Highly effective in bronchial asthma, though used with caution due to its systemic effects.
Side Effects and Safety Profile
The main issue with prednisolone is the high risk of systemic side effects (unlike topical inhaled drugs such as beclomethasone or budesonide, which have high first-pass pre-systemic elimination).
Due to its pronounced catabolic action, long-term administration of prednisolone leads to skin and muscle atrophy, and negatively affects bone tissue, causing osteoporosis.
Note: When long-term therapy is required, methylprednisolone is often the drug of choice because it selectively accumulates in inflamed tissues and has a better safety profile (lower risk of tissue atrophy and osteoporosis).
Formulations and Dosing
According to reference formularies, prednisolone is available in the following forms:
- Tablets of 0.001 g (1 mg) and 0.005 g (5 mg).
- Solution in ampoules of 2.5% and 3% (1 mL).
Dosing Regimen:
- Replacement therapy: 0.02–0.03 g/day (20–30 mg/day).
- Maintenance dose: 0.005–0.01 g/day (5–10 mg/day).
- For intramuscular (IM) administration: 1 mL of a 2.5% or 3% solution must be pre-diluted in 5 mL of water for injections.