BISMUTH
Place in Therapy
After reviewing the literature for bismuth salts in the
treatment of gastroesophageal reflux disease (GERD) and dyspepsia it is
determined that its use within the algorithm is limited. Due to the side effect of greyish-black
discolored stools, which, may mask or falsely alarm patients of gastric bleeds
its use is discouraged. Additionally,
many of the studies conducted on bismuth and its salts were done in the 70’s
to the late 80’s which, precedes the introduction of proton pump inhibitors
(PPI) to the market. As a result few
studies have been done comparing the efficacy of bismuth to PPI’s, which, are
currently considered the agent of choice for GERD and dyspepsia. Therefore, the evidence for bismuth is
considered somewhat outdated and its use is limited due to lack of
comparative data.
In the primary and secondary literature colloidal bismuth citrate has not been associated with any adverse effects at doses of 240mg twice daily in adults.5 At this dose, researchers have found it to be effective at alleviating pain, gastritis, duodenitis and gas bloating secondary to non-ulcer dyspepsia.5 However, this data supporting was obtained using an open-label study that selected for subjects with mild cases of dyspepsia. Therefore, this data should be used with caution as the degree of symptom alleviation using bismuth may be exaggerated due to the selection criteria used for the study.
However, in a systematic-review comparing antacids, H2-antagonists, prokinetic agents, bismuth and sucralfate for the treatment of non-ulcer dyspepsia researchers found that bismuth performed slightly better than placebo.9 In this review, prokinetic agents and H2-receptor antagonists were discovered to be significantly more effective than placebo.9 Therefore, in consideration of this evidence bismuth should be trialed after failure with antacids, H2-receptor antagonists and prokinetic agents.
Evidence exists that colloidal bismuth subcitrate may be used as an adjunct to H2 antagonist therapy for the treatment of ulcerative reflux esophagitis. In one trial 120mg of bismuth was used four times daily in combination with 800mg of cimetidine at bedtime.8 Treatment using this combination therapy has shown to increase healing of ulcerations and improve esophagitis grading in as little as a week.8 However, the trial size was small (n=10) and should be used in persistent reflux esophagitis or in patients requiring rapid healing before surgical interventions.8
Despite evidence suggesting that bismuth salts can alleviate the symptoms of GERD and dyspepsia many guidelines have only recommended its use as an agent in H.pylori eradiction.10,12 In this case, quadruple therapy consisting of a PPI, bismuth, metronidazole and tetracycline is considered second line therapy to a triple therapy regimen of PPI, amoxicillin and clarithromycin. 1,10,12 Where quadruple therapy should only be used in patients with clarithromycin resistant H.pylori.1,6 Here, bismuth has been added as an agent not for gastric acid suppression but as an anti-bacterial agent as evidence supports its inhibitory effect on H.pylori.7,10,12
References
1. UP TO DATE http://www.uptodate.com.proxy1.lib.uwo.ca:2048/contents/bismuth-drug-information?source=search_result&search=bismuth+ulcer&selectedTitle=2%7E150 (Accessed Mar 10, 2012)
2. Johnson PC, Ericsson CD, DuPont HL, et al. Comparison of loperamide with bismuth subsalicylate for the treatment of acute travelers’ diarrhea. JAMA 1986; 255(6): 757-760.
3. http://www.pepto-bismol.com/pepto-original-liquid.php (Accessed Mar 10, 2012)
4. https://www.e-therapeutics.ca/tc.showChapter.action?documentId=c0046#c0046n00237 (Accessed Mar 10, 2012)
5. http://www.canadadrugs.com/search.php?keyword=Pepto+Bismol+Chewables (accessed Mar 10, 2012)
6. http://www.uptodate.com.proxy1.lib.uwo.ca:2048/contents/treatment-regimens-for-helicobacter-pylori?source=search_result&search=bismuth&selectedTitle=10%7E82 (Accessed Mar 10, 2012)
7. Khanna MU, Abraham P, Nair NG, et al. Colloidal bismuth subcitrate innon-ulcer dyspepsia. J Postgrad Med 1992; 38(3): 106-8.
8. Borkent MV, Beker MA. Treatment of ulcerative reflux oesophagitis with colloidal bismuth subcitrate in combination with cimetidine. Gut 1988; 29: 385-389.
9. Moayyedi P, Soo S, Deeks J, et al. Systematic review: antacids, H2 antagonists, prokinetics, bismuth and sucralfate therapy for non-ulcer dyspepsia. Aliment Pharmcol Ther 2003; 17: 1215-1227.
10. Locke RG, Talley NJ. Current Clinical Practice: Management of non-ulcer dyspepsia. J Gastroenterology and Hepatology 1993; 8: 279-286.
11. Bernstein RK. Bismuth subsalicylate- an aid to the diagnosis and treatment of reflux esophagitis. Diabetes Care 1984; 7(4): 404-405.
12. Soll AH, Feldman M, and Grover S. Up to Date – Pharmacology of antiulcer medications. Jan 19, 2011.
In the primary and secondary literature colloidal bismuth citrate has not been associated with any adverse effects at doses of 240mg twice daily in adults.5 At this dose, researchers have found it to be effective at alleviating pain, gastritis, duodenitis and gas bloating secondary to non-ulcer dyspepsia.5 However, this data supporting was obtained using an open-label study that selected for subjects with mild cases of dyspepsia. Therefore, this data should be used with caution as the degree of symptom alleviation using bismuth may be exaggerated due to the selection criteria used for the study.
However, in a systematic-review comparing antacids, H2-antagonists, prokinetic agents, bismuth and sucralfate for the treatment of non-ulcer dyspepsia researchers found that bismuth performed slightly better than placebo.9 In this review, prokinetic agents and H2-receptor antagonists were discovered to be significantly more effective than placebo.9 Therefore, in consideration of this evidence bismuth should be trialed after failure with antacids, H2-receptor antagonists and prokinetic agents.
Evidence exists that colloidal bismuth subcitrate may be used as an adjunct to H2 antagonist therapy for the treatment of ulcerative reflux esophagitis. In one trial 120mg of bismuth was used four times daily in combination with 800mg of cimetidine at bedtime.8 Treatment using this combination therapy has shown to increase healing of ulcerations and improve esophagitis grading in as little as a week.8 However, the trial size was small (n=10) and should be used in persistent reflux esophagitis or in patients requiring rapid healing before surgical interventions.8
Despite evidence suggesting that bismuth salts can alleviate the symptoms of GERD and dyspepsia many guidelines have only recommended its use as an agent in H.pylori eradiction.10,12 In this case, quadruple therapy consisting of a PPI, bismuth, metronidazole and tetracycline is considered second line therapy to a triple therapy regimen of PPI, amoxicillin and clarithromycin. 1,10,12 Where quadruple therapy should only be used in patients with clarithromycin resistant H.pylori.1,6 Here, bismuth has been added as an agent not for gastric acid suppression but as an anti-bacterial agent as evidence supports its inhibitory effect on H.pylori.7,10,12
References
1. UP TO DATE http://www.uptodate.com.proxy1.lib.uwo.ca:2048/contents/bismuth-drug-information?source=search_result&search=bismuth+ulcer&selectedTitle=2%7E150 (Accessed Mar 10, 2012)
2. Johnson PC, Ericsson CD, DuPont HL, et al. Comparison of loperamide with bismuth subsalicylate for the treatment of acute travelers’ diarrhea. JAMA 1986; 255(6): 757-760.
3. http://www.pepto-bismol.com/pepto-original-liquid.php (Accessed Mar 10, 2012)
4. https://www.e-therapeutics.ca/tc.showChapter.action?documentId=c0046#c0046n00237 (Accessed Mar 10, 2012)
5. http://www.canadadrugs.com/search.php?keyword=Pepto+Bismol+Chewables (accessed Mar 10, 2012)
6. http://www.uptodate.com.proxy1.lib.uwo.ca:2048/contents/treatment-regimens-for-helicobacter-pylori?source=search_result&search=bismuth&selectedTitle=10%7E82 (Accessed Mar 10, 2012)
7. Khanna MU, Abraham P, Nair NG, et al. Colloidal bismuth subcitrate innon-ulcer dyspepsia. J Postgrad Med 1992; 38(3): 106-8.
8. Borkent MV, Beker MA. Treatment of ulcerative reflux oesophagitis with colloidal bismuth subcitrate in combination with cimetidine. Gut 1988; 29: 385-389.
9. Moayyedi P, Soo S, Deeks J, et al. Systematic review: antacids, H2 antagonists, prokinetics, bismuth and sucralfate therapy for non-ulcer dyspepsia. Aliment Pharmcol Ther 2003; 17: 1215-1227.
10. Locke RG, Talley NJ. Current Clinical Practice: Management of non-ulcer dyspepsia. J Gastroenterology and Hepatology 1993; 8: 279-286.
11. Bernstein RK. Bismuth subsalicylate- an aid to the diagnosis and treatment of reflux esophagitis. Diabetes Care 1984; 7(4): 404-405.
12. Soll AH, Feldman M, and Grover S. Up to Date – Pharmacology of antiulcer medications. Jan 19, 2011.