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Pharmacology of Glucocorticoids

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Adrenal Disorders

Part of the book series: Contemporary Endocrinology ((COE))

Abstract

Natural and synthetic glucocorticoids are one of the most commonly used medications as they are utilized not only as replacement therapy for patients with deficiencies but also to treat others suffering from a variety of illnesses that require immune suppression or others associated with inflammation or allergic reactions, to name a few. The doses of glucocorticoids required to treat the latter conditions are almost always supraphysiological, and therefore they are associated with side effects. Even when glucocorticoids are used as replacement therapy in patients with deficiencies, some side effects are still encountered, an indication that commonly used replacement doses are supraphysiological. In this chapter, we will review the basic structure of the primary naturally occurring glucocorticoid, namely, cortisol (also called hydrocortisone), and compare that to the commonly available synthetic compounds. The chapter will also discuss pharmacologic use of glucocorticoids factors influencing their bioavailability and metabolism, their side effects and the approach to minimizing these.

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References

  1. Dluhy RG, Newmark SR, Lauler DP, Thorn GW. Pharmacology and chemistry of adrenal glucocorticoids. In: Azarnoff DL, editor. Steroid therapy. Philadelphia: WB Saunders; 1975.

    Google Scholar 

  2. Charmandari E, Kino T, Chrousos GP. Glucocorticoids and their actions: an introduction. Ann N Y Acad Sci. 2004;1024:1–8.

    Article  CAS  PubMed  Google Scholar 

  3. Miller WL, Auchus RJ. The molecular biology, biochemistry and physiology of human steroidogenesis and its disorders. Endocr Rev. 2011;32:81–151.

    Article  CAS  PubMed  Google Scholar 

  4. Ballard PL. Delivery and transport of glucocorticoids to target cells. In: Baxter JD, Rousseau GG, editors. Glucocorticoid hormone action. Berlin: Springer; 1979. p. 279.

    Google Scholar 

  5. Brien TG. Human corticosteroid binding globulin (review article). Clin Endocrinol. 1981;14:193–212.

    Article  CAS  Google Scholar 

  6. Dunn JF, Nisula BC, Rodbard D. Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroids-binding globulin in human plasma. J Clin Endocrinol Metab. 1981;53:58–68.

    Article  CAS  PubMed  Google Scholar 

  7. Mueller UW, Potter JM. Binding of cortisol to human albumin and serum: the effect of protein concentration. Biochem Pharmacol. 1981;30:727–33.

    Article  CAS  PubMed  Google Scholar 

  8. Coolens J, Baelen HV, Heyns W. Clinical use of unbound plasma cortisol as calculated from total cortisol and corticosteroid-binding globulin. J Steroid Biochem. 1987;26:197–202.

    Article  CAS  PubMed  Google Scholar 

  9. Olivesi A. Modified elimination of prednisolone in epileptic patients on carbamazepine monotherapy and in women using low dose oral contraceptives. Biomed Pharmacother. 1986;40:301–8.

    CAS  PubMed  Google Scholar 

  10. Bansal V, El Asmar N, Selman WR, Arafah BM. Pitfalls in the diagnosis and management of Cushing’s syndrome. Neurological Focus. 2015;38:1–11.

    Google Scholar 

  11. Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill patients. N Engl J Med. 2004;350:1629–38.

    Article  CAS  PubMed  Google Scholar 

  12. Arafah BM. The hypothalamic pituitary adrenal function during critical illness: limitations of current assessment methods. J Clin Endocrinol Metab. 2006;91:3725–45.

    Article  CAS  PubMed  Google Scholar 

  13. Ho JT, Al-Musalhi H, Chapman MJ, Quach T, Thomas PD, Bagely CJ, Lewis JG, Torpy DJ. Septic shock and sepsis: a comparison of total and free plasma cortisol levels. J Clin Endocrinol Metab. 2006;91:105–14.

    Article  CAS  PubMed  Google Scholar 

  14. Arafah BM, Nishiyama FJ, Tlaygeh H, Hejal R. Measurement of salivary cortisol concentration in the assessment of adrenal function in critically ill subjects: a surrogate marker of the circulating free cortisol. J Clin Endocrinol Metab. 2007;92:2965–71.

    Article  CAS  PubMed  Google Scholar 

  15. Good M, Albert JM, Arafah BM, Anderson GC, Wotman S, Cong X, Lane D, Ahn S. Effects on postoperative salivary cortisol of relaxation/music and patient teaching about pain management. Biol Res Nurs. 2013;15:318–29.

    Article  CAS  PubMed  Google Scholar 

  16. Laudat MH, Cerdas S, Fournier C, Guiban D, Guilhaume B, Luton JP. Salivary cortisol measurement: a practical approach to assess pituitary-adrenal function. J Clin Endocrinol Metab. 1988;66:343–8.

    Article  CAS  PubMed  Google Scholar 

  17. Dulin WE. Anti-inflammatory activity of delta 1-9 alpha fluorohydrocortisone acetate. Proc Soc Exp Biol Med. 1955;90:115–21.

    Article  CAS  PubMed  Google Scholar 

  18. Peterson RE. Metabolism of adrenal cortical steroids. In: Christy NP, editor. The human adrenal cortex. New York: Harper and Row; 1971. p. 87.

    Google Scholar 

  19. Meikle AW, Weed JA, Tyler FH. Kinetics and interconversion of prednisolone and prednisone studied with new radioimmunoassays. J Clin Endocrinol Metab. 1975;41:717–21.

    Article  CAS  PubMed  Google Scholar 

  20. Axelrod L. Glucocorticoid therapy. Medicine (Baltimore). 1976;55:39–52.

    Article  CAS  Google Scholar 

  21. Meikle AW, Tyler FH. Potency and duration of action of glucocorticoids. Effects of hydrocortisone, prednisone and dexamethasone on human pituitary adrenal function. Am J Med. 1977;63:200–7.

    Article  CAS  PubMed  Google Scholar 

  22. Frey FJ, Frey BM. Altered plasma protein binding of prednisolone in patients with nephrotic syndrome. Am J Kidney Dis. 1984;3:161–4.

    Article  Google Scholar 

  23. Hill MR, Szefler SJ, Ball BD, Bartoszek M, Brenner AM. Monitoring glucocorticoid therapy: a pharmacokinetic approach. Clin Pharmacol Ther. 1990;48:390–8.

    Article  CAS  PubMed  Google Scholar 

  24. Legler UF, Frey FJ, Benet LZ. Prednisolone clearance at steady state in man. J Clin Endocrinol Metab. 1982;55:762–7.

    Article  CAS  PubMed  Google Scholar 

  25. Diederich S, Eigendorff E, Burkhardt P, Quinkler M, Bumke-Vogt C, Rochel M, Seidelmann D, Esperling P, Oelkers W, Bahr V. 11 beta hydroxyl-steroid dehydrogenase types 1 and 2: an important pharmacologic determinant for the activity of synthetic mineralo- and glucocorticoids. J Clin Endocrinol Metab. 2002;87:5695–701.

    Article  CAS  PubMed  Google Scholar 

  26. Schacke DWD, Asadullah K. Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther. 2002;96:23–43.

    Article  CAS  PubMed  Google Scholar 

  27. Cooper MS, Stewart PM. 11 beta hydroxyl-steroid dehydrogenase type-1 and its role in the hypothalamus-pituitary adrenal axis, metabolic syndrome and inflammation. J Clin Endocrinol Metab. 2009;94:4655–61.

    Article  Google Scholar 

  28. Yamada S. Iwai km, letter: induction of hepatic cortisol-6 hydroxylase by rifampicin. Lancet. 1976;2:366.

    Article  CAS  PubMed  Google Scholar 

  29. Voccia E, Saenger P, Peterson RE, Rauth W, Gottesdiener K, Levine LS, New MI. 6 beta hydroxycortisol excretion in hypercortisolemic states. J Clin Endocrinol Metab. 1979;48:467–71.

    Article  CAS  PubMed  Google Scholar 

  30. Peterson RE. The influence of the thyroid on adrenal cortical function. J Clin Invest. 1958;37:736–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Frey FJ, Horber FF, Frey BM. Altered metabolism and decreased efficacy of prednisolone and prednisone in patients with hyperthyroidism. Clin Pharmacol Ther. 1988;44:510–21.

    Article  CAS  PubMed  Google Scholar 

  32. Boonen E, Vervenne H, Meersseman P, Andrew R, Mortier L, Declercq PE, Vanwijngaerden YM, Spriet I, Wouters PJ, Vander Perre S, Langouche L, Vanhorebeek I, Walker BR, Van den Bergh G. Reduced cortisol metabolism during critical illness. N Engl J Med. 2013;368:1477–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sherlock JE, Letteri JM. Effect of hemodialysis on methylprednisolone plasma levels. Nephron. 1977;18:208–12.

    Article  CAS  PubMed  Google Scholar 

  34. Olsen H, Mjoman M. Moderately impaired renal function increases morning cortisol and cortisol levels at dexamethasone suppression test in patients with incidentally detected adrenal adenomas. Clin Endocrinol. 2015;83:762–7.

    Article  CAS  Google Scholar 

  35. Bledsoe T, Island DP, Ney RL, Liddle GW. An effect of O,P-DDD on the extra adrenal metabolism of cortisol in man. J Clin Endocrinol Metab 1964; 24:1303-1311.

    Google Scholar 

  36. Werk EE Jr, MacGee J, Sholto LJ. Effect of diphenylhydantoin on cortisol metabolism in man. J Clin Invest. 1964;43:1824–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Frey BM, Frey FJ. Phenytoin modulates the pharmacokinetics of prednisolone and the pharmacodynamics of prednisolone as assessed by the inhibition of the mixed lymphocyte reaction in humans. Eur J Clin Investig. 1984;14:1–8.

    Article  CAS  Google Scholar 

  38. Sm B, Werk EE, Ackerman SJ, Sullivan I, Trasher K. Adverse effects of phenobarbital on corticosteroid metabolism in patients with bronchial asthma. N Engl J Med. 1972;286:1125–8.

    Article  Google Scholar 

  39. Kyriazopoulou V, Parparousi O, Vagenakis AG. Rifampicin-induced adrenal crisis in addisonian patients receiving corticosteroid replacement therapy. J Clin Endocrinol Metab. 1984;59:1204–6.

    Article  CAS  PubMed  Google Scholar 

  40. Meffin PJ, Wing LM, Sallustio BC, Brooks PM. Alterations in prednisolone disposition as a result of oral contraceptive use and dose. Br J Clin Pharmacol. 1984;17:655–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Gustavson LE, Legler UF, Benet LZ. Impairment of prednisolone disposition in women taking oral contraceptives or conjugated estrogen. J Clin Endocrinol Metab. 1986;62:234–7.

    Article  CAS  PubMed  Google Scholar 

  42. Fost DA, Leung DY, Martin RJ, Brown EE, Szefler SJ, Spahn JD. Inhibition of methyprednisolone elimination in the presence of erythromycin therapy. J Allergy Clin Immuno. 1999;103:1031–5.

    Article  CAS  Google Scholar 

  43. Renner E, Horber FF, Jost G, Frey BM, Frey FJ. Effect of liver function on the metabolism of prednisone and prednisolone in humans. Gastroenterology. 1986;90:819–28.

    Article  CAS  PubMed  Google Scholar 

  44. Uribe M, Casian C, Rojas S, Sierra JG, Go VL. Decreased bioavailability of prednisone due to antiacids in patients with chronic active liver diseases and in healthy volunteers. Gastroenterology. 1981;80:661–5.

    CAS  PubMed  Google Scholar 

  45. Tsuei SE, Petersen MC, Ashley JJ, et al. Disposition of synthetic glucocorticoids II. Dexamethasone in parturient women. Clin Pharmacol Ther. 1980;28:88.

    Article  CAS  PubMed  Google Scholar 

  46. Tanner AR, Caffin JA, Halliday JW, Powell LW. Concurrent administration of antiacids and prednisone effect on serum levels of prednisolone. Br J Clin Pharmacol. 1979;7:397.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Kozower M, Veatch L, Kaplan MM. Decreased clearance of prednisolone, a factor in the development of corticosteroid side effects. J Clin Endocrinol Metab. 1974;38:407–12.

    Article  CAS  PubMed  Google Scholar 

  48. Lima JJ, Giller J, Mackichan JJ, Jusko WJ. Bioavailability of hydrocortisone retention enemas in normal subjects. Am J Gastroenterology. 1980;73:232–7.

    CAS  Google Scholar 

  49. Walsh P, Aeling JL, Huff L, Weston WL. Hypothalamus-pituitary –adrenal axis suppression by super potent topical steroids. J Am Acad Dermatol. 1993;29:501–3.

    Article  CAS  PubMed  Google Scholar 

  50. Fisher DA. Adverse effects of topical corticosteroid use. West J Med. 1995;91:661–8.

    Google Scholar 

  51. Johnson M. Pharmacodynamics and pharmacokinetics of inhaled glucocorticoids. J Allerg Clin Immuno. 1996;97:169–76.

    Article  CAS  Google Scholar 

  52. Schaaf MJM, Gidlowski JA. Molecular mechanisms of glucocorticoid action and resistance. J Steroid Biochem Molec Biol. 2003;179:1–12.

    Google Scholar 

  53. Buttgereit F, Saag KG, Cutolo M, Da Silva JA, Bulsma JW. The molecular basis for the effectiveness, toxicity, and resistance to glucocorticoids: focus on the treatment of rheumatoid arthritis. Scand J Rheumatology. 2005;34:14–21.

    Article  CAS  Google Scholar 

  54. Stahn C, Lowenberg M, Hommes DW, Buttgereit F. Molecular mechanisms of glucocorticoid action and selective glucocorticoid receptor agonists. Molec Cell Endocrinol. 2007;275:71–8.

    Article  CAS  PubMed  Google Scholar 

  55. Barnes PJ. Mechanisms and resistance in glucocorticoid control of inflammation. L Steroid Biochem and Mol Biol. 2010;120:76–85.

    Article  CAS  Google Scholar 

  56. Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Molec and Cellular Endocrinol. 2011;335:2–13.

    Article  CAS  Google Scholar 

  57. Loriaux L. Glucocorticoid therapy in the intensive care unit. N Engl J Med. 2004;350:1601–2.

    Article  CAS  PubMed  Google Scholar 

  58. Collins S, Caron MG, Lefkowitz RJ. Beta-adrenergic receptors in hamster smooth muscle cells are transcriptionally regulated by glucocorticoids. J Biol Chem. 1988;263(19):9067–70.

    CAS  PubMed  Google Scholar 

  59. Ullian ME. The role of corticosteroids in the regulation of vascular tone. Cardiovasc Res. 1999;41:55–64.

    Article  CAS  PubMed  Google Scholar 

  60. Yang S, Zhang L. Glucocorticoids and vascular reactivity. Curr Vasc Pharm. 2004;2:1–12.

    Article  Google Scholar 

  61. Hoen S, Mazoit JX, Asehnoune K, Brailly-Tabard S, Benhamou D, Moine P, Edouard AR. Hydrocortisone increases the sensitivity to alpha1-adrenoceptor stimulation in humans following hemorrhagic shock. Crit Care Med. 2005;33:2737–43.

    Article  CAS  PubMed  Google Scholar 

  62. Allen DB, Julius JR, Breen TJ, Attie KM. Treatment of glucocorticoid-induced growth suppression with growth hormone. National cooperative growth study. J Clin Endocrinol Metab. 1998;83:2824–9.

    Article  CAS  PubMed  Google Scholar 

  63. Laan RF, van Riel PL, van de Putte LB, Van Erning LJ, Vant Hof MA, Lemmens JA. Low-dose prednisone induces reversible axial bone loss in patients with rheumatoid arthritis. A randomized controlled study. Ann Intern Med. 1993;119:963–8.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Clinical and Molecular Endocrinology, Case Western Reserve University and University Hospitals/Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH, 44106, USA

    Baha M. Arafah M.D.

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  1. Baha M. Arafah M.D.
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Correspondence to Baha M. Arafah M.D. .

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Editors and Affiliations

  1. Div of Endocrinology and Bone Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA

    Alice C. Levine

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Arafah, B.M. (2018). Pharmacology of Glucocorticoids. In: Levine, A. (eds) Adrenal Disorders. Contemporary Endocrinology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-62470-9_3

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  • DOI: https://doi.org/10.1007/978-3-319-62470-9_3

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  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-62469-3

  • Online ISBN: 978-3-319-62470-9

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