In this essay we will discuss about the drugs used for the treatment of chronic inflammatory disease:- 1. Corticosteroids 2. 5-Amino Salicylates (ASA) Compounds 3. Immunosuppressants 4. Antibacterial Drugs.
Corticosteroids are used to produce remission in both disorders. Prednisolone is given orally until the disease remits, then it is reduced stepwise. Alternatively budesonide, a retarded-release steroid, may be more preferable, because of its more marked local action in the terminal small intestine. Prednisolone enemas can be used, instead, in mild ulcerative colitis, if confined to the descending colon.
Extra-colonic manifestations of inflammatory bowel disease (ocular lesions, skin disease and peripheral arthritis) also respond to corticosteroids. Corticosteroids are not the preferred drugs, particularly for mild disease and for maintenance therapy, because of high incidence of side effects. They should not be used before ruling out an infectious process.
2. 5-Amino Salicylate (ASA) Compounds:
Drugs that deliver 5-ASA to the bowel mucosa constitute first- line therapy in inflammatory bowel disease.
Once the patient is in remission after treatment with corticosteroids, sulfasalazine can be started to keep the patient in remission. Sulfasalazine is a combination of 5-ASA and sulfa pyridine and reaches the colon intact, where it releases the active component – 5-ASA, which is anti-inflammatory. It is effective in ulcerative colitis and Crohn’s disease limited to the colon.
Adverse effects are mainly caused by the sulfa pyridine moiety and include headache, nausea, vomiting and abdominal pain. Hypersensitivity reactions are less common and include skin rash, fever, and hepatotoxicity and blood disorders. Male fertility may be temporarily reduced. Folic acid supplementation may be required as sulfasalazine impairs folate absorption.
Mesalazine (5-ASA) lacks the sulfa moiety and is associated with fewer side effects. It is effective in ulcerative colitis as well as ileocecal/colonic Crohn’s disease. Mesalazine enemas can be used to treat distal lesions. Asacol and balsalazide are delayed release preparations of mesalazine useful in distal disease. Pentasa, a time and pH-dependent release preparation of mesalazine throughout the GIT is useful in diffuse Crohn’s disease that also affects the small bowel; it can be used in ulcerative colitis as well.
Olsalazine is a 5-ASA dimmer that is cleaved by bacteria in the colon and is useful in inflammatory bowel disease. Diarrhea is a major side effect of 5-ASA and can limit its use. Rarely hypersensitivity reactions may occur, which include blood disorders, pneumonitis, pancreatitis, hepatitis and nephritis and calls for an immediate withdrawal of the drug. 5-ASA is contraindicated in salicylate hypersensitivity and renal impairment.
Immunosuppressant reduces inflammation by inhibiting the production of immune cells and/or inflammatory proteins. Azathioprine, methotrexate, and cyclosporine have favorable side effect profile than corticosteroids and are used as steroid-sparing agents in severe or refractory inflammatory bowel disease. Adverse effects include bone marrow depression, allergic reactions and teratogenicity.
Infliximab is a monoclonal antibody against tumor necrosis factor α (TNF-α) that induces inflammatory cell lysis by binding to TNF-α receptors on cell surface. It is given by IV infusion in fistulous as well as refractory inflammatory type Crohn’s disease, which is generally unresponsive to other treatments.
The results are very rapid and dramatic. Constant monitoring with infliximab therapy is necessary because of serious transfusion reactions, sepsis, and shortness of breath or chest pain, reactivation of latent tuberculosis (TB). It is contraindicated in patients who have had TB, patients with cancer or with existing infections.
4. Antibacterial Drugs:
Metronidazole can be used as an alternative first-line agent or adjunctive therapy in mild to moderate perianal Crohn’s disease. Ciprofloxacin or co-trimoxazole is the alternative agent.