A patient with carcinoid syndrome presents with diarrhoea, flushing, and bronchospasm. Telotristat ethyl is added to his octreotide therapy. Its mechanism targets:

• A Inhibition of tryptophan hydroxylase (TPH1) in enterochromaffin cells of the gut, reducing peripheral serotonin synthesis and alleviating diarrhoea caused by GI serotonin excess ✓
• B Antagonism of 5-HT3 receptors in the GI tract, blocking serotonin-mediated pro-secretory and pro-motility effects
• C Competitive antagonism of serotonin 5-HT4 receptors in enteric neurons, reducing peristalsis
• D Inhibition of aromatic L-amino acid decarboxylase (DOPA decarboxylase), blocking serotonin synthesis from 5-HTP

Explanation

Telotristat ethyl is a peripherally acting inhibitor of tryptophan hydroxylase-1 (TPH1), the rate-limiting enzyme converting tryptophan to 5-hydroxytryptophan (5-HTP) in the gut. In carcinoid tumours, ECL cells overproduce serotonin, driving the diarrhoea component of carcinoid syndrome. By reducing peripheral (not central) serotonin synthesis without crossing the blood-brain barrier, telotristat significantly reduces bowel movement frequency when added to somatostatin analogue therapy. This is approved for carcinoid syndrome diarrhoea inadequately controlled by somatostatin analogues alone. It does not affect CNS serotonin levels.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.