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Corticosteroids: Clinical Pharmacology and Therapeutic Use

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The widespread use of corticosteroids in clinical practice emphasises the need for a thorough understanding of their metabolic effects. In general, the actions of corticosteroids on carbohydrate, protein, and lipid metabolism result in increased hepatic capacity for gluconeogenesis and enhanced catabolic actions upon muscle, skin, lymphoid, adipose and connective tissues. Because of the morbidity associated with steroid therapy, the clinician must carefully consider in each case the gains that can reasonably be expected from corticosteroid therapy versus the inevitable undesirable side effects of prolonged therapy. Thus, it is important to remember that the enhanced anti-inflammatory activity of the various synthetic analogues of cortisol is not dissociated from the expected catabolic actions of glucocorticoid hormones.

Replacement therapy with physiological doses of cortisol in primary or secondary adrenal insufficiency is intended to simulate the normal daily secretion of cortisol. Short term, high dose suppressive glucocorticoid therapy is indicated in the treatment of medical emergencies such as necrotising vasculitis, status asthmaticus and anaphylactic shock. With improvement of the underlying disorder, the steroid dosage can be rapidly tapered and then discontinued over a 2 to 3 day period. Long term, high dose suppressive therapy is often commonly used to treat certain diseases (see sections 4.7.2 and 4.7.3). In this setting, suppression of the hypothalamic-pituitary-adrenal axis may persist for as long as 9 to 12 months following steroid withdrawal if steroid doses are administered in the supraphysiological range for longer than 2 weeks. In general, higher doses, longer duration of usage, and frequent daily administration are all correlated with the severity of pituitary ACTH suppression.

When steroid therapy is to be withdrawn, gradual tapering of the dosage is necessary; the steroid dosage should also be given as a single morning dose if possible. Rapid or total withdrawal of the steroid therapy may be associated with exacerbation of the underlying disease or with a steroid withdrawal syndrome. An additional important point to remember in any withdrawal programme is that the steroid dosage should be appropriately increased for an exacerbation of the underlying disease or for intercurrent major stress. Alternate day therapy is recommended as a steroid maintenance programme for patients requiring high dose glucocorticoid therapy over a prolonged period of time. Thus, it is usually employed to maintain a therapeutic benefit which had previously been established by daily steroid treatment.

Complications resulting from corticosteroid therapy include: (1) proximal muscle weakness; (2) osteopenia; (3) unmasking of latent diabetes mellitus; (4) sodium retention and / or elevation of mean arterial blood pressure; (5) adverse psychiatric reactions; (6) development of glaucoma; and (7) reactivation of latent infections (such as tuberculosis).

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References

  • Afifi, A.K.; Berman, R.A. and Harvey, M.C.: Steroid myopathy; clinical, histologic observations. Johns Hopkins Medical Journal 123: 158–174 (1968).

    PubMed  CAS  Google Scholar 

  • Alavi, I.A.; Sharma, B.K. and Pillary, V.K.: Steroid-induced diabetic ketoacidosis. American Journal of Medical Science 262: 15–23 (1971).

    Article  CAS  Google Scholar 

  • Bagdade, J.D.; Porte, D. Jr. and Bierman, E.L.: Steroid-induced lipemia. A complication of high-dose corticosteroid therapy. Archives of Internal Medicine 125: 129–134 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Baxter, J.D. and Forsham, P.H.: Tissue effects of glucocorticoids. American Journal of Medicine 53: 573–589 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Baxter, J.D.; Harris, A.W.; Tomkins, G.M. and Cohn, M.: Glucocorticoid receptors in lymphoma cells in culture: Relationship to glucocorticoid killing activity. Science 171: 189–191 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Byyny, R.L.: Withdrawal from glucocorticoid therapy. New England Journal of Medicine 295: 30–32 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Cahill, G.F.: Action of adrenal cortical steroids on carbohydrate metabolism; in Christy (Ed) The Human Adrenal Cortex. p.205–241 (Harper and Row, New York 1971).

    Google Scholar 

  • Cahill, G.F.: Glucagon. New England Journal of Medicine 228: 157–158 (1973).

    Article  Google Scholar 

  • Conn, H. and Blitzer, B.L.: Nonassociation of adrenocorticosteroid therapy and peptic ulcer. New England Journal of Medicine 294: 473–479 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Cooke, A.R.: Drugs and gastric damage. Drugs 11: 36–44 (1976).

    Article  PubMed  CAS  Google Scholar 

  • David, D.S.; Grieco, M.H. and Cashman, P.J.: Adrenal glucocorticoids after twenty years: A review of their clinically relevant consequences. J. Chronic Dis. 22: 637–711 (1970).

    Article  PubMed  CAS  Google Scholar 

  • David, J.R.; Al-Askari, S.; Lawrence, H.S. and Thomas, L.: Delayed hypersensitivity in vitro. Journal of Immunology 93: 264–273 (1964).

    CAS  Google Scholar 

  • Dluhy, R.G.; Newmark, S.R.; Lauler, D.P. and Thorn, G.W.: Pharmacology and chemistry of adrenal glucocorticoids; in Azarnoff (Ed) Steroid Therapy, p.1–14 (Saunders, Philadelphia 1975).

    Google Scholar 

  • Dujorne, C.A. and Azarnoff, D.L.: Clinical complications of corticosteroid therapy: A selected review; in Azarnoff (Ed) Steroid Therapy, p.27–41 (Saunders, Philadelphia 1975).

    Google Scholar 

  • Feigelson, P.; Yu, F.L. and Hanorine, J.: Effect of glucocorticoids on hepatic enzymes induction and purine nucleotide and RNA metabolic; in Christy (Ed) The Human Adrenal Cortex, p.257–272 (Harper and Row, New York 1971).

    Google Scholar 

  • Feldman, D.; Funder, J.W. and Edelman, J.S.: Subcellular mechanisms in the action of adrenal steroids. American Journal of Medicine 53: 545–560 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Fleisher, N.; Ake, K.; Liddle, G.W.; Orth, D.N. and Nicholson, W.E.: ACTH antibodies in patients receiving depot porcine ACTH to hasten recovery from pituitary-ad renal suppression. Journal of Clinical Investigation 46: 196–204 (1967).

    Article  Google Scholar 

  • Gharib, H. and Munoz, J.M.: Endocrine manifestations of diphenylhydantoin therapy. Metabolism 23: 515–524 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Giles, C.L.: The ocular complications of steroid therapy. Michigan Medicine 66: 298–301 (1967).

    PubMed  CAS  Google Scholar 

  • Glaser, G.H.: Psychotic reactions induced by corticotropin (ACTH) and cortisone. Psychosomatic Medicine 15: 280–291 (1953).

    PubMed  CAS  Google Scholar 

  • Graber, A.L.; Ney, R.L.; Nicholson, W.E.; Island, D.P. and Liddle, G.W.: Natural history of pituitary-adrenal recovery following long-term suppression with corticosteroids. Journal of Clinical Endocrinology and Metabolism 25: 11–16 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Graham, G.G.; Champion, G.D.; Day, R.O. and Pauli, P.D.: Patterns of plasma concentrations and urinary excretion of salicylate in rheumatoid arthritis. Clinical Pharmacology and Therapeutics 22: 410–420 (1977).

    PubMed  CAS  Google Scholar 

  • Green, J.P.: Steroid therapy and wound healing in surgical patients. British Journal of Surgery 52: 523–525 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Kahn, C.R.; Goldfine, I.D.; Neville, D.M. Jr.; Roth, J.; Garrison, M. and Bates, R.: Insulin receptor defect: A major factor in the insulin resistance of glucocorticoid excess. Endocrinology 93 (Suppl.): 168 (1973).

    Google Scholar 

  • Kimball, C.P.: Psychological dependency on steroids. Annals of Internal Medicine 75: 111–113 (1971).

    PubMed  CAS  Google Scholar 

  • Klein, R.G.; Arnaud, S.B.; Gallangher, J.C.; DeLuca, H.F. and Riggs, B.L.: Intestinal calcium absorption in exogenous hypercortisonism — role of 25-hydroxyvitamin D and corticosteroid dose. Journal of Clinical Investigation 60: 253–259 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Klinenberg, J.R. and Miller, R.: Effect of corticosteroids on blood salicylate concentration. Journal of the American Medical Association 194: 601–604 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Lewis, G.P.; Jusko, W.J.; Burke, C.W. and Graves, Linda: Prednisone side effects and serum protein levels. Lancet 2: 778 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Marco, J.; Calle, C.; Roman, D.; Diaz-Fierros, M.; Villanueva, M. and Valverde, I.: Hyperglucogonism induced by glucocorticoid treatment in men. New England Journal of Medicine 288: 128–131 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Melby, J.C.: Systemic corticosteroid therapy: Pharmacology and endocrinologic considerations. Annals of Internal Medicine 81: 505–512 (1974).

    PubMed  CAS  Google Scholar 

  • Munck, A.: Glucocorticoid inhibition of glucose uptake by peripheral tissues: Old and new evidence, molecular mechanism, and physiological significance. Perspectives in Biology and Medicine 14: 265–289 (1971).

    PubMed  CAS  Google Scholar 

  • Nelp, W.B.: Acute pancreatitis associated with steroid therapy. Archives of Internal Medicine 108: 702–710 (1961).

    Article  PubMed  CAS  Google Scholar 

  • Nelson, D.H.; Sandberg, A.A.; Palmer, J.G. and Tyler, F.H.: Blood levels of 17-hydroxycorticosteroids following the administration of adrenal steroids and their relation to levels of circulating leukocytes. Journal of Clinical Investigation 31: 843–849 (1952).

    Article  PubMed  CAS  Google Scholar 

  • Peterson, R.E.: Metabolism of adrenal cortical steroids; in Christy (Ed.) The Human Adrenal Cortex, pp.87–191 (Harper and Row, New York 1971).

    Google Scholar 

  • Rudman, D. and DiGirolarno, M.: Effect of adrenal cortical steroids on lipid metabolism; in Christy (Ed) The Human Adrenal Cortex, p.241–256 (Harper and Row, New York 1971).

    Google Scholar 

  • Sterioff, S.; Oringer, M.G. and Cameron, J.L.: Colon perforations associated with steroid therapy. Surgery 75: 56–58 (1974).

    PubMed  CAS  Google Scholar 

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Swartz, S.L., Dluhy, R.G. Corticosteroids: Clinical Pharmacology and Therapeutic Use. Drugs 16, 238–255 (1978). https://doi.org/10.2165/00003495-197816030-00006

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