Necrotizing enterotyphlocolitis in dogs treated with a potent antimuscarinic.
To assess the safety of a potent muscarinic receptor antagonist (antimuscarinic) for human clinical testing, repeat-dose oral toxicity studies were conducted in the Beagle dog. Treatment resulted in unexpected gastrointestinal system effects that were likely mediated by the exaggerated pharmacologic effects of the antimuscarinic on intestinal motility. Dogs developed profound anorexia followed by severe bloody diarrhea, and at necropsy, the intestinal tract was distended, filled with red-tinged fluid, and the mucosa was reddened. Histologically, intestinal lesions consisted of severe epithelial necrosis and mucosal atrophy localized predominantly to the ileum and large intestine. Feces from dogs with diarrhea were culture-positive for Clostridium perfringens (CP), suggesting that CP might be the etiologic agent; however, the intestinal lesions were not consistent with histologic findings reported in dogs with hemorrhagic canine enteritis.
Rudmann
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DG
Eli Lilly and Co., 2001 W. Main Street, P.O. Box 708, Drop Code GL44, Greenfield, IN 46140, USA. dgrudmann@lilly.com
VanderEide
S L
SL
D000818:Animals; D003015:Clostridium Infections / Q000473:pathology / Q000662:veterinary*; D003016:Clostridium perfringens; D004283:Dog Diseases / Q000139:chemically induced* / Q000473:pathology; D004285:Dogs; D020345:Enterocolitis, Necrotizing / Q000139:chemically induced / Q000473:pathology / Q000662:veterinary*; D005243:Feces / Q000382:microbiology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006652:Histological Techniques; D007082:Ileum / Q000473:pathology; D007413:Intestinal Mucosa / Q000473:pathology; D007420:Intestine, Large / Q000473:pathology; D023421:Models, Animal; D018727:Muscarinic Antagonists / Q000009:adverse effects*; D023382:Toxicity Tests, Acute / Q000662:veterinary
D018727:Muscarinic Antagonists