Pharmacological modulation of gut mucosal and large vessel blood flow

Abstract

Vasoactive agents may reduce gut mucosal blood flow in the absence of reduced large vessel flow. Constipating drugs do not necessarily reduce gut blood flow. Rectal mucosal blood flow correlates with splenic flexure mucosal flow, and potentially may be used as a more convenient surrogate for studying splenic flexure blood flow.

Safety of Eluxadoline in Patients with Irritable Bowel Syndrome with Diarrhea

“…The single case of colon ischemia occurred in a patient with multiple comorbidities known to be associated with colon ischemia (including age (72 years), recent polymicrobial sepsis, type II diabetes mellitus, pulmonary hypertension, and concomitant selective serotonin reuptake inhibitor use). A causal association with eluxadoline was felt to be unlikely, given the lack of diary reports of constipation and the lack of evidence supporting a physiologic effect on systemic or GI blood flow with eluxadoline or other poorly absorbed OR-targeting anti-diarrheals ( 55 ).…”

Constipation and evacuation disorders

“…A number of agents have been developed with a mixture of antagonistic effect at the 5HT-3 and agonist action at 5HT-4 receptors. However, agents such as tegaserod and alosetron have had to be withdrawn from general use due to concerns about cardiovascular rhythm disturbance and potential risk of ischaemic colitis [39,40]. These are plainly unacceptable risks in patients with a benign, albeit annoying, condition.…”