Crohn's Disease (cont.)
In this Article
- Crohn's disease facts
- What is Crohn's disease?
- What causes Crohn's disease?
- How does Crohn's disease affect the intestines?
- How is Crohn's disease different from ulcerative colitis?
- What are the symptoms of Crohn's disease?
- What are the complications of Crohn's disease?
- How is Crohn's disease diagnosed?
- How is Crohn's disease treated?
- Crohn's Disease Medications
- Anti-inflammatory medications
- 5-ASA (mesalamine) oral medications
- 5-ASA rectal medications (Rowasa, Canasa)
- Budesonide (Entocort EC)
- Immuno-modulator medications
- Azathioprine (Imuran) and 6-mercaptopurine (6-MP, Purinethol)
- Infliximab (Remicade)
- Adalimumab (Humira)
- Certolizumab pegol (Cimzia)
- Natalizumab (Tysabri)
- Surgery in Crohn's disease
- Are there any recommendations for diet and supplementation for Crohn's disease?
- View the Crohn's Disease Slideshow
- Crohn's Disease Quiz
- Inflammatory Bowel Disease (IBD) Slideshow
- Crohn's Disease FAQs
- Find a local Gastroenterologist in your town
Anti-inflammatory medications that decrease intestinal inflammation are analogous to arthritis medications that decrease joint inflammation. Different types of anti-inflammatory medications used in the treatment of Crohn's disease are:
- 5 aminosalicylic acid (5-ASA) compounds such as sulfasalazine (Azulfidine) and mesalamine (Pentasa, Asacol, Dipentum, Colazal, Rowasa enema, Canasa suppository) that act via direct contact (topically) with the inflamed tissue in order to be effective.
- Corticosteroids that act systemically (without the need for direct contact with the inflamed tissue) to decrease inflammation throughout the body. Systemic corticosteroids have important and predictable side effects if used long-term.
- A new class of topical corticosteroid (for example, budesonide [Entocort EC]) that acts via direct contact (topically) with the inflamed tissue. This class of corticosteroids has fewer side effects than systemic corticosteroids which are absorbed into the body.
- Antibiotics such as metronidazole (Flagyl) and ciprofloxacin (Cipro) that decrease inflammation by an unknown mechanism
5-ASA (mesalamine) oral medications
5-aminosalicylic acid (5-ASA), also called mesalamine, is similar chemically to aspirin. Aspirin is an anti-inflammatory drug that has been used for many years for treating arthritis, bursitis, and tendonitis (conditions of tissue inflammation). Aspirin, however, is not effective in treating Crohn's disease and ulcerative colitis, and even may worsen the inflammation. Aspirin, however, is not effective in treating Crohn's disease and ulcerative colitis and may even worsen the inflammation. Recent studies suggest that aspirin might actually decrease future risk of developing colorectal cancer in the general population.
On the other hand, 5-ASA can be effective in treating Crohn's disease and ulcerative colitis if the drug can be delivered topically onto the inflamed intestinal lining. For example, mesalamine (Rowasa) is an enema containing 5-ASA that is effective in treating inflammation in the rectum. However, the enema solution cannot reach high enough to treat inflammation in the upper colon and the small intestine. Therefore, for most patients with Crohn's disease involving both the ileum (distal small intestine) and colon, 5-ASA must be taken orally.
If pure 5-ASA is taken orally, however, most of the 5-ASA would be absorbed in the stomach and the upper small intestine, and very little 5-ASA would reach the ileum and colon. To be effective as an oral agent in treating Crohn's disease, 5-ASA has to be modified chemically to escape absorption by the stomach and the upper intestines.
Sulfasalazine (Azulfidine) was the first modified 5-ASA compound used in the treatment of Crohn's colitis and ulcerative colitis. It has been used successfully for many years to induce remissions among patients with mild to moderate ulcerative colitis. Sulfasalazine also has been used for prolonged periods for maintaining remissions.
Sulfasalazine consists of a 5-ASA molecule linked chemically to a sulfapyridine molecule. (Sulfapyridine is a sulfa antibiotic.) Connecting the two molecules together prevents absorption by the stomach and the upper intestines. When sulfasalazine reaches the ileum and the colon, the bacteria that normally are present in the ilium and colon break the link between the two molecules. After breaking away from 5-ASA, sulfapyridine is absorbed into the body and later eliminated in the urine. Most of the active 5-ASA, however, is available within the terminal ileum and colon to treat the colitis.
Most of the side effects of sulfasalazine are due to the sulfapyridine molecule. These side effects include nausea, heartburn, headache, anemia, skin rashes, and, in rare instances, hepatitis and kidney inflammation. In men, sulfasalazine can reduce the sperm count. The reduction in sperm count is reversible, and the count usually becomes normal after the sulfasalazine is discontinued or changed to a different 5- ASA compound.
Because the newer 5-ASA compounds, for example, mesalamine (Asacol and Pentasa), do not have the sulfapyridine component and have fewer side effects than sulfasalazine, they are being used more frequently for treating Crohn's disease and ulcerative colitis.
Asacol is a tablet consisting of the 5-ASA compound surrounded by an acrylic resin coating. Asacol is sulfa-free. The resin coating prevents the 5-ASA from being absorbed as it passes through the stomach and the small intestine. When the tablet reaches the terminal ileum and the colon, the resin coating dissolves, and the active 5-ASA drug is released.
Asacol is effective in inducing remissions in patients with mild to moderate ulcerative colitis. It also is effective when used in the longer term to maintain remissions. Some studies have shown that Asacol also is effective in treating Crohn's ileitis and ileo-colitis, as well as in maintaining remission in patients with Crohn's disease.
The recommended dose of Asacol for inducing remissions is two 400 mg tablets three times daily (a total of 2.4 grams a day). At least two tablets of Asacol twice daily (1.6 grams a day) is recommended for maintaining remission. Occasionally, the maintenance dose is higher.
As with Azulfidine, the benefits of Asacol are dose-related. If patients do not respond to 2.4 grams a day of Asacol, the dose frequently is increased to 3.6 - 4.8 grams a day to induce remission. If patients fail to respond to the higher doses of Asacol, then other alternatives such as corticosteroids are considered.
Pentasa is a capsule consisting of small spheres containing 5-ASA. Pentasa is sulfa-free. As the capsule travels down the intestines, the 5-ASA inside the spheres is released slowly into the intestine. Unlike Asacol, the active drug 5-ASA in Pentasa is released into the small intestine as well as the colon. Therefore, Pentasa can be effective in treating inflammation in the small intestine and is currently the most commonly used 5-ASA compound for treating mild to moderate Crohn's disease in the small intestine.
Patients with Crohn's disease occasionally undergo surgery to relieve small intestinal obstruction, drain abscesses, or remove fistulae. Usually, the diseased portions of the intestines are removed during surgery. After successful surgery, patients can be free of disease and symptoms (in remission) for a while. In many patients, however, Crohn's disease eventually returns. Pentasa helps maintain remissions and reduces the chances of the recurrence of Crohn's disease after surgery.
In the treatment of Crohn's ileitis or ileocolitis, the dose of Pentasa usually is four 250 mg capsules four times daily (a total of 4 grams a day). For maintenance of remission in patients after surgery, the dose of Pentasa is between 3-4 grams daily.
Olsalazine (Dipentum) is a capsule filled with a drug in which two molecules of 5-ASA are joined together by a chemical bond. In this form, the 5-ASA cannot be absorbed from the stomach and intestine. Intestinal bacteria are able to break apart the two molecules releasing the active individual 5-ASA molecules into the intestine. Since intestinal bacteria are more abundant in the ileum and colon, most of the active 5-ASA is released in these areas. Therefore, olsalazine is most effective for disease that is limited to the ileum or colon. Although clinical studies have shown that olsalazine is effective for maintenance of remission in ulcerative colitis, some patients experience diarrhea when taking olsalazine. Because of this, olsalazine is not often used. The recommended dose of olsalazine is 500 mg twice a day.
Balsalazide (Colazal) is a capsule in which the 5-ASA is linked by a chemical bond to another molecule that is inert (without effect on the intestine) and prevents the 5-ASA from being absorbed. This drug is able to travel through the intestine unchanged until it reaches the end of the small bowel (terminal ileum) and colon. There, intestinal bacteria split the 5-ASA and the inert molecule releasing the 5-ASA. Because intestinal bacteria are most abundant in the terminal ileum and colon, balsalazide is used to treat inflammation predominantly localized to the colon.
Side effects of oral 5-ASA compounds
The 5-ASA compounds have fewer side effects than Azulfidine and also do not reduce sperm counts. They are safe medications for long-term use and are well-tolerated.
Patients allergic to aspirin should avoid 5-ASA compounds because they are similar chemically to aspirin.
Rare kidney and lung inflammation has been reported with the use of 5-ASA compounds. Therefore, 5-ASA should be used with caution in patients with kidney disease. It also is recommended that blood tests of kidney function be done before starting and periodically during treatment.
Rare instances of worsening of diarrhea, cramps, and abdominal pain, at times accompanied by fever, rash, and malaise, may occur. This reaction is believed to represent an allergy to the 5-ASA compound.
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