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Clinical Pharmacokinetics

, Volume 41, Issue 7, pp 505–516 | Cite as

β-Adrenergic Blockers in Systemic Hypertension

Pharmacokinetic Considerations Related to the Current Guidelines
  • William H. Frishman
  • Mamata Alwarshetty
Review Article Special Populations

Abstract

β-Adrenergic blockade has provided one of the major pharmacotherapeutic advances of the 20th century. β-Blockers are first-line drugs for the management of systemic hypertension, used alone and in combination with other antihypertensive agents. Drugs in the β-blocking class have the common property of blocking the binding of catecholamines to β-adrenergic receptor sites; however, there are significant pharmacodynamic and pharmacokinetic differences between the individual agents that are of clinical importance. Among these differences are the completeness of gastrointestinal absorption, the degree of hepatic first-pass metabolism, lipid solubility, protein binding, brain penetration, concentration within the cardiac tissue, rate of hepatic biotransformation, and renal clearance of drug and/or metabolites. Long-acting formulations of existing β-blockers are currently in use, and ultra-short-acting agents are also available.

Age, race, cigarette smoking and concomitant drug therapy can also influence the pharmacokinetics of β-blocking drugs. The wide interpatient variability in plasma drug concentrations observed with β-blockers makes this parameter unreliable in routine patient management. Despite the pharmacokinetic differences among β-blockers, these drugs should always be titrated to achieve the desired individual patient response.

Keywords

Propranolol Metoprolol Carvedilol Sotalol Plasma Drug Concentration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this manuscript. There are no potential conflicts of interest directly relevant to the contents of this manuscript.

References

  1. 1.
    The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Arch Intern Med 1997; 157: 2413–46CrossRefGoogle Scholar
  2. 2.
    Chalmers J, MacMahon S, Mancia G, et al. 1999 World Health Organization/International Society of Hypertension Guidelines for the Management of Hypertension: Guidelines Subcommittee. Clin Exp Hypertens 1999; 21: 1009–60PubMedCrossRefGoogle Scholar
  3. 3.
    Cruickshank JM, Prichard BNC. Beta blockers in clinical practice. Edinburgh: Churchill Livingstone, 1988: 177–273Google Scholar
  4. 4.
    Frishman WH. Alpha- and beta-adrenergic blocking drags. In: Frishman WH, Sonnenblick EH, editors. Cardiovascular pharmacotherapeutics. New York: McGraw Hill, 1997: 59–94Google Scholar
  5. 5.
    Conolly ME, Kersting F, Dollery CT. The clinical pharmacology of beta-adreno-receptor blocking drugs. Prog Cardiovasc Dis 1976; 19: 203–34PubMedCrossRefGoogle Scholar
  6. 6.
    Frishman W. Clinical pharmacology of the new beta blocking drags. Part 1. Pharmacodynamic and pharmacokinetic properties. Am Heart J 1979; 97: 663–70PubMedCrossRefGoogle Scholar
  7. 7.
    Frishman W. β-Adrenoceptor antagonists: new drugs and new indications. N Engl J Med 1981; 305: 505–6Google Scholar
  8. 8.
    Singh BN, Deedwania P, Nademanee K, et al. Sotalol: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic use. Drugs 1987; 34: 311–49PubMedCrossRefGoogle Scholar
  9. 9.
    Waeber B. Nebivolol: a beta blocker with vasodilatory properties. Schweiz Rundsch Med Prax 2000; 89: 631–3Google Scholar
  10. 10.
    Mangrella M, Rossi F, Fici F, et al. Pharmacology of nebivolol. Pharmacol Res 1998; 38: 419–31PubMedCrossRefGoogle Scholar
  11. 11.
    McNelly W, Goa KL. Nebivolol in the management of essential hypertension: a review. Drugs 1999; 57: 633–51CrossRefGoogle Scholar
  12. 12.
    Frishman WH, Sonnenblick EH. Beta-adrenergic blocking drags and calcium channel blockers. In: Alexander RW, Schlant RC, Fuster V, editors. Hurst’s the heart. 9th ed. New York: McGraw Hill, 1998: 1583–618Google Scholar
  13. 13.
    Opie LH, Sonnenblick EH, Frishman WH, et al. Beta blocking agents. In: Opie LH, Chatterjee K, Frishman W, et al., editors. Drags for the heart. 4th ed. Philadelphia: W.B. Saunders Co., 1995: 1–30Google Scholar
  14. 14.
    Frishman WH. Clinical pharmacology of the β-adrenoceptor blocking drugs. 2nd ed. Norwalk: Appleton-Century-Crofts, 1984: 21–2Google Scholar
  15. 15.
    Frishman WH. Alpha- and beta-adrenergic blocking drugs. In: Frishman WH, Sonnenblick EH, editors. Cardiovascular pharmacotherapeutics companion handbook. New York: McGraw Hill, 1998: 23–64Google Scholar
  16. 16.
    Frishman WH. Atenolol and timolol: two new systemic beta adrenoceptor antagonists. N Engl J Med 1982; 306: 1456–62PubMedCrossRefGoogle Scholar
  17. 17.
    Frishman WH, Teicher M. New therapy update: long-acting propranolol. Cardiovasc Rev Rep 1983; 4: 1100–2Google Scholar
  18. 18.
    Rekhi GS, Jambhekar SS. Bioavailability and in vitro/in vivo correlation for propranolol hydrochloride extended-release bead products prepared using aqueous polymeric dispersions. J Pharm Pharmacol 1996; 48: 1276–84PubMedCrossRefGoogle Scholar
  19. 19.
    Parker JO, Porter A, Parker JD. Propranolol in angina pectoris: comparison of long acting and standard formulation propranolol. Circulation 1982; 65: 1351–5PubMedCrossRefGoogle Scholar
  20. 20.
    Kitsis G, Niopas I. A study on the in vitro percutaneous absorption of propranolol from disperse systems. J Pharm Pharmacol 1998; 50: 413–8Google Scholar
  21. 21.
    Verma PR, Iyer SS. Controlled transdermal delivery of propranolol using HPMC matrices: design and in vitro and in vivo evaluation. J Pharm Pharmacol 2000; 52: 151–6PubMedCrossRefGoogle Scholar
  22. 22.
    Frishman WH, Murthy VS, Strom JA. Ultra-short acting betaadrenergic blockers. Med Clin North Am 1988; 72: 359–72PubMedGoogle Scholar
  23. 23.
    Atarashi H, Kurama A, Yashima M, et al. Pharmacokinetics of landiolol hydrochloride: a new ultra-short acting beta blocker in patients with cardiac arrhythmias. Clin Pharmacol Ther 2000; 68: 143–50PubMedCrossRefGoogle Scholar
  24. 24.
    Murthy VS, Frishman WH. Controlled beta-receptor blockade with esmolol and flestolol. Pharmacotherapy 1988; 8: 168–82PubMedGoogle Scholar
  25. 25.
    Kendall MJ, Maxwell SR, Sandberg A, et al. Controlled release metoprolol: clinical pharmacokinetic and therapeutic implications. Clin Pharmacokinet 1991; 21: 319–30PubMedCrossRefGoogle Scholar
  26. 26.
    Feliciano NR, Bouvet AA, Redalieu E, et al. Pharmacokinetic and pharmacodynamic comparison of an osmotic release oral metoprolol tablet and the metoprolol conventional tablet. Am Heart J 1990; 120: 483–9PubMedCrossRefGoogle Scholar
  27. 27.
    Sandberg A, Blomqvist I, Jonsson UE, et al. Pharmacokinetic and pharmacodynamic properties of a new controlled release formulation of metoprolol: a comparison with conventional tablets. Eur J Clin Pharmacol 1988; 33: 9–14CrossRefGoogle Scholar
  28. 28.
    Katz B, Frishman WH. Controlled-release drag delivery systems in cardiovascular disease treatment. In: Frishman WH, Sonnenblick EH, editors. Cardiovascular pharmacotherapeutics. New York: McGraw Hill, 1997: 1363–73Google Scholar
  29. 29.
    Sandberg A, Ragnarsson G, Jonsson VE, et al. Design of a new multiple-unit controlled-release formulation of metoprololmetoprolol SR. Eur J Clin Pharmacol 1988; 33: S3–7PubMedCrossRefGoogle Scholar
  30. 30.
    Matier WL, Patil G. Esprolol hydrochloride: a new beta adrenergic antagonist with a rapid onset of effect. Heart Dis 2000; 2: 146–50PubMedGoogle Scholar
  31. 31.
    Morgan T. Clinical pharmacokinetics and pharmacodynamics of carvedilol. Clin Pharmacokinet 1994; 26: 335–46PubMedCrossRefGoogle Scholar
  32. 32.
    Ablad B, Ervik M, Hallgren J, et al. Pharmacological effects and serum levels of orally administered alprenolol in man. Eur J Clin Pharmacol 1972; 5: 44–52CrossRefGoogle Scholar
  33. 33.
    Shand DG, Ragno RE. The disposition of propranolol: elimination during oral absorption in man. Pharmacology 1972; 7: 159–68PubMedCrossRefGoogle Scholar
  34. 34.
    Gugler R, Herold W, Dengler HJ. Pharmacokinetics of pindolol in man. Eur J Clin Pharmacol 1974; 7: 17–24PubMedCrossRefGoogle Scholar
  35. 35.
    Frishman WH. Nadolol: a new beta-adrenoreceptor antagonist. N Engl J Med 1981; 305: 678–82PubMedCrossRefGoogle Scholar
  36. 36.
    Wood AJJ, Carr K, Vestal RE, et al. Direct measurement of propranolol bioavailability during accumulation to steady state. Br J Clin Pharmacol 1978; 6: 345–50PubMedCrossRefGoogle Scholar
  37. 37.
    Kendall MJ, John VA, Quaterman CP, et al. A single and multiple dose pharmacokinetic and pharmacodynamic comparison of conventional and slow release metoprolol. Eur J Clin Pharmacol 1980; 17: 87–92PubMedCrossRefGoogle Scholar
  38. 38.
    Johnson G, Regardh CG. Clinical pharmacokinetics of adrenoreceptor blocking drags. Clin Pharmacokinet 1976; 1: 233–63CrossRefGoogle Scholar
  39. 39.
    Shand DG. Pharmacokinetic properties of the beta-adrenergic receptor blocking drugs. Drugs 1974; 7: 39–47PubMedCrossRefGoogle Scholar
  40. 40.
    Cheymol G, Woestenborghs R, Snoeck E, et al. Pharmacokinetic study and cardiovascular monitoring of nebivolol in normal and obese subjects. Eur J Clin Pharmacol 1997; 51: 493–8PubMedCrossRefGoogle Scholar
  41. 41.
    Cheymol G, Poirier JM, Carrapt PA, et al. Pharmacokinetics of beta-adrenoceptor blockers in obese and normal volunteers. Br J Clin Pharmacol 1997; 43: 563–70PubMedCrossRefGoogle Scholar
  42. 42.
    Frishman WH, Cheng A. Use of cardiovascular drags in special populations. In: Frishman WH, Sonnenblick EH, editors. Cardiovascular Pharmacotherapeutics companion handbook. New York: McGraw Hill, 1997: 651–86Google Scholar
  43. 43.
    Neugebauer G, Akpan W, von Mollendorff E, et al. Pharmacokinetics and disposition of carvedilol in humans. J Cardiovasc Pharmacol 1987; 10 Suppl. 11: S85–8PubMedGoogle Scholar
  44. 44.
    Meadowcroft AM, Williamson KM, Patterson JH, et al. Pharmacogenetics and heart failure: a convergence with carvedilol. Pharmacotherapy 1997; 17: 637–9PubMedGoogle Scholar
  45. 45.
    Frishman WH. Carvedilol. N Engl J Med 1998; 339: 1759–65PubMedCrossRefGoogle Scholar
  46. 46.
    von Bahr C, Collste P, Frisk-Holmsberg M, et al. Plasma levels of metoprolol on blood pressure, adrenergic beta-receptor blockade, and plasma renin activity in essential hypertension. Clin Pharmacol Ther 1976; 20: 130–7Google Scholar
  47. 47.
    Tjandramaga TB, Verbeeck R, Thomas J, et al. The effect of end-stage renal failure and haemodialysis on the elimination kinetics of sotalol. Br J Clin Pharmacol 1976; 3: 259–65PubMedCrossRefGoogle Scholar
  48. 48.
    Ohnhaus EE, Nuesch E, Meier J, et al. Pharmacokinetics of unlabelled and 14C-labelled pindolol in uraemia. Eur J Clin Pharmacol 1974; 7: 25–9PubMedCrossRefGoogle Scholar
  49. 49.
    Frishman W, Smithen C, Befler B, et al. Noninvasive assessment of clinical response to oral propranolol therapy. Am J Cardiol 1975; 35: 635–44PubMedCrossRefGoogle Scholar
  50. 50.
    Galletti F, Fasano ML, Ferrara LA, et al. Obesity and beta blockers: influence of body fat on their kinetics and cardiovascular effects. J Clin Pharmacol 1989 29: 212–6PubMedGoogle Scholar
  51. 51.
    Zhou HH, Koshakji RP, Silberstein DJ, et al. Altered sensitivity to and clearance of propranolol in men of Chinese descent as compared with American whites. N Engl J Med 1989; 320: 565–70PubMedCrossRefGoogle Scholar
  52. 52.
    Johnson JA, Burlew BS. Racial differences in propranolol pharmacokinetics. Clin Pharmacol Ther 1992; 51: 495–500PubMedCrossRefGoogle Scholar
  53. 53.
    Sowinski KM, Lima JJ, Burlew BS, et al. Racial differences in propranolol enantiomer kinetics following simultaneous IV and oral administration. Br J Clin Pharmacol 1996; 42: 339–46PubMedCrossRefGoogle Scholar
  54. 54.
    Charney B, Meyer BR, Frishman WH, et al. Gender, race, and genetic issues in cardiovascular pharmacotherapeutics. In: Frishman WH, Sonnenblick EH, editors. Cardiovascular pharmacotherapeutics. New York: McGraw Hill, 1997: 1347–61Google Scholar
  55. 55.
    The Beta Blocker Evaluation of Survival Trial Investigators. A trial of the beta blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med 2001; 344: 1659–67CrossRefGoogle Scholar
  56. 56.
    Nadelmann J, Frishman WH. Clinical use of beta-adrenoceptor blockade in systemic hypertension. Drugs 1990; 39: 862–76PubMedCrossRefGoogle Scholar
  57. 57.
    Vestal RE, Wood AJ, Shand DG. Reduced beta-adrenoceptor sensitivity in the elderly. Clin Pharmacol Ther 1979; 26: 181–6PubMedGoogle Scholar
  58. 58.
    O’Malley K, Crooks J, Duke E, et al. Effect of age and sex on human drug metabolism. BMJ 1971; 3: 607–9PubMedCrossRefGoogle Scholar
  59. 59.
    Aronow WS, Frishman WH, Cheng-Lai A. Cardiovascular drug therapy in the elderly. Heart Dis 2000; 2: 151–67PubMedGoogle Scholar
  60. 60.
    Frishman WH, Cheng-Lai A, Chen J. Current cardiovascular drugs. 3rd ed. Philadelphia: Current Medicine, 2000: 324–5Google Scholar
  61. 61.
    Vestal RE, Wood AJ, Branch RA, et al. Effects of age and cigarette smoking on propranolol disposition. Clin Pharmacol Ther 1979; 26: 8–15PubMedGoogle Scholar
  62. 62.
    Opie LH, Frishman WH. Adverse cardiovascular drug interactions and complications. In: Fuster V, Alexander RW, O’Rourke RA, editors. Hurst’s the heart. 10th ed. New York: McGraw Hill, 2001: 2253Google Scholar
  63. 63.
    Kirch W, Spahn H, Kohler H, et al. Influence of β-receptor antagonists on pharmacokinetics of cimetidine. Drugs 1983; 25 Suppl. 2: 127–30CrossRefGoogle Scholar
  64. 64.
    McLean AJ, Knight R, Harrison PM, et al. Clearance-based oral drug interaction between verapamil and metoprolol and comparison with atenolol. Am J Cardiol 1985; 55: 1628–9PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  • William H. Frishman
    • 1
  • Mamata Alwarshetty
    • 2
  1. 1.Department of MedicineNew York Medical College/Westchester Medical CenterValhallaUSA
  2. 2.Department of MedicineWeill Cornell Medical School/St. Barnabas Hospital CenterNew YorkUSA

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