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drug adverse effects of glucocorticoids

also see drug adverse effects of topical glucocorticoids Adverse effects: 1) easy bruising 2) osteoporosis, osteopenia, fractures* a) may inhibit osteoblast activity b) may promote osteoblast apoptosis c) inhibition of intestinal Ca+2 transport [8] d) systemic glucocorticoids associated with increased risk of fractures in children with asthma [15] - no increase in risk with inhaled glucocorticoids e) long-term glucocorticoids <= 5 mg/day of prednisone do not seem to adversely affect bone mineral density [20] 3) aseptic necrosis (osteonecrosis) 4) ocular adverse effects - cataracts, glaucoma, cataracts, optic neuritis, retinopathy 5) hypertension 6) weight gain, fluid retention, edema 7) glucose intolerance/diabetes mellitus 8) depression 9) central nervous system effects a) insomnia, anxiety, irritability (60%) [10] b) steroid psychosis 1] bipolar symptoms 2] begins 7-10 days after starting c) memory impairment, confusion d) elevated incidence of suicide attempts, depression, mania, & delirium [11] 10) acne 11) gastrointestinal a) GI intolerance b) reduced tone of gastroesophageal sphincter c) gastroesophageal reflux d) upper GI bleed [5] 12) increased cardiovascular risk - accelerated atherogenesis, hypercholesterolemia, insulin resistance, hypertension [21] 13) immunosuppression a) disorder of neutrophil phagocytosis b) lymphopenia & monocytopenia c) decreased cell-mediated immunity d) opportunistic infections e) prophylaxis for pneumocystis pneumonia may be appropriate with chronic high-dose glucocorticoids [3,16] 14) Cushingoid features: a) puffed facies b) buffalo hump c) abdominal striae - glucocorticoids synergistic with pregnancy d) Cushing's syndrome due to glucocorticoids is associated with increased cardiovascular risk [12] 15) impaired wound healing 16) steroid myopathy (long-term use) - proximal muscle weakness 17) seizures 18) increased risk of atrial fibrillation a) odds ratio 3.6 (current use) b) odds ratio 1.7 (long-term use) c) no increase risk for former users [9] 19) mediastinal lipomatosis 20) inhaled corticosteroids a) oral candidiasis b) dysphonia (laryngeal myopathy) 21) topical glucocorticoids may cause contact dermatitis (3-5%) 22) inhaled glucocorticoids have no significant effect on final height or bone density in children [7] 23) long-term effects or antenatal exposure may be minimal (see betamethasone) 24) short-term use of oral glucocorticoids associated with increased risks for sepsis (RR=1.8), venous thromboembolism (RR=1.9), & fracture (RR=1.5) [13], gastrointestinal bleeding, & heart failure [18] 24) short courses of oral glucocorticoids in children pose risks for pneumonia, GI bleed, & sepsis [19] 25) erythroderma following use of systemic glucocorticoids [3] Management: - Calcium 1.0-1.5 g QD & vitamin D 400-800 IU QD may be helpful & should be prescribed for vulnerable older adults taking equivalent of 7.5 mg of prednisone QD for 1 month or longer [8] - alendronate (or other bisphosphonate) may reduce bone loss & reduce risk of fractures [4,14] & should be prescribed for vulnerable older adults taking equivalent of 5-7.5 mg of prednisone QD for 4 weeks or longer [3,8] unless contraindicated

Properties

DRUGS: glucocorticoid FORM: drug adverse effects glucocorticoid

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 792, 799
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 17, 18. American College of Physicians, Philadelphia 1998, 2015, 2018.
  4. Journal Watch 21(6):46, 2001 Arthritis Rheum 44:202, 2001
  5. Journal Watch 21(14):118, 2001 Hernandez-Diaz & Rodriguez, Am J Epidemiol 153:1089, 2001
  6. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  7. Prescriber's Letter 9(8):48 2002
  8. Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004; 7th edition 2010
  9. Christiansen CF et al. Glucocorticoid use and risk of atrial fibrillation or flutter: A population-based, case-control study. Arch Intern Med 2009 Oct 12; 169:1677. PMID: 19822824
  10. Prescriber's Letter 18(5): 2011 Corticosteroid-Induced Psychiatric Effects Detail-Document#: 270508 (subscription needed) http://www.prescribersletter.com
  11. Fardet L et al. Suicidal behavior and severe neuropsychiatric disorders following glucocorticoid therapy in primary care. Am J Psychiatry 2012 May 1; 169:491 PMID: 22362393
  12. Fardet L et al Risk of cardiovascular events in people prescribed glucocorticoids with iatrogenic Cushing's syndrome: cohort study BMJ 2012;345:e4928 PMID: 22846415 http://www.bmj.com/content/345/bmj.e4928
  13. Waljee AK, Rogers MA, Lin P et al Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ 2017;357:j1415 PMID: 28404617 http://www.bmj.com/content/357/bmj.j1415
  14. Axelsson KF, Nilsson AG, Wedel H, Lundh D, Lorentzon M. Association Between Alendronate Use and Hip Fracture Risk in Older Patients Using Oral Prednisolone. JAMA. 2017;318(2):146-155 PMID: 28697254 http://jamanetwork.com/journals/jama/article-abstract/2643309
  15. Gray N, Howard A, Zhu J et al Association Between Inhaled Corticosteroid Use and Bone Fracture in Children With Asthma. JAMA Pediatr. Published online November 13, 2017 PMID: 29131874 https://jamanetwork.com/journals/jamapediatrics/article-abstract/2661821
  16. Park JW, Curtis JR, Moon J et al. Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids. Ann Rheum Dis 2018 May; 77:644. PMID: 29092853 Free PMC Article http://ard.bmj.com/content/77/5/644 - Winthrop KL , Baddley JW. Pneumocystis and glucocorticoid use: To prophylax or not to prophylax (and when?); that is the question. Ann Rheum Dis 2018 May; 77:631 PMID: 29459427 http://ard.bmj.com/content/77/5/631
  17. Rotaus C Glucocorticoid-Induced Osteoporosis NEJM Resident 360. Dec 26, 2018 https://resident360.nejm.org/content_items/glucocorticoid-induced-osteoporosis
  18. Yao TC et al. Association between oral corticosteroid bursts and severe adverse events: A nationwide population-based cohort study. Ann Intern Med 2020 Sep 1; 173:325 PMID: 32628532 https://www.acpjournals.org/doi/10.7326/M20-0432 - Wallace BI, Waljee AK. Burst case scenario: Why shorter may not be any better when it comes to corticosteroids. Ann Intern Med 2020 Sep 1; 173:390 PMID: 32628530 https://www.acpjournals.org/doi/10.7326/M20-4234
  19. Yao TC et al. Association of oral corticosteroid bursts with severe adverse events in children. JAMA Pediatr 2021 Apr 19; [e-pub]. PMID: 33871562 https://jamanetwork.com/journals/jamapediatrics/fullarticle/2778775
  20. Wiebe E, Huscher D, Schaumburg D, et al. Optimising both disease control and glucocorticoid dosing is essential for bone protection in patients with rheumatic disease. Ann Rheum Dis. Published online ahead of print June 9, 2022. PMID: 35680387
  21. NEJM Knowledge+ Complex Medical Care