PHARMASOLONE Ophthalmic

Indications

• Asthma
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Ulcerative colitis
• Crohn's disease
• Allergic reactions
• Skin disorders (e.g., eczema, psoriasis)
• Adrenal insufficiency
• Certain cancers
• Organ transplantation

Dosage

Adults: The dosage of prednisone varies depending on the condition being treated.

Mechanism of action

Prednisone is metabolized to prednisolone, which acts as a glucocorticoid agonist corticosteroid. It decreases vasodilation and capillary permeability, inhibits leukocyte migration to sites of inflammation, and promotes changes in gene expression that lead to anti-inflammatory effects. Prednisone inhibits neutrophil apoptosis, phospholipase A2, and NF-Kappa B, while enhancing the expression of anti-inflammatory genes such as interleukin-10. Its effects can vary based on the dosing, with lower doses primarily providing anti-inflammatory effects and higher doses exerting immunosuppressive effects.

Pharmacodynamics

Corticosteroids, including prednisone, bind to the glucocorticoid receptor, which leads to inhibition of pro-inflammatory signals and promotion of anti-inflammatory signals. Prednisone has a relatively short half-life of 2-3 hours, indicating a short duration of action. The therapeutic window for corticosteroids is wide, allowing for significantly higher doses than the body's natural production. Patients on corticosteroids are at risk for hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.

Pharmacokinetics

Following oral administration, prednisone is rapidly absorbed and extensively metabolized in the liver to prednisolone, the active form. The bioavailability of prednisone can be affected by factors such as food intake. It has a short half-life of approximately 2-3 hours, necessitating multiple daily doses for sustained effects. The elimination of prednisone occurs primarily through hepatic metabolism, with metabolites excreted in urine.

Contra-indications

• Systemic fungal infections
• Hypersensitivity to prednisone or any component of the formulation
• Live vaccines during corticosteroid therapy

Adverse effects

• Increased risk of infections
• Gastrointestinal disturbances (e.g., peptic ulcer, pancreatitis)
• Mood changes (e.g., euphoria, depression)
• Hypertension
• Osteoporosis
• Hyperglycemia
• Weight gain
• Skin changes (e.g., thinning, striae)

Interactions

• NSAIDs may increase the risk of gastrointestinal side effects
• Antidiabetic agents may require dosage adjustments due to hyperglycemic effects
• Live vaccines may be less effective
• Barbiturates, phenytoin, and rifampicin may decrease the effectiveness of prednisone
• CYP3A4 inhibitors may increase plasma concentrations of prednisone

Precautions

• Use with caution in patients with diabetes, hypertension, or osteoporosis
• Gradual withdrawal is advisable to avoid adrenal insufficiency after prolonged therapy
• Monitor for signs of infection
• Consider the impact on growth in children

Pregnancy

Prednisone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is categorized as Category C.

Breast-feeding

Prednisone is excreted in breast milk, and caution is advised when used during lactation; potential effects on the infant should be considered.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Tablets (various strengths)
• Oral solution
• Injectable form (for intravenous or intramuscular use)

Mechanism of action

Prednisone is first metabolized in the liver to its active form, prednisolone, a glucocorticoid agonist corticosteroid. The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days. Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10. Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels. In physiologic doses, corticosteroids are administered to replace deficient endogenous hormones. In larger (pharmacologic) doses, glucocorticoids decrease inflammation by stabilizing leukocyte lysosomal membranes, preventing release of destructive acid hydrolases from leukocytes; inhibiting macrophage accumulation in inflamed areas; reducing leukocyte adhesion to capillary endothelium; reducing capillary wall permeability and edema formation; decreasing complement components; antagonizing histamine activity and release of kinin from substrates; reducing fibroblast proliferation, collagen deposition, and subsequent scar tissue formation; and possibly by other mechanisms as yet unknown. The drugs suppress the immune response by reducing activity and volume of the lymphatic system, producing lymphocytopenia, decreasing immunoglobulin and complement concentrations, decreasing passage of immune complexes through basement membranes, and possibly by depressing reactivity of tissue to antigen-antibody interactions. Glucocorticoids stimulate erythroid cells of bone marrow, prolong survival time of erythrocytes and platelets, and produce neutrophilia and eosinopenia. Glucocorticoids promote gluconeogenesis, redistribution of fat from peripheral to central areas of the body, and protein catabolism, which results in negative nitrogen balance. They reduce intestinal absorption and increase renal excretion of calcium. /Corticosteroids/ Glucocorticoids are capable of suppressing the inflammatory process through numerous pathways. They interact with specific intracellular receptor proteins in target tissues to alter the expression of corticosteroid-responsive genes. Glucocorticoid-specific receptors in the cell cytoplasm bind with steroid ligands to form hormone-receptor complexes that eventually translocate to the cell nucleus. There these complexes bind to specific DNA sequences and alter their expression. The complexes may induce the transcription of mRNA leading to synthesis of new proteins. Such proteins include lipocortin, a protein known to inhibit PLA2a and thereby block the synthesis of prostaglandins, leukotrienes, and PAF. Glucocorticoids also inhibit the production of other mediators including AA metabolites such as COX, cytokines, the interleukins, adhesion molecules, and enzymes such as collagenase. /Glucocorticoids/

Pharmacodynamics

Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Prednisone has a short duration of action as the half life is 2-3 hours. Corticosteroids have a wide therapeutic window as patients make require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.