Calcium-sensing receptor: A new target for therapy of diarrhea

Table 1 Current antidiarrheal therapies and their mechanisms of action

Therapies	Mechanisms of action	Comments	Ref.
Proabsorptive
ORS/RS-ORS	↑glucose/SCFA absorption	Limited efficacy to reduce diarrhea	[98-100]
Antisecretory
Crofelemer	↓CFTR and CaCC→↓ secretion	Less efficacious as anticipated	[15]
Cholestyramine resin	↓bile salt in lumen→↓secretion	Concerns for vitamin malabsorption	[101]
Bismuth subsalicylate	↓PG synthesis→↓secretion	Safety concerns in children (Reye syndrome)	[102,103]
Antimotility/ENS modulatory
Loperamide/Diphenoxylate	↑μ opioid receptor →↓motility	Safety concerns in children (ileus)	[13,14]
Hyoscyamine/Dicyclomine	↓Ach action→↓muscle contraction	Safety concerns in children (seizure)
Alosetron	↓5-HT3R →↓motility and secretion	Safety concerns in children (ischemic colitis)	[104]
Racecadotril	↑encephalin→↓secretion	Not widely available	[105,106]
Clonidine	↑α2 adrenoceptor→↑absorption	No efficacy and safety study in children
Anti-inflammatory
TEN	Unknown mechanism of action	Slow action	[107]
Corticosteroids	Immunosuppression (↓PGs, ↑IL-10)	Concerns for adverse effects
Anti-TNFα	↓blood and tissue TNFα	Limited by expenses and adverse effects

ACh: Acetylcholine; CaCC: Ca²⁺ activated chloride channels; CFTR: Cystic fibrosis transmembrane conductance regulator; ORS: Oral rehydration solution; PG: Prostaglandins; RS-ORS: Resistant starch-based oral rehydration solution; SCFA: Short-chain fatty acids; VIP: Vasoactive intestinal polypeptide; TEN: Total enteral nutrition.