Inflammatory Bowel Disease Medication

Many inflammatory mediators have been identified in IBD; antibodies against these mediators or methods to block the production or receptors for these mediators hold great promise for potential therapy for IBD.

Therapy for Crohn disease is generally less effective than that for ulcerative colitis. In addition to the therapies outlined herein, IV cyclosporine is helpful in refractory ulcerative colitis. Zileuton, a 5-lipoxygenase inhibitor, has shown some efficacy in treating Crohn disease.

Although several drugs have been used successfully for the treatment of IBD for many years, medical treatment has advanced rapidly. The medications used are broken down into several classes based on the chemical similarities of the individual agents and similarities in the mechanisms of action.

A step-wise approach may be taken. With this approach, the most benign (or temporary) drugs are used first. As they fail to provide relief, drugs from a higher step are used.

The step-wise approach is as follows:

1. The aminosalicylates and symptomatic agents are step I drugs; antibiotics are step IA drugs, given the limited situations in which they are used.
2. The corticosteroids constitute the step II drugs to be used if the step I drugs fail to adequately control the IBD.
3. The immune-modifying agents are step III drugs and are used if corticosteroids fail or are required for prolonged periods. Infliximab and adalimumab are also step III drugs that can be used in some situations in patients with Crohn disease and ulcerative colitis.
4. The experimental agents are step IV drugs and are used only after the previous steps fail and, then, are administered only by physicians familiar with their use.

Note that drugs from all steps may be used additively; in general, the goal is to wean the patient off steroids as soon as possible to prevent long-term adverse effects from these agents. Opinions differ regarding the use of certain agents in this step-wise approach.

Class Summary

These agents are effective in reducing inflammatory reactions. All of the aminosalicylates are useful for treating flares of IBD and for maintaining remission.

Sulfasalazine (Azulfidine, Azulfidine EN-tabs)

This agent is considered best for colonic disease, although it is also considered first-line therapy for Crohn disease. It is used for acute disease and for maintenance of remission.

Mesalamine (Asacol, Pentasa, Canasa, Rowasa, Lialda, Apriso)

Mesalamine is a 5-ASA and acts systemically. It also has activity as a topical anti-inflammatory.

Balsalazide (Colazal)

Balsalazide is a prodrug 5-ASA connected to a 4-aminobenzoyl-(beta)-alanine carrier by an azo bond; colonic bacteria break the azo bond, releasing the active 5-ASA. Metabolites of the drug may decrease inflammation by blocking the production of arachidonic acid metabolites in colonic mucosa.

Olsalazine (Dipentum)

This aminosalicylate is useful for active disease and maintenance of remission in ulcerative colitis. Dipentum is 5-ASA connected to a 5-ASA by an azo bond; colonic bacteria break the azo bond, releasing the active 5-ASA.

Class Summary

Antimicrobial therapy must cover all likely pathogens in the context of the clinical setting. Metronidazole (Flagyl) and ciprofloxacin (Cipro) are the most commonly used antibiotics in persons with IBD. Antibiotics are used sparingly in persons with ulcerative colitis, because ulcerative colitis increases the risk of developing antibiotic-associated pseudomembranous colitis. Rifaximin (Xifaxan) is a newly approved broad-spectrum antibiotic that may also help treat patients with IBD.

Metronidazole (Flagyl)

Metronidazole is a widely available, inexpensive antibiotic and antiprotozoal agent.

Ciprofloxacin (Cipro)

Ciprofloxacin is a fluoroquinolone antibiotic commonly used for the treatment of urinary, skin, and respiratory tract infections.

Rifaximin (Xifaxan)

Rifaximin is a nonabsorbed (< 0.4%), broad-spectrum antibiotic specific for enteric pathogens of the gastrointestinal tract (ie, gram-positive, gram-negative, aerobic, anaerobic). It is a rifampin structural analog and it binds to the beta-subunit of bacterial DNA-dependent RNA polymerase, thereby inhibiting RNA synthesis.

Class Summary

These agents are the treatments of choice for an acute inflammatory bowel disease (IBD) attack; administer IV in severe disease. Administer increased or stress doses to patients already on steroids. Do not use steroids for maintaining remission because of their lack of efficacy and potential complications, including avascular necrosis, osteoporosis, cataracts, emotional lability, hypertension, diabetes mellitus, cushingoid features, acne, and facial hair. Cortenema, Cortifoam, and Anusol-HC suppositories are useful in treating distal disease (proctitis and proctosigmoiditis).

Hydrocortisone (Solu-Cortef, Cortenema, Cortifoam, Anusol-HC)

Adrenocortical steroids act as potent inhibitors of inflammation. It may cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body. Alternative adrenocortical steroids may be used in equivalent dosage.

Prednisone (Deltasone, Orasone, Sterapred)

Prednisone acts as a potent inhibitor of inflammation. It may cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body. Alternative corticosteroids may be used in equivalent dosage.

Methylprednisolone (Solu-Medrol, Depo-Medrol)

Adrenocortical steroids act as potent inhibitors of inflammation. They may cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body. Alternative adrenocortical steroids may be used in equivalent dosage

Prednisolone (AK-Pred, Pred Forte)

Corticosteroids act as potent inhibitors of inflammation. They may cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body. Alternative corticosteroids may be used in equivalent dosage.

Budesonide (Entocort)

Budesonide alters the level of inflammation in tissues by inhibiting multiple types of inflammatory cells and decreasing the production of cytokines and other mediators involved in inflammatory reactions.

Dexamethasone (Baycadron)

Dexamethasone has many pharmacologic benefits, but also significant adverse effects. It stabilizes cell and lysosomal membranes, increases surfactant synthesis, increases serum vitamin A concentrations, and inhibits prostaglandin and proinflammatory cytokines.

Class Summary

These agents are useful as steroid-sparing agents, in healing fistulas, or when the patient has serious contraindications to surgery.^[8] They are used in patients refractory to or unable to tolerate steroids and in patients in whom remission is difficult to maintain with the aminosalicylates alone. Some agents, including azathioprine and its metabolite, 6-MP, have been useful in Crohn disease complicated by recurrent rectal fistulas or perianal disease; response can take up to 6 months. Methotrexate has also been tried.

Azathioprine (Imuran)

Azathioprine inhibits mitosis and cellular metabolism by antagonizing purine metabolism and inhibiting synthesis of DNA, RNA, and proteins; these effects may decrease proliferation of immune cells and result in lower autoimmune activity.

6-Mercaptopurine (Purinethol)

6-Mercaptopurine is a purine analog that inhibits DNA and RNA synthesis, causing cell proliferation to arrest.

Methotrexate (Rheumatrex, Trexail)

Methotrexate impairs DNA synthesis and induces the apoptosis and reduction in interleukin 1 production. It is indicated for moderate-to-severe disease and maintenance of remission. The onset of action is delayed.

Class Summary

Infliximab (Remicade), given intravenously, consists of monoclonal antibodies to TNF-alpha. Infliximab is approved by the FDA for use in IBD, in both Crohn disease and ulcerative colitis.^[9] Infliximab is somewhat more effective against CD than UC. The drug appears to promote mucosal healing, which not even prednisone does. Furthermore, it heals perianal and enterocutaneous fistulae and has been shown to reduce signs and symptoms, achieve clinical remission and mucosal healing, and eliminate corticosteroid use.^[25] Infliximab is indicated for patients who have experienced inadequate response to conventional therapy.^[8]

Certolizumab pegol (Cimzia) is a pegylated antitumor necrosis factor (TNF)–alpha blocker, which results in disruption of the inflammatory process. Certolizumab pegol (Cimzia) is indicated for moderate-to-severe Crohn disease in individuals who have not responded to conventional therapies.

Adalimumab (Humira) and certolizumab (Cimzia) are TNF blocking agents that have been FDA approved for the treatment of Crohn disease. They are administered by subcutaneous injection. They are not FDA approved for ulcerative colitis.

Infliximab (Remicade)

Infliximab neutralizes cytokine TNF-alpha and inhibits its binding to the TNF-alpha receptor. Mix in 250 mL normal saline for infusion over 2 hours.

Adalimumab (Humira)

Adalimumab is recombinant human IgG1 monoclonal antibody specific for human TNF. It binds specifically to TNF-alpha and blocks the interaction with p55 and p75 cell-surface TNF receptors.

Certolizumab pegol (Cimzia)

Certolizumab pegol is a pegylated antitumor necrosis factor (TNF)–alpha blocker, which results in disruption of the inflammatory process. It is indicated for moderate-to-severe Crohn disease in individuals who have not responded to conventional therapies.

Class Summary

Natalizumab (Tysabri) is a recombinant humanized IgG4-1C monoclonal antibody that works by preventing the accumulation of lymphocytes in the diseased bowel by blocking the effects of integrin. It has been approved by the FDA, but is only available through a restricted distribution program. Natalizumab is an IV medication that has shown efficacy in Crohn disease, but it is not as effective as anti-TNF agents. Natalizumab has been linked to reports of progressive multifocal leukoencephalopathy

Natalizumab (Tysabri)

This is a recombinant humanized IgG4-1C monoclonal antibody produced in murine myeloma cells. It binds to alpha-4 subunits of alpha-4-beta-1 and alpha-4-beta-7 integrins expressed on the leukocyte surface, which inhibits alpha-4-mediated leukocyte adhesion to their receptors. In Crohn disease, the interaction of the alpha-4-beta-7 integrin with the endothelial receptor MAdCAM-1 has been implicated as an important contributor to the chronic inflammation that is a hallmark of the disease.

Class Summary

H2-receptor antagonists are reversible competitive blockers of histamines at the H2 receptors, particularly those in the gastric parietal cells, where they inhibit acid secretion. The H2 antagonists are highly selective, do not affect the H1 receptors, and are not anticholinergic agents.

Cimetidine (Tagamet)

Cimetidine inhibits histamine at H2 receptors of gastric parietal cells, which results in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.

Ranitidine (Zantac)

Ranitidine inhibits histamine stimulation of the H2 receptor in gastric parietal cells, which, in turn, reduces gastric acid secretion, gastric volume, and hydrogen ion concentrations.

Famotidine (Pepcid)

Famotidine competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen ion concentrations.

Nizatidine (Axid)

Nizatidine competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and reduced hydrogen concentrations.

Class Summary

Proton pump inhibitors inhibit gastric acid secretion by inhibition of the H⁺ -K⁺ -ATPase enzyme system in the gastric parietal cells. Used in cases of severe esophagitis and in patients whose disease is not responsive to H2-antagonist therapy.

Omeprazole (Prilosec)

Omeprazole decreases gastric acid secretion by inhibiting the parietal cell H+/K+-ATPase pump.

Lansoprazole (Prevacid)

Lansoprazole suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase enzyme system (ie, proton pump) at the secretory surface of the gastric parietal cell. It blocks the final step of acid production. The effect is dose-related and inhibits both basal and stimulated gastric acid secretion, thus increasing gastric pH.

Esomeprazole magnesium (Nexium)

Esomeprazole magnesium is an S-isomer of omeprazole. It inhibits gastric acid secretion by inhibiting the H+/K+-ATPase enzyme system at secretory surface of gastric parietal cells. It is used in severe cases and in patients not responding to H2 antagonist therapy. It is used for up to 4 weeks to treat and relieve symptoms of active duodenal ulcers; it may be used for up to 8 weeks to treat all grades of erosive esophagitis.

Rabeprazole sodium (Aciphex)

Rabeprazole sodium decreases gastric acid secretion by inhibiting the parietal cell H+/K+ ATP pump.

Pantoprazole (Pantoloc, Protonix)

Pantoprazole suppresses gastric acid secretion by specifically inhibiting the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells.

Class Summary

These agents provide symptomatic relief when patients report symptoms of diarrhea.

Diphenoxylate and atropine (Lomotil)

This is an antidiarrheal agent chemically related to the narcotic analgesic meperidine. It acts on intestinal muscles to inhibit peristalsis and slow intestinal motility. It prolongs the movement of electrolytes and fluid through the bowel and increases viscosity and loss of fluids and electrolytes. Also, diphenoxylate and atropine is a drug combination. A subtherapeutic dose of anticholinergic atropine sulfate is added to discourage overdosage, in which case diphenoxylate may clinically mimic the effects of codeine.

Loperamide (Imodium)

Loperamide acts on intestinal muscles to inhibit peristalsis and slow intestinal motility. It prolongs the movement of electrolytes and fluid through the bowel and increases viscosity and loss of fluids and electrolytes.

Cholestyramine (Questran)

It binds bile acids, thus reducing damage to the intestinal mucosa. It also reduces the induction of colonic fluid secretion. It forms a nonabsorbable complex with bile acids in the intestine, which, in turn, inhibits enterohepatic reuptake of intestinal bile salts.

Class Summary

These agents are used to treat spastic disorders of the GI tract.

Dicyclomine (Bentyl)

This agent treats gastrointestinal motility disturbances. It blocks the action of acetylcholine at parasympathetic sites in secretory glands, smooth muscle, and the CNS.

Hyoscyamine (Levbid, Levsin, Levsin-SL)

Hyoscyamine blocks the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the CNS, which, in turn, has antispasmodic effects. SL tablets may be administered orally, sublingually, or chewed.