Prednisolone Acetate EP6

Details:

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.

Adverse effects

Possible side-effects include fluid retention of the face (moon face, Cushing's syndrome), acne,constipation, and mood swings.

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.

Swelling of the pancreas has also been reported.

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 dementiain otherwise-healthy elderly patients, and nervousness.

Loteprednol is an analog drug that has reduced adverse ocular effects.