Lviv clinical bulletin 2019, 4(28): 49-55

https://doi.org/10.25040/lkv2019.04.039

Peculiarities of influence of single intragastric administration of H2-histamine receptor blockers of the second (nisatidine) and third (famotidine) generation on acid-peptic and mucoid-electrolyte secretion of the stomach in patients with duodenal ulcer

Posted onAuthorAdminЗалишити коментар / Leave a comment

M. Pliatsko

Danylo Halytsky Lviv National Medical University

Introduction. Antisecretory drugs are commonly used in the complex treatment of most diseases of the upper gastrointestinal tract. Today, proton pomp inhibitors (PPI) have a priority in the basic treatment for acid-dependent diseases of the gastrointestinal tract due to its higher acid-blocking ability. However, PPI have a number of disadvantages, including resistance, nocturnal acid breakthrough, hyperplastic processes stimulation, mucosa atrophic changes and dysbiosis. To eliminate these undesirable effects H2-histamine receptor blockers which don’t interfere in intracellular metabolism are recommended. Moreover, it was shown that H2-histamine receptor blockers have a reciprocal effect on the production of mucosal defense factors, namely enhancing the synthesis of mucoid component and bicarbonate in gastric juice. The most commonly used in clinical practice are blockers of the second and third generation. The impact of the H2-histamine blockers (second and third generation) on acid-peptic and mucoid-bicarbonate secretion in patients with acid-dependent lesions of the gastrointestinal tract has not been sufficiently studied, but comparative estimation of their impact on the gastric protective factors in both media (gastric juice and insoluble mucus) have not been studied before

The aim of the study. To investigate the peculiarities of the impact of H2-histamine receptors blockers (second and third generation) on gastric acid-peptic and mucoid-electrolyte secretion in patients with duodenal ulcer after single intragastric administration of nizatidine and famotidin.

Materials and methods. It involved 51 randomized patients with endoscopically confirmed diagnosis of duodenal ulcer in the exacerbation phase were investigated: nizatidine administered in 26 patients (f/m – 5/21) aged 18-68 years and famotidine – in 25 patients (f/m – 7/18) in age 21-70 years. All patients had a positive urease test for Helicobacter pylori. Fractional gastric tubing with submaximal histamine stimulation with further intragastral administration of H2-histamine blocker was performed. Hydrochloric acid and pepsin in the gastric juice and N-acetylneuraminic acid and Na+ ions in the gastric juice and insoluble mucus were analyzed in three portions: basal, after histamine stimulation and after nizatidine or famotidine administration. Finally, comparison between impacts of these preparations on the acid-peptic and mucoid-electrolyte secretion of the stomach was carried out

Results of the study. Intragastric administration of 150.0 mg nizatidine after submaximal histamine stimulation decreased total acidity by 33.1 % and pepsin secretion decreased by 23.9 %, meanwhile it increased N acetylneuraminic acid content in gastric juice and insoluble mucus by 24.5 % and 21.2 % respectively. Analogous changes are also revealed in the dynamics of Na+ release, which directly correlates with the secretion of gastric mucosa of hydrocarbonate compounds. The production of this ion both in gastric juice and insoluble mucus increased by 6.7 % and 12.0 % respectively.

Intragastric administration of 40.0 mg famodine after submaximal histamine stimulation decreased total acidity by 45.0 % and pepsin secretion decreased by 28.4 %, meanwhile it increased N-acetylneuraminic acid content in gastric juice and insoluble mucus by 24.6 % and 33.6 % respectively. Analogous changes are also revealed in the dynamics of Na+ release, which directly correlates with the secretion of gastric mucosa of hydrocarbonate compounds. The production of this ion both in gastric juice and insoluble mucus increased by 5.1 % and 15.5 % respectively.

The comparative characteristic of H2–histamine receptor blockers impact on acid-peptic function shows higher efficiency of third-generation (famotidine) drug against second-generation drug (nizatidine) in acid-peptic secretion blocking, their influence on production of N-acetylneuraminic acids as a marker of mucoid secretion and sodium ions as an indicator of hydrocarbon secretion did not differ significantly.

Conclusions. Famotidine more effectively blocked acid and peptic secretion compared to nizatidine, but their stimulating impact on mucoid-electrolyte secretion was not significantly different.

References

  1. Aruin LI. The quality of gastroduodenal ulcers healing: functional morphology. The role of pathogenetic therapy methods. Contemporary Gastroenterology. 2013;5(73):92-103. (Ukrainian).
  2. Burchinskyj GI, Dehtjareva II. Relationship of aggressive and protective factors in patients with peptic ulcer. Abstracts. doc. XIX Congress of Therapists. 1987; 2:124-125. (Russian).
  3. Vdovichenko VI, Sklyarova OJ. The state of the aggression and defensive factors in patients with peptic ulcers before and after antihelicobacter therapy. Contemporary Gastroenterology. 2010;3(53):31-34. (Ukrainian).
  4. Zub RI, Bychkova SV, Bychkov MA. Sialic acids and pepsin content in saliva and gastric juice in patients with the stomach and esophagus diseases. Fiziologichnyi Zhurnal. 2017;63(6);99-105. (Ukrainian). https://doi.org/10.15407/fz63.06.099
  5. Krajdashenko OV, Kremzer OO, Myhailyk OO. Clinical pharmacology and pharmacotherapy in gastroenterology. Tutorial for students of the High medical scientific institutions (Health Ministry of Ukraine). Zaporizhzhia; 2016. 187 c. (Ukrainian).
  6. Kononov AV. Cytoprotection of gastric mucosa: molecular cellular mechanisms. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2006;3:12-16) (Russian).
  7. Mysh VG. Determination of gastric juice acidity. Laboratory 1986;4:212-215. (Russian).
  8. Oparin AG, Oparin AA, Jakovenko JL. Role and pathogenetic mechanisms of protective mucous barrier damage in peptic ulcer. Problems of Medical Sciences and Education. 2002;1:35-36. (Russian).
  9. Perederiy VG, Cherniavsky VV, Sitnikov AS. Proton pomp inhibitors 1 and 2nd generation, omeprazole and rabeprazole in the clinical practice – advantages and disadvantages. Medicine Today. 2006;5:20. (Russian).
  10. Sklyarov JJ, Shalko IV, Varivoda VI. Factors of aggression and protection in gastric and duodenal peptic ulcer. Pract Med. 2004;3:65-67. (Ukrainian).
  11. Tin VP. Method for determination of pepsin in gastric juice using colorimetry. Laboratory 1976;11:656-657. (Russian).
  12. Zimmerman JS. Modern methods of stomach functions research and their diagnostic possibilities. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2011;21(5):4-16. (Russian).
  13. Sharaev PN. Determination of sialic acids by resorcinol. method. Laboratory 1990;11:38-40. (Russian).
  14. Jung G. Instrumental methods of chemical analysis. T. English. Ransl. 5th ed. Moskow: Mir; 1989. 608 p.) (Russian).
  15. Adachi K, Komazawa Y, Mihara T et al. Comparative study of the speed of acid-suppressing effects of oral administration of cimetidine and famotidine. J Gastroenterol Hepatol. 2005;20:1012-1015. https://doi.org/10.1111/j.1440-1746.2005.03917.x
  16. Cheung KS, Chan EW, Wong AYS, Chen L, Wong I, Leung WK. Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study. Gut. 2018;67(1):28-35. https://doi.org/10.1136/gutjnl-2017-314605
  17. Hamano H, Niimura T, Horinouchi Y, Zamami Y, Takechi K, Goda M et al. Proton pump inhibitors block iron absorption through direct regulation of hepcidin via the aryl hydrocarbon receptor-mediated pathway. Toxicol Lett. 2020;318:86-91. https://doi.org/10.1016/j.toxlet.2019.10.016
  18. Ichikawa T1, Ota H, Sugiyama A, Maruta F, Ikezawa T, Hotta K et al. Effects of a novel histamine H2-receptor antagonist, lafutidine, on the mucus barrier of human gastric mucosa. J Gastroenterol Hepatol. 2007;22(11):1800-1805. https://doi.org/10.1111/j.1440-1746.2006.04721.x
  19. Kagoshima, Kodaira H, Shimada H. Effects of FRG-8813, a new histamine H2-receptor antagonist, on gastric mucus in rats. Nihon Yakurigaku Zasshi. 1994;104(5):379-389. https://doi.org/10.1254/fpj.104.379
  20. Mimaki H1, Kawauchi S, Kagawa S, Ueki S, Takeuchi K. Bicarbonate stimulatory action of nizatidine, a histamine H(2)-receptor antagonist, in rat duodenums. Physiol Paris. 2001;95(1-6):165-171. https://doi.org/10.1016/S0928-4257(01)00022-5
  21. Nehra AN, Alexander JA, Loftus CG, Nehra V. Proton Pump Inhibitors: Review of Emerging Concerns. Mayo Clinic Proceedings. 2018;93(2):240-246. https://doi.org/10.1016/j.mayocp.2017.10.022
  22. Okazaki M, Shimizu I, Ishikawa M, Fujiwara S, Yamamoto H, Shiraishi T et al. Gastric mucosal levels of prostaglandins and leukotrienes in patients with gastric ulcer after treatment with rabeprazole in comparison to treatment with ranitidine. J Med Invest. 2007;54(1-2):83-90. https://doi.org/10.2152/jmi.54.83
  23. Rosenfeld L. Gastric tubes, meals, acid, and analysis: rise and decline. Clin Chem. 1997;43(5):837-842. https://doi.org/10.1093/clinchem/43.5.837
  24. Schwartz NRM, Hutfless S, Herrinton LJ, Amsden LB, Fevrier HB, Giefer M et al. Proton Pump Inhibitors, H2 Blocker Use, and Risk of Inflammatory Bowel Disease in Children. Pediatr Pharmacol Ther. 2019;24(6):489-496. https://doi.org/10.5863/1551-6776-24.6.489
  25. Tanaka M, Banba M, Joko A, Moriyama Y. Pharmacological and therapeutic properties of lafutidine (stogar and protecadin), a novel histamine H2 receptor antagonist with gastroprotective activity. Nihon Yakurigaku Zasshi. 2001;117(6):377-386. https://doi.org/10.1254/fpj.117.377
  26. Tran-Duy A, Spaetgens B, Hoes AW, de Wit NJ, Stehouwer CD. Use of Proton Pump Inhibitors and Risks of Fundic Gland Polyps and Gastric Cancer: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2016;14(12):1706-1719. https://doi.org/10.1016/j.cgh.2016.05.018
  27. Kinoshita Y, Ishimura N, Ishihara S. Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use. J Neurogastroenterol Motil. 2018;24(2):182-196. https://doi.org/10.5056/jnm18001