Drug-induced Gastrointestinal Disorders

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]

Medscape Pharmacotherapy. 2002;4(1) © 2002  Medscape

Cite this: Drug-induced Gastrointestinal Disorders - Medscape - Jun 27, 2002.