Clinical Significance of Genetic Influences on Cardiovascular Drug Metabolism

Overview

Journal Cardiovasc Drugs Ther

Specialties Cardiology & Vascular Diseases
Pharmacology

Date 1993 Jun 1

PMID 8103355

Citations 2

Authors

L Arcavi

N L Benowitz

Affiliations

Soon will be listed here.

Abstract

Inherited differences in metabolism may be responsible for individual variability in the efficacy of drugs and the occurrence of adverse drug reactions. Among the cardiovascular drugs reported to exhibit genetic polymorphism are debrisoquine, sparteine, some beta-adrenoceptor antagonists, flecainide, encainide, propafenone, nifedipine, procainamide, and hydralazine. The implications of genetic differences in the metabolism of these drugs for cardiovascular therapeutics is the subject of this review.

Citing Articles

Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry.

Zanger U, Raimundo S, Eichelbaum M Naunyn Schmiedebergs Arch Pharmacol. 2003; 369(1):23-37.

PMID: 14618296 DOI: 10.1007/s00210-003-0832-2.

Selecting the right drug for initial antihypertensive therapy.

Weder A Curr Hypertens Rep. 2000; 2(1):13-5.

PMID: 10981122 DOI: 10.1007/s11906-000-0052-9.

References

Wagner F, Kalusche D, Trenk D, Jahnchen E, ROSKAMM H . Drug interaction between propafenone and metoprolol. Br J Clin Pharmacol. 1987; 24(2):213-20. PMC: 1387752. DOI: 10.1111/j.1365-2125.1987.tb03164.x. View

Evans D, Mahgoub A, Sloan T, Idle J, Smith R . A family and population study of the genetic polymorphism of debrisoquine oxidation in a white British population. J Med Genet. 1980; 17(2):102-5. PMC: 1048511. DOI: 10.1136/jmg.17.2.102. View

Walle T, Byington R, Furberg C, McIntyre K, Vokonas P . Biologic determinants of propranolol disposition: results from 1308 patients in the Beta-Blocker Heart Attack Trial. Clin Pharmacol Ther. 1985; 38(5):509-18. DOI: 10.1038/clpt.1985.216. View

Cooper R, Evans D, Whibley E . Polymorphic hydroxylation of perhexiline maleate in man. J Med Genet. 1984; 21(1):27-33. PMC: 1049202. DOI: 10.1136/jmg.21.1.27. View

Zhou H, Koshakji R, Silberstein D, Wilkinson G, Wood A . Racial differences in drug response. Altered sensitivity to and clearance of propranolol in men of Chinese descent as compared with American whites. N Engl J Med. 1989; 320(9):565-70. DOI: 10.1056/NEJM198903023200905. View

Strandberg I, Boman G, Hassler L, Sjoqvist F . Acetylator phenotype in patients with hydralazine-induced lupoid syndrome. Acta Med Scand. 1976; 200(5):367-71. DOI: 10.1111/j.0954-6820.1976.tb08248.x. View

Alvan G, von Bahr C, Seidemann P, Sjoqvist F . High plasma concentrations of beta-receptor blocking drugs and deficient debrisoquine hydroxylation. Lancet. 1982; 1(8267):333. DOI: 10.1016/s0140-6736(82)91583-5. View

Mikus G, Gross A, Beckmann J, Hertrampf R, Gundert-Remy U, Eichelbaum M . The influence of the sparteine/debrisoquin phenotype on the disposition of flecainide. Clin Pharmacol Ther. 1989; 45(5):562-7. DOI: 10.1038/clpt.1989.73. View

Roden D, Reele S, Higgins S, Mayol R, Gammans R, OATES J . Total suppression of ventricular arrhythmias by encainide. Pharmacokinetic and electrocardiographic characteristics. N Engl J Med. 1980; 302(16):877-82. DOI: 10.1056/NEJM198004173021601. View

10.

Carey Jr E, Duff H, Roden D, Primm R, Wilkinson G, Wang T . Encainide and its metabolites. Comparative effects in man on ventricular arrhythmia and electrocardiographic intervals. J Clin Invest. 1984; 73(2):539-47. PMC: 425046. DOI: 10.1172/JCI111241. View

11.

Schmid B, BIRCHER J, Preisig R, Kupfer A . Polymorphic dextromethorphan metabolism: co-segregation of oxidative O-demethylation with debrisoquin hydroxylation. Clin Pharmacol Ther. 1985; 38(6):618-24. DOI: 10.1038/clpt.1985.235. View

12.

Silber B, Holford N, RIEGELMAN S . Dose-dependent elimination of propranolol and its major metabolites in humans. J Pharm Sci. 1983; 72(7):725-32. DOI: 10.1002/jps.2600720703. View

13.

Alarcon-Segovia D . Drug-induced lupus syndromes. Mayo Clin Proc. 1969; 44(9):664-81. View

14.

Hou Z, Pickle L, Meyer P, Woosley R . Salivary analysis for determination of dextromethorphan metabolic phenotype. Clin Pharmacol Ther. 1991; 49(4):410-9. DOI: 10.1038/clpt.1991.48. View

15.

Silas J, Lennard M, Tucker G, Ramsay L, Woods H . Polymorphic metabolism of beta-adrenoceptor antagonists. Br J Clin Pharmacol. 1984; 17 Suppl 1:11S-19S. PMC: 1463263. DOI: 10.1111/j.1365-2125.1984.tb02423.x. View

16.

Siddoway L, Thompson K, McALLISTER C, Wang T, Wilkinson G, Roden D . Polymorphism of propafenone metabolism and disposition in man: clinical and pharmacokinetic consequences. Circulation. 1987; 75(4):785-91. DOI: 10.1161/01.cir.75.4.785. View

17.

Speirs C, Murray S, Boobis A, Seddon C, Davies D . Quinidine and the identification of drugs whose elimination is impaired in subjects classified as poor metabolizers of debrisoquine. Br J Clin Pharmacol. 1986; 22(6):739-43. PMC: 1401220. DOI: 10.1111/j.1365-2125.1986.tb02969.x. View

18.

Schneck D, PRITCHARD J, Gibson T, Vary J, HAYES Jr A . Effect of dose and uremia on plasma and urine profiles of propranolol metabolites. Clin Pharmacol Ther. 1980; 27(6):744-55. DOI: 10.1038/clpt.1980.105. View

19.

Otton S, Inaba T, KALOW W . Competitive inhibition of sparteine oxidation in human liver by beta-adrenoceptor antagonists and other cardiovascular drugs. Life Sci. 1984; 34(1):73-80. DOI: 10.1016/0024-3205(84)90332-1. View

20.

Wagner F, Jahnchen E, Trenk D, Eichelbaum M, HARNASCH P, Hauf G . Severe complications of antianginal drug therapy in a patient identified as a poor metabolizer of metoprolol, propafenone, diltiazem, and sparteine. Klin Wochenschr. 1987; 65(24):1164-8. DOI: 10.1007/BF01733250. View