Glucocorticoids

GLUCOCORTICOIDS

Pharmacokinetics & Pharmacodynamics

In gastrointestinal practice, prednisone and prednisolone are the most commonly used oral glucocorticoids. These drugs have an intermedi-ate duration of biologic activity allowing once-daily dosing. 

Hydrocortisone enemas, foam, or suppositories are used to maximize colonic tissue effects and minimize systemic absorption via topical treatment of active inflammatory bowel disease in the rectum and sigmoid colon. Absorption of hydrocortisone is reduced with rectal administration, although 15–30% of the administered dosage is still absorbed.

Budesonide is a potent synthetic analog of prednisolone thathas high affinity for the glucocorticoid receptor but is subject to rapid first-pass hepatic metabolism (in part by CYP3A4), resulting in low oral bioavailability. A controlled-release oral formulation of budesonide (Entocort) is available that releases the drug in the distal ileum and colon, where it is absorbed. The bioavailability of controlled-release budesonide capsules is approximately 10%. 

As in other tissues, glucocorticoids inhibit production of inflammatory cytokines (TNF-α, IL-1) and chemokines (IL-8); reduce expression of inflammatory cell adhesion molecules; and inhibit gene transcription of nitric oxide synthase, phospholipase A₂, cyclooxygenase-2, and NF-κB.

Clinical Uses

Glucocorticoids are commonly used in the treatment of patients with moderate to severe active inflammatory bowel disease. Active disease is commonly treated with an initial oral dosage of 40–60 mg/d of prednisone or prednisolone. Higher doses have

not been shown to be more efficacious but have significantly greater adverse effects. Once a patient responds to initial therapy (usually within 1–2 weeks), the dosage is tapered to minimize development of adverse effects. In severely ill patients, the drugs are usually administered intravenously. 

For the treatment of inflammatory bowel disease involving the rectum or sigmoid colon, rectally administered glucocorticoids are preferred because of their lower systemic absorption.

Oral controlled-release budesonide (9 mg/d) is commonly used in the treatment of mild to moderate Crohn’s disease involving the ileum and proximal colon. It appears to be slightly less effective than prednisolone in achieving clinical remission, but has signifi-cantly less adverse systemic effects.

Corticosteroids are not useful for maintaining disease remis-sion. Other medications such as aminosalicylates or immunosup-pressive agents should be used for this purpose.