Rational Pharmacotherapy in Cardiology

Advanced search

Study of the Effect of Proton Pump Inhibitors on the Development of Hypomagnesemia in Patients with Paroxysmal Atrial Fibrillation on the Background of Autonomic Sinus Node Dysfunction

Full Text:


Aim. To study the effect of proton pump inhibitors (PPIs) on the development of hypomagnesemia in patients with paroxysmal atrial fibrillation (AF) on the background of autonomic sinus node dysfunction (ASND).

Material and methods. A prospective cohort study included 32 patients with an established diagnosis of ASND and often recurrent paroxysmal AF. The main group consisted of 17 patients who took pantoprazole at a dose of 20 mg 2 times a day as treatment of diagnosed duodenal erosions within 6 weeks from the time of the initial visit to an arrhythmologist. The remaining 15 patients did not take PPIs and were included in the control group. The determination of magnesium in whole blood, plasma and formed elements was carried out twice in all patients – at the initial visit and after 6 weeks. In addition, in the experiment, complex-forming activity of solutions of various PPIs (esomeprazole, pantoprazole, rabeprazole and omeprazole) with respect to magnesium ions was studied. The author’s method was used, based on turbidimitric determination of the light transmission during the heterogeneous reaction of the formation of magnesium phosphates in the presence of the analyzed drug or without it.

Results. There were no significant differences in the magnesium content in the blood of patients of the main and control groups before taking PPIs. After taking of pantoprazole by the patients of the main group there were significant differences between main and control groups in magnesium in whole blood (0.48 [0.44-0.51] mmol/l vs 0.55 [0.5-0.61] mmol/l, p=0.01) and its values in formed elements (0.52 [0.45-0.67] mmol/l vs 0.75 [0.65-1.2] mmol/l, p=0.009). Analysis of magnesium content in patients of the main group before and after taking of pantoprazole also showed a significant decrease in intracellular concentrations of the element (0.6 [0.51-1.0] mmol/l vs 0.52 [0.45-0.67] mmol/l, p=0.002), as well as decrease in its total content in whole blood (0.51 [0.45-0.59] mmol/l vs 0.48 [0.44-0.51] mmol/l, p=0.04). To substantiate the observed effects it was experimentally proved the possibility of formation of strong complex compounds between the ions of magnesium and PPIs: the highest activity was demonstrated by rabeprazole and pantoprazole (coefficients of complex formation per unit of total organic carbon – 1.5 and 0.72, respectively) and the lowest – omeprazole and esomeprazole (0.04 and 0.09, respectively).

Conclusion. A decrease of magnesium content in whole blood and formed elements in patients with paroxysmal AF on the background of ADSN was mediated by a six-week intake of pantoprazole in a dose of 20 mg 2 times a day for the treatment of concomitant erosion of the duodenum. When choosing PPIs for arrhythmological patients with concomitant gastro-duodenal pathology, it is advisable to be guided by the complexing activity of drugs with respect to magnesium ions: the most pronounced metal-ligand interaction with magnesium was shown by rabeprazole and pantoprazole, and the least – omeprazole and esomeprazole.

About the Authors

Ya. G. Bozhko
Ural State Medical University
Russian Federation

Yakov G. Bozhko – Post-Graduate Student, Chair of Therapy

Repina ul. 3, Ekaterinburg, 620028

M. V. Arkhipov
Ural State Medical University
Russian Federation

Mikhail V. Arkhipov – MD, PhD, Professor, Head of Chair of Therapy

Repina ul. 3, Ekaterinburg, 620028

N. A. Belokonova
Ural State Medical University
Russian Federation

Nadezhda A. Belokonova – PhD (in Engineering), Associate Professor, Head of Chair of General Chemistry

Repina ul. 3, Ekaterinburg, 620028


1. Heidelbaugh J.J. Proton pump inhibitors and risk of vitamin and mineral deficiency. Therapeutic Advances in Drug Safety. 2013;4(3):125-33. DOI: 10.1177/2042098613482484.

2. Andersen B.N., Johansen P.B., Abrahamsen B. Proton pump inhibitors and osteoporosis. Curr Opin Rheum. 2016;28(4):420-5. DOI:10.1097/BOR.0000000000000291.

3. Cheungpasitporn W., Thongprayoo C, Kittanamongkolchai W., et al. Proton pump inhibitors linked to hypomagnesemia: a systematic review and meta-analysis of observational studies. Ren Fail. 2015;37(7):21237-41. DOI:10.3109/0886022X.2015.1057800.

4. Kieboom B.C., Kiefte-de Jong J.C., Eijgelsheim M., et al. Proton pump inhibitors and hypomagnesemia in the general population: apopulation-based cohort study. Am J Kidney. 2015;66(5):775-82. DOI: 10.1053/j.ajkd.2015.05.012.

5. Hoorn E., van der Hoek J., de Man R.A., et al. A case series of proton pump inhibitor-induced hypomagnesemia. Am J Kidney Dis. 2010;56:112-6. DOI:10.1053/j.ajkd.2009.11.019.

6. Markovits N., Kurnik D, Halkin H., et al., Database evaluation of the association between serum magnesium levels and the risk of atrial fibrillation in the community. Int J Cardiol. 2015;205:142-6. DOI:10.1016/j.ijcard.2015.12.014.

7. Ganga H.V., Noyes A., White C.M., Kluger J. Magnesium adjunctive therapy in atrial arrhythmias. Pacing Clin Electrophysiol. 2013;36(10):1308-18. DOI: 10.1111/pace.12189.

8. Khan A.M., Lubitz S.A., Sullivan L.M. Low serum magnesium and the development of atrial fibrillation in the community: the Framingham heart study. Circulation. 2013;127(1):33-8. DOI:10.1161/CIRCULATIONAHA.111.082511.

9. Burke G.H., Calaresu F.R. An experimental analysis of the tachycardia that follows vagal stimulation. J Physiol. 1972;226(2):491-510. DOI:10.1113/jphysiol.1972.sp009995.

10. Dokos S., Celler B.G., Lovell N.H. Simulations of postvagal tachycardia at the single cell pacemaker level: a new hypothesis. Ann Biomed Eng. 1997;25(5):769-82. DOI:10.1007/bf02684161.

11. Bozhko Y.G., Molodykh S.V., Arkhipov M.V., Belokonova N.A. Clinical and functional peculiar features of atrial fibrillation in patients with sinus node dysfunction and vagotonia before and after implantation of a dual-chamber pacemaker. Journal of Arrhythmology. 2018;94:5-10 (In Russ.) DOI: 10.25760/VA-2018-94-17-21.

12. Ivashkin V.T., Sheptulin A.A., Mayev I.V., et al. Clinical recommendations of the Russian Gastroenterological Association for the diagnosis and treatment of peptic ulcer. Russian Journal of Gastroenterology, Hepatology and Coloproctology. 2016; 26(6):40-54 (In Russ.) DOI:10.22416/1382-4376-2016-6-3239.

13. Belokonova N.A., Izmozherova N.V., Bakhtin V.M. Method for evaluating the complexing properties of drugs with respect to magnesium. Patent 2680519, Russian Federation. Jul 11, 2017 (In Russ.)

14. Gromova O.A. About the diagnosis of magnesium deficiency. Archive of Internal Medicine. 2014;2(16):5-10 (In Russ.)

15. Shulman V.A., Egorov D.F., Matyushin G.V., et al. Sick sinus syndrome weakness syndrome. Saint Petersburg: Publishing house of St. Petersburg center for surgery of arrhythmias and pacing;1995 (In Russ.)

16. Linz D., Elliott A.D., Hohl M., et al. Role of autonomic nervous system in atrial fibrillation. Int J Cardiol. 2019;287:181-8. DOI:10.1016/j.ijcard.2018.11.091.

17. Mubagva K., Gwanyanya A., Zakharov S., et al. Regulation of cation channels in cardiac and smooth muscule cells by intracellular magnesium. Arch Biochem Biophys. 2007;458:73-9. DOI:10.1016/

18. Bozhko Y.G., Arkhipov M.V., Belokonova N.A., et al. Clinical and methodological aspects in the diagnosis of magnesium deficiency in patients with paroxysmal atrial fibrillation. Kazan Medical Journal. 2019;100(2):197-203 (In Russ.) DOI:10.17816/KMJ2019-197


For citations:

Bozhko Y.G., Arkhipov M.V., Belokonova N.A. Study of the Effect of Proton Pump Inhibitors on the Development of Hypomagnesemia in Patients with Paroxysmal Atrial Fibrillation on the Background of Autonomic Sinus Node Dysfunction. Rational Pharmacotherapy in Cardiology. 2019;15(6):840-846. (In Russ.)

Views: 723

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)