Drugs

, Volume 57, Supplement 1, pp 1–10 | Cite as

Role of a Third Generation Calcium Antagonist in the Management of Hypertension

  • Murray Epstein
Review Article

Abstract

Calcium antagonists are uniquely suitable for managing hypertension by virtue of their efficacy, metabolic neutrality and their ability to countervail counter-regulatory adaptive changes, thereby enhancing blood pressure lowering. Recent evidence has accrued underscoring the concept that calcium antagonists are heterogeneous and consist of chemically dissimilar agents. The difference in formulations and pharmacokinetics affect clinical events including the effect on blood pressure, heart rate and the degree with which sympathetic activity is activated. Lacidipine is a new calcium antagonist that is the prototype of the lipophilic dihydropyridines. Of great importance, lacidipine has a slow onset of vasodilator/ antihypertensive effect and does not promote an excessive sympathetic drive. These attributes commend its selection as an antihypertensive agent.

Keywords

Adis International Limited Nifedipine Calcium Antagonist Amlodipine Felodipine 

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References

  1. 1.
    Manolio TA, Cutler JA, Furberg CD, et al. Trends in pharmacologic management of hypertension in the United States. Arch Intern Med 1995; 155: 829–37PubMedCrossRefGoogle Scholar
  2. 2.
    Epstein M. Calcium antagonists in the management of hypertension. In: Epstein M, editor. Calcium antagonists in clinical medicine. 2nd ed. Philadelphia: Hanley and Belfus, 1998: 155–76Google Scholar
  3. 3.
    Frishman WH. Current status of calcium channel blockers. Curr Prob Cardiol 1994; 19: 637–88CrossRefGoogle Scholar
  4. 4.
    Epstein M. Calcium antagonists and renal protection: current status and future perspectives. Arch Intern Med 1992; 152: 1573–84PubMedCrossRefGoogle Scholar
  5. 5.
    Messerli FH, Michalewitz L. Cardiac effects of calcium antagonists in hypertension. In: Epstein M, editor. Calcium antagonists in clinical medicine. 2nd ed. Philadelphia: Hanley & Belfus, 1998:81–98Google Scholar
  6. 6.
    Pahor M, Guralnik JM, Salive ME, et al. Do calcium channel blockers increase the risk of cancer? Am J Hypertens 1996; 9: 695–9PubMedCrossRefGoogle Scholar
  7. 7.
    Pahor M, Guralnik JM, Ferrucci L, et al. Calcium channel blockade and incidence of cancer in aged populations. Lancet 1996; 348: 493–7PubMedCrossRefGoogle Scholar
  8. 8.
    Held PH, Yusuf S, Furberg CD. Calcium channel blockers in acute myocardial infarction and unstable angina: an overview of the result from the randomized trials. BMJ 1989; 299: 1187–92PubMedCrossRefGoogle Scholar
  9. 9.
    Furberg CD, Psaty BM. Calcium antagonists: not appropriate as first line antihypertensive agents. Am J Hypertens 1996; 9: 122–5PubMedCrossRefGoogle Scholar
  10. 10.
    Psaty BM, Heckbert SR, Koepsell TD, et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA 1995; 274: 620–5PubMedCrossRefGoogle Scholar
  11. 11.
    Angell M. Science on trial. New York: WW Norton and Company, 1996Google Scholar
  12. 12.
    Epstein M. Safety of calcium antagonists as antihypertensive agents: an update. In: pstein M, editor. Calcium antagonists in clinical medicine. 2nd ed. Philadelphia: Hanley & Belfus, 1998: 553–71Google Scholar
  13. 13.
    Buring JE, Glynn RJ, Hennekens CH. Calcium channel blockers and myocardial infarction: a hypothesis formulated but not yet tested. JAMA 1995; 274: 654–5PubMedCrossRefGoogle Scholar
  14. 14.
    Opie LH, Messerli FH. Nifedipine and mortality. Grave defects in the dossier. Circulation 1995; 92: 1068–73PubMedCrossRefGoogle Scholar
  15. 15.
    Epstein M. Calcium antagonists should continue to be used for first-line treatment of hypertension? Arch Intern Med 1995; 155: 2150–6PubMedCrossRefGoogle Scholar
  16. 16.
    Epstein M. Calcium antagonists: still appropriate as first-line antihypertensive agents. Am J Hypertens 1996; 9: 110–21PubMedCrossRefGoogle Scholar
  17. 17.
    Epstein M. Calcium antagonists and the kidney: implications for renal protection. In: Epstein M, editor. Calcium antagonists in clinical medicine. 2nd ed. Philadelphia: Hanley & Belfus, 1998: 433–65Google Scholar
  18. 18.
    Hayashi K, Saruta T, Epstein, M. The renal hemodynamic effects of calcium antagonists. In: Epstein M, editor. Calcium antagonists in clinical medicine. 2nd ed. Philadelphia: Hanley & Belfus, 1998: 393–411Google Scholar
  19. 19.
    Rappelli A, Baldinelli A, Zingaretti O, et al. The effects of antihypertensive therapy on renal function. J Hypertens 1991; 9 Suppl. 3: S37–S40Google Scholar
  20. 20.
    Epstein M, Loutzenhiser R. Potential applicability of calcium antagonists as renal protective agents. In: Epstein M, Loutzenhiser R, editors. Calcium antagonists and the kidney. Philadelphia: Hanley & Belfus, 1990: 275–98Google Scholar
  21. 21.
    Elliot HL, Meredith PA, Reid JL. Pharmacokinetics of calcium antagonists: implications for therapy. In: Epstein M, editor. Calcium antagonists in clinical medicine. 2nd ed. Philadelphia: Hanley & Belfus, 1998: 35–56Google Scholar
  22. 22.
    Triggle DJ. Mechanisms of action of calcium channel antagonists. In: Epstein M, editor. Calcium antagonists in clinical medicine. 2nd ed. Philadelphia: Hanley & Belfus, 1998: 1–26Google Scholar
  23. 23.
    Ruzicka M, Leenen FHH. Relevance of intermittent increases in sympathetic activity for adverse outcome on short-acting calcium antagonists. In: Laragh JH, Brenner BM, editors. Hypertension: pathophysiology, diagnosis, and management. 2nd ed. New York: Raven Press, 1995: 2815–25Google Scholar
  24. 24.
    Kleinbloesem CH, van Brummelen P, Danlöf M, et al. Rate of increase in the plasma concentration of nifedipine as a major determinant of its hemodynamic effects in humans. Clin Pharmacol Ther 1987; 41: 26–30PubMedCrossRefGoogle Scholar
  25. 25.
    Myers MG, Raemsch KD. Comparative pharmacokinetics and antihypertensive effects of the nifedipine tablet and capsule. J Cardiovasc Pharmacol 1987; 10 Suppl. 10: S76–S78PubMedGoogle Scholar
  26. 26.
    Leenen FHH. Dihydropyridine calcium antagonists and sympathetic activity: relevance to cardiovascular morbidity and mortality. In: Epstein M, editors. Calcium antagonists in clinical medicine. 2nd ed. Philadelphia: Hanley & Belfus, 1998: 527–52Google Scholar
  27. 27.
    Epstein M. The calcium antagonist controversy: the emerging importance of drug formulation as a determinant of risk. Am J Cardiol 1997; 79(10A): 9–19PubMedCrossRefGoogle Scholar
  28. 28.
    Swanson DR, Barclay BL, Wong PSL, et al. Nifedipine gastrointestinal therapeutic system. Am J Med 1987; 83 Suppl. 6B: 3–9PubMedCrossRefGoogle Scholar
  29. 29.
    Chung M, Reitberg DP, Gafney M, et al. Clinical pharmacokinetics of nifedipine gastrointestinal therapeutic system. A controlled release formulation of nifedipine. Am J Med 1987; 83 Suppl. 6B: 10–14PubMedCrossRefGoogle Scholar
  30. 30.
    Stokes GS, Shenfield GM, Johnston HJ, et al. Timing of blood pressure measurements in determining anomalies in duration of effect of an antihypertensive drug: assessment of isradipine. J Cardiovasc Pharmacol 1990; 15 Suppl. 1: S65–S69PubMedGoogle Scholar
  31. 31.
    Frohlich ED, McLoughlin MJ, Losem CJ, et al. Hemodynamic comparison of two nifedipine formulations in patients with essential hypertension. Am J Cardiol 1991; 68: 1346–1350PubMedCrossRefGoogle Scholar
  32. 32.
    van Zwieten PA, Hansson L, Epstein M. Slowly acting calcium antagonists and their merits. Blood Press 1997; 6: 78–80PubMedCrossRefGoogle Scholar
  33. 33.
    Leenen FHH. Clinical relevance of 24 hour blood pressure control by 1,4-dihydropyridines. Am J Hypertens 1996; 9: 97S–104PubMedGoogle Scholar
  34. 34.
    Middlemost SJ, Sack M, Davis J, et al. Effects of long-acting nifedipine on casual office blood pressure measurements, 24-hour ambulatory blood pressure profiles, exercise parameters and left ventricular mass and function in black patients with mild to moderate systemic hypertension. Am J Cardiol 1992; 70: 474–8PubMedCrossRefGoogle Scholar
  35. 35.
    Zanchetti A. Trough and peak effects of a single daily dose of nifedipine gastrointestinal therapeutic system (GITS) as assessed by ambulatory blood pressure monitoring. J Hypertens 1994; 12 Suppl. 5: S23–S27Google Scholar
  36. 36.
    Bailey DG, Arnold JMO, Bend JR, et al. Grapefruit juice-felodipine interaction: reproducibility and characterization with the extended release drug formulation. Br J Clin Pharmacol 1995; 40: 135–40PubMedGoogle Scholar
  37. 37.
    Myers MG, Leenen FHH, Tanner J. Differential effects of felodipine and nifedipine on 24-hour blood pressure and left ventricular mass. Am J Hypertens 1995; 8: 712–8PubMedCrossRefGoogle Scholar
  38. 38.
    Abernethy DR, Gutkowska J, Winterbottom LM. Effects of amlodipine, a long-acting dihydropyridine calcium antagonist in aging hypertension: pharmacokinetics in relation to disposition. Clin Pharmacol Ther 1990; 48: 76–86PubMedCrossRefGoogle Scholar
  39. 39.
    Donnelly R, Meredith PA, Miller SHK, et al. Pharmacokinetic modeling of the antihypertensive response to amlodipine. Clin Pharmacol Ther 1993; 54: 303–10PubMedCrossRefGoogle Scholar
  40. 40.
    Leenen FHH, Fourney A, Notman G, et al. Persistence of antihypertensive effect after ‘missed doses’ of calcium antagonist with long (amlodipine) vs. short (diltiazem) elimination half-life. Br J Clin Pharmacol 1996; 41: 83–8PubMedCrossRefGoogle Scholar
  41. 41.
    Herbette LG, Mason PE, Gaviraghi G, et al. The molecular basis for lacidipine’s unique pharmacokinetics: optimal hydrophobicity results in membrane interactions that may facilitate the treatment of atherosclerosis. J Cardiovasc Pharmacol 1994; 23 Suppl. 5: S16–S25PubMedCrossRefGoogle Scholar
  42. 42.
    Mallion JM, Dutrey-Dupagne C, Vaur L, et al. Benefits of electronic pillboxes in evaluating treatment compliance of patients with mild to moderate hypertension. J Hypertens 1996; 14: 137–44PubMedGoogle Scholar
  43. 43.
    Leenen FHH, Wilson TW, Bolli P, et al. Patterns of compliance with once vs. twice daily antihypertenisve drug therapy in primary care. Can J Cardiol 1997; 13: 914–20PubMedGoogle Scholar
  44. 44.
    Zanchetti A. Lacidipine: Aclinical monograph. Caester: ADIS, 1994: 1–60Google Scholar
  45. 45.
    Hall ST, Harding SM, Evans GL, et al. Clinical pharmacology of lacidipine. J Cardiovasc Pharmacol 1991; 17 Suppl. 4: S9–S13PubMedGoogle Scholar
  46. 46.
    Raftery EB. Lacidipine and circadian variation in blood pressure: considerations for therapy. J Cardiovasc Pharmacol 1991; 17 Suppl. 4: S20–S26PubMedGoogle Scholar
  47. 47.
    Meredith PA. Effectiveness and tolerability of lacidipine in the treatment of mild-to-moderate hypertension in general practice. J Cardiovasc Pharmacol 1997; 30 Suppl. 2: S10–S14Google Scholar
  48. 48.
    Zanchetti A, Bond MG, Hennig M, et al. Risk factors associated with alterations in carotid intima-media thickness in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis. J Hypertens 1998; 16(7): 949–61PubMedCrossRefGoogle Scholar
  49. 49.
    DeVries RJM, Dunselman PHJM, ChinKon Sung UG, et al. Effects of lacidipine on peak oxygen consumption, neurohormones and invasive haemodynamics in patients with mild to moderate chronic heart failure. Heart 1996; 75: 159–64CrossRefGoogle Scholar
  50. 50.
    Lucini D, Strappazzon P, Colombo F, et al. Maintained autonomic responses to moderate exercise in hypertensive patients treated with lacidipine. J Hypertens 1997; 15: 1751–4PubMedCrossRefGoogle Scholar
  51. 51.
    Lindholm LH, Tcherdakoff P, Zanchetti A. Safety profile of lacidipine: update from a clinical trials database. Drugs 1999; 57 Suppl. 1:27–29PubMedCrossRefGoogle Scholar
  52. 52.
    Packer M, O’Connor CM, Ghali JK, et al., for the Prospective Randomized Amlodipine Survival Evaluation Study Group (PRAISE). Effect of amlodipine on morbidity and mortality in severe chronic heart failure. N Engl J Med 1996; 335: 1107–114PubMedCrossRefGoogle Scholar
  53. 53.
    Gong L, Zhang W, Zhu Y, et al. Shanghai trial of nifedipine in the elderly (STONE). J Hypertens 1996; 14: 1237–1245PubMedCrossRefGoogle Scholar
  54. 54.
    Cohn JN, Ziesche SM, Loss LE, et al. Effect of felodipine on short term exercise and neurohormone and long term mortality in heart failure: results of VHeFT VIII. Circulation 1995; 92: I–143Google Scholar
  55. 55.
    Poole-Wilson PA, and the DEFIANT-II Research Group. Doppler flow and echocardiography in functional cardiac insufficiency: assessment of nisoldipine therapy. Eur Heart J 1997; 18: 31–40Google Scholar
  56. 56.
    Staessen JA, Fagard R, Thijs L, et al. A randomized double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet 1997; 350: 757–64PubMedCrossRefGoogle Scholar
  57. 57.
    Kloner RA, Vetrovec GW, Materson BJ, et al. Safety of long-acting dihydropyridine calcium channel blockers in hypertensive patients. Am J Cardiol 1998; 81: 163–9PubMedCrossRefGoogle Scholar
  58. 58.
    Abascal VM, Larson MG, Evans JC, et al. Calcium antagonists and mortality risk in men and women with hypertension in the Framingham Heart Study. Arch Intern Med 1998; 158: 1882–6PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1999

Authors and Affiliations

  • Murray Epstein
    • 1
  1. 1.Department of MedicineUniversity of Miami School of MedicineMiamiUSA

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