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Bismuth subsalicylate

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Bismuth subsalicylate
Clinical data
Trade namesPepto-Bismol, BisBacter
AHFS/Drugs.comMultum Consumer Information
Routes of
ATC code
  • none
Legal status
Legal status
  • 2-Hydroxy-2H,4H-benzo[d]1,3-dioxa-2-bismacyclohexan-4-one
    Simplified molecular structure of bismuth subsalicylate. The material is layered and each layer consists of a bismuth-oxo-rod decorated with salicylic acid molecules that join the rods, giving a layered material.
    Simplified molecular structure of bismuth subsalicylate.
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard100.035.397 Edit this at Wikidata
Chemical and physical data
Molar mass362.093 g·mol−1
3D model (JSmol)
  • O[Bi]1OC(=O)C2CCCCC2O1
  • InChI=1S/C7H6O3.Bi.H2O/c8-6-4-2-1-3-5(6)7(9)10;;/h1-4,8H,(H,9,10);;1H2/q;+3;/p-3 checkY
 ☒NcheckY (what is this?)  (verify)

Bismuth subsalicylate, sold generically as pink bismuth and under brand names including Pepto-Bismol, Pepti-Calm and BisBacter, is a medication used to treat temporary discomfort of the stomach and gastrointestinal tract, such as nausea, heartburn, indigestion, upset stomach, and diarrhea.

Bismuth subsalicylate has the empirical chemical formula C7H5BiO4,[1] and is a colloidal substance obtained by hydrolysis of bismuth salicylate (Bi(C6H4(OH)CO2)3).

Medical uses

A generic version of Pepto-Bismol, back view

As a derivative of salicylic acid, bismuth subsalicylate displays anti-inflammatory[2] and bactericidal action.[3] It also acts as an antacid.

Mechanism of action


Bismuth subsalicylate is used as an antacid and antidiarrheal, and to treat some other gastrointestinal symptoms, such as nausea. The means by which this occurs is still not well documented. It is thought to be some combination of the following:[4]

  • Stimulation of absorption of fluids and electrolytes by the intestinal wall (antisecretory action)
  • As a salicylate, reducing inflammation/irritation of stomach and intestinal lining through inhibition of prostaglandin G/H synthase 1/2
  • Reduction in hypermotility of the stomach
  • Inhibits adhesion and filmogenesis by Escherichia coli
  • Bactericidal action of a number of its subcomponents, including salicylic acid[5]
  • Bactericidal action via a so-called oligodynamic effect in which small amounts of heavy metals such as bismuth damage many different bacteria species.
  • Weak antacid properties

In vitro and in vivo data have shown that bismuth subsalicylate hydrolyzes in the gut to bismuth oxychloride and salicylic acid and less commonly bismuth hydroxide. In the stomach, this is likely an acid-catalyzed hydrolysis. The salicylic acid is absorbed and therapeutical concentrations of salicylic acid can be found in blood after bismuth subsalicylate administration. Bismuth oxychloride and bismuth hydroxide are both believed to have bactericidal effects, as is salicylic acid for enterotoxigenic E. coli a common cause of "traveler's diarrhea".[5]

Organobismuth compounds have historically been used in growth media for selective isolation of microorganisms. Such salts have been shown to inhibit proliferation of Helicobacter pylori, other enteric bacteria, and some fungi.[6]

Adverse effects


There are some adverse effects. It can cause a black tongue and black stools in some users of the drug when it combines with trace amounts of sulfur in saliva and the colon to form bismuth sulfide.[7] Bismuth sulfide is a highly insoluble black salt, and the discoloration seen is temporary and harmless.

Long-term use (more than six weeks) may lead to accumulation and toxicity.[8] High daily intake over a period of months can possibly cause severe fatigue, weakness and neurological symptoms that reverse with discontinuation.[9] Some of the risks of salicylism can apply to the use of bismuth subsalicylate.[10][11][12]

Children should not take medication with bismuth subsalicylate while recovering from influenza or chicken pox, as epidemiologic evidence points to an association between the use of salicylate-containing medications during certain viral infections and the onset of Reye syndrome.[13] For the same reason, it is typically recommended that nursing mothers not use medication containing bismuth subsalicylate because small amounts of the medication are excreted in human breast milk, and these pose a theoretical risk of Reye's syndrome to nursing children.[14]

Salicylates are very toxic to cats, and thus bismuth subsalicylate should not be administered to cats.[15]

The British National Formulary does not recommend bismuth-containing antacids (unless chelated), cautioning that absorbed bismuth can be neurotoxic, causing encephalopathy, and that such antacids tend to be constipating.[16]

Drug interactions


There is an increased risk of bleeding when using bismuth subsalicylate and anticoagulation therapy, like Coumadin (Warfarin).[17][18][19]


1957 Life magazine ad for the product

Bismuth salts were in use in Europe by the late 1700s. The combination of bismuth subsalicylate and zinc salts for astringency with salol (phenyl salicylate) appears to have begun in the US in the early 20th century as a remedy for life-threatening diarrhea in infants with cholera. At first sold directly to physicians, it was first marketed as Bismosal in 1918.[20]

Pepto-Bismol was first sold in 1900[20] by a doctor in New York. It was originally sold as a remedy for infant diarrhea by Norwich Pharmacal Company under the name "Bismosal: Mixture Cholera Infantum".[20] It was renamed Pepto-Bismol in 1919. Norwich Eaton Pharmaceuticals was acquired by Procter and Gamble in 1982.[21]

As of 1946 and 1959, Canadian advertisements placed by Norwich show the product as Pepto-Besmal both in graphic and text.[22][23]

Pepto-Bismol is an over-the-counter drug currently produced by the Procter & Gamble company in the United States, Canada and the United Kingdom. Pepto-Bismol is made in chewable tablets[24] and swallowable caplets,[25] but it is best known for its original formula, which is a thick liquid. This original formula is a medium pink in color, with a teaberry (methyl salicylate) flavor.[26]

Generic bismuth subsalicylate and other branded versions of the drug are widely available in pill and liquid form.


The crystal structure of bismuth subsalicylate.[27]

Despite its common usage and commercial significance, the exact structure of the pharmaceutical long remained undetermined, but was revealed, through the use of advanced electron crystallography techniques, to be a layered coordination polymer with the formula BiO(C7H5O3).[27] In the structure, both the carboxylate and phenol groups of the salicylate coordinate towards the bismuth cations. The determination of bismuth subsalicylate had long been hindered due to the small particle size as well as defects within the structure, arising from variations in the stacking arrangement of the bismuth subsalicylate layers, which could be observed as part of the structural investigation.[28]


  1. ^ Merck Index, 11th Edition, 1299
  2. ^ Madisch A, Morgner A, Stolte M, Miehlke S (December 2008). "Investigational treatment options in microscopic colitis". Expert Opinion on Investigational Drugs. 17 (12): 1829–37. doi:10.1517/13543780802514500. PMID 19012499. S2CID 72294495.
  3. ^ DuPont HL (April 2005). "Travelers' diarrhea: antimicrobial therapy and chemoprevention". Nature Clinical Practice. Gastroenterology & Hepatology. 2 (4): 191–8, quiz 1 p following 198. doi:10.1038/ncpgasthep0142. PMID 16265184. S2CID 10666532.
  4. ^ Bismuth subsalicylate, DrugBank.
  5. ^ a b Sox TE, Olson CA (December 1989). "Binding and killing of bacteria by bismuth subsalicylate". Antimicrobial Agents and Chemotherapy. 33 (12): 2075–82. doi:10.1128/AAC.33.12.2075. PMC 172824. PMID 2694949.
  6. ^ Dodge AG, Wackett LP (February 2005). "Metabolism of bismuth subsalicylate and intracellular accumulation of bismuth by Fusarium sp. strain BI". Applied and Environmental Microbiology. 71 (2): 876–82. Bibcode:2005ApEnM..71..876D. doi:10.1128/AEM.71.2.876-882.2005. PMC 546758. PMID 15691943.
  7. ^ "Why does Pepto-Bismol sometimes darken the tongue/stool and how long does it last?". Pepto-Bismol FAQ. Pepto-Bismol.
  8. ^ Gorbach SL (September 1990). "Bismuth therapy in gastrointestinal diseases". Gastroenterology. 99 (3): 863–75. doi:10.1016/0016-5085(90)90983-8. PMID 2199292.
  9. ^ Sanders, Lisa (7 March 2024). "It Was Like the Vigor Had Suddenly Been Sucked Out of His Body. What Was It? (March 7, 2024)". New York Times.
  10. ^ "Bismuth Subsalicylate". MedlinePlus. National Institutes of Health.
  11. ^ Sainsbury SJ (December 1991). "Fatal salicylate toxicity from bismuth subsalicylate". The Western Journal of Medicine. 155 (6): 637–9. PMC 1003120. PMID 1812638.
  12. ^ Vernace MA, Bellucci AG, Wilkes BM (September 1994). "Chronic salicylate toxicity due to consumption of over-the-counter bismuth subsalicylate". The American Journal of Medicine. 97 (3): 308–9. doi:10.1016/0002-9343(94)90017-5. PMID 8092182.
  13. ^ Aspirin or Salicylate-Containing Medications, reyessyndrome.org
  14. ^ "Food-borne and Waterborne Illness - Breastfeeding – CDC". cdc.gov.
  15. ^ Cat Owner's Home Veterinary Handbook, Carlson and Giffin, page 390.
  16. ^ "1.1.1 Antacids and simeticone". Archived from the original on 2018-05-02. Retrieved 2018-06-17.
  17. ^ "Drug Interactions between Pepto-Bismol and warfarin". Archived from the original on 2016-02-06.
  18. ^ Rose SR, Keystone JS (2006). International Travel Health Guide 2006-2007. Mosby. pp. 89–103. ISBN 978-0-323-04050-1.
  19. ^ Bingham AL, Brown RO, Dickerson RN (December 2013). "Inadvertent exaggerated anticoagulation following use of bismuth subsalicylate in an enterally fed patient receiving warfarin therapy". Nutrition in Clinical Practice. 28 (6): 766–769. doi:10.1177/0884533613507606. PMID 24163322.
  20. ^ a b c Bierer DW (January–February 1990). "Bismuth subsalicylate: history, chemistry, and safety". Reviews of Infectious Diseases. 12 Suppl 1 (Supplement 1): S3-8. doi:10.1093/clinids/12.supplement_1.s3. JSTOR 4455445. PMID 2406853.
  21. ^ Dyer D, Dalzell F, Olegario R (May 1, 2004). Rising Tide: Lessons from 165 Years of Brand Building at Procter and Gamble. Harvard Business Press. p. 424. ISBN 9781591391470.
  22. ^ "'Simple Diarrhea' ad". Toronto Daily Star. August 16, 1946. p. 33.
  23. ^ "'Pepto-Besmal puts out the fire of an upset stomach' ad". Toronto Daily Star. June 6, 1959.
  24. ^ http://tess2.uspto.gov/bin/showfield?f=doc&state=b8i462.2.2 The trademark was extended to cover the tablets in 1973. Registration No. 0972198], November 6, 1973.
  25. ^ The capsules were introduced in 1983. Registration No. 1269605, March 13, 1984; cancelled July 16, 1990. http://tess2.uspto.gov/bin/showfield?f=doc&state=b8i462.2.1.
  26. ^ "Pepto-Bismol Original Liquid" (PDF). Material Safety Data Sheet. Procter & Gamble. Archived from the original (PDF) on 17 June 2018.
  27. ^ a b Svensson Grape E, Rooth V, Nero M, Willhammar T, Inge AK (April 2022). "Structure of the active pharmaceutical ingredient bismuth subsalicylate". Nature Communications. 13 (1984): 1984. Bibcode:2022NatCo..13.1984S. doi:10.1038/s41467-022-29566-0. PMC 9008038. PMID 35418171.
  28. ^ Henry Arnaud, Celia (April 26, 2022). "Structure of Pepto-Bismol active ingredient solved". Chemical & Engineering News. 100 (44): 34–35. doi:10.1021/cen-10044-cover6. ISSN 0009-2347. S2CID 254899845. Retrieved 15 April 2023.
  • Andrews PC, Deacon GB, Forsyth CM, Junk PC, Kumar I, Maguire M (August 2006). "Towards a structural understanding of the anti-ulcer and anti-gastritis drug bismuth subsalicylate". Angewandte Chemie. 45 (34): 5638–42. doi:10.1002/anie.200600469. PMID 16865763.