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 The stomach is a muscular, hollow organ in the upper gastrointestinal tract of Human, humans and many other animals, including several invertebrates. The Ancient Greek name for the stomach is ''gaster'' which is used as ''gastric'' in medical t ...

and

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

. This includes an

upset stomach Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Since the abdomen contains most of the body's vital organs, it can be an indicator of a wide variety of diseases. Given th ...

heartburn Heartburn is a burning sensation felt behind the breastbone. It is a symptom that is commonly linked to acid reflux and is often triggered by food, particularly fatty, sugary, spicy, chocolate, citrus, onion-based and tomato-based products. Ly ...

, or other similar symptoms. Bismuth subsalicylate has the empirical chemical formula C₇H₅BiO₄, and is a

colloid A colloid is a mixture in which one substance consisting of microscopically dispersed insoluble particles is suspended throughout another substance. Some definitions specify that the particles must be dispersed in a liquid, while others exte ...

al substance obtained by

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

bismuth Bismuth is a chemical element; it has symbol Bi and atomic number 83. It is a post-transition metal and one of the pnictogens, with chemical properties resembling its lighter group 15 siblings arsenic and antimony. Elemental bismuth occurs nat ...

salicylate Salicylic acid is an organic compound with the formula HOC6H4COOH. A colorless (or white), bitter-tasting solid, it is a precursor to and a metabolite of acetylsalicylic acid (aspirin). It is a plant hormone, and has been listed by the EPA To ...

(Bi(C₆H₄(OH)CO₂)₃).

Medical uses

As a derivative of

salicylic acid Salicylic acid is an organic compound with the formula HOC6H4COOH. A colorless (or white), bitter-tasting solid, it is a precursor to and a active metabolite, metabolite of acetylsalicylic acid (aspirin). It is a plant hormone, and has been lis ...

, bismuth subsalicylate displays

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechan ...

and

bactericidal A bactericide or bacteriocide, sometimes abbreviated Bcidal, is a substance which kills bacteria. Bactericides are disinfectants, antiseptics, or antibiotics. However, material surfaces can also have bactericidal properties based solely on their p ...

action. It also acts as an

antacid An antacid is a substance which neutralization (chemistry), neutralizes gastric acid, stomach acidity and is used to relieve heartburn, indigestion, or an upset stomach. Some antacids have been used in the treatment of constipation and diarrhe ...

Mechanism of action

Bismuth subsalicylate is used as an

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:Bismuth subsalicylate
DrugBank. *Stimulation of absorption of fluids and electrolytes by the intestinal wall (antisecretory action) *As a

, 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 ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...

'' *Bactericidal action of a number of its subcomponents, including salicylic acid *Bactericidal action via a so-called

oligodynamic effect The oligodynamic effect (from Greek language, Greek ''oligos'', "few", and ''dynamis'', "force") is a biocide, biocidal effect of metals, especially heavy metal (chemical element), heavy metals, that occurs even in low concentrations. This effec ...

in which small amounts of heavy metals such as

damage many different bacteria species. *Weak antacid properties ''

In vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'' and ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...

'' data have shown that bismuth subsalicylate hydrolyzes in the gut to

bismuth oxychloride Bismuth oxychloride is an inorganic compound of bismuth with the formula Bi O Cl. It is a lustrous white solid used since antiquity, notably in ancient Egypt. Light wave interference from its plate-like structure gives a pearly iridescent light r ...

and

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 Travelers' diarrhea (TD) is a stomach and intestinal infection. TD is defined as the passage of unformed stool (one or more by some definitions, three or more by others) while traveling. It may be accompanied by abdominal cramps, nausea, fever, ...

". 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 ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, Flagellum#bacterial, flagellated, Bacterial cellular morphologies#Helical, helical bacterium. Mutants can have a rod or curved rod shape that exhibits l ...

'', other enteric bacteria, and some fungi.

Adverse effects

There are some

adverse effect An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term compli ...

s. It can cause a black tongue and black stools in some users of the drug when it combines with trace amounts of

sulfur Sulfur ( American spelling and the preferred IUPAC name) or sulphur ( Commonwealth spelling) is a chemical element; it has symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms ...

in saliva and the colon to form bismuth sulfide. 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. High daily intake over a period of months can possibly cause severe fatigue, weakness and neurological symptoms that reverse with discontinuation. Some of the risks of salicylism can apply to the use of bismuth subsalicylate. Children should not take medication with bismuth subsalicylate while recovering from

influenza Influenza, commonly known as the flu, is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These sympto ...

chickenpox Chickenpox, also known as varicella ( ), is a highly contagious disease caused by varicella zoster virus (VZV), a member of the herpesvirus family. The disease results in a characteristic skin rash that forms small, itchy blisters, which ...

, as epidemiologic evidence points to an association between the use of

-containing medications during certain viral infections and the onset of

Reye syndrome Reye syndrome is a rapidly worsening brain disease. Symptoms of Reye syndrome may include vomiting, personality changes, confusion, seizures, and loss of consciousness. While liver toxicity typically occurs in the syndrome, jaundice usually ...

. 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 syndrome to nursing children. Salicylates are very toxic to cats, and thus bismuth subsalicylate should not be administered to cats. The

British National Formulary The ''British National Formulary'' (BNF) is a United Kingdom (UK) pharmaceutical reference book that contains a wide spectrum of information and advice on prescribing and pharmacology, along with specific facts and details about many medicin ...

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.

Drug interactions

There is an increased risk of

bleeding Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethr ...

when using bismuth subsalicylate and anticoagulation therapy, like

warfarin Warfarin, sold under the brand name Coumadin among others. It is used as an anticoagulant, anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who ha ...

History

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 Cholera () is an infection of the small intestine by some Strain (biology), strains of the Bacteria, bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea last ...

. At first sold directly to physicians, it was first marketed as ''Bismosal'' in 1918. Pepto-Bismol was first sold in 1900 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". It was renamed Pepto-Bismol in 1919. Norwich Eaton Pharmaceuticals was acquired by Procter and Gamble in 1982. As of 1946 and 1959, Canadian advertisements placed by Norwich show the product as Pepto-Besmal both in graphic and text. Pepto-Bismol is an

over-the-counter drug Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid pres ...

currently produced by the

Procter & Gamble The Procter & Gamble Company (P&G) is an American multinational consumer goods corporation headquartered in Cincinnati, Ohio. It was founded in 1837 by William Procter and James Gamble. It specializes in a wide range of personal health/con ...

company in the United States, Canada and the United Kingdom. Pepto-Bismol is made in chewable tablets and swallowable caplets, 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 Methyl salicylate (oil of wintergreen or wintergreen oil) is an organic compound with the formula C8H8O3. It is the methyl ester of salicylic acid. It is a colorless, viscous liquid with a sweet, fruity odor reminiscent of root beer (in which it ...

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

Structure

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 Electron crystallography is a subset of methods in electron diffraction focusing upon detailed determination of the positions of atoms in solids using a transmission electron microscope (TEM). It can involve the use of high-resolution transmissi ...

techniques, to be a layered coordination polymer with the formula BiO(C₇H₅O₃). 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.

References

External links

* {{Bismuth compounds Antidiarrhoeals Drugs acting on the gastrointestinal system and metabolism Salicylates Bismuth compounds Antacids Heterocyclic compounds with 2 rings