Drug-induced Gastrointestinal Disorders

Linda G. Tolstoi, RPh, MS, MEd

Disclosures

June 26, 2002

In This Article

Small Intestine

In the small intestine, drugs can cause ulcers, hemorrhage, malabsorption, and intestinal dysmotility. They can also produce cytotoxic effects on the intestinal mucosal cells.[23]

Ulcers

NSAIDs and potassium supplements are the primary culprits of drug-induced ulcers of the small intestine.[23] Risk factors for NSAID-induced ulcers include age > 60 years, a previous history of NSAID complications, and concomitant corticosteroid therapy.[23] Like NSAIDs, potassium can cause direct irritation to the mucosal lining. Enteric-coated potassium chloride was formulated to resist the acidic environment of the stomach.[2] However, when the enteric-coated tablets dissolve in the small intestines, a high concentration of ionized potassium accumulates adjacent to the dissolving tablet and causes direct epithelial damage and mucosal ischemia as a result of local vasoconstriction.[35] These changes in the epithelium and mucosa lead to ulceration, bleeding, or perforation.[35] In addition, a stricture may develop secondary to fibrosis associated with the healing process. To prevent this damage, the formulations of potassium chloride tablets were changed to a controlled-release wax matrix system and to microencapsulation to reduce the risk of injuring the gastrointestinal mucosa.

Hemorrhage

Anticoagulants may cause gastrointestinal hemorrhage.[23] Risk factors include intensity of therapy, adequacy of monitoring dosage, route of administration, concurrent pharmacotherapy, and the patient's age and underlying clinical status.[23] GI bleeding associated with anticoagulant therapy usually occurs in patients with preexisting intestinal lesions. The clinical features of anticoagulant-induced hemorrhage include hematemesis, melena, and hematochezia.[23]

Malabsorption

Drug-induced malabsorption interferes with the absorption of specific nutrients. For example, tetracycline chelates calcium, cholestyramine binds iron and vitamin B12, mineral oil reduces the absorption of carotene and fat-soluble vitamins, thiazide diuretics impair ileal transport of sodium, and aluminum/magnesium hydroxide precipitate calcium and phosphate ions.[23] Colchicine, neomycin, methotrexate, methyldopa, and allopurinol interfere with absorption of nutrients by causing mucosal damage. Drug-induced malabsorption may exacerbate the patient's poor nutritional status.[23]

Dysmotility

The motor activity of the small intestine is less likely to be affected by drugs than is the colon.[23] However, drugs such as phenothiazines, antiparkinsonian agents, tricyclic antidepressants, anticholinergics, opiates, loperamide, and calcium channel blockers can also inhibit the motility of the small intestine.[23] The reduction of small bowel motility may be severe enough that it can cause paralytic ileus or pseudo-obstruction.[5] Paralytic ileus is usually temporary and is associated with abdominal distention and symptoms of acute obstruction. Loperamide, an antidiarrheal drug, may cause paralytic ileus.[5] Vincristine, a chemotherapeutic agent, may cause pseudo-obstruction probably as a result of its neurotoxic effects on enteric motor function.[5,23] Intestinal motility usually returns shortly after discontinuation of the drug.[23]

Cytotoxic Effects

Many chemotherapeutic drugs have cytotoxic effects on mucosal cells of the small intestine because these cells have a high turnover rate.[23] Chemotherapeutic drugs such as actinomycin D, bleomycin, cytosine, arabinoside, doxorubicin, 5-fluorouracil, methotrexate, and vincristine can cause erosive enteritis. The clinical features include pain, bleeding, vomiting, ileus, and diarrhea.[23]

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