14882-18-9 Usage
Description
Bismuth subsalicylate, an active ingredient in popular medications like Pepto-Bismol and Kaopectate, is a white crystalline powder or fluffy white solid with chemical properties of a white or almost white powder. It is a colloidal substance obtained by hydrolysis of bismuth salicylate and has the empirical chemical formula C7H5BiO4. Bismuth subsalicylate is known for its anti-inflammatory action, acting as an antacid, and possessing mild antibiotic properties. It is widely used in the treatment of various gastrointestinal issues and has been a commonly prescribed medication for nearly a century.
Uses
1. Used in Pharmaceutical Industry:
Bismuth subsalicylate is used as an active ingredient in medications for the treatment of nausea, heartburn, indigestion, upset stomach, diarrhea, and other temporary discomforts of the stomach and gastrointestinal tract.
2. Used in Antacid Applications:
Bismuth subsalicylate is used as an antacid to neutralize stomach acid and provide relief from heartburn and indigestion.
3. Used in Antidiarrheal Applications:
Bismuth subsalicylate is used as an antidiarrheal agent, working by decreasing the flow of fluids and electrolytes into the bowel, reducing inflammation within the intestine, and potentially killing the organisms that cause diarrhea.
4. Used in Anti-Inflammatory Applications:
Bismuth subsalicylate is used for its anti-inflammatory action, which is attributed to its salicylic acid component and possibly the bismuth element as well.
5. Used in Antibacterial Applications:
Bismuth subsalicylate is known for its antibacterial properties and has been effective in the treatment and eradication of Helicobacter pylori, a bacterium linked to gastritis, ulceration, and the development of gastric cancer and gastric lymphoma.
6. Used in Coating and Resin Industry:
Bismuth subsalicylate is used to impart a pearly surface to cellulose-based, polystyrene, and phenolformaldehyde resins.
7. Used in Growth Media for Microbiology:
Bismuth subsalicylate is used in growth media for the selective isolation of microorganisms.
8. Used in Traveler's Diarrhea Prevention:
Bismuth subsalicylate has become the medication of choice for the prevention of traveler's diarrhea and is useful for other forms of toxigenic diarrhea.
9. Used in Non-Syndromic Episodic Diarrhea Treatment:
Bismuth subsalicylate has been a commonly prescribed antidiarrheal medication for non-syndromic episodic diarrhea in both children and adults for nearly a century.
Bismush salts
Bismuth salts have been promoted for therapeutic use for over two centuries for a range of clinical conditions including dyspepsia, diarrhoea, syphilis, oral and upper respiratory tract infections, veruccae and warts[22-25]. The bismuth salts or complexes used have also been diverse including such compounds as bismuth subnitrate, bismuth subgallate, bismuth subsalicylate, and bismuth subcarbonate as well as tripotassium dicitrato bismuthate.
The use of the majority of bismuth salts has fallen into dis-favour because of the potential adverse effects, and indeed a number of drug-regulatory authorities are actively delisting bismuth-containing products from medicinal use. Nonetheless, over recent years two bismuth compounds, bismuth subsalicylate and bismuth sub-citrate, have attracted renewed interest because of their newly discovered activities for conditions which respond sub-optimally to existing therapies: travellers’ diarrhoea and peptic ulcer disease, respectively. In travellers’ diarrhoea, effective prophylaxis has been claimed for bismuth subsalicylate[26-29] while in peptic ulcer disease, relapse rates have been shown to be lower following bismuth sub-citrate therapy than following histamine H2antagonist therapy[30-32].
Pharmacokinetics
Bismuth subsalicylate displays anti-inflammatory action[due to salicylic acid] and can also act as an antacid and mild antibiotic. It can cause a black tongue and black stools in some users of the drug, when it combines with trace amounts of sulfur in their saliva and gastrointestinal tract. This discoloration is temporary and harmless[5].
In vitro dissociation data and in vivo animal data has demonstrated that bismuth subsalicylate is largely hydrolyzed in the stomach to bismuth oxychloride and salicylic acid. When reaching the small intestine, nondissociated bismuth subsalicylate can further react with other anions[bicarbonate and phosphate] to form insoluble bismuth salts. In the colon, nondissociated bismuth subsalicylate and other bismuth salts react with hydrogen sulfide to produce bismuth sulfide, a highly insoluble black salt responsible for the darkening of the stools[5].
Mode of action
As an antidiarrheal, the exact mechanism still remains unclear. Several in vitro studies have shown that the mechanisms of bismuth subsalicylate are related to two distinct effects: an action directed against pathogenic microorganisms[34] and an intestinal antisecretory or proabsorptive effect on ion and water transport. This is clearly demonstrated for aspirin[which is a salycilate compound] and probably related to the inhibition of prostaglandin synthesis[35]. Experimental data are indeed solid and consistent and provide the basis to support the concept that bismuth subsalicylate is an anti-diarrhoea drug. Bismuth subsalicylate may exert its antidiarrheal action not only by stimulating absorption of fluid and electrolytes across the intestinal wall[antisecretory action] but also, when hydrolyzed to salicylic acid, by inhibiting synthesis of a prostaglandin responsible for intestinal inflammation and hypermotility. In addition, bismuth subsalicylate binds toxins produced by Escherichia coli. Both bismuth subsalicylate and the intestinal reaction products, bismuth oxychloride and bismuth hydroxide, are believed to have bactericidal action. As an antacid, bismuth has weak antacid properties[5].
Side effects
Side effect associated with the bismuth subsalicylate include anxiety, any loss of hearing, confusion, constipation, diarrhea, difficulty in speaking or slurred speech, dizziness or lightheadedness, drowsiness, fast or deep breathing, headache[severe or continuing], increasing sweating, increased thirst, mental depression, muscle spasms, muscle weakness, nausea or vomiting, ringing or buzzing in ears, stomach pain, trembling, uncontrollable flapping movements of the hands[especially in elderly patients] or other uncontrolled body movements vision problems[36].
Side effects
This compound is a salicylate and may therefore produce
signs of salicylate toxicity (e.g., ringing of the ears)
if taken chronically, especially with aspirin. Bismuth is
radiopaque and may interfere with radiological examinations.
Its use may cause temporary gray-black discoloration
of the stool and brown pigmentation of the
tongue. High dose Pepto-Bismol (8 tablets/day) has
been efficacious in some patients with diarrhea secondary
to collagenous or lymphocytic colitis.
Precautions
Before taking bismuth subsalicylate, you should consult your doctor in the following few conditions as detailed below[33]:
You are allergic to salicylate pain relievers such as aspirin, choline magnesium trisalicylate, choline salicylate[Arthropan], diflunisal[Dolobid], magnesium salicylate[Doan's, others], and salsalate[Argesic, Disalcid, Salgesic]; or any other medication.
You are taking or plant to take specific prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products. Be sure to talk to your doctor or pharmacist about taking bismuth subsalicylate if you take: anticoagulants['blood thinners'] such as warfarin[Coumadin]; a daily aspirin; or medication for diabetes, arthritis or gout.
You are taking tetracycline antibiotics such as minocycline[Dynacin, Minocin], demeclocycline[Declomycin], doxycycline[Doryx, Vibramycin], and tetracycline[Sumycin], take them at least 1 hour before or 3 hours after taking bismuth subsalicylate.
You have ever had an ulcer, bleeding problem, stools that are bloody or blackened, or kidney disease. You have a fever or mucus in your stool. If you will be giving bismuth subsalicylate to a child or teenager, tell the child's doctor if the child has any of the following symptoms before he or she receives the medication: yellowing of the skin or eyes, vomiting, listlessness, drowsiness, aggression, seizures, confusion, weakness, or flu-like symptoms. Also tell the child's doctor if the child has not been drinking normally, has had excessive vomiting or diarrhea, or appears dehydrated.
You are pregnant or are breast-feeding.
References
F. L. Suarez, J. Furne, J. Stiehm, C. Garten, M. D. Levitt, Dig. Dis. Sci. 2000, 45, 1444.
G. G. Briand, N. Burford, Chem. Rev. 1999, 99, 2601.
P. J. Sadler, H. Li, H. Sun, Coord. Chem. Rev. 1999, 689.
R. Iffland, Bismuth, Handbook on Metals in Clinical and Analytical Chemistry[Eds.: H. G. Seiler, A. Sigel, H. Sigel], Marcel Dekker, New York, 1994.
https://www.drugbank.ca/drugs/DB01294
J. Houghton, J. G. Fox, T. C. Wang, Eur. J. Gastroenterol. Hepatol. 2002, 17, 495.
S. Marchi, F. Costa, M. Bellini, C. Belcari, M. G. Mumolo, A. Tornar, R. Spisni, E. Torelli, G. Maltinti, Eur. J. Gastroenterol. Hepatol. 2002, 13, 547.
N. Chiba, Can. J. Gastro. 2000, 14, 885.
D. Y. Graham, G. M. Lew, D. G. Evans, P. D. Klein, Ann. Intern. Med. 1991, 115, 266.
Merck Index, 11th Edition, 1299
Gorbach SL. Bismuth therapy in gastrointestinal diseases. Gastroenterology 1990;99:863–875.
DuPont HL, Sullivan P, Evans DG, Pickering LK, Evans DJ Jr, Vollet JJ, Ericsson CD, Ackerman PB, Tjoa WS. Prevention of traveler’s diarrhea[emporiatric enteritis]. Prophylactic administration of subsalicylate bismuth. JAMA 1980;243:237–241.
Ericsson CD, Tannenbaum C, Charles TT. Antisecretory and antiinflammatory properties of bismuth subsalicylate. Rev Infect Dis 1990;12:S16–S20.
DuPont HL, Sullivan P, Pickering LK, Haynes G, Ackerman PB. Symptomatic treatment of diarrhea with bismuth subsalicylate among students attending a Mexican university. Gastroenterology 1977;73:715–718.
Bierer DW. Bismuth subsalicylate: history, chemistry, and safety. Rev Infect Dis 1990;12:S3–S8.
Gryboski JD, Kocoshis S. Effect of bismuth subsalicylate on chronic diarrhea in childhood: a preliminary report. Rev Infect Dis 1990;12(Suppl]:S36–S40.
Figueroa-Quintanilla D, Salazar-Lindo E, Sack RB, Leo′n-Baru′a R, Sarabia-Arce S, Campos-Sa′nchez M, Eyzaguirre-Maccan E. A controlled trial of bismuth subsalicylate in infants with acute watery diarrheal disease. N Engl J Med 1993;328:1653–1658.
Farris RK, Tapper EJ, Powell DW, Morris SM. Effect of aspirin on normal and cholera toxin–stimulated intestinal electrolyte transport. J Clin Invest 1976;57:916–924.
Graham DY, Estes MK, Gentry LO. Double-blind comparison of bismuth subsalicylate and placebo in the prevention and treatment of enterotoxigenic Escherichia coli–induced diarrhea in volunteers. Gastroenterology 1983;85:1017–1022.
Manhart MD. In vitro antimicrobial activity of bismuth subsalicylate and other bismuth salts. Rev Infect Dis 1990;12:S11–S15.
Chambers TK. Lectures on the management of the digestion in disease. Lecture 5 on diarrhea. Lancet 1857; 2: 185–7
Thomas, C.C.[1937] A clinical evaluation of oral bismuth[bismutrate] therapy in early infectious syphilis in the female, American Journat of Syphilis, Gonorrhoea and Venereal Diseases, 21,513523.
Dodd, K., Johnston,L .M. & Buddingh, G.H.[1938] Herpetic stornatitis. Journal of Paedzarrics, 12,
Lipman Cohen, E.[1958] Inefficacy of sodium bismuth triglycollamate in the treatment of warts. British Journal of Dermatology, 70,254-255.
Konturek, S.J., Radecki,T, Piastucki, I. & Drozdowicz, D.[1986] Advances in the understanding of the mechanism of cytoprotective action by colloidal bismuth subcitrate. Scandinavian Journal of gastroenterology 122,610.
Albert, K.S., Welch, R.D., Desante, K.A. & Disanto, A.R.[1979] Decreased tetracycline bioavailability caused by a bismuth subsalicylate antidiarrheal mixture. Journal of pharmaceutical Sciences, 68,586-588.?
Anonymous[1980] Salicylate in Pepto-Bismol. MedicaI Letter on Drugs and Therapeurics, 22,63.
Feldman, S., Chen, S.L., Pickering, L.K., Cleary, T.G., Ericsson, C.D. & Hulse, M.[1981] Salicylate absorption from a bismuth subsalicylate tid diarrheal preparation[Pepto-Bismol]. Clinical Pharmacology and Therapeurics, 29,788-792.
Du Pont, H.L.[1987] Bismuth subsalicylate in the treatment and prevention of diarrhoea1 disease. Drug Intelligence and Clinical Pharmacy, 21,687-693.
Marshall, B.J., Goodwin, C.S., Warren, J.R. et @I.[1987] Long term healing of gastritis and low duodenal ulcer relapse after eradication of campylobacter pyloridis: a prospective double-blind study. Gastroenterology, 92, 1518-1521.
Lee, F.I., Samloff, I.M. & Hardman, M.[1985] Comparison of tri-potassium di-citrato bismuthate tablets with ranitidine in healing and relapse of duodenal ulcers. Lancer, i, 1299-1303.
Hamilton, I., O'Connor, H.J., Wood, N.C., Bradbury, I. & Axton, A.T.R.[1986] Healing and recurrence of duodenal ulcer after treatment with tripotassium dicitrato bismuthate[TDB] tablets or cimetidine. Gut, 27, 1061 10
https://medlineplus.gov/druginfo/meds/a607040.html
Manhart MD. In vitro antimicrobia l activity of bismuth subsalicylat e and other bismuth salts. Rev Infect Dis 1990; 12: S11–S15
Gorbach SL. Bismuth therapy in gastrointestina l diseases. Gastroenterolog y 1990; 99: 863–75
https://www.drugs.com/sfx/kaopectate-side-effects.html
Indications
Bismuth subsalicylate (Pepto-Bismol) also binds intestinal
toxins and may coat irritated mucosal surfaces.
Air & Water Reactions
Insoluble in water.
Reactivity Profile
BISMUTH SUBSALICYLATE is stable in air but is sensitive to light. BISMUTH SUBSALICYLATE is unstable in alkaline solutions. BISMUTH SUBSALICYLATE decomposes in boiling water and alkalis into a more basic salt.
Hazard
A poison by ingestion. Human systemic
effects.
Health Hazard
SYMPTOMS: Symptoms of exposure to BISMUTH SUBSALICYLATE may include headache, nausea, foul breath, blue-black line on the gums and stomatitis.
Fire Hazard
Flash point data for BISMUTH SUBSALICYLATE are not available, but BISMUTH SUBSALICYLATE is probably combustible.
Flammability and Explosibility
Nonflammable
Veterinary Drugs and Treatments
In veterinary medicine, bismuth subsalicylate products are used to
treat diarrhea and as a component of “triple therapy” for treating
Helicobacter GI infections. The drug is also used in humans for other
GI symptoms (indigestion, cramps, gas pains) and in the treatment
and prophylaxis
of traveler’s diarrhea.
Check Digit Verification of cas no
The CAS Registry Mumber 14882-18-9 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,4,8,8 and 2 respectively; the second part has 2 digits, 1 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 14882-18:
(7*1)+(6*4)+(5*8)+(4*8)+(3*2)+(2*1)+(1*8)=119
119 % 10 = 9
So 14882-18-9 is a valid CAS Registry Number.
InChI:InChI=1/C7H6O3.Bi.O/c8-6-4-2-1-3-5(6)7(9)10;;/h1-4,8H,(H,9,10);;/q;+3;-2/p-1
