Bismuth subsalicylate

Bismuth subsalicylate
Systematic (IUPAC) name
2-Hydroxy-2H,4H-benzo[d]1,3-dioxa-2-bismacyclohexan-4-one
Clinical data
Trade names Pepto-Bismol
AHFS/Drugs.com Multum Consumer Information
MedlinePlus a607040
Routes of
administration		 Oral
Legal status
Legal status
Identifiers
CAS Number 14882-18-9 YesY
ATC code none
PubChem CID 16682734
DrugBank DB01294 YesY
ChemSpider 17215772 YesY
UNII 62TEY51RR1 YesY
KEGG D00728 N
ChEBI CHEBI:261649 YesY
ChEMBL CHEMBL1120 YesY
Chemical data
Formula C7H5BiO4
Molar mass 362.093 g/mol
 NYesY (what is this?)  (verify)

Bismuth subsalicylate, sold under the brand name Pepto-Bismol, is an antacid medication used to treat temporary discomforts of the stomach and gastrointestinal tract, such as diarrhea, indigestion, heartburn and nausea. Commonly known as pink bismuth, it is also sometimes the active ingredient in Kaopectate.

Bismuth subsalicylate has the empirical chemical formula of C7H5BiO4,[1] and it is a colloidal substance obtained by hydrolysis of bismuth salicylate (Bi{C6H4(OH)CO2}3). The actual structure is unknown and the formulation is only approximate. Recent evidence dictates that it is composed of a bismuth oxide core structure with salicylate ions attached to the surface. A model structure has recently been published having the composition Bi38O44{C6H3(OH)CO2}26.

Medical uses

A generic version of Pepto-Bismol, back view.

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

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.[4] Bismuth sulfide is a highly insoluble black salt, and the discoloration seen is temporary and harmless.

Long-term use (greater than 6 weeks) may lead to accumulation and toxicity.[5] Some of the risks of salicylism can apply to the use of bismuth subsalicylate.[6][7][8]

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's syndrome.[9] 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 breast milk and pose a theoretical risk of Reye's syndrome to nursing children.[10]

Salicylates are very toxic to cats, and thus bismuth subsalicylate should not be administered to cats.[11]

Structure

The term "sub" in the chemical name refers to the high oxygen content in the molecule and the presence of Bi-O moieties.

Characterization of the properties of bismuth subsalicylate has been difficult due to its insolubility and its partial hydrolysis. Two crystal structures are observed, they are:

It is believed that the latter cluster gives rise to the former, leading researchers to believe that they may be extrapolated to form larger clusters. This may be the basis for bismuth subsalicylate's extreme insolubility.

Other bismuth carboxylates have typically been trapped using chelating amines such as bipyridine. Attempts to do so with bismuth subsalicylate have typically led to a loss of the "sub" portion of the molecule.

Mechanism of action

Bismuth subsalicylate is used as an antacid and antidiarrheal, and to treat some other gastro-intestinal 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:[12]

In vitro and in vivo data has 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 Escherichia coli a common cause of "traveler's diarrhea."[13]

Organobismuth compounds have historically been used in growth media for selective isolation of microorganisms. Such salts have been shown to inhibit proliferation of H. pylori, other enteric bacteria, and some fungi.[14]

Decomposition

Bismuth slag from decomposition of Pepto-Bismol

Bismuth subsalicylate is the only active ingredient in an over-the-counter drug that can leave a shiny metal oxide slag behind after being completely burnt with a blow torch.[15]

History

1957 ad for the product. from Life Magazine.

While bismuth salts were in use in Europe by the late 1700s, the combination of bismuth subsalicylate and zinc salts for astringency with salol (phenyl salicilate) appears to have begun in the US in the early 1900s 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.[16]

Pepto-Bismol began being sold in 1901 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".[17] It was renamed Pepto-Bismol in 1919. Norwich Eaton Pharmaceuticals was acquired by Procter and Gamble in 1982.[18]

As of 1946, Canadian advertisements placed by Norwich show the product as Pepto-Besmol both in graphic and text.[19]

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[20] and swallowable caplets,[21] but is best known for its original formula which is a thick liquid. This original formula is a medium pink color with a strong wintergreen or cherry flavor.

In popular culture

References

  1. ↑ Merck Index, 11th Edition, 1299
  2. ↑ Madisch, A.; Morgner, A.; Stolte, M.; Miehlke, S. (Dec 2008). "Investigational treatment options in microscopic colitis.". Expert Opin Investig Drugs 17 (12): 1829–37. doi:10.1517/13543780802514500. PMID 19012499.
  3. ↑ DuPont, HL. (Apr 2005). "Travelers' diarrhea: antimicrobial therapy and chemoprevention.". Nat Clin Pract Gastroenterol Hepatol 2 (4): 191–8; quiz 1 p following 198. doi:10.1038/ncpgasthep0142. PMID 16265184.
  4. ↑ "Why does Pepto-Bismol sometimes darken the tongue/stool and how long does it last?". Pepto-Bismol FAQ. Pepto-Bismol.
  5. ↑ Gorbach, SL. (Sep 1990). "Bismuth therapy in gastrointestinal diseases.". Gastroenterology 99 (3): 863–75. PMID 2199292.
  6. ↑ "Bismuth Subsalicylate". MedlinePlus. National Institutes of Health.
  7. ↑ Sainsbury, S. J. (December 1991). "Fatal salicylate toxicity from bismuth subsalicylate". The Western Journal of Medicine 155 (6): 637–639. PMC 1003120. PMID 1812638.
  8. ↑ Vernace, M. A.; Bellucci, A. G; Wilkes B. M. (September 1994). "Chronic salicylate toxicity due to consumption of over-the-counter bismuth subsalicylate". The American Journal of Medicine 97 (3): 308–309. doi:10.1016/0002-9343(94)90017-5. PMID 8092182.
  9. ↑ Aspirin or Salicylate-Containing Medications, reyessyndrome.org
  10. ↑ CDC warning about breastfeeding while taking bismuth subsalicylate compounds
  11. ↑ Cat Owner's Home Veterinary Handbook, Carlson and Giffin, page 390
  12. ↑ Bismuth subsalicylate, DrugBank
  13. 1 2 Sox, TE; Olson, CA (December 1989). "Binding and killing of bacteria by bismuth subsalicylate". Antimicrob. Agents Chemother. 33 (12): 2075–82. doi:10.1128/AAC.33.12.2075. PMC 172824. PMID 2694949.
  14. ↑ Dodge, A. G.; Wackett, L. P. (2005). "Metabolism of Bismuth Subsalicylate and Intracellular Accumulation of Bismuth by Fusarium sp. Strain BI". Applied and Environmental Microbiology 71 (2): 876–82. doi:10.1128/AEM.71.2.876-882.2005. PMC 546758. PMID 15691943.
  15. ↑ Wesołowski, M. (1982). "Thermal decomposition of pharmaceutical preparations containing inorganic components". Microchimica Acta (Vienna) 77 (5–6): 451–464. doi:10.1007/BF01197125.
  16. ↑ Bierer, Douglas Ws. (Jan–Feb 1990). "Bismuth Subsalicylate: History, Chemistry, and Safety". Reviews of Infectious Diseases (Oxford University Press) 12 (Supplement 1): S3–S8. doi:10.1093/clinids/12.Supplement_1.S3. JSTOR 4455445.
  17. ↑ Bierer, Douglas Ws. (Jan–Feb 1990). "Bismuth Subsalicylate: History, Chemistry, and Safety". Reviews of Infectious Diseases (Oxford University Press) 12 (Supplement 1): S3–S8. doi:10.1093/clinids/12.supplement_1.s3. JSTOR 4455445.
  18. ↑ Davis, Dyer; et al. (May 1, 2004). Rising Tide: Lessons from 165 Years of Brand Building at Procter and Gamble. Harvard Business Press. p. 424. Retrieved 2013-05-07.
  19. ↑ ""Simple Diarrhoea" ad". Toronto Daily Star. 16 August 1946. p. 33.
  20. ↑ The trademark was extended to cover the tablets in 1973. Registration No. 0972198, November 6, 1973. http://tess2.uspto.gov/bin/showfield?f=doc&state=b8i462.2.2.
  21. ↑ 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.
  22. ↑ "Episode Capsule: 3ACV10 - Where the Buggalo Roam". Can't Get Enough Futurama. Retrieved 2015-07-24.
  23. ↑ "Transcript:Where the Buggalo Roam". The Infosphere, the Futurama Wiki. Retrieved 2015-07-24.

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