Alosetron toxicity

Constipation Serious complications of constipation, including obstruction, perforation, impaction, toxic megacolon, secondary colonic ischemia, and death have been reported with use of alosetron. Immediately discontinue alosetron treatment in patients who develop constipation. 

In contrast to the excellent safety profile of other 5-HT3-receptor antagonists, alosetron is associated with rare but serious gastrointestinal toxicity. Constipation occurs in up to 30% of patients with diarrhea-predominant IBS, reguiring discontinuation of the drug in 10%. Serious complications of constipation requiring hospitalization or surgery have occurred in 1 of every 1000 patients. Episodes of ischemic colitis—some fatal—have been reported in up to 3 per 1000 patients. Given the seriousness of these adverse events, alosetron is restricted to women with severe diarrhea-predominant IBS who have not responded to conventional therapies and who have been educated about the relative risks and benefits. 

Ondansetron, other 5-HT3 antagonists 5-HT3 blockade in gut and CNS with shorter duration of binding than alosetron Extremely effective in preventing chemotherapy-induced and postoperative nausea and vomiting First-line agents in cancer chemotherapy also useful for postop emesis Usually given IV but orally active in prophylaxis. 4-9 h duration of action very low toxicity but may slow colonic transit... 

D. Toxicity Adverse effects of ketanserin are those of alpha blockade and Hj blockade. The toxicides of ondansetron, granisetron, and dolasetron include diarrhea and headache. Dolasetron has been associated with QRS and QT prolongation in the ECG and should not be used in patients with heart disease. Alosetron caused significant constipation in some patients. 

Gastrointestinal Ischemic colitis and complications of constipation (obstruction, perforation, intestinal ulceration, toxic megacolon, ileus, and impaction resulting in hospital admission) have been reported in association with alosetron. Alosetron was initially withdrawn from the market, but in the USA restricted access is allowed, with a risk management plan. 

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