Category:Antidiarrheals

An antidiarrheal is a medicine used to treat diarrhoea, either symptomatically (by slowing intestinal motility, increasing intestinal water absorption, or both) or by addressing an underlying cause (treatment of infection, replacement of malabsorbed substrate, modulation of secretory pathology). The category overlaps substantially with opioid receptor agonists (the gut-restricted peripheral mu agonists), with antibacterials (in infectious diarrhoea), and with electrolyte replacements (for the dehydration and electrolyte loss that accompanies severe or prolonged diarrhoea).

The clinical history of antidiarrheal pharmacology is dominated by two strands. The first is the use of opium and opium derivatives for diarrhoea, documented from antiquity through the modern era; opium tincture (laudanum), paregoric (camphorated tincture of opium), and the synthetic peripheral mu-agonist loperamide (Janssen, 1976) act on the mu opioid receptor of the myenteric plexus to slow gastrointestinal transit and increase intestinal water reabsorption. The second is the oral rehydration story (described in detail under electrolyte replacements): the demonstration by Dilip Mahalanabis in the 1971 West Bengal cholera epidemic that oral salt-glucose solution reduced cholera mortality from 30 percent to under 4 percent, perhaps the most consequential single antidiarrheal intervention in public-health terms.

The contemporary outpatient pharmacopoeia is organised by mechanism. The opioid receptor agonists, most notably loperamide (Imodium, OTC since 1988), are the standard symptomatic antidiarrheal; loperamide does not cross the blood-brain barrier in clinically meaningful concentrations and so does not produce the central opioid effects of its parent class, although high-dose abuse for euphoria has been described and produces QT-prolongation and torsades de pointes. The related diphenoxylate (Lomotil, in combination with low-dose atropine to deter abuse) provides similar mechanism with somewhat more central penetration. The opium-derivative paregoric remains available as a Schedule III medicine in selected jurisdictions. The peripheral mu agonist eluxadoline, described under IBS treatments, is the newest medicine in this group.

Bismuth subsalicylate (Pepto-Bismol, since 1900) has antidiarrheal, anti-emetic, antacid, and weak antibacterial activity through multiple mechanisms (antibacterial action against Vibrio cholerae and selected enteropathogens; antisecretory action through prostaglandin pathway inhibition; gastric coating; binding of bacterial toxin). It is the standard medicine for traveller's-diarrhoea prophylaxis (60 mL or two tablets four times daily during travel; not for trips over three weeks because of bismuth-related neurotoxicity) and for symptomatic relief of mild acute infectious diarrhoea.

Octreotide, the somatostatin analogue described under hormones, reduces gastrointestinal secretion and motility and is used for severe diarrhoea of carcinoid syndrome, of VIPoma, of chemotherapy-induced diarrhoea refractory to loperamide, and of high-output ileostomy or short-bowel syndrome. The newer telotristat (Xermelo, Lexicon 2017) blocks tryptophan hydroxylase 1 in carcinoid tumours and reduces serotonin-mediated secretory diarrhoea by a different upstream mechanism.

For specific causes of diarrhoea, mechanism-targeted antidiarrheals exist. Bile-acid sequestrants (cholestyramine, colesevelam) treat bile-acid diarrhoea (the consequence of ileal resection, of post-cholecystectomy state, of selective bile-acid malabsorption that accounts for approximately a quarter of "diarrhoea-predominant IBS" on dedicated testing). The non-absorbable disaccharidase substitutes for lactose intolerance (lactase enzyme preparations) prevent rather than treat lactose-malabsorption diarrhoea. The pancreatic enzyme replacement preparations (pancrelipase, pancreatin) treat steatorrhoea of pancreatic exocrine insufficiency. Crofelemer (Mytesi, Napo Pharmaceuticals 2012), an extract of the South American Croton lechleri tree, is approved for non-infectious diarrhoea in HIV patients on antiretroviral therapy and acts by blocking the cAMP-activated chloride channel CFTR and the calcium-activated chloride channel CaCC.

The infectious diarrhoeas are treated with the appropriate antibacterials, antivirals, or antiparasitics, listed under anti-infectives and its sub-categories. Of specific relevance to this category: the non-absorbable rifaximin (Xifaxan, Salix/Bausch 2004 for traveller's diarrhoea; 2010 for hepatic encephalopathy prevention; 2015 for IBS-D) is also indicated for travellers' diarrhoea (the IDSA recommends azithromycin first-line for moderate-to-severe travellers' diarrhoea in most regions; rifaximin or single-dose fluoroquinolone are alternatives). Nitazoxanide (described under antiprotozoals) is used for cryptosporidial and giardial diarrhoea.

The non-pharmacological foundation of antidiarrheal practice is rehydration, addressed under electrolyte replacements. Oral rehydration solution (WHO reduced-osmolarity formula or commercial Pedialyte / Hydralyte equivalents) is first-line for almost all paediatric and most adult acute diarrhoea; intravenous fluid resuscitation is reserved for haemodynamic instability or for vomiting that prevents oral intake.

By mechanism:

• Opioid receptor agonists (peripheral, gut-restricted; cross-indexed under opioid analgesics / opioid receptor agonists):
  • Loperamide (Imodium)
  • Diphenoxylate-atropine (Lomotil)
  • Paregoric (Schedule III opium tincture)
  • Eluxadoline (Viberzi; mu agonist + delta antagonist; primarily for IBS-D)
• Bismuth-based:
  • Bismuth subsalicylate (Pepto-Bismol)
  • Bismuth subcitrate (component of quadruple-therapy H. pylori eradication regimens)
• Somatostatin and serotonin-axis:
  • Octreotide (carcinoid, VIPoma, chemotherapy-induced refractory diarrhoea, high-output ileostomy, dumping syndrome)
  • Lanreotide (alternative somatostatin analogue)
  • Telotristat (carcinoid diarrhoea, tryptophan hydroxylase inhibitor)
• Bile-acid sequestrants (cross-indexed under lipid-lowering agents; bile-acid diarrhoea is the antidiarrheal indication):
  • Cholestyramine, colesevelam, colestipol
• Pancreatic enzyme replacement:
  • Pancrelipase (Creon, Zenpep, Pancreaze, Ultresa, Viokace, Pertzye)
• Other mechanistic:
  • Crofelemer (Mytesi; HIV-associated diarrhoea on antiretrovirals)
  • Lactase preparations (lactose-intolerance prevention)
  • Probiotics (selected strains; Saccharomyces boulardii has evidence for C. difficile and antibiotic-associated diarrhoea; Lactobacillus species have mixed evidence)
• Gut-restricted antibacterials (cross-indexed under antibacterials):
  • Rifaximin (travellers' diarrhoea, IBS-D, hepatic encephalopathy prevention)
  • Vancomycin oral (C. difficile colitis)
  • Fidaxomicin (C. difficile colitis)

The boundary of this category is "medicine used to treat or symptomatically manage diarrhoea." The infectious-cause-targeted anti-infectives (azithromycin and fluoroquinolones for bacterial traveller's diarrhoea, metronidazole for amoebic dysentery, vancomycin and fidaxomicin for C. difficile colitis, antivirals for cytomegalovirus colitis) are listed under their primary class. The medicines used in inflammatory bowel disease and irritable bowel syndrome are cross-listed where the indication overlaps but are organised under their primary disease categories. The medicines used in chronic diarrhoea of specific causes (microscopic colitis with budesonide; coeliac disease with gluten avoidance plus selected experimental medicines; pancreatic exocrine insufficiency with enzyme replacement) are listed under those primary indications. Oral rehydration solution is the foundational supportive-care medicine for acute diarrhoea and is listed under electrolyte replacements.

This category page is an encyclopedia article about its subject. The actual index of medicines belonging to the category is generated automatically by the wiki engine, from category-membership declarations on the individual medicine pages, and appears at the foot of the page below the references.