Sulfasalazine ulcerative colitis

The ongoing assessment for patients receiving sulfasalazine for ulcerative colitis includes observation for evidence of Hie relief or intensification of the symptoms of the disease. The nurse inspects all stool samples and records Hieir number and appearance... 

Maintenance of remission of ulcerative colitis in patients intolerant of sulfasalazine Active duodenal ulcer... 

Bismudi subsalicylate is used in combination witii otiier dru > to treat gastric and duodenal ulcers caused by H. pylori bacteria Mesalamine is used in the treatment of chronic inflammatoiy bowel disease Misoprostol is used to prevent gastric ulcers in those taking aspirin or nonsteroidal anti-inflammatory dragp in high doses for a prolonged time Olsalazine is used in the treatment of ulcerative colitis in those allergic to sulfasalazine. Sulfasalazine is used in the treatment of Crohn s disease and ulcerative colitis. Sucralfate is used in the treatment of duodenal ulcer. 

Molin, L. and Stendahl, O. (1979). The effect of sulfasalazine and its active components on human polymorphonuclear leukocyte function in relation to ulcerative colitis. Acta Med. Scand. 206, 451-457. 

The answers are 484-k 485-j. (tlardman, pp 1061-1062, 1682-1685.) Sulfonamides can cause acute hemolytic anemia. In some patients it mayr be related to a sensitization phenomenon, and in other patients the hemolysis is due to a glucose-6-phosphate dehydrogenase deficiency Sulfamethoxazole alone or in combination with trimethoprim is used to treat UTls. The sulfonamide sulfasalazine is employed in the treatment of ulcerative colitis. Daps one, a drug that is used in the treatment of leprosy, and primaquine, an anti mala rial agent, can produce hemolysis, particularly in patients with a glucose-6-phosphate dehydrogenase deficiency. 

Oral mesalamine derivatives (such as those listed in Table 26-5) are reasonable alternatives to sulfasalazine for treatment of ulcerative colitis but they are not more effective than sulfasalazine. 

Steroids have a place in the treatment of moderate to severe ulcerative colitis that is unresponsive to maximal doses of oral and topical mesalamine. Prednisone up to 1 mg/kg/day or 40 to 60 mg daily may be used for patients who do not have an adequate response to sulfasalazine or mesalamine. 

Prevention of recurrence of disease is clearly more difficult with Crohn s disease than with ulcerative colitis. Sulfasalazine and oral mesalamine derivatives are effective in preventing acute recurrences in quiescent Crohn s disease. 

A four-electron reduction of the azo group leads to the cleavage of the molecule and the production of two amines (Fig. 5.10). There are few drugs that contain an azo bond but a good example is sulfasalazine, which is reductively cleaved to 4-aminosalicylic acid and sulfapyridine (18). This reduction is mediated by anaerobic bacteria in the intestine, and it leads to the formation of two agents that are pharmacologically active in the treatment of ulcerative colitis. 

Sulfasalazine Antimicrobial anti-inflammatory ulcerative colitis/inflammatory bowel diseases Suppresses NK cells impaired lymphocyte function... 

Ricart, E., Taylor, W. R., Loftus, E. V., et al. (2002) iV-Acetyltransferase 1 and 2 genotypes do not predict response or toxicity to treatment with mesalamine and sulfasalazine in patients with ulcerative colitis. Am. J. Gastroenterol. 97, 1763-1768. 

Ulcerative colitis In the treatment of mild to moderate ulcerative colitis, and as adjunctive therapy in severe ulcerative colitis for the prolongation of the remission period between acute attacks of ulcerative colitis (refer to the sulfasalazine monograph in the Gl chapter). 

Pharmacology The mode of action of sulfasalazine or its metabolites, 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), is still under investigation but may be related to the anti-inflammatory or immunomodulatory properties that have been observed in animals and in vitro, to its affinity for connective tissue, or to the relatively high concentration it reaches in serous fluids, the liver, and intestinal walls. In ulcerative colitis, the major therapeutic action may reside in the 5-ASA moiety. P.842... 

Lactation Sulfonamides are excreted in breast milk. In newborns, they compete with bilirubin for binding sites on the plasma proteins and may cause kernicterus. Children The safety and efficacy of sulfasalazine in pediatric patients younger than 2 years of age with ulcerative colitis have not been established. 

Ulcerative colitis Inform patients with this condition that ulcerative colitis rarely remits completely, and that the risk of relapse can be substantially reduced by continued administration of sulfasalazine at a maintenance dosage. Glucose-6-phosphate dehydrogenase deficiency Observe patients with glucose-6-phosphate dehydrogenase deficiency closely for signs of hemolytic anemia. This reaction is frequently dose-related. 

Sulfasalazine (Azulfidine, Azulfidine EN) [Anti-inflammatory/ Antirheumatic (DMARD)/Sulfonamide] Uses Ulcerative colitis, RA, juvenile RA, active Crohn Dz, ankylosing spondylitis, psoriasis Action Sulfonamide actions unclear Dose Adults. Initial, 1 g PO tid-qid T to a max of 8 g/d in 3 -5- doses maint 500 mg PO qid Feds. Initial 40-60 mg/kg/24 h PO -s- q4-6h maint 20-30 mg/kg/24 h PO q6h RA >6 y 30-50 mg/kg/d in 2 doses, start w/ 1/4-1/3 maint dose, T wkly until dose reached at 1 mo, 2 g/d max -i in renal failure... 

Sulfasalazine was the first of the 5-aminosalicylic acid (5-ASA) congeners that was shown to be effective in the treatment of active Crohn s disease with involvement of the colon and of ulcerative colitis. 

Sulfasalazine (Azulfidine) is approved for the treatment of rheumatoid arthritis and ulcerative colitis. It is also used to treat ankylosing spondylitis and Crohn s disease. Comparisons of sulfasalazine with other DMARDs suggest that it is more effective than hydroxychloroquine, azathioprine, and oral gold compounds. It is at least as effective as intramuscular gold and penicillamine. It has a greater degree of toxicity than hydroxychloroquine but less than gold compounds and penicillamine. After 5 years, approximately 75% of patients have discontinued sulfasalazine therapy, primarily because of a lack of efficacy as opposed to intolerable side effects. 

Sulfasalazine treatment results in an 85% remission rate in mild to moderate ulcerative colitis. Termination of therapy leads to an 80% relapse within the next year. In Crohn s disease, sulfasalazine acts primarily on involved colonic mucosa, although remission of ileal disease also has been reported. The National Cooperative Crohn s Disease Study found sulfasalazine to be better in the treatment of colonic disease, while corticosteroids were judged better in the treatment of small bowel disease. Since sulfasalazine does not prevent relapse of Crohn s disease once remission is achieved, maintenance therapy is not characteristically used. 

To avoid the side effects of sulfapyridine, various preparations to target 5-ASA directly to sites of disease have been formulated. Also known as mesalamine, 5-ASA has been formulated in oral forms (Pentasa, Asacoi). Pentasa is a time-release capsule that releases the drug throughout the GI tract. Asacoi is a pH-dependent-release preparation that delivers drug to the distal small bowel and colon. The response of ulcerative colitis to this formulation appears to be identical to that seen with sulfasalazine. Mesalamine can also be administered as a suppository (Canasa) or enema (Rowasa) for distal colonic disease. 

C. The information provided suggests the patient has mild to moderate disease. Initial therapy should be a 5-ASA containing product, which includes sulfasalazine and mesalamine. However, the patient has a sulfa allergy, precluding the use of sulfasalazine. Metronidazole is useful in the treatment of some patients with Crohn s disease. Cyclosporine has been used in patients with fulminant ulcerative colitis. Prednisone may have to be added to this patient s therapy, but only if he fails to respond to the mesalamine. It should not be used initially. 

Sulfasalazine (salicylazosulfapyridine) is widely used in ulcerative colitis, enteritis, and other inflammatory bowel disease (see Chapter 62). 

Aminosalicylates, eg, mesalamine in many formulations Mechanism uncertain t may be inhibition of eicosanoid inflammatory mediators Topical therapeutic action systemic absorption may cause toxicity Mild to moderately severe Crohn s disease and ulcerative colitis Sulfasalazine causes sulfonamide toxicity and may cause GI upset, myalgias, arthralgias, myelosuppression other aminosalicylates much less toxic... 

Sulfasalazine. Salicylazosulfapyridine or Azulfadine [599-79-1] (2-hydroxy-5-[[4[(2-pyridylamino)sulfonyl]-phenyl]azo] benzoic acid) (15) is a light brownish yellow-to-bright yellow fine powder that is practically tasteless and odorless. It melts at ca 255°C with decomposition, is very slightly soluble in ethanol, is practically insoluble in water, diethyl ether, chloroform, and benzene, and is soluble in aqueous solutions of alkali hydroxides. Sulfasalazine may be made by the synthesis described in Reference 13. It is not used as an antidiarrheal as such, but is indicated for the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn s disease. Its action is purported to result from the breakdown in the colon to 5-aminosalicylic acid [89-57-6] (5-AS A) and sulfapyridine [144-83-2]. It may cause infertility in males, as well as producing idiosyncratic reactions in some patients these reactions have been attributed to the sulfa component of the compound. The mechanism of 5-ASA is attributed to inhibition of the arachidonic acid cascade preventing leukotriene B4 production and the ability to scavenge oxygen free radicals. The active component appears to be 5-aminosalicylic acid. 

Administration Most sulfa drugs are well absorbed after oral administration. Sulfasalazine [sul fa SAL a zeen], when administered orally or as a suppository, is reserved for treatment of chronic inflammatory bowel disease (for example, Crohn s disease or ulcerative colitis), because it is not absorbed. Similarly, succinylsulfathiazole [suks in ill sul fa THI a zole] is used for the treatment of salmonella and shigella carriers. Intravenous sulfonamides are generally reserved for patients who are unable to take oral preparations. Because of the risk of sensitization, sulfas are not usually applied topically. In burn units, creams of mafenide acetate (p-aminomethylbenzensulfonamide) or silver sulfadiazine have been effective in reducing burn sepsis. However, superinfections with resistant bacteria or fungi may occur. 

Correct answer = A. Sulfasalazine is reserved for treatment of ulcerative colitis because the drug is not absorbed from the gut and acts locally. 

Sulfasalazine is also licensed for treatment of mild to moderate and severe ulcerative colitis and maintenance of remission, and active Crohn s disease. 

Alternatively, the enzyme in the gut can be utilized to control the release of the active drug in the gut. For example, sulfasalazine, which is employed in the treatment of ulcerative colitis, is a combination of sul-fapyridine and 5-aminosalicylate chemically linked via an azo bond. It remains absorbed and intact throughout the GI tract until it reaches the large intestine, where bacterial azoreductase enzymes degrade the azo bond and release sulfapyridine and 5-aminosalicylate to act locally on the lesions. 

The prodrug sulfasalazine (SAS), used in the treatment of Crohn s disease, ulcerative colitis, and rheumatoid... 

A 79-year-old woman who had been taking sulfasalazine for ulcerative colitis for 5 years developed a positive Coombs test and a hemoglobin of 8.2 g/dl. 

However, about 1.7% of patients with ulcerative colitis develop immune hemolytic anemia, even in the absence of sulfasalazine, so cause and effect is not always possible to determine. 

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