Połączenie diklofenaku z witaminami z grupy B – skuteczność i bezpieczeństwo w praktyce klinicznej Artykuł przeglądowy
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Opublikowane:
mar 31, 2021
Słowa kluczowe:
COX-1, COX-2, ryzyko sercowo-naczyniowe, NLPZ, bóle odcinka lędźwiowo-krzyżowego kręgosłupa
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Abstrakt
Diklofenak jest jednym z najczęściej stosowanych na świecie niesteroidowych leków przeciwzapalnych, chętnie wybieranym w terapii bólów kostno-stawowych czy mięśniowych. Jego zastosowanie wiąże się jednak z działaniami niepożądanymi charakterystycznymi dla całej klasy leków, w tym niekorzystnym wpływem na ryzyko sercowo-naczyniowe. Wykazano, że witaminy z grupy B biorą udział w wielu procesach istotnych dla prawidłowego funkcjonowania układu nerwowego, a także w mechanizmie tworzenia i przewodzenia bodźców bólowych. Ponadto mają one synergistyczne działanie przeciwbólowe w połączeniu z diklofenakiem. Wspólne zastosowanie obu leków w terapii przeciwbólowej nie tylko skuteczniej łagodzi dolegliwości bólowe, ale również umożliwia zmniejszenie dawek diklofenaku, co pozwala na minimalizację ryzyka wystąpienia działań niepożądanych. Połączenie witamin z grupy B ma więc korzystny wpływ na bezpieczeństwo terapii, co jest istotne zwłaszcza dla pacjentów z grup niskiego ryzyka sercowo-naczyniowego.
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Jak cytować
Postuła, M., Czajka , P., & Fitas , A. (2021). Połączenie diklofenaku z witaminami z grupy B – skuteczność i bezpieczeństwo w praktyce klinicznej. Medycyna Faktów , 14(1(50), 44-51. https://doi.org/10.24292/01.MF.0121.5
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Bibliografia
1. Curatolo M, Sveticic G. Drug combinations in pain treatment: a review of the published evidence and a method for finding the optimal combination. Best Pract Res Clin Anaesthesiol. 2002; 16(4): 507-19.
2. Meek IL, Van de Laar MAFJ, E Vonkeman H. Non-Steroidal Anti-Inflammatory Drugs: An Overview of Cardiovascular Risks. Pharmaceuticals. 2010; 3(7): 2146-62.
3. Edwards SR, Mather LE, Lin Y et al. Glutamate and kynurenate in the rat central nervous system following treatments with tail ischaemia or diclofenac. J Pharm Pharmacol. 2000; 52(1): 59-66.
4. Voilley N, de Weille J, Mamet J et al. Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. J Neurosci. 2001; 21(20): 8026-33.
5. Ortiz MI, Granados-Soto V, Castañeda-Hernández G. The NO–cGMP–K+ channel pathway participates in the antinociceptive effect of diclofenac, but not of indomethacin. Pharmacol Biochem Behav. 2003; 76(1): 187-95.
6. León-Reyes MR, Castañeda-Hernández G, Ortiz MI. Pharmacokinetic of diclofenac in the presence and absence of glibenclamide in the rat. J Pharm Pharm Sci. 2009; 12(3): 280-7.
7. Ortiz MI. Blockade of the antinociception induced by diclofenac, but not of indomethacin, by sulfonylureas and biguanides. Pharmacol Biochem Behav. 2011; 99: 1-6.
8. Benson MD, Aldo-Benson M, Brandt KD. Synovial fluid concentrations of diclofenac in patients with rheumatoid arthritis or osteoarthritis. Semin Arthritis Rheum. 1985; 15: 65-7.
9. Van Hecken A, Schwartz JI, Depré M et al. Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers. J Clin Pharmacol. 2000; 40: 1109-20.
10. Bhala N, Emberson J, Merhi A et al.; on behalf of the Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013; 382(9894): 769-79.
11. Patrono C, Baigent C. Nonsteroidal Anti-Inflammatory Drugs and the Heart. Circulation. 2014; 129(8): 907-16. http://doi.org/10.1161/CIRCULATIONAHA.113.004480.
12. Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy – A Review. Nutrients. 2016; 8: 68.
13. Said HM. Intestinal absorption of water-soluble vitamins in health and disease. Biochem J. 2011; 437: 357-72.
14. Zimmermann M. Possibilities for B-vitamins to modulate basic biological mechanisms involved in pain. In: Gerbershagen HU, Zimmermann M (ed). B-Vitamins in Pain. pmi-Verlag, Frankfurt 1988: 1-8.
15. Altun I, Kurutaş EB. Vitamin B complex and vitamin B12 levels after peripheral nerve injury. Neural Regen Res. 2016; 11(5): 842-5.
16. Izhar M, Alausa T, Folker A et al. Effects of COX inhibition on blood pressure and kidney function in ACE inhibitor-treated blacks and hispanics. Hypertension. 2004; 43: 573-7.
17. Schmidt M, Sørensen HT, Pedersen L. Diclofenac use and cardiovascular risks: series of nationwide cohort studies. BMJ. 2018; 362: k3426.
18. Grosser T, Fries S, FitzGerald GA. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Clin Invest. 2006; 116(1): 4-15.
19. Zingler G, Hermann B, Fischer T et al. Cardiovascular adverse events by non-steroidal anti-inflammatory drugs: when the benefits outweigh the risks. Expert Rev Clin Pharmacol. 2016; 9: 1479-92.
20. Haupt E, Ledermann H, Köpcke W. Benfotiamine in the treatment of diabetic polyneuropathy – a three-week randomized, controlled pilot study (BEDIP Study). Int J Clin Pharmacol Ther. 2005; 43(2): 71-7. http://doi.org/10.5414/cpp43071.
21. Meador KJ, Nichols ME, Franke P. Evidence for a central cholinergic effect of high‐dose thiamine. Ann Neurol. 1993; 34(5): 724-6.
22. Fu QG, Carstens E, Stelzer B et al. B vitamins suppress spinal dorsal horn nociceptive neurons in the cat. Neurosci Lett. 1988; 95: 192-7.
23. Jolivalt CG, Mizisin LM, Nelson A et al. B vitamins alleviate indices of neuropathic pain in diabetic rats. Eur J Pharmacol. 2009; 612: 41-7.
24. Song X-S, Huang Z-J, Song X-J. Thiamine suppresses thermal hyperalgesia, inhibits hyperexcitability, and lessens alterations of sodium currents in injured, dorsal root ganglion neurons in rats. Anesthesiology. 2009; 110(2): 387-400.
25. Reyes-García G, Medina-Santillán R, Flores-Murrieta FJ et al. Analgesic effects of B vitamins: a review. Curr Topics Pharmacol. 2006; 10(1): 1-31.
26. Rocha-González HI, Terán-Rosales F, Reyes-García G et al. B vitamins increase the analgesic effect of diclofenac in the rat. Proc West Pharmacol Soc. 2004; 47: 84-7.
27. Hoy D, Bain C, Williams G et al. A systematic review of the global prevalence of low back pain. Arthritis Rheum. 2012; 64: 2028-37.
28. Bartoszyk GD, Wild A. B-vitamins potentiate the antinociceptive effect of diclofenac in carrageenin-induced hyperalgesia in the rat tail pressure test. Neurosci Lett. 1989; 101: 95-100.
29. Brüggemann G, Koehler CO, Koch EM. Results of a double-blind study of diclofenac + vitamin B1, B6, B12 versus diclofenac in patients with acute pain of the lumbar vertebrae. A multicenter study. Klin Wochenschr. 1990; 68(2): 116-20.
30. Levin OS, Moseĭkin IA. Vitamin B complex (milgamma) in the treatment of vertebrogenic lumbosacral radiculopathy. Zh Nevrol Psikhiatr Im S S Korsakova. 2009; 109(10): 30-5.
31. Mibielli MA, Geller M, Cohen JC et al. Diclofenac plus B vitamins versus diclofenac monotherapy in lumbago: the DOLOR study. Curr Med Res Opin. 2009; 25(11): 2589-99. http://doi.org/10.3111/13696990903246911.
32. Enthoven WTM, Roelofs PD, Deyo RA et al. Non-steroidal anti-inflammatory drugs for chronic low back pain. Cochrane Database Syst Rev. 2016; 2(2): CD012087. http://doi.org/10.1002/14651858.cd012087.
33. Márquez M, Guzman S. Systemic Review on the Use of Diclofenac/B Complex as an Anti-Inflammatory Treatment with Pain Relief Effect for Patients with Acute Lower Back Pain. Journal of Pain & Relief. 2015; 04(06): 1000216. http://doi.org/10.4172/2167-0846.1000216.
34. Geller M, Mibielli MA, Nunes CP et al. Comparison of the action of diclofenac alone versus diclofenac plus B vitamins on mobility in patients with low back pain. J Drug Assess. 2016; 5(1): 1-3. http://doi.org/10.3109/21556660.2016.1163263.
35. Cooper C, Chapurlat R, Al-Daghri N et al. Safety of Oral Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: What Does the Literature Say? Drugs Aging. 2019; 36: 15-24.
36. Elliott WJ. Do the blood pressure effects of nonsteroidal antiinflammatory drugs influence cardiovascular morbidity and mortality? Curr Hypertens Rep. 2010; 12: 258-66.
37. Chan CC, Reid CM, Aw T-J et al. Do COX-2 inhibitors raise blood pressure more than nonselective NSAIDs and placebo? An updated meta-analysis. J Hypertens. 2009; 27(12): 2332-41. http://doi.org/10.1097/hjh.0b013e3283310dc9.
38. Brater DC. Resistance to Loop Diuretics Why it Happens and What to Do About It. Drugs. 1985; 30(5): 427-43. http://doi.org/10.2165/00003495-198530050-00003.
39. Laiwah AC, Mactier RA. Antagonistic effect of non-steroidal anti-inflammatory drugs on frusemide-induced diuresis in cardiac failure. Br Med J. 1981; 283(6293): 714.
40. Bhagat K. Effects of non-steroidal anti-inflammatory drugs on hypertension control using angiotensin converting enzyme inhibitors and thiazide diuretics. East Afr Med J. 2001; 78: 507-9.
41. Palmer R, Weiss R, Zusman RM et al. Effects of nabumetone, celecoxib, and ibuprofen on blood pressure control in hypertensive patients on angiotensin converting enzyme inhibitors. Am J Hypertens. 2003; 16: 135-9.
42. White WB. Defining the problem of treating the patient with hypertension and arthritis pain. Am J Med. 2009; 122: S3-9.
43. Webster J. Interactions of NSAIDs with diuretics and beta-blockers mechanisms and clinical implications. Drugs. 1985; 30: 32-41.
44. Krum H, Swergold G, Curtis SP et al. Factors associated with blood pressure changes in patients receiving diclofenac or etoricoxib: results from the MEDAL study. J Hypertens. 2009; 27: 886-93.
45. Pavlicević I, Kuzmanić M, Rumboldt M et al. Interaction between antihypertensives and NSAIDs in primary care: a controlled trial. Can J Clin Pharmacol. 2008; 15: e372-82.
46. Sharman JE, La Gerche A, Coombes JS. Exercise and cardiovascular risk in patients with hypertension. Am J Hypertens. 2015; 28: 147-58.
47. Dong Y-H, Chang C-H, Wu L-C et al. Comparative cardiovascular safety of nonsteroidal anti-inflammatory drugs in patients with hypertension: a population-based cohort study. Br J Clin Pharmacol. 2018; 84: 1045-56.
48. Bruno A, Tacconelli S, Patrignani P. Variability in the response to non-steroidal anti-inflammatory drugs: mechanisms and perspectives. Basic Clin Pharmacol Toxicol. 2014; 114: 56-63.
49. Odom DM, Mladsi DM, Saag KG et al. Relationship between diclofenac dose and risk of gastrointestinal and cardiovascular events: meta-regression based on two systematic literature reviews. Clin Ther. 2014; 36: 906-17.
50. Moore N, Salvo F, Duong M et al. Cardiovascular risks associated with low-dose ibuprofen and diclofenac as used OTC. Expert Opin Drug Saf. 2014; 13: 167-79.
51. García Rodríguez LA, Tacconelli S, Patrignani P. Role of dose potency in the prediction of risk of myocardial infarction associated with nonsteroidal anti-inflammatory drugs in the general population. J Am Coll Cardiol. 2008; 52(20): 1628-36.
52. McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med. 2011; 8: e1001098.
53.Varas-Lorenzo C, Castellsague J, Stang MR et al. The use of selective cyclooxygenase-2 inhibitors and the risk of acute myocardial infarction in Saskatchewan, Canada. Pharmacoepidemiol Drug Saf. 2009; 18(11): 1016-25. http://doi.org/10.1002/pds.1815.
54. Andersohn F, Suissa S, Garbe E. Use of First- and Second-Generation Cyclooxygenase-2–Selective Nonsteroidal Antiinflammatory Drugs and Risk of Acute Myocardial Infarction. Circulation. 2006; 113(16): 1950-7. http://doi.org/10.1161/CIRCULATIONAHA.105.602425.
55. Salvo F, Antoniazzi S, Duong M et al. Cardiovascular events associated with the long-term use of NSAIDs: a review of randomized controlled trials and observational studies. Expert Opin Drug Saf. 2014; 13: 573-85.
56. Abdulmajeed NA, Alnahdi HS, Ayas NO et al. Amelioration of cardiotoxic impacts of diclofenac sodium by vitamin B complex. Eur Rev Med Pharmacol Sci. 2015; 19: 671-81.
57. Tanaka T, Kono T, Terasaki F et al. Thiamine prevents obesity and obesity-associated metabolic disorders in OLETF rats. J Nutr Sci Vitaminol. 2010; 56: 335-46.
58. Babaei-Jadidi R, Karachalias N, Kupich C et al. High-dose thiamine therapy counters dyslipidaemia in streptozotocin-induced diabetic rats. Diabetologia. 2004; 47(12): 2235-46.
59. Earnest CP, Wood KA, Church TS. Complex multivitamin supplementation improves homocysteine and resistance to LDL-C oxidation. J Am Coll Nutr. 2003; 22: 400-7.
60. Göksemin A, Sati L, Seval Y et al. Effects of Excess Vitamin B6 Intake on Serum Lipid Profile and Cerebral Cortex in Rats. Turk J Med Sci. 2006; 36(6): 327-35.
61. Schuijt MP, Huntjens-Fleuren HWHA, de Metz M et al. The interaction of ibuprofen and diclofenac with aspirin in healthy volunteers. Br J Pharmacol. 2009; 157: 931-4.
62. Catella-Lawson F, Reilly MP, Kapoor SC et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. 2001; 345: 1809-17.
63. FDA Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. 2019.
64. Diclofenac-containing medicines 2013.
65. Altman R, Bosch B, Brune K et al. Advances in NSAID development: evolution of diclofenac products using pharmaceutical technology. Drugs. 2015; 75: 859-77.
2. Meek IL, Van de Laar MAFJ, E Vonkeman H. Non-Steroidal Anti-Inflammatory Drugs: An Overview of Cardiovascular Risks. Pharmaceuticals. 2010; 3(7): 2146-62.
3. Edwards SR, Mather LE, Lin Y et al. Glutamate and kynurenate in the rat central nervous system following treatments with tail ischaemia or diclofenac. J Pharm Pharmacol. 2000; 52(1): 59-66.
4. Voilley N, de Weille J, Mamet J et al. Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. J Neurosci. 2001; 21(20): 8026-33.
5. Ortiz MI, Granados-Soto V, Castañeda-Hernández G. The NO–cGMP–K+ channel pathway participates in the antinociceptive effect of diclofenac, but not of indomethacin. Pharmacol Biochem Behav. 2003; 76(1): 187-95.
6. León-Reyes MR, Castañeda-Hernández G, Ortiz MI. Pharmacokinetic of diclofenac in the presence and absence of glibenclamide in the rat. J Pharm Pharm Sci. 2009; 12(3): 280-7.
7. Ortiz MI. Blockade of the antinociception induced by diclofenac, but not of indomethacin, by sulfonylureas and biguanides. Pharmacol Biochem Behav. 2011; 99: 1-6.
8. Benson MD, Aldo-Benson M, Brandt KD. Synovial fluid concentrations of diclofenac in patients with rheumatoid arthritis or osteoarthritis. Semin Arthritis Rheum. 1985; 15: 65-7.
9. Van Hecken A, Schwartz JI, Depré M et al. Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers. J Clin Pharmacol. 2000; 40: 1109-20.
10. Bhala N, Emberson J, Merhi A et al.; on behalf of the Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013; 382(9894): 769-79.
11. Patrono C, Baigent C. Nonsteroidal Anti-Inflammatory Drugs and the Heart. Circulation. 2014; 129(8): 907-16. http://doi.org/10.1161/CIRCULATIONAHA.113.004480.
12. Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy – A Review. Nutrients. 2016; 8: 68.
13. Said HM. Intestinal absorption of water-soluble vitamins in health and disease. Biochem J. 2011; 437: 357-72.
14. Zimmermann M. Possibilities for B-vitamins to modulate basic biological mechanisms involved in pain. In: Gerbershagen HU, Zimmermann M (ed). B-Vitamins in Pain. pmi-Verlag, Frankfurt 1988: 1-8.
15. Altun I, Kurutaş EB. Vitamin B complex and vitamin B12 levels after peripheral nerve injury. Neural Regen Res. 2016; 11(5): 842-5.
16. Izhar M, Alausa T, Folker A et al. Effects of COX inhibition on blood pressure and kidney function in ACE inhibitor-treated blacks and hispanics. Hypertension. 2004; 43: 573-7.
17. Schmidt M, Sørensen HT, Pedersen L. Diclofenac use and cardiovascular risks: series of nationwide cohort studies. BMJ. 2018; 362: k3426.
18. Grosser T, Fries S, FitzGerald GA. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Clin Invest. 2006; 116(1): 4-15.
19. Zingler G, Hermann B, Fischer T et al. Cardiovascular adverse events by non-steroidal anti-inflammatory drugs: when the benefits outweigh the risks. Expert Rev Clin Pharmacol. 2016; 9: 1479-92.
20. Haupt E, Ledermann H, Köpcke W. Benfotiamine in the treatment of diabetic polyneuropathy – a three-week randomized, controlled pilot study (BEDIP Study). Int J Clin Pharmacol Ther. 2005; 43(2): 71-7. http://doi.org/10.5414/cpp43071.
21. Meador KJ, Nichols ME, Franke P. Evidence for a central cholinergic effect of high‐dose thiamine. Ann Neurol. 1993; 34(5): 724-6.
22. Fu QG, Carstens E, Stelzer B et al. B vitamins suppress spinal dorsal horn nociceptive neurons in the cat. Neurosci Lett. 1988; 95: 192-7.
23. Jolivalt CG, Mizisin LM, Nelson A et al. B vitamins alleviate indices of neuropathic pain in diabetic rats. Eur J Pharmacol. 2009; 612: 41-7.
24. Song X-S, Huang Z-J, Song X-J. Thiamine suppresses thermal hyperalgesia, inhibits hyperexcitability, and lessens alterations of sodium currents in injured, dorsal root ganglion neurons in rats. Anesthesiology. 2009; 110(2): 387-400.
25. Reyes-García G, Medina-Santillán R, Flores-Murrieta FJ et al. Analgesic effects of B vitamins: a review. Curr Topics Pharmacol. 2006; 10(1): 1-31.
26. Rocha-González HI, Terán-Rosales F, Reyes-García G et al. B vitamins increase the analgesic effect of diclofenac in the rat. Proc West Pharmacol Soc. 2004; 47: 84-7.
27. Hoy D, Bain C, Williams G et al. A systematic review of the global prevalence of low back pain. Arthritis Rheum. 2012; 64: 2028-37.
28. Bartoszyk GD, Wild A. B-vitamins potentiate the antinociceptive effect of diclofenac in carrageenin-induced hyperalgesia in the rat tail pressure test. Neurosci Lett. 1989; 101: 95-100.
29. Brüggemann G, Koehler CO, Koch EM. Results of a double-blind study of diclofenac + vitamin B1, B6, B12 versus diclofenac in patients with acute pain of the lumbar vertebrae. A multicenter study. Klin Wochenschr. 1990; 68(2): 116-20.
30. Levin OS, Moseĭkin IA. Vitamin B complex (milgamma) in the treatment of vertebrogenic lumbosacral radiculopathy. Zh Nevrol Psikhiatr Im S S Korsakova. 2009; 109(10): 30-5.
31. Mibielli MA, Geller M, Cohen JC et al. Diclofenac plus B vitamins versus diclofenac monotherapy in lumbago: the DOLOR study. Curr Med Res Opin. 2009; 25(11): 2589-99. http://doi.org/10.3111/13696990903246911.
32. Enthoven WTM, Roelofs PD, Deyo RA et al. Non-steroidal anti-inflammatory drugs for chronic low back pain. Cochrane Database Syst Rev. 2016; 2(2): CD012087. http://doi.org/10.1002/14651858.cd012087.
33. Márquez M, Guzman S. Systemic Review on the Use of Diclofenac/B Complex as an Anti-Inflammatory Treatment with Pain Relief Effect for Patients with Acute Lower Back Pain. Journal of Pain & Relief. 2015; 04(06): 1000216. http://doi.org/10.4172/2167-0846.1000216.
34. Geller M, Mibielli MA, Nunes CP et al. Comparison of the action of diclofenac alone versus diclofenac plus B vitamins on mobility in patients with low back pain. J Drug Assess. 2016; 5(1): 1-3. http://doi.org/10.3109/21556660.2016.1163263.
35. Cooper C, Chapurlat R, Al-Daghri N et al. Safety of Oral Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: What Does the Literature Say? Drugs Aging. 2019; 36: 15-24.
36. Elliott WJ. Do the blood pressure effects of nonsteroidal antiinflammatory drugs influence cardiovascular morbidity and mortality? Curr Hypertens Rep. 2010; 12: 258-66.
37. Chan CC, Reid CM, Aw T-J et al. Do COX-2 inhibitors raise blood pressure more than nonselective NSAIDs and placebo? An updated meta-analysis. J Hypertens. 2009; 27(12): 2332-41. http://doi.org/10.1097/hjh.0b013e3283310dc9.
38. Brater DC. Resistance to Loop Diuretics Why it Happens and What to Do About It. Drugs. 1985; 30(5): 427-43. http://doi.org/10.2165/00003495-198530050-00003.
39. Laiwah AC, Mactier RA. Antagonistic effect of non-steroidal anti-inflammatory drugs on frusemide-induced diuresis in cardiac failure. Br Med J. 1981; 283(6293): 714.
40. Bhagat K. Effects of non-steroidal anti-inflammatory drugs on hypertension control using angiotensin converting enzyme inhibitors and thiazide diuretics. East Afr Med J. 2001; 78: 507-9.
41. Palmer R, Weiss R, Zusman RM et al. Effects of nabumetone, celecoxib, and ibuprofen on blood pressure control in hypertensive patients on angiotensin converting enzyme inhibitors. Am J Hypertens. 2003; 16: 135-9.
42. White WB. Defining the problem of treating the patient with hypertension and arthritis pain. Am J Med. 2009; 122: S3-9.
43. Webster J. Interactions of NSAIDs with diuretics and beta-blockers mechanisms and clinical implications. Drugs. 1985; 30: 32-41.
44. Krum H, Swergold G, Curtis SP et al. Factors associated with blood pressure changes in patients receiving diclofenac or etoricoxib: results from the MEDAL study. J Hypertens. 2009; 27: 886-93.
45. Pavlicević I, Kuzmanić M, Rumboldt M et al. Interaction between antihypertensives and NSAIDs in primary care: a controlled trial. Can J Clin Pharmacol. 2008; 15: e372-82.
46. Sharman JE, La Gerche A, Coombes JS. Exercise and cardiovascular risk in patients with hypertension. Am J Hypertens. 2015; 28: 147-58.
47. Dong Y-H, Chang C-H, Wu L-C et al. Comparative cardiovascular safety of nonsteroidal anti-inflammatory drugs in patients with hypertension: a population-based cohort study. Br J Clin Pharmacol. 2018; 84: 1045-56.
48. Bruno A, Tacconelli S, Patrignani P. Variability in the response to non-steroidal anti-inflammatory drugs: mechanisms and perspectives. Basic Clin Pharmacol Toxicol. 2014; 114: 56-63.
49. Odom DM, Mladsi DM, Saag KG et al. Relationship between diclofenac dose and risk of gastrointestinal and cardiovascular events: meta-regression based on two systematic literature reviews. Clin Ther. 2014; 36: 906-17.
50. Moore N, Salvo F, Duong M et al. Cardiovascular risks associated with low-dose ibuprofen and diclofenac as used OTC. Expert Opin Drug Saf. 2014; 13: 167-79.
51. García Rodríguez LA, Tacconelli S, Patrignani P. Role of dose potency in the prediction of risk of myocardial infarction associated with nonsteroidal anti-inflammatory drugs in the general population. J Am Coll Cardiol. 2008; 52(20): 1628-36.
52. McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med. 2011; 8: e1001098.
53.Varas-Lorenzo C, Castellsague J, Stang MR et al. The use of selective cyclooxygenase-2 inhibitors and the risk of acute myocardial infarction in Saskatchewan, Canada. Pharmacoepidemiol Drug Saf. 2009; 18(11): 1016-25. http://doi.org/10.1002/pds.1815.
54. Andersohn F, Suissa S, Garbe E. Use of First- and Second-Generation Cyclooxygenase-2–Selective Nonsteroidal Antiinflammatory Drugs and Risk of Acute Myocardial Infarction. Circulation. 2006; 113(16): 1950-7. http://doi.org/10.1161/CIRCULATIONAHA.105.602425.
55. Salvo F, Antoniazzi S, Duong M et al. Cardiovascular events associated with the long-term use of NSAIDs: a review of randomized controlled trials and observational studies. Expert Opin Drug Saf. 2014; 13: 573-85.
56. Abdulmajeed NA, Alnahdi HS, Ayas NO et al. Amelioration of cardiotoxic impacts of diclofenac sodium by vitamin B complex. Eur Rev Med Pharmacol Sci. 2015; 19: 671-81.
57. Tanaka T, Kono T, Terasaki F et al. Thiamine prevents obesity and obesity-associated metabolic disorders in OLETF rats. J Nutr Sci Vitaminol. 2010; 56: 335-46.
58. Babaei-Jadidi R, Karachalias N, Kupich C et al. High-dose thiamine therapy counters dyslipidaemia in streptozotocin-induced diabetic rats. Diabetologia. 2004; 47(12): 2235-46.
59. Earnest CP, Wood KA, Church TS. Complex multivitamin supplementation improves homocysteine and resistance to LDL-C oxidation. J Am Coll Nutr. 2003; 22: 400-7.
60. Göksemin A, Sati L, Seval Y et al. Effects of Excess Vitamin B6 Intake on Serum Lipid Profile and Cerebral Cortex in Rats. Turk J Med Sci. 2006; 36(6): 327-35.
61. Schuijt MP, Huntjens-Fleuren HWHA, de Metz M et al. The interaction of ibuprofen and diclofenac with aspirin in healthy volunteers. Br J Pharmacol. 2009; 157: 931-4.
62. Catella-Lawson F, Reilly MP, Kapoor SC et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. 2001; 345: 1809-17.
63. FDA Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. 2019.
64. Diclofenac-containing medicines 2013.
65. Altman R, Bosch B, Brune K et al. Advances in NSAID development: evolution of diclofenac products using pharmaceutical technology. Drugs. 2015; 75: 859-77.