|Systematic (IUPAC) name|
|Licence data||US FDA:|
|Excretion||Prednisolone is excreted via urine|
|ATC code||A07 C05, D07, H02, R01, S01, S02, S03|
|Synonyms||11,17-dihydroxy-17- (2-hydroxyacetyl)- 10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17- dodecahydrocyclopenta [a]phenanthren-3-one|
|Mol. mass||360.444 g/mol|
|(what is this?)|
Prednisolone is a synthetic glucocorticoid, a derivative of cortisol, which is used to treat a variety of inflammatory and auto-immune conditions. It is the active metabolite of the drug prednisone and is used especially in patients with hepatic failure, as these individuals are unable to metabolise prednisone into prednisolone.
Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and auto-immune conditions such as asthma, uveitis, pyoderma gangrenosum, rheumatoid arthritis, ulcerative colitis, pericarditis, temporal arteritis and Crohn's disease, Bell's palsy, multiple sclerosis, cluster headaches, vasculitis, acute lymphoblastic leukemia and autoimmune hepatitis, systemic lupus erythematosus, Kawasaki disease and dermatomyositis. It is also used for treatment of sarcoidosis, though the mechanism is unknown.
Prednisolone acetate ophthalmic suspension (eye drops) is an adrenocortical steroid product, prepared as a sterile ophthalmic suspension and used to reduce swelling, redness, itching, and allergic reactions affecting the eye.
Corticosteroids inhibit the inflammatory response to a variety of inciting agents and, it is presumed, delay or slow healing. They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation with inflammation.
Mechanism of action
Prednisolone irreversibly binds with glucocorticoid receptors (GR) alpha and beta for which they have a high affinity. AlphaGR and BetaGR are found in virtually all tissues with variable numbers between 3000 and 10000 per cell, depending on the tissue involved. Prednisolone can activate and influence biochemical behaviour of most cells. The steroid/receptor complexes dimerise and interact with cellular DNA in the nucleus, binding to steroid-response elements and modifying gene transcription. They induce synthesis of some proteins, and inhibit synthesis of others.
Not all metabolic actions on genes are known. Most mediator proteins are enzymes, e.g., cAMP-dependent kinase
Anti-inflammatory and immunosuppressive actions:
- Inhibition of gene transcription for COX-2, cytokines, cell adhesion molecules, and inducible NO synthase
- Blockage of Vit D3-mediated induction of osteocalcin gene in osteoblasts
- Modification of collegenase gene transcription
- Increase synthesis annexin-1, important in negative feedback on hypothalamus and anterior pituitary gland
Regulation of gene suppression leads to systemic suppression of inflammation and immune response. This is of clinical usefulness but ultimately leads to gluconeogenesis, proteolysis and lipolysis. Gene transcription returns to normal after cessation, but sudden stoppage can cause Addison's disease. Osteoporosis is permanent.
A lengthy course of prednisolone can cause bloody or black tarry stools from bleeding into the stomach (this requires urgent medical attention); filling or rounding out of the face; muscle cramps or pain; muscle weakness; nausea; pain in back, hips, ribs, arms, shoulders, or legs; reddish-purple stretch marks on arms, face, legs, trunk, or groin; thin and shiny skin; unusual bruising; urinating at night; rapid weight gain; and wounds that will not heal.
Prolonged use of prednisolone can lead to the development of osteoporosis which makes bones more fragile and susceptible to fractures. One way to help alleviate this side effect is through the use of calcium and vitamin D supplements.
Prednisolone can cause increased blood sugar levels for diabetics.
Other effects include decreased or blurred vision, increased eye pressure, increased thirst, cataract formation, confusion, rare cases of dementia in otherwise-healthy elderly patients, and nervousness.
Loteprednol is an analog drug that has reduced adverse ocular effects.
- depression, including suicidal thoughts
- feeling high (mania) or mood swings
- difficulty in thinking / confusion
- memory loss
- visual, auditory or tactile hallucinations
- having strange and frightening thoughts, changing behaviour or having feelings of being alone
Withdrawal from prednisolone can be problematic after taking large doses or over more than two weeks. This is caused by prednisolone inhibiting the natural production of corticosteroids in the "Hypothalamic-Pituitary-Adrenal Axis" (HPAA)
Banned status in athletics
As a glucocorticosteroid, unauthorized or ad-hoc use of prednisolone during competition via oral, intravenous, intramuscular or rectal routes is banned under WADA anti-doping rules. The drug may be used in competition with a TUE (Therapeutic Use Exemption), in compliance with WADA regulations. Local or topical use of prednisolone during competition as well as any use out of competition is not regulated.
Prednisolone differs from prednisone in that the keto-group at C11 of prednisone is replaced by a hydroxyl group.
Hydrocortisone acetate yields the widely used corticoid prednisolone acetate; in the same vein, cortisone acetate goes to prednisone acetate. Mild saponification of either of these products yields the free alcohols prednisolone and prednisone, respectively.
The increase in potency observed in the progestin series by incorporation of additional unsaturation in the A ring (see delmadinone, applies in the corticoid series as well; the majority of commercial steroid anti-inflammatory agents in fact include this feature.
Alternatively, 21-acetoxy-11β,17α-dihydroxy-5α-pregnane-3,20-dione undergoes dibromination by molecular bromine in acetic acid at positions C2 and C4, and then the resulting dibromide is dehydrobrominated by heating it in collidine, which gives prednisolone as an acetate at position C21. Hydrolyzing this compound then leads to formation of prednisolone.
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