Anti-inflammation medications are one type of medication used to treat Crohn's Disease. Anti-inflammatory drugs are, obviously, used to reduce inflammation in the digestive tract. Inflammation is cause by a surplus of white blood cells. White blood cells are the bodys defense against infection and disease. With Crohn's Disease the body starts to attack itself causing inflammation, usually in theintestines. With inflammation the bodys core temperature raises. This can cause damage to other organs and is why it can be very dangerous. Below are several different types of medications and the side effects associated with each medication. Your physician will discuss the pros and cons to each medication as well as what, or the combination of, medications should be used to treat the symptoms of Crohn's Disease. To read about the medications used to suppress your immune system click on the link below.
5-ASA (Mesalamine) Oral Medications
5-aminosalicylic acid (5-ASA)), also called mesalamine, is similar chemically to aspirin. Aspirin 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. 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, 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.
Azulfidine (sulfasalazine) 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. Azulfidine 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 Azulfidine reaches the ileum and the colon, the bacteria that normally are present 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 Azulfidine 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, Azulfidine can reduce the sperm count. The reduction in sperm count is reversible, and the count usually becomes normal after the Azulfidine is discontinued or changed to a different 5- ASA compound. Because the newer 5-ASA compounds (e.g., Asacol and Pentasa) do not have the sulfapyridine component and have fewer side effects than Azulfidine, they are being used more frequently in 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. It 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.
Dipentum (olsalazine) is a capsule 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, Dipentum is most effective for disease that is limited to the ileum or colon. Although clinical studies have shown that Dipentum is effective for maintenance of remission in ulcerative colitis, up to 11% of patients experience diarrhea when taking Dipentum. Because of this, Dipentum is not often used. The recommended dose of Dipentum is 500 mg twice a day.
Colazal (balsalazide) 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 break apart the 5-ASA and the inert molecule, releasing the 5-ASA. Because intestinal bacteria are most abundant in the terminal ileum and colon, Colazal is used to treat inflammatory bowel disease predominantly localized to the colon. Colazal recently has been approved by the FDA for use in the United States.
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.
5-ASA rectal medications (Rowasa Canasa)
Rowasa is 5-ASA in enema form. 5-ASA by enema is most useful for treating ulcerative colitis involving only the distal colon since the enema easily can reach the inflamed tissues of the distal colon. Rowasa also is used in treating Crohn's disease in which there is inflammation in and near the rectum. Each Rowasa enema contains 4 grams of 5-ASA. The enema usually is administered at bedtime, and patients are encouraged to retain the enema through the night. The enema contains sulfite and should not be used by patients with sulfite allergy. Otherwise, Rowasa enemas are safe and well-tolerated. Canasa is 5-ASA in suppository form. It is used for treating ulcerative proctitis. Each suppository contains 500 mg of 5-ASA and usually is administered twice daily. Both enemas and suppositories have been shown to be effective in maintaining remission in patients with ulcerative colitis limited to the distal colon and rectum. Corticosteroids Corticosteroids (e.g., prednisone, prednisolone, hydrocortisone, etc.) have been used for many years to treat patients with moderate to severe Crohn's disease and ulcerative colitis and to treat patients who fail to respond to 5-ASA. Unlike 5-ASA, corticosteroids do not require direct contact with the inflamed intestinal tissues to be effective. Oral corticosteroids are potent anti-inflammatory medications. After absorption, corticosteroids exert prompt anti-inflammatory actions throughout the body, including the intestines. Consequently, they are used in treating Crohn's disease anywhere in the small intestine, as well as ulcerative and Crohn's colitis. In critically ill patients, intravenous corticosteroids (such as hydrocortisone) can be given in the hospital. For patients with proctitis, hydrocortisone enemas (Cortenema) can be used to deliver the corticosteroid directly to the inflamed tissue. By using the corticosteroid topically, less of it is absorbed into the body and the frequency and severity of side effects are lessened (but not eliminated) as compared with systemic corticosteroids. Corticosteroids are faster-acting than 5-ASA, and patients frequently experience improvement in their symptoms within days of beginning them. Corticosteroids, however, do not appear to be useful in maintaining remission in Crohn's disease and ulcerative colitis or in preventing the return of Crohn's disease after surgery.
Side effects of corticosteroids
The frequency and severity of side effects of corticosteroids depend on the dose and duration of their use. Short courses of corticosteroids, for example, usually are well-tolerated with few and mild side effects. Long-term use of high doses of corticosteroids usually produces predictable and potentially serious side effects. Common side effects include rounding of the face (moon face), acne, increased body hair, diabetes, weight gain, high blood pressure, cataracts, glaucoma, increased susceptibility to infections, muscle weakness, depression, insomnia, mood swings, personality changes, irritability, and thinning of the bones (osteoporosis) with fractures of the spine. Children receiving corticosteroids experience stunted growth. The most serious complication from long term corticosteroid use is aseptic necrosis of the hip joints. Aseptic necrosis is a condition in which there is death and degeneration of the hip bone. It is a painful condition that can ultimately lead to the need for surgical replacement of the hip. Aseptic necrosis also has been reported in the knee joints. It is not known how corticosteroids cause aseptic necrosis. The estimated incidence of aseptic necrosis among corticosteroid users is 3-4%. Patients on corticosteroids who develop pain in the hips or knees should report the pain to their doctors promptly. Early diagnosis of aseptic necrosis with cessation of corticosteroids might decrease the severity of the aseptic necrosis and the need for hip replacement surgery. Prolonged use of corticosteroids can depress the ability of the body's adrenal glands to produce cortisol (a natural corticosteroid necessary for proper functioning of the body). Therefore, abruptly discontinuing corticosteroids can cause symptoms due to a lack of natural cortisol (a condition called adrenal insufficiency). Symptoms of adrenal insufficiency include nausea, vomiting, and even shock. Withdrawing corticosteroids too quickly also can produce symptoms of joint pain, fever, and malaise. Therefore, when corticosteroids are discontinued, the dose usually is tapered gradually rather than stopped abruptly. Even after corticosteroids are discontinued, the adrenal glands' ability to produce cortisol can remain depressed from months up to two years. The depressed adrenal glands may not be able to produce increased amounts of cortisol to help the body handle the stress of accidents, surgery, and infections. Therefore, patients need additional corticosteroids during stressful situations to avoid developing adrenal insufficiency. Because corticosteroids are not useful in maintaining remission in ulcerative colitis and Crohn's disease, and because they have predictable and potentially serious side effects, they should be used for the shortest possible length of time.
Proper use of corticosteroids
Once the decision is made to use systemic corticosteroids, treatment usually is initiated with prednisone, 40-60 mg daily. The majority of patients with Crohn's disease respond with an improvement in symptoms within a few weeks. Once symptoms have improved, prednisone is reduced by 5-10 mg per week until a dose of 20 mg per day is reached. The dose then is reduced at a slower rate until the corticosteroid is discontinued. Gradually reducing corticosteroids not only minimizes the symptoms of adrenal insufficiency, it also reduces the chances of an abrupt recurrence of inflammation. Many doctors use 5-ASA compounds and corticosteroids together. In patients who achieve remission with corticosteroids, 5-ASA compounds often are continued alone to maintain remission. In patients whose symptoms return corticosteroids are slowly being reduced, the dose of corticosteroids is increased slightly to control the symptoms. Once the symptoms are under control, the reduction of corticosteroids can resume at a slower pace. Unfortunately, many patients who require corticosteroids to induce remissions become corticosteroid dependent. These patients consistently develop symptoms whenever the corticosteroid dose falls below a certain level. In such patients who are corticosteroid dependent as well as in patients who are unresponsive to corticosteroids and other anti-inflammatory medications, immuno-modulator medications or surgery must be considered. The management of patients who are corticosteroid dependent or patients with severe disease that responds poorly to medications is complex. Doctors who are experienced in treating ulcerative colitis and Crohn's disease and in using immuno-modulators should evaluate these patients.
Prevention of Osteoporosis
Long-term use of corticosteroids can cause osteoporosis. Calcium is very important in the formation and maintenance of healthy bones. Corticosteroids decrease the absorption of calcium from the intestine and increase the loss of calcium from the kidneys. Increasing dietary calcium intake is important but alone cannot halt corticosteroid-induced osteoporosis. To prevent or minimize osteoporosis, management of patients on long-term corticosteroids should include:
Budesonide (Entocort EC) is a new type of corticosteroid for treating Crohn's disease. Like other corticosteroids, budesonide is a potent anti-inflammatory medication. Unlike other corticosteroids, however, budesonide acts only via direct contact with the inflamed tissues (topically) and not systemically. As soon as budesonide is absorbed into the body, the liver converts it into inactive chemicals. Therefore, for effective treatment of Crohn's disease, budesonide, like topical 5-ASA, must be brought into direct contact with the inflamed intestinal tissue. Budesonide capsules contain granules that allow a slow release of the drug into the ileum and the colon. In a double-blind multicenter study (published in 1998), 182 patients with Crohn's ileitis and/or Crohn's disease of the right colon were treated with either budesonide (9 mg daily) or Pentasa (2 grams twice daily). Budesonide was more effective than Pentasa in inducing remissions while the side effects were similar to Pentasa. In another study comparing the effectiveness of budesonide with corticosteroids, budesonide was not better than corticosteroids in treating Crohn's disease but had fewer side effects. Because budesonide is broken down by the liver into inactive chemicals, it has fewer side effects than systemic corticosteroids. It also suppresses the adrenal glands less than systemic corticosteroids. Budesonide will be available as an enema for the treatment of proctitis. Budesonide has not been shown to be effective in maintaining remission in patients with Crohn's disease. If used long-term, budesonide also may cause some of the same side effects as corticosteroids. Because of this, the use of budesonide should be limited to short-term treatment for inducing remission. Most budesonide is released in the terminal ileum, it will have its best results in Crohn's disease limited to the terminal ileum. It is not known whether budesonide is effective in treating patients with ulcerative colitis, and it is currently not recommended for the treatment of ulcerative colitis.
Antibiotics for Crohn's Disease
Antibiotics such as metronidazole (Flagyl) and ciprofloxacin (Cipro) have been used for treating Crohn's colitis. Flagyl also has been useful in treating anal fistulae in patients with Crohn's disease. The mechanism of action of these antibiotics in Crohn's disease is not well understood.
Metronidazole (Flagyl) is an antibiotic that is used for treating several infections caused by parasites (e.g., giardia) and bacteria (e.g., infections caused by anaerobic bacteria, and vaginal infections). It is effective in treating Crohn's colitis and is particularly useful in treating patients with anal fistulae. Chronic use of metronidazole in doses higher than 1 gram daily can be associated with permanent nerve damage (peripheral neuropathy). The early symptoms of peripheral neuropathy are numbness and tingling in the fingertips, toes, and other parts of the extremities. Metronidazole should be stopped promptly if these symptoms appear. Metronidazole and alcohol together can cause severe nausea, vomiting, cramps, flushing, and headache. Patients taking metronidazole should avoid alcohol. Other side effects of metronidazole include nausea, headaches, loss of appetite, a metallic taste, and, rarely, a rash.
Ciprofloxacin (Cipro) is another antibiotic used in the treatment of Crohn's disease. It can be used in combination with metronidazole.
Summary of anti-inflammatory medications