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. 1991 Mar-Apr;64(2):177–186.

Effects of calcium channel blockers on potassium homeostasis.

M I Freed 1, A Rastegar 1, M J Bia 1
PMCID: PMC2589467  PMID: 1750228

Abstract

The known effects of calcium channel blockers on various aspects of potassium homeostasis are reviewed. Regulation of potassium homeostasis requires both renal and external handling mechanisms. Signaling by calcium appears to mediate both of these. Calcium channels have been identified in adrenal glomerulosa cells, and cellular calcium entry has been demonstrated in vitro to be necessary for the synthesis and secretion of aldosterone. Calcium channel antagonists such as verapamil and nifedipine, at pharmacologic doses, can block aldosterone production. In vivo, however, only chronic administration of verapamil appears to attenuate aldosterone responsiveness to angiotensin II. Chronic administration of nifedipine does not have a dramatic effect on aldosterone production following potassium loading. Other studies have demonstrated improved extrarenal potassium disposal following treatment with calcium channel blocking agents. Clinically, there are no reports of either hyperkalemia or hypokalemia with the routine therapeutic use of these agents given alone. This review was prompted by the development of hyperkalemia in a patient with chronic renal failure following the initiation of therapy with the calcium channel blocker diltiazem: however, numerous other etiologies may also have contributed to the development of hyperkalemia in this case. Review of the data indicates that current evidence implicating this class of drugs in the pathogenesis of disordered potassium regulation remains equivocal.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blanchouin-Emeric N., Zenatti M., Defaye G., Aupetit B. Verapamil directly inhibits aldosterone synthesis by adrenal mitochondria in vitro. J Steroid Biochem. 1988;30(1-6):453–456. doi: 10.1016/0022-4731(88)90141-0. [DOI] [PubMed] [Google Scholar]
  2. Bursztyn M., Grossman E., Rosenthal T. The absence of long-term therapeutic effect of calcium channel blockade in the primary aldosteronism of adrenal adenomas. Am J Hypertens. 1988 Jul;1(3 Pt 3):88S–90S. doi: 10.1093/ajh/1.3.88s. [DOI] [PubMed] [Google Scholar]
  3. Cohen C. J., McCarthy R. T., Barrett P. Q., Rasmussen H. Ca channels in adrenal glomerulosa cells: K+ and angiotensin II increase T-type Ca channel current. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2412–2416. doi: 10.1073/pnas.85.7.2412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ethier J. H., Kamel K. S., Magner P. O., Lemann J., Jr, Halperin M. L. The transtubular potassium concentration in patients with hypokalemia and hyperkalemia. Am J Kidney Dis. 1990 Apr;15(4):309–315. doi: 10.1016/s0272-6386(12)80076-x. [DOI] [PubMed] [Google Scholar]
  5. Fakunding J. L., Catt K. J. Dependence of aldosterone stimulation in adrenal glomerulosa cells on calcium uptake: effects of lanthanum nd verapamil. Endocrinology. 1980 Nov;107(5):1345–1353. doi: 10.1210/endo-107-5-1345. [DOI] [PubMed] [Google Scholar]
  6. Favre L., Riondel A., Vallotton M. B. Effect of calcium-channel blockade on the aldosterone response to sodium depletion and potassium loading in man. Am J Hypertens. 1988 Jul;1(3 Pt 1):245–248. doi: 10.1093/ajh/1.3.245. [DOI] [PubMed] [Google Scholar]
  7. Flicker M. R., Quigley M. A., Caldwell E. G. Diltiazem and hyperkalemia. JAMA. 1987 Oct 9;258(14):1891–1892. doi: 10.1001/jama.1987.03400140053014. [DOI] [PubMed] [Google Scholar]
  8. Foster R., Lobo M. V., Rasmussen H., Marusic E. T. Calcium: its role in the mechanism of action of angiotensin II and potassium in aldosterone production. Endocrinology. 1981 Dec;109(6):2196–2201. doi: 10.1210/endo-109-6-2196. [DOI] [PubMed] [Google Scholar]
  9. Foster T. S., Hamann S. R., Richards V. R., Bryant P. J., Graves D. A., McAllister R. G. Nifedipine kinetics and bioavailability after single intravenous and oral doses in normal subjects. J Clin Pharmacol. 1983 Apr;23(4):161–170. doi: 10.1002/j.1552-4604.1983.tb02720.x. [DOI] [PubMed] [Google Scholar]
  10. Freedman S. B., Richmond D. R., Ashley J. J., Kelly D. T. Verapamil kinetics in normal subjects and patients with coronary artery spasm. Clin Pharmacol Ther. 1981 Nov;30(5):644–652. doi: 10.1038/clpt.1981.216. [DOI] [PubMed] [Google Scholar]
  11. Frishman W. H., Stroh J. A., Greenberg S., Suarez T., Karp A., Peled H. Calcium channel blockers in systemic hypertension. Med Clin North Am. 1988 Mar;72(2):449–499. doi: 10.1016/s0025-7125(16)30779-9. [DOI] [PubMed] [Google Scholar]
  12. Hamann S. R., Blouin R. A., McAllister R. G., Jr Clinical pharmacokinetics of verapamil. Clin Pharmacokinet. 1984 Jan-Feb;9(1):26–41. doi: 10.2165/00003088-198409010-00002. [DOI] [PubMed] [Google Scholar]
  13. Hoyt R. E. Hyperkalemia due to salt substitutes. JAMA. 1986 Oct 3;256(13):1726–1726. [PubMed] [Google Scholar]
  14. Kleinbloesem C. H., van Brummelen P., Faber H., Breimer D. D. Pharmacokinetics and hemodynamic effects of long-term nifedipine treatment in hypertensive patients. J Cardiovasc Pharmacol. 1987 Feb;9(2):202–208. doi: 10.1097/00005344-198702000-00012. [DOI] [PubMed] [Google Scholar]
  15. Kotchen T. A., Galla J. H., Luke R. G. Effects of calcium on renin and aldosterone in the rat. Am J Physiol. 1977 Apr;232(4):E388–E393. doi: 10.1152/ajpendo.1977.232.4.E388. [DOI] [PubMed] [Google Scholar]
  16. Kotchen T. A., Guthrie G. P., Jr Effects of calcium on renin and aldosterone. Am J Cardiol. 1988 Oct 5;62(11):41G–46G. doi: 10.1016/0002-9149(88)90031-8. [DOI] [PubMed] [Google Scholar]
  17. Kotchen T. A., Mauli K. I., Luke R., Rees D., Flamenbaum W. Effect of acute and chronic calcium administration on plasma renin. J Clin Invest. 1974 Dec;54(6):1279–1286. doi: 10.1172/JCI107873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. McAllister R. G., Jr, Hamann S. R., Blouin R. A. Pharmacokinetics of calcium-entry blockers. Am J Cardiol. 1985 Jan 25;55(3):30B–40B. doi: 10.1016/0002-9149(85)90611-3. [DOI] [PubMed] [Google Scholar]
  19. Nadler J. L., Hsueh W., Horton R. Therapeutic effect of calcium channel blockade in primary aldosteronism. J Clin Endocrinol Metab. 1985 May;60(5):896–899. doi: 10.1210/jcem-60-5-896. [DOI] [PubMed] [Google Scholar]
  20. Schiffrin E. L., Lis M., Gutkowska J., Genest J. Role of Ca2+ in response of adrenal glomerulosa cells to angiotensin II, ACTH, K+, and ouabain. Am J Physiol. 1981 Jul;241(1):E42–E46. doi: 10.1152/ajpendo.1981.241.1.E42. [DOI] [PubMed] [Google Scholar]
  21. Soliman A. R., Akmal M., Massry S. G. Parathyroid hormone interferes with extrarenal disposition of potassium in chronic renal failure. Nephron. 1989;52(3):262–267. doi: 10.1159/000185654. [DOI] [PubMed] [Google Scholar]
  22. Sugarman A., Brown R. S. The role of aldosterone in potassium tolerance: studies in anephric humans. Kidney Int. 1988 Sep;34(3):397–403. doi: 10.1038/ki.1988.194. [DOI] [PubMed] [Google Scholar]
  23. Sugarman A., Kahn T. Calcium channel blockers enhance extrarenal potassium disposal in the rat. Am J Physiol. 1986 Apr;250(4 Pt 2):F695–F701. doi: 10.1152/ajprenal.1986.250.4.F695. [DOI] [PubMed] [Google Scholar]
  24. Sugarman A., Kahn T. Parathyroid hormone impairs extrarenal potassium tolerance in the rat. Am J Physiol. 1988 Mar;254(3 Pt 2):F385–F390. doi: 10.1152/ajprenal.1988.254.3.F385. [DOI] [PubMed] [Google Scholar]
  25. West M. L., Bendz O., Chen C. B., Singer G. G., Richardson R. M., Sonnenberg H., Halperin M. L. Development of a test to evaluate the transtubular potassium concentration gradient in the cortical collecting duct in vivo. Miner Electrolyte Metab. 1986;12(4):226–233. [PubMed] [Google Scholar]
  26. West M. L., Marsden P. A., Richardson R. M., Zettle R. M., Halperin M. L. New clinical approach to evaluate disorders of potassium excretion. Miner Electrolyte Metab. 1986;12(4):234–238. [PubMed] [Google Scholar]
  27. White W. B., Yeh S. C., Krol G. J. Nitrendipine in human plasma and breast milk. Eur J Clin Pharmacol. 1989;36(5):531–534. doi: 10.1007/BF00558082. [DOI] [PubMed] [Google Scholar]
  28. Zettle R. M., West M. L., Josse R. G., Richardson R. M., Marsden P. A., Halperin M. L. Renal potassium handling during states of low aldosterone bio-activity: a method to differentiate renal and non-renal causes. Am J Nephrol. 1987;7(5):360–366. doi: 10.1159/000167502. [DOI] [PubMed] [Google Scholar]

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