Aminosalicylates are a class of medications containing 5-aminosalicylic acid (5-ASA) used to manage inflammation in certain chronic conditions. Chemically related to aspirin, they work by directly affecting inflamed tissues. This targeted approach helps control symptoms and maintain health in specific long-term diseases.
Conditions Treated by Aminosalicylates
Aminosalicylates are most frequently prescribed for inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn’s disease. Their primary application is managing mild-to-moderate ulcerative colitis (UC) by treating the inflammation and ulcers that characterize the condition. For patients with UC, these drugs are effective for inducing remission and for maintenance therapy to prevent flare-ups.
Oral 5-ASA drugs are recommended for treating mild ulcerative colitis. When inflammation is confined to the rectum (proctitis), a rectal form like an enema or suppository is used for more direct application. For colitis affecting the left side of the colon, a combination of oral and rectal 5-ASA may be suggested to ensure the medication reaches all inflamed areas.
While central to UC treatment, their role in Crohn’s disease is more limited. Aminosalicylates are most effective when the inflammation is located in the colon. A drug like sulfasalazine might be used for mild-to-moderate Crohn’s disease confined to the large intestine, but they are less common for inflammation in the small intestine.
Mechanism of Action
The benefit of aminosalicylates comes from their topical anti-inflammatory effect on the lining of the intestine. The active ingredient, 5-aminosalicylic acid (5-ASA), works directly at the site of inflammation rather than circulating throughout the body. This local action distinguishes them from systemic anti-inflammatories that affect the entire body.
The medication diminishes inflammation by interfering with the production of chemicals that promote it. In IBD, the intestinal lining produces an excess of prostaglandins and leukotrienes through the cyclooxygenase and lipoxygenase pathways. Aminosalicylates block these pathways, reducing the synthesis of these inflammatory substances in the colon.
By preventing the production of prostaglandins and leukotrienes, 5-ASA also inhibits the migration of immune cells to the inflamed tissue and scavenges harmful molecules known as free radicals. This action at the mucosal surface helps alleviate symptoms like diarrhea and abdominal pain.
Common Aminosalicylate Drugs and Formulations
The choice of aminosalicylate drug and its formulation is tailored to the location of inflammation. The main drugs in this class include sulfasalazine, mesalamine (the 5-ASA compound), olsalazine, and balsalazide. Sulfasalazine, the first widely used drug, links a 5-ASA molecule to a sulfapyridine molecule. Newer drugs were developed to deliver 5-ASA with better tolerance.
Oral formulations are designed to release medication at different points in the digestive system. Since standard 5-ASA is absorbed too early, special coatings are needed to deliver the drug to the lower small bowel or colon. Some mesalamine tablets have a pH-dependent coating that dissolves only in the higher pH of the distal small bowel and colon. Other formulations use microgranules for a slow, continuous release.
Rectal formulations deliver mesalamine directly to the end of the large intestine. Suppositories are for inflammation in the rectum (proctitis), while enemas or foams can reach higher into the distal colon. Olsalazine and balsalazide are also designed for colon-specific delivery, as they require gut bacteria to break a bond and release the active 5-ASA.
Potential Side Effects and Considerations
While well-tolerated, aminosalicylates can cause side effects. Common issues are often dose-related and may improve over time. These include:
- Headache
- Nausea
- Loss of appetite
- Abdominal pain or cramping
Diarrhea can also occur, particularly with olsalazine and balsalazide.
A small number of patients may experience more serious reactions. Rarely, these drugs can cause kidney impairment (interstitial nephritis) or hypersensitivity reactions, leading to inflammation of the pancreas (pancreatitis) or lungs (pneumonitis). Patients should report any new or worsening symptoms to their healthcare provider.
Sulfasalazine has specific considerations due to its sulfa component, and patients with a sulfa allergy should not take it. This medication can interfere with the body’s metabolism of folic acid, so supplementation is often recommended. A rare but serious side effect is agranulocytosis, a sharp drop in white blood cells that requires immediate discontinuation of the drug.