Molecular Diagnosis & Therapy

, Volume 15, Issue 3, pp 177–180 | Cite as

Development of Cocaine-Induced Interstitial Lung Damage in Two CYP2C and VKORC1 Variant Allele Carriers

  • Petal A.H.M. Wijnen
  • Otto Bekers
  • Marjolein Drent
Case Report

Abstract

Background: Often, the connection between drug use and the development of related inflammatory damage or idiosyncratic toxicities is hard to recognize and objectify. The presence of cytochrome P450 (CYP) variant genotypes appears to be a substantial susceptibility risk factor in the development of drug-induced pulmonary adverse events. We hypothesized that the presence of variant alleles may be associated with serious complications of illicit drug use.

Case Report: We report the cases of two cocaine users who developed a ‘flu-like’ syndrome with diffuse interstitial infiltrates after cocaine abuse. Genotyping for CYP (CYP2C9, CYP2C19) and vitamin K epoxide reductase complex 1 (VKORC1) allelic variants (−1639G/A and 1173C/T) was performed in these two patients. Both cases were heterozygous for VKORC1 variant alleles, and both possessed a CYP2C polymorphism (case 1: CYP2C19*1/*2; case 2: CYP2C9*1/*3).

Conclusions: The described drug abuse cases suggest that an association between the presence of CYP2C and VKORC1 allelic variants and cocaine-induced interstitial lung damage is highly likely. It is assumed that these polymorphisms contribute to intra-individual variability in drug response and toxicity, including cocaine response and toxicity. Moreover, the importance of including pharmacogenomics in the work-up of patients with suspected drug-induced (lung) toxicity, such as alveolar hemorrhage, is highlighted by these cases.

Notes

Acknowledgments

The authors have no conflicts of interest to report. The study was performed without funding.

References

  1. 1.
    Restrepo CS, Carrillo JA, Martinez S, et al. Pulmonary complications from cocaine and cocaine-based substances: imaging manifestations. Radiographics 2007 Jul–Aug; 27(4): 941–56PubMedCrossRefGoogle Scholar
  2. 2.
    Tashkin DP. Airway effects of marijuana, cocaine, and other inhaled illicit agents. Curr Opin Pulm Med 2001 Mar; 7(2): 43–61PubMedCrossRefGoogle Scholar
  3. 3.
    Gotway MB, Marder SR, Hanks DK, et al. Thoracic complications of illicit drug use: an organ system approach. Radiographics 2002 Oct; 22 Spec. No.: S119-35Google Scholar
  4. 4.
    Wijnen PA, Drent M, Nelemans PJ, et al. Role of cytochrome P450 polymorphisms in the development of pulmonary drug toxicity: a case-control study in the Netherlands. Drug Saf 2008; 31(12): 1125–34PubMedGoogle Scholar
  5. 5.
    Ding X, Kaminsky LS. Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts. Annu Rev Pharmacol Toxicol 2003; 43: 149–73PubMedCrossRefGoogle Scholar
  6. 6.
    Nishimura M, Yaguti H, Yoshitsugu H, et al. Tissue distribution of mRNA expression of human cytochrome P450 isoforms assessed by high-sensitivity realtime reverse transcription PCR. Yakugaku Zasshi 2003 May; 123(5): 369–75PubMedCrossRefGoogle Scholar
  7. 7.
    Sarikaya D, Bilgen C, Kamataki T, et al. Comparative cytochrome P450 -1A1, -2A6, -2B6, -2C, -2D6, -2E1, -3A5 and -4B1 expressions in human larynx tissue analysed at mRNA level. Biopharm Drug Dispos 2006 Nov; 27(8): 353–9PubMedCrossRefGoogle Scholar
  8. 8.
    Carlson GP. Critical appraisal of the expression of cytochrome P450 enzymes in human lung and evaluation of the possibility that such expression provides evidence of potential styrene tumorigenicity in humans. Toxicology 2008 Dec 5; 254(1-2): 1–10PubMedCrossRefGoogle Scholar
  9. 9.
    Pasanen M, Pellinen P, Stenback F, et al. The role of CYP enzymes in cocaine-induced liver damage. Arch Toxicol 1995; 69(5): 287–90PubMedCrossRefGoogle Scholar
  10. 10.
    Wijnen PA, Linssen CF, Haenen GR, et al. Variant VKORC1 and CYP2C9 alleles in patients with diffuse alveolar hemorrhage caused by oral anticoagulants. Mol Diagn Ther 2010 Feb 1; 14(1): 23–30PubMedCrossRefGoogle Scholar
  11. 11.
    Wijnen PA, Drent M, van Dieijen-Visser MP, et al. Pharmacogenetic testing after a simple DNA isolation method on buccal swab samples. Pharmacogenomics 2009 Jun; 10(6): 983–7PubMedCrossRefGoogle Scholar
  12. 12.
    Camus P, Fanton A, Bonniaud P, et al. Interstitial lung disease induced by drugs and radiation. Respiration 2004 Jul–Aug; 71(4): 301–26PubMedCrossRefGoogle Scholar
  13. 13.
    Wijnen PA, Limantoro I, Drent M, et al. Depressive effect of an antidepressant: therapeutic failure of venlafaxine in a case lacking CYP2D6 activity. Ann Clin Biochem 2009 Nov; 46 (Pt 6): 527–30PubMedCrossRefGoogle Scholar
  14. 14.
    Wijnen PA, Bekers O, Drent M. Relationship between drug-induced interstitial lung diseases and cytochrome P450 polymorphisms. Curr Opin Pulm Med 2010 Sep; 16(5): 496–502PubMedCrossRefGoogle Scholar
  15. 15.
    Ben-Zaken Cohen S, Pare PD, Man SF, et al. The growing burden of chronic obstructive pulmonary disease and lung cancer in women: examining sex differences in cigarette smoke metabolism. Am J Respir Crit Care Med 2007 Jul 15; 176(2): 113–20CrossRefGoogle Scholar
  16. 16.
    Nebert DW, Russell DW. Clinical importance of the cytochromes P450. Lancet 2002 Oct 12; 360(9340): 1155–62PubMedCrossRefGoogle Scholar
  17. 17.
    Bland TM, Haining RL, Tracy TS, et al. CYP2C-catalyzed delta9-tetrahydrocannabinol metabolism: kinetics, pharmacogenetics and interaction with phenytoin. Biochem Pharmacol 2005 Oct 1; 70(7): 1096–103PubMedCrossRefGoogle Scholar
  18. 18.
    Tashkin DP, Khalsa ME, Gorelick D, et al. Pulmonary status of habitual cocaine smokers. Am Rev Respir Dis 1992 Jan; 145(1): 92–100PubMedCrossRefGoogle Scholar
  19. 19.
    Waien SA, Hayes Jr D, Leonardo JM. Severe coagulopathy as a consequence of smoking crack cocaine laced with rodenticide. N Engl J Med 2001 Aug 30; 345(9): 700–1PubMedCrossRefGoogle Scholar
  20. 20.
    Spahr JE, Maul JS, Rodgers GM. Superwarfarin poisoning: a report of two cases and review of the literature. Am J Hematol 2007 Jul; 82(7): 656–60PubMedCrossRefGoogle Scholar
  21. 21.
    Sconce E, Avery P, Wynne H, et al. Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin. Blood 2007 Mar 15; 109(6): 2419–23PubMedCrossRefGoogle Scholar
  22. 22.
    Sconce EA, Avery PJ, Wynne HA, et al. Vitamin K epoxide reductase complex subunit 1 (VKORC1) polymorphism influences the anticoagulation response subsequent to vitamin K intake: a pilot study. J Thromb Haemost 2008 Jul; 6(7): 1226–8PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  • Petal A.H.M. Wijnen
    • 1
    • 2
  • Otto Bekers
    • 1
    • 2
  • Marjolein Drent
    • 2
    • 3
  1. 1.Department of Clinical ChemistryMaastricht University Medical Centre (MUMC)Maastrichtthe Netherlands
  2. 2.interstitial lung disease (ild) care consultancyBC Maastrichtthe Netherlands
  3. 3.Department of Respiratory MedicineMUMCMaastrichtthe Netherlands

Personalised recommendations