Enemas corticosteroids

See Table 10.6. PR. Administered as retention enema. Corticosteroids discussed in Tables 10.6. 

Treatment of acute episodes of ulcerative colitis is dictated by the severity and extent of disease, and first-line therapy of mild to moderate disease involves oral or topical aminosalicylate derivatives. Topical suppositories and enemas are preferred for active distal UC (left-sided disease and proctitis), as they deliver mesalamine directly to the site of inflammation. Topical mesalamine is superior to both topical corticosteroids and oral aminosalicylates for inducing remission in active mild to moderate UC.1,33,34 Enemas are appropriate for patients with... 

Maintenance of remission of ulcerative colitis may be achieved with oral or topical aminosalicylates. Mesalamine suppositories 1 g daily may prevent relapse in up to 90% of patients with proctitis.1 Mesalamine enemas are appropriate for left-sided disease and may often be dosed three times weekly. Oral mesalamine at lower doses (e.g., 1.6 g per day) may be combined with topical therapies to maintain remission. Topical or oral corticosteroids are not effective for maintaining remission of distal UC and should be avoided. 

Prednisone, which in the body is converted to the active form prednisolone, is the most widely used corticosteroid. Maximal activity occurs mostly within 1-2 hours after oral administration, and the effects last up to 36 hours. For patients with colitis localized in the lower part of the colon prednisolone sodium phosphate is formulated for rectal administration as an enema. 

Braverman DL, Lachmann EA, Nagler W. Avascular necrosis of bilateral knees secondary to corticosteroid enemas. Arch Phys Med Rehabil 1998 79(4) 449-52. 

Although systemic absorption of the prednisolone from the enema probably does occur, especially when the colon is particularly inflamed, corticosteroids usually have less systemic effects when given this way. Furthermore, by giving an enema, the drug is being delivered directly to its site of action - remember that in ulcerative colitis the disease is confined to the lower gastrointestinal tract. 

Her prednisolone should be replaced with full dose corticosteroid - most commonly intravenous hydrocortisone 100 mg four times daily to control the inflammation. Predsol enemas are often also given. 

In more severe disease corticosteroids are needed to induce remission (prednisolone 60 mg/day until remission induced, tailing the dose by 5 mg/week). Approximately 75% of patients respond. Budesonide, a potent topically active corticosteroid, is an alternative which can be administered either orally or as an enema. The oral preparation is presented as a delayed release formulation which delivers drug to the terminal ileum and ascending colon. Extensive first pass metabolism in the liver limits its systemic availability and potential for adverse effects. Budesonide is also useful as maintenance therapy of the 30% of patients with Crohn s disease who are steroid dependent. 

Topical corticosteroid use is limited to disease located in the distal colon or rectum. Topical steroids are available for use as suppositories, enemas, or foams. The advantage of using topical steroids in acute mild to moderate disease is that it provides higher doses localized to the affected area. Although it was thought that topical therapy would decrease systemic effects of steroids, extensive anastomoses in the rectal area may lead to significant systemic absorption. 

D Hydrocortisone. Hydrocortisone is the only corticosteroid that is available as suppositories, enemas, and foams for rectal use. It is the best choice for this patient since the rectal route may have the potential to minimize systemic toxicities (i.e., behavioral disturbances, insomnia) that the patient previously experienced with the iV and PO corticosteroids. This patient s exacerbation is mild and his disease is localized to the rectum and distal colon. Therefore, per rectum corticosteroids wiil be able to target these areas successfully. 

The fall in serum corticosteroid levels is established and of clinical importance in systemic treatment, but it seems unlikely to affect the response to steroids given topically or by inhalation, intra-articular injection or enema. The interaction can be accommodated in several ways ... 

A corticosteroid such as beclometasone acts almost exclusively locally due to a large first-pass effect in the gut wall and the liver and is therefore ideal for local application. Beclometasone dipropionate in a suspension enema of 100 mL is used for chronic intestinal inflammations. A beclometasone suppository may be used to treat proctitis. There is clinical experience with beclometasone dipropionate in an oily base, but literature is still lacking. 

Dexamethasone, prednisolone and hydrocortisone are systemically active via the rectal route. The best chemical form of the active substance must be chosen and a dosage form that provides good release of the active substance. A corticosteroid as salt in solution is often optimal for an enema and the preparation is easy. As a solution in water it avoids problems such as release from a fatty base and subsequent dissolution. Dexamethasone and prednisolone for instance are used as sodium phosphate salts. Conversion and factorisation must not be forgotten. For stability reasons... 

In aqueous solution, prednisolone sodium phosphate and dexamethasone sodium phosphate are more stable than hydrocortisone sodium succinate. At a pH of about 8, the acid groups are sufficiently ionised to make the substance very soluble, while the phosphate ester is reasonably stable at this pH. Water soluble corticosteroids are mainly used in parenteral preparations, eye drops, oral mixtures and enemas. Examples are prednisolone oral mixtures and dexamethasone injections. 

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