Skip to main content
SpringerLink
Log in

Genetic variation and cardiac pharmacotherapy

  • Chapter
Genetic factors in coronary heart disease

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 156))

  • 170 Accesses

Abstract

Inherited differences in metabolism may be responsible for individual variability in the efficacy of drugs and in the occurrence of adverse drug reactions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Eichelbaum M, Spannbrucker N, Steincke B, Dengler HJ. Defective N-oxidation of sparteine in man: a new pharmacogenetic defect. Eur J Clin Pharmacol. 1979;16:183–7.

    Article  PubMed  CAS  Google Scholar 

  2. Mahgoub A, Idle J, Dring L, Lancaster R, Smith RL. Polymorphic hydroxylation of debrisoquine in man. Lancet. 1977;2:584–6.

    Article  PubMed  CAS  Google Scholar 

  3. Eichelbaum M, Gross A. The genetic polymorphism of debrisoquine/sparteine metabolism-clinical aspects. Pharmacol Ther. 1990;46:377–94.

    Article  PubMed  CAS  Google Scholar 

  4. Nebert D, Gonzalez F. P450 genes. Their structure, evolution and regulation. Annu Rev Biochem. 1987;56:945–93.

    Article  PubMed  CAS  Google Scholar 

  5. Eichelbaum M, Bertilsson L, Sawe J, Zekorn C. Polymorphic oxidation of sparteine and debrisoquine: related pharmacogenetic entities. Clin Pharmacol Ther. 1982;31:184–6.

    Article  PubMed  CAS  Google Scholar 

  6. Schmid B, Birche J, Preisig R, Kupfer A. Polymorphic dextromethorphan metabolism: co-segregation of oxidative O-demethylation with debrisoquin hydroxylation. Clin Pharmacol Ther. 1985;38:618–24.

    Article  PubMed  CAS  Google Scholar 

  7. Heim M, Meyer U. Genotyping of poor metabolisers of debrisoquine by allele-specific PCR amplification. Lancet. 1990;336:520–32.

    Article  Google Scholar 

  8. Steiner E, Bertilssonl, Sawe J, Bertlin I, Sjoqvist F. Polymorphic debrisoquine hydroxylation in 757 Swedish subjects. Clin Pharmacol Ther. 1988;44:431–5.

    Article  PubMed  CAS  Google Scholar 

  9. Kupfer A, Preisig R. Pharmacogenetics of mephenytoin: a new drug hydroxilation polymorphism in man. Eur J Clin Pharmacol. 1984;26:753–9.

    Article  PubMed  CAS  Google Scholar 

  10. Kleinbloessem C, van Brummelen P, Faber H, Danhof M, Vermeulen NPE, Breimer D. Variability in nifedipine pharmacokinetics and dynamics: new oxidation polymorphism in man. Biochem Pharmacol. 1984;33:3721–4.

    Article  Google Scholar 

  11. Sloan T, Lancaster R, Shah R, Idle JR, Smith RL. Genetically determined oxidation capacity and the disposition of debrisoquine. Br J Clin Pharmacol. 1983;15:443–50.

    Article  PubMed  CAS  Google Scholar 

  12. Jacqz E, Hall D, Branch R. Genetically determined polymorphisms in drug oxidation. Hepatology. 1986;6:1020–32.

    Article  PubMed  CAS  Google Scholar 

  13. Leeman T, Dayer P, Meyer U. Single dose quinidine treatment inhibits metoprolol oxidation in extensive metabolizers. Eur J Clin Pharmacol. 1986;29:739–41.

    Article  Google Scholar 

  14. Du Souich P, Erill S. Patterns of acetylation of procainamide and procainamide-derived p-aminobenzoic acid in man. Eur J Clin Pharmacol. 1976;10:283–7.

    Article  Google Scholar 

  15. Nebert D, Weber W. Pharmacogenetics. In: Principles of drug action. 1990;399–530.

    Google Scholar 

  16. Lennard M, Tucker G, Silas J, Freestone S, Ramsay LE, Woods HF. Differential stereoselective metabolism of metoprolol in extensive and poor debrisoquine metabolizers. Clin Pharmacol Ther. 1983;34:732–7.

    Article  PubMed  CAS  Google Scholar 

  17. Alvan G, Von Bahr C, Seideman P, Sjoqvist F. High plasma concentrations of beta-receptor blocking drugs and deficient debrisoquine hydroxylation. Lancet. 1982;1:333.

    Article  PubMed  CAS  Google Scholar 

  18. Dayer P, Leemann T, Kupfer A, Kronbach T, Meyer UA. Stereo-and regioselectivity of hepatic oxidation in man — effect of the debrisoquine/sparteine phenotype on bufuralol hydroxylation. Eur J Clin Pharmacol. 1986;31:313–18.

    Article  PubMed  CAS  Google Scholar 

  19. Lewis R, Lennard M, Jackson P, Tucker G, Ramsay L, Woods H. Timolol and atenolol: relationships between oxidation phenotype, pharmacokinetics and pharmacodynamics. Br J Clin Pharmacol. 1985;19:329–33.

    Article  PubMed  CAS  Google Scholar 

  20. Lennard M, Silas J, Freestone S, Ramsay L, Tucker G, Woods, H. Oxidation phenotype-a major determinant of metoprolol metabolism and response. N Engl J Med. 1982;307:1558–60.

    Article  PubMed  CAS  Google Scholar 

  21. Walle T, Walle U, Olanoff L. Quantitative account of propranolol metabolism in urine of normal man. Drug Metab Dispos. 1985;13:204–5.

    PubMed  CAS  Google Scholar 

  22. Lennard M, Jackson P, Freestone S, Tucker G, Ramsay L, Woods H. The relationship between debrisoquine oxidation phenotype and the pharmacokinetics and pharmacodynamics of propranolol. Br J Clin Pharmacol. 1984;17:670–85.

    Google Scholar 

  23. Ward S, Walle T, Walle K, Wilkinson G, Branch R. Propranolol’s metabolism is determined by both mephenytoin and debrisoquin hydroxylase activities. Clin Pharmacol Ther. 1989;45:72–9.

    Article  PubMed  CAS  Google Scholar 

  24. Zhou Hong-Hao, Koshaji R, Silberstein D, Wilkinson G, Wood A. Racial differences in drug response. N Engl J Med. 1989;320:565–70.

    Article  Google Scholar 

  25. Formgren H. The effect of metoprolol and practolol on lung function and blood pressure in hypertensive asthmatics. Br J Clin Pharmacol. 1976;3:1007–14.

    Article  PubMed  CAS  Google Scholar 

  26. Greenblatt D, Koch-Weser J. Adverse reactions to beta-adrenergic receptor blocking drugs: a report from the Boston Collaborative Surveillance Program. Drugs. 1974;7:118–29.

    Article  PubMed  CAS  Google Scholar 

  27. Betts T, Alford C. Beta-blocking drugs and sleep. A controlled trial. Drugs. 1983;25(Suppl. 2):268–72.

    Article  Google Scholar 

  28. Woosley A, Roden D, Duff H, et al. Co-inheritance of deficient oxidative metabolism of encainamide and debrisoquine. Clin Res. 1981;29:501A.

    Google Scholar 

  29. Wang D, Roden H, Wolfenden R, Woosley R, Wood A, Wilkinson G. Influence of genetic polymorphism on the metabolism and disposition of encainamide in man. J Pharmacol Exp Ther. 1984;228:605–11.

    PubMed  CAS  Google Scholar 

  30. Woosley A, Roden D, Dai G, et al. Co-inheritance of the polymorphic metabolism of encainide and debrisoquine. Clin Pharmacol Ther. 1986;39:282–7.

    Article  PubMed  CAS  Google Scholar 

  31. Carey E, Duff H, Roden D, et al. Encainide and its metabolites; comparative effects in man in ventricular arrhythmia and electrocardiographic intervals. J Clin Invest. 1984;73:539–47.

    Article  PubMed  Google Scholar 

  32. Bergstrand R, Wang T, Roden D, et al. Encainide disposition in patients with renal failure. Clin Pharmacol Ther. 1986;40:64–70.

    Article  PubMed  CAS  Google Scholar 

  33. Salerno D, Granrud G, Sharkey P, et al. Pharmacodynamics and side effects of flecainide acetate. Clin Pharmacol Ther. 1986;40:101–7.

    Article  PubMed  CAS  Google Scholar 

  34. Conard G, Ober R. Metabolism of flecainide. Am J Cardiol. 1984;53:41B–51B.

    Article  PubMed  CAS  Google Scholar 

  35. Forland S, Burgess E, Blair A, et al. Oral flecainide pharmacokinetics in patients with impaired renal function. J Clin Pharmacol. 1988;28:259–67.

    Article  PubMed  CAS  Google Scholar 

  36. Bennet W. Guide to drug dosage in renal failure. In: Clin Pharmacokinetics Drug Data Handbook 1989. Auckland: Adis Press; 1989.

    Google Scholar 

  37. Siddoway L, Thompson K, McAllister B, et al. Polymorphism of propafenone metabolism and disposition in man: clinical and pharmacokinetic consequences. Circulation. 1987;75:785–91.

    Article  PubMed  CAS  Google Scholar 

  38. Thompson K, Ianasmith D, Siddoway L, Woosley R, Roden D. Potent electrophysiologic effects of the major metabolites of propafenone in canine purkinje fibers. J Pharmacol Exp Ther. 1988;244:950–5.

    PubMed  CAS  Google Scholar 

  39. Kroemer H, Mikus G, Kronbach T, Meyer U, Eichelbaum M. In vitro characterization of the human cytochrome P-450 involved in polymorphic oxidation of propafenone. Clin Pharmacol Ther. 1989;45:28–33.

    Article  PubMed  CAS  Google Scholar 

  40. McLeod A, Stiles G, Shand D. Demonstration of beta-adrenoceptor blockade by propafenone hydrochloride: clinical pharmacologic, radioligand binding and adenylatecyclase activation studies. J Pharmacol Exp Ther. 1984;228:461–6.

    PubMed  CAS  Google Scholar 

  41. Lee J, Kroemer H, Silberstein D, et al. The role of genetically determined polymorphic drug metabolism in the beta-blockade produced by propafenone. N Engl J Med. 1990;322:1764–8.

    Article  PubMed  CAS  Google Scholar 

  42. von Philipsborn G, Gries J, Hofmann H, et al. Pharmacological studies on propafenone and its main metabolite 5-hydroxypropafenone. Arzneimittelforsch. 1984;34:1489.

    Google Scholar 

  43. Wagner F, Kalusche D, Trenk D, Jahnchen E, Roskamm H. Drug interaction between propafenone and metoprolol. Br J Clin Pharmacol. 1987;24:213–20.

    Article  PubMed  CAS  Google Scholar 

  44. Otton S, Inaba T, Kalow W. Competitive inhibition of sparteine oxidation in human liver by beta-adrenoceptors antagonists and other cardiovascular drugs. Life Sci. 1984;34:7380.

    Article  Google Scholar 

  45. Otton S, Crewe H, Lennard M, Tucker G, Woods H. Use of quinidine inhibition to define the role of the sparteine/debrisoquine cytochrome P-450 in metoprolol oxidation by human liver microsomes. J Pharmacol Exp Ther. 1988;247:242–7.

    PubMed  CAS  Google Scholar 

  46. Funck-Brentano C, Turgeon J, Woosley R, Roden D. Effect of low dose quinidine on encainide pharmacokinetics and pharmacodynamics. Influence of genetic polymorphism. J Pharmacol Exp Ther. 1989;243:134–42.

    Google Scholar 

  47. Hori R, Okumura K, Inui K, et al. Quinidine-induced rise in ajmaline plasma concentration. J Pharm Pharmacol. 1984;36:202–4.

    Article  PubMed  CAS  Google Scholar 

  48. Drayer D, Reidenberg M. Clinical consequences of polymorphic acetylation of basic drugs. Clin Pharmacol Ther. 1977;22:251–8.

    PubMed  CAS  Google Scholar 

  49. Henningsen N, Cederberg A, Hanson A, Johansson B. Effects of long term treatment with procaine amide. Acta Med Scand. 1975;198:475–82.

    Article  PubMed  CAS  Google Scholar 

  50. Blomgren S, Condemi J, Bignall M, et al. Antinuclear antibody induced by procainamide. A prospective study. N Engl J Med. 1969;281:64–6.

    Article  PubMed  CAS  Google Scholar 

  51. Lertora J, Arthur J, Atkinson J, et al. Long-term antiarrhythmic therapy with N-acetylprocainamide. Clin Pharmacol Ther. 1979;25:273–82.

    PubMed  CAS  Google Scholar 

  52. Cooper R, Evans D, Whibley E. Polymorphic hydroxylation of perhexiline maleate in man. J Med Genet. 1984;21:27–33.

    Article  PubMed  CAS  Google Scholar 

  53. Shah R, Oates N, Idle J, Smith R, Lockhart J. Impaired oxidation of debrisoquine in patients with perhexiline neuropathy. Br Med J. 1982;284:295–9.

    Article  CAS  Google Scholar 

  54. Challenor V, Waller D, Renwick A, Gruchy B, George C. The transhepatic extraction of nifedipine. Br J Clin Pharmacol. 1987;24:473–7.

    Article  PubMed  CAS  Google Scholar 

  55. Schellens J, Soons P, Breimer D. Lack of bimodality in nifedipine plasma kinetics in a large population of healthy subjects. Biochem Pharmacol. 1988;37:2507–10.

    Article  PubMed  CAS  Google Scholar 

  56. Lobo J, Jack D, Kendall M. The intra-and inter-subject variability of nifedipine pharmacokinetics in young volunteers. Eur J Clin Pharmacol. 1986;30:57–60.

    Article  PubMed  CAS  Google Scholar 

  57. Hoyo-Vadillo C, Castañeda-Hernández G, Herrera J, et al. Pharmacokinetics of nifedipine slow release tablet in Mexican subjects: further evidence for an oxidation polymorphism. J Clin Pharmacol. 1989;29:816–20.

    Article  PubMed  CAS  Google Scholar 

  58. Clark D, Edwards R. Adverse drug reaction reporting and retrospective phenotyping for oxidation polymorphism. Med Toxicol. 1988;3:241–7.

    Article  CAS  Google Scholar 

  59. Alarcon-Segovia D. Drug-induced lupus syndromes. Mayo Clin Proc. 1969;44:664–81.

    PubMed  CAS  Google Scholar 

  60. Perry H, Tan E, Carmody S, Sakamoto A. Relationship of acetyl transferase activity to antinuclear antibodies and toxic symptoms in hypertensive patients treated with hydralazine. J Lab Clin Med. 1970;76:114–25.

    PubMed  Google Scholar 

  61. Mansilla-Tinoco R, Harland S, Ryan P, et al. Hydralazine, antinuclear antibodies, and the lupus syndrome. Br Med J. 1982;284:936.

    Article  CAS  Google Scholar 

  62. Batchelor J, Welsh K, Mansilla-Tinoco R, et al. Hydralazine-induced systemic lupus erythematosus: Influence of HLA-DR and sex on susceptibility. Lancet. 1980;1:1107–9.

    Article  PubMed  CAS  Google Scholar 

  63. Strandberg I, Boman G, Hassler L, et al. Acetylator phenotype in patients with hydralazine-induced lupoid syndrome. Acta Med Scand. 1976;200:367–72.

    Article  PubMed  CAS  Google Scholar 

  64. Zhou Hong-Hao, Anthony L, Roden D, Wood A. Quinidine reduces clearance of (+)-propranolol more than (-)-propranolol through marked reduction in 4-hydroxylation. Clin Pharmacol Ther. 1990;47:686–93.

    Article  PubMed  CAS  Google Scholar 

  65. Evans D, Mahgoub A, Sloan T, et al. A family and population study of the genetic polymorphism of debrisoquine oxidation in a white British population. J Met Genet. 1980;17:102–5.

    Article  CAS  Google Scholar 

  66. Dayer P, Kuble A, Kupfer A, et al. Defective hydroxylation of bufuralol associated with side effects of the drug in poor metabolisers. Br J Clin Pharmacol. 1982;13:750–2.

    Article  PubMed  CAS  Google Scholar 

  67. Raghuram T, Koshakji R, Wilkinson G, et al. Polymorphic ability to metabolize propranolol alters 4-hydroxypropranolol levels, but no beta blockade. Clin Pharmacol Ther. 1984;36:51–6.

    Article  PubMed  CAS  Google Scholar 

  68. Zekorn C, Achtert G, Hausleiter H. Pharmacokinetics of N-propylajmaline in relation to polymorphic sparteine oxidation. Klin Wochenschr. 1985;63:1180–6.

    Article  PubMed  CAS  Google Scholar 

  69. Beckman J, Hertrampf R, Gundert-Remy U, et al. Is there a genetic factor in flecainide toxicity? Br Med J. 1988;297:1316.

    Article  Google Scholar 

  70. Shah R, Oates N, Idle J, et al. Beta-blockers and drug oxidation status. Lancet. 1982;1:508–9.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Internal Medicine B, Kaplan Hospital, Rehovot, 76100, Israel

    Lidia Arcavi

Authors
  1. Lidia Arcavi
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Sackler Medical Faculty, Epidemiology and Biostatistics, the Neufeld Cardiac Research Institute, Sheba Medical Center and Tel Aviv University, Israel

    Uri Goldbourt (Professor of Epidemiology and Preventive Medicine, Head) (Professor of Epidemiology and Preventive Medicine, Head)

  2. Division of Epidemiology, Institute of Environmental Medicine, Karolinska Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, Karolinska Hospital, Stockholm, Sweden

    Ulf de Faire (Professor) (Professor)

  3. Institute of Medical Genetics, Department of Medical Genetics, Ullevål University Hospital, Oslo, Norway

    KÃ¥re Berg (Professor of Medicine, Chairman, Director and Physician-in-Chief) (Professor of Medicine, Chairman, Director and Physician-in-Chief)

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Arcavi, L. (1994). Genetic variation and cardiac pharmacotherapy. In: Goldbourt, U., de Faire, U., Berg, K. (eds) Genetic factors in coronary heart disease. Developments in Cardiovascular Medicine, vol 156. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-1130-0_29

Download citation

  • DOI: https://doi.org/10.1007/978-94-011-1130-0_29

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-4494-3

  • Online ISBN: 978-94-011-1130-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation