Loss of antinociceptive effectiveness of morphine and oxycodone following titration of levothyroxine: Case reports and a brief review of published literature

Authors

  • Theresa A. Matoushek, PharmD
  • Tina C. Kearney, MD
  • Tammy J. Lindsay, MD, FAAFP
  • Christopher M. Herndon, PharmD, BCPS, CPE, FASHP

DOI:

https://doi.org/10.5055/jom.2012.0115

Keywords:

morphine, oxycodone, levothyroxine, thyroid, hypothyroid, opioid

Abstract

Chronic pain management is a complex process involving numerous facets of care. Although pharmacotherapy is a part of the treatment plan for these patients, it often represents the most complex of the modalities to manage. Two chronic pain patients with loss of pain control following dosage increase in levothyroxine supplementation are presented. The authors sought to identify relationships among thyroid status, opioid pharmacokinetics, and nociceptive processing. In conclusion, well-designed human studies using pain models and controlling for thyroid status are warranted to better understand the impact this system has on pain control.

Author Biographies

Theresa A. Matoushek, PharmD

Southern Illinois University Edwardsville, Edwardsville, Illinois

Tina C. Kearney, MD

Faculty Physician, Southern Illinois Healthcare Foundation, Illinois; Assistant Clinical Professor, Department of Family and Community Medicine, St. Louis University School of Medicine, Belleville, Illinois

Tammy J. Lindsay, MD, FAAFP

Clinical Associate Professor, St. Louis University Family Medicine Residency, St. Louis, Missouri; Military Program Director, United States Air Force

Christopher M. Herndon, PharmD, BCPS, CPE, FASHP

Associate Professor, School of Pharmacy, Southern Illinois University Edwardsville, Edwardsville, Illinois; Clinical Assistant Professor, St. Louis University School of Medicine, Edwardsville, Illinois

References

Johannes CB, Le TK, Zhou X, et al.: The prevalence of chronic pain in United States adults: Results of an internet-based survey. J Pain. 2010; 11(11): 1230-1239.

Joo DT: Mechanisms of opioid tolerance: Merging evidence and therapeutic implications. Can J Anaesth (Journal canadien d’anesthesie). 2007; 54(12): 969-976.

Rajagopal A, Vassilopoulou-Sellin R, Palmer JL, et al.: Hypogonadism and sexual dysfunction in male cancer survivors receiving chronic opioid therapy. J Pain Symptom Manag. 2003; 26(5): 1055-1061.

Reddy RG, Aung T, Karavitaki N, et al.: Opioid induced hypogonadism. BMJ. 2010; 341: c4462.

Bouknight AL: Thyroid physiology and thyroid function testing. Otolaryngol Clin North Am. 2003; 36(1): 9-15.

Larsen PR: Thyroid physiology becomes more complicated. Nat Clin Pract Endocrinol Metab. 2007; 3(7): 495.

Ilias I, Kakoulas I, Christakopoulou I, et al.: Thyroid function of former opioid addicts on naltrexone treatment. Acta Med (Hradec Kralove). 2001; 44(1): 33-35.

Judd AM, Hedge GA: The roles of opioid peptides in controlling thyroid stimulating hormone release. Life Sci. 1982; 31(22): 2529-2536.

Glattard E, Muller A, Aunis D, et al.: Rethinking the opiate system? Morphine and morphine-6-glucuronide as new endocrine and neuroendocrine mediators. Med Sci Monit. 2006; 12(6): SR25-SR27.

Daniell HW: Opioid endocrinopathy in women consuming prescribed sustained-action opioids for control of nonmalignant pain. J Pain. 2008; 9(1): 28-36.

Berglund LA, Millard WJ, Gabriel SM, et al.: Opiate-thyroid hormone interactions in the regulation of thyrotropin secretion in the rat. Neuroendocrinology. 1990; 52(3): 303-308.

Clur A: Iodothyronines and iodotyrosines as hypothetical receptors for catecholamines and opiates. Med hypotheses. 1985; 16(2): 97-131.

Kot M, Daniel WA: Cytochrome P450 is regulated by noradrenergic and serotonergic systems. Pharmacol Res. 2011; 64(4): 371-380.

Hasselstrom J, Sawe J: Morphine pharmacokinetics and metabolism in humans. Enterohepatic cycling and relative contribution of metabolites to active opioid concentrations. Clin Pharmacokinet. 1993; 24(4): 344-354.

McRorie TI, Lynn AM, Nespeca MK, et al.: The maturation of morphine clearance and metabolism. Am J Dis Child. 1992; 146(8): 972-976.

Mitchell JM, Paul BD, Welch P, et al.: Forensic drug testing for opiates. II. Metabolism and excretion rate of morphine in humans after morphine administration. J Anal Toxicol. 1991; 15(2): 49-53.

Smith GD, Smith MT: Morphine-3-glucuronide: Evidence to support its putative role in the development of tolerance to the antinociceptive effects of morphine in the rat. Pain. 1995; 62(1): 51-60.

Takeda S, Kitajima Y, Ishii Y, et al.: Inhibition of UDP-glucuronosyltransferase 2b7-catalyzed morphine glucuronidation by ketoconazole: Dual mechanisms involving a novel noncompetitive mode. Drug Metab Dispos: Biol Fate Chem. 2006; 34(8): 1277-1282.

Ohno S, Kawana K, Nakajin S: Contribution of UDP-glucuronosyltransferase 1A1 and 1A8 to morphine-6-glucuronidation and its kinetic properties. Drug Metab Dispos: Biol Fate Chem. 2008; 36(4): 688-694.

Bostrom E, Simonsson US, Hammarlund-Udenaes M: Oxycodone pharmacokinetics and pharmacodynamics in the rat in the presence of the P-glycoprotein inhibitor PSC833. J Pharm Sci. 2005; 94(5): 1060-1066.

Campa D, Gioia A, Tomei A, et al.: Association of ABCB1/MDR1 and OPRM1 gene polymorphisms with morphine pain relief. Clin Pharmacol Therapeut. 2008; 83(4): 559-566.

Jin M, Shimada T, Shintani M, et al.: Long-term levothyroxine treatment decreases the oral bioavailability of cyclosporin A by inducing P-glycoprotein in small intestine. Drug Metab Pharmacokinet. 2005; 20(5): 324-330.

Mitin T, Von Moltke LL, Court MH, et al.: Levothyroxine up-regulates P-glycoprotein independent of the pregnane X receptor. Drug Metab Dispos: Biol Fate Chem. 2004; 32(8): 779-782.

Siegmund W, Altmannsberger S, Paneitz A, et al.: Effect of levothyroxine administration on intestinal P-glycoprotein expression: Consequences for drug disposition. Clin Pharmacol Therapeut. 2002; 72(3): 256-264.

Lalovic B, Kharasch E, Hoffer C, et al.: Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: Role of circulating active metabolites. Clin Pharmacol Therapeut. 2006; 79(5): 461-479.

Lalovic B, Phillips B, Risler LL, et al.: Quantitative contribution of CYP2D6 and CYP3A to oxycodone metabolism in human liver and intestinal microsomes. Drug Metab Dispos: Biol Fate Chem. 2004; 32(4): 447-454.

Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005; 45(1): 68-78.

Persson KP, Ekehed S, Otter C, et al.: Evaluation of human liver slices and reporter gene assays as systems for predicting the cytochrome p450 induction potential of drugs in vivo in humans. Pharmaceut Res. 2006; 23(1): 56-69.

Hagen K, Bjoro T, Zwart JA, et al.: Do high TSH values protect against chronic musculoskeletal complaints? The Nord-Trondelag Health Study (HUNT). Pain. 2005; 113(3): 416-421.

Vigario P, Teixeira P, Reuters V, et al.: Perceived health status of women with overt and subclinical hypothyroidism. Med Princ Pract. 2009; 18(4): 317-322.

Orstavik K, Norheim I, Jorum E: Pain and small-fiber neuropathy in patients with hypothyroidism. Neurology. 2006; 67(5): 786-791.

Penza P, Lombardi R, Camozzi F, et al.: Painful neuropathy in subclinical hypothyroidism: Clinical and neuropathological recovery after hormone replacement therapy. Neurol Sci. 2009; 30(2): 149-151.

Wiens SC, Trudeau VL: Thyroid hormone and gammaaminobutyric acid (GABA) interactions in neuroendocrine systems. Comp Biochem Physiol. 2006; 144(3): 332-344.

Arendt-Nielsen L, Curatolo M, Drewes A: Human experimental pain models in drug development: Translational pain research. Curr Opin Investig Drugs. 2007; 8(1): 41-53.

Schmelz M: Translating nociceptive processing into human pain models. Exp Brain Res (Experimentelle Hirnforschung). 2009; 196(1): 173-178.

Published

05/01/2012

How to Cite

Matoushek, PharmD, T. A., T. C. Kearney, MD, T. J. Lindsay, MD, FAAFP, and C. M. Herndon, PharmD, BCPS, CPE, FASHP. “Loss of Antinociceptive Effectiveness of Morphine and Oxycodone Following Titration of Levothyroxine: Case Reports and a Brief Review of Published Literature”. Journal of Opioid Management, vol. 8, no. 3, May 2012, pp. 193-8, doi:10.5055/jom.2012.0115.

Issue

Section

Case Studies