gastrointestinal disorders
Medications for Inflammatory Bowel Disease
5 Aminosalicylic Acid (5 ASA, Mesalamine)
5-ASA blocks production of prostaglandins and leukotrienes and has other beneficial effects on the inflammatory cascade. Because 5-ASA is active only intraluminally and is rapidly absorbed by the proximal small bowel, it must be formulated for delayed absorption when given orally. Sulfasalazine,the original agent in this class, delays absorption by complexing 5-ASA with a sulfa moiety, sulfapyridine. The complex is cleaved by bacterial flora in the lower ileum and colon, releasing the 5-ASA. The sulfa moiety, however, causes numerous adverse effects (eg, nausea, dyspepsia, headache), interferes with folate (folic acid) absorption, and occasionally causes serious adverse reactions (eg, hemolytic anemia or agranulocytosis and, rarely, hepatitis, pneumonitis, or myocarditis). Reversible decreases in sperm count and motility occur in up to 80% of men. If used,sulfasalazineshould be given with food, initially in a low dosage (eg, 0.5 g orally 2 times a day) and the dose and frequency gradually increased over several days to 1 to 1.5 g 4 times a day. Patients should take daily folate supplements (1 mg orally) and have complete blood count and liver tests every 6 to 12 months. Acute interstitial nephritis secondary tomesalamineoccurs rarely; periodic monitoring of renal function is advisable because most cases are reversible if recognized early. Medications that complex 5-ASA with other vehicles seem almost equally effective but have fewer adverse effects.Olsalazine(a 5-ASA dimer) andbalsalazide(5-ASA conjugated to an inactive compound) are cleaved by bacterial azoreductases (as issulfasalazine). These drugs are activated mainly in the colon and are less effective for proximal small-bowel disease. The effectiveness of the tablet form ofbalsalazidein female patients has not been shown in clinical studies.Olsalazinesometimes causes diarrhea, especially in patients with pancolitis. This problem is minimized by gradual escalation of dose and administration with meals. Other formulations of 5-ASA use delayed-release and/or extended-release coatings to delay release of the drug until entry into the distal ileum and colon. Combination delayed-release and extended-release formulations may be given once a day; their less frequent dosing may improve the patient's adherence to taking them. All of these formulations of 5-ASA are therapeutically roughly equivalent. 5-ASA is also available as a suppository or enema for proctitis and left-sided colon disease. These rectal preparations are effective for both acute treatment and long-term maintenance in proctitis and proctosigmoiditis and they have incremental benefit in combination with oral 5-ASA. Patients who cannot tolerate enemas due to rectal irritation should be given 5-ASA foam. 