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glucocorticoid

Indications: - treatment of acute inflammation - prevention of adrenal insufficiency* * see perioperative glucocorticoids Contraindications: - gastrointestinal bleeding - renal failure - active infection - evidence for use in cancer pain control is weak [35] Benefit/risk: - acute respiratory distress syndrome (ARDS) [16] - early high-dose glucocorticoid of no benefit [16] - number need to harm = 3 (infection) [16] - bronchiolitis [17] - glucocorticoids do not prevent hospital admission or reduce the length of hospital stay [17] - sepsis & septic shock [18] - of no benefit; no harm noted [18] - prevention of post-herpetic neuralgia [19] - of no benefit; no harm noted - pharyngitis - prednisone 60 mg, dexamethasone <= 10 mg, or betamethasone 8 mg shortens duration of symptoms [20] - number needed to treat (NNT) = 3 - no harms noted [20] - COPD exacerbation - number needed to treat (NNT) = 10 to prevent 1 treatment failure [21] - number needed to harm (NNH) = 7 for drug adverse effect [21] - croup - number needed to treat (NNT) - 5 for respiratory benefit [22] - 11 to avoid return visit [22] - no harm noted - bacterial meningitis - non-significant reduction in mortality [23] - significant reduction in mortality for S pneumoniae meningitis (RR=084) [23] - number needed to treat (NNT) - 21 to prevent severe hearing loss - only significant for H influenzae meningitis (RR=0.34) [23] - 27 to prevent short-term neurologic sequellae [23] - no beneficial effect of glucocorticoids in low-income countries [23] - number need to harm = 16 for recurrent fever [23] - pneumocystis pneumonia - number needed to treat = 9-22 to reduce mortality [24] - number need to harm = 5 to precipitate other infection [24] - Bell's palsy - number needed to treat = 6-11 for complete recovery [25] - no harm noted [25] - migraine headache - number needed to treat = 10 to prevent 1 recurrence [26] - unknown harms [26] Dosage: Equivalent anti-inflammatory doses of glucocorticoids: glucocorticoid equivalent dose betamethasone 0.6 dexamethasone 0.75 triamcinolone 4 methylprednisolone 4 prednisolone 5 prednisone 5 hydrocortisone 20 cortisone 25 * when glucocorticoid therapy is > 3-4 weeks, a taper is necessary to minimize withdrawal & promote recovery of the hypothalamic-pituitary-adrenal axis [39] - taper to disontinue if > 7.5 mg prednisone equivalent for > 3 weeks [3] - a taper is unnecessary when glucocorticoid therapy is < 3-4 weeks, regardless of dose [39] - see glucocorticoid taper * dosage adjustment in settings of physiological stress or acute illness [3] Pharmacokinetics: - metabolized by cyt P450 3A4 - biologic 1/2life* - hydrocortisone: 8-12 hours - methylprednisolone: 4 hours - prednisolone: 18-36 hours - prednisone: 18-36 hours - dexamethasone: 36-54 hours * may be substantially different from elimination 1/2life - non-fluorinated glucocorticoids (prednisone, prednisolone, methylprednisolone) - limited ability to cross the placenta - preferred for treating mom during pregnancy Monitor: 1) blood glucose every 3 months 2) blood pressure 3) serum calcium 4) serum potassium every 3 months 5) serum triglycerides 6) ophthalmologic exam for long-term glucocorticoid use 7) serum creatine kinase to detect steroid myopathy with use > 4 weeks 8) fracture risk should be assessed within 3-6 months of long-term use (prednisone > 2.5 mg qd for > 3 months) [3] - bone mineral density - use of FRAX tool for adults > 40 years of age - reassess fracture risk every 12 months [28] Adverse effects: 1) bruising 2) osteoporosis, osteopenia, fractures* a) may inhibit osteoblast activity b) may promote osteoblast apoptosis c) inhibition of intestinal Ca+2 transport [8] d) optimize calcium & vitamin D intake [28] e) systemic glucocorticoids associated with increased risk of fractures in children with asthma [30] - no increase in risk with inhaled glucocorticoids f) long-term glucocorticoids <= 5 mg/day of prednisone do not seem to adversely affect bone mineral density [36] 3) aseptic necrosis (avascular osteonecrosis) 4) ocular adverse effects - cataracts, glaucoma, optic neuritis, retinopathy 5) hypertension 6) weight gain, fluid retention, edema 7) glucose intolerance/hyperglycemia/diabetes mellitus - manage glucocorticoid-induced hyperglycemia in patients who are eating with basal, prandial & correctional insulin [3] 8) depression, anxiety, insomnia 9) central nervous system effects a) insomnia, anxiety, irritability (60%) [12] b) steroid psychosis 1] bipolar symptoms 2] begins 7-10 days after starting 3] dose-dependent c) memory impairment, confusion d) elevated incidence of suicide attempts, depression, mania, & delirium [13] 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 with chronic use - accelerated atherogenesis, hypercholesterolemia, hypertension, insulin resistance [38] 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 [3,31] 14) Cushingoid features: a) puffed facies b) buffalo hump c) abdominal striae 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) [27], gastrointestinal bleeding, & heart failure [33] 25) short courses of oral glucocorticoids in children pose risks for pneumonia, GI bleed, & sepsis [34] 26) erythroderma following use of systemic glucocorticoids [3] * Calcium 1.0-1.5 g QD & vitamin D 400-800 IU QD may be helpful. Alendronate (or other bisphosphonate) may reduce bone loss & diminish risk of fractures [4,11,29]. Drug interactions: 1) any drug that inhibits cyt P450 3A4 may increase levels of corticosteroids 2) any drug that induces cyt P450 3A4 may diminish levels of corticosteroids Test interactions: 1) increased neutrophil count (in vivo effect) 2) increase serum glucose (in vivo effect) 3) decreased thyroid binding globulin (TBG) a) decreased total T4 b) normal free T4 Mechanism of action: 1) decrease vascular permeability 2) inhibition of airway mucous gland secretion 3) decrease in number of inflammatory cells, mast cells & T helper cells in airways 4) decrease in mRNA expression of cytokines 5) normalization of respiratory epithelium a) increased numbers of ciliated airway cells b) decreased number of goblet cells 6) inhibition of phospholipase A2 7) physiologic activator of apoptosis 8) immunosuppression

Interactions

molecular events drug interactions drug adverse effects (more general classes) monitor with drug (more general classes)

Related

glucocorticoid myopathy (steroid myopathy) glucocorticoid receptor; GR; nuclear receptor subfamily 3 group C member 1 (NR3C1, GRL) steroid (glucocorticoid) injection

Specific

alclometasone dipropionate amcinonide beclomethasone; meclometasone (Vancenase, Beconase, Vanceril, Beclovent, Qvar) betamethasone dipropionate; betamethasone valerate (Celestone, Soluspan, Betasone) budesonide (Rhinocort, Pulmicort, Turbuhaler, Flexhaler, Entocort EC, Uceris, Cortiment, Eohilia) clobetasol propionate corticosterone cortisol; hydrocortisone (Cortef, Solu-Cortef, Alphaderm, Cetacort, Cortenema, Nutracort) cortisone (Cortone) deflazacort (Emflaza) desonide; prednacinolone desoximetasone dexamethasone (Decadron, Maxidex, AK-Dex, Ozurdex) diflorasone diacetate flumethasone (Bimasone) flunisolide (Nasalide, Nasarel AeroBid) fluocinolone acetonide fluocinonide (Fluonex) fluorinated glucocorticoid fluoromethalone fluorometholone (FML) flurandrenolide fluticasone (Flonase, Veramyst, Flovent, Arnuity Ellipta) halcinonide halobetasol propionate halogenated steroid (glucocorticoid) inhaled glucocorticoid isoflupredone (PREDEF) loteprednol (Lotemax, Alrex) medrysone methylprednisolone (Medrol, Solu-Medrol, Depo-Medrol) mometasone furoate (Asmanex, Nasonex) nasal glucocorticoid (nasal steroid) ophthalmic glucocorticoid (ophthalmic steroid) perioperative glucocorticoids prednisolone; deltahydrocortisone; metacortandralone (Pred Forte, AK-Pred, Inflamase, Pediapred, Pred Mild, Prelone, Flo-Pred, Veripred 20) prednisone (Deltasone, Orasone, Liquid Pred, Meticortin, Rayos) rimexolone (Vexol) topical glucocorticoid (topical steroid) triamcinolone (TAC, Arsitospan, Kenalog, Trivaris)

General

anti-inflammatory agent endocrine agent immunosuppressive agent

Figures/Diagrams

Physiologic Activators of Apoptosis

Properties

References

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  9. deprecated reference
  10. Prescriber's Letter 17(5): 2010 Using Oral Corticosteroids: a Toolbox Detail-Document#: 260507 (subscription needed) http://www.prescribersletter.com
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  16. The NNT: Corticosteroids for Acute Respiratory Distress Syndrome (ARDS) http://www.thennt.com/nnt/steroids-for-acute-respiratory-distress-syndrome-ards/ - Adhikari N, Burns KE, Meade MO Pharmacologic therapies for adults with acute lung injury and acute respiratory distress syndrome. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD004477. PMID: 15495113
  17. The NNT: Glucocorticoids for Bronchiolitis. http://www.thennt.com/nnt/steroids-for-bronchiolitis/ - Fernandes RM, Bialy LM, Vandermeer B et al Glucocorticoids for acute viral bronchiolitis in infants and young children. Cochrane Database Syst Rev. 2013 Jun 4;6:CD004878 PMID: 23733383
  18. The NNT: Systemic Steroids for Sepsis Syndromes http://www.thennt.com/nnt/steroids-for-sepsis/ - Sprung CL et al, Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008, 358:111 PMID: 18184957 - Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, Kupfer Y Corticosteroids for treating severe sepsis and septic shock. Cochrane Database Syst Rev. 2004;(1):CD002243. PMID: 14973984
  19. The NNT: Corticosteroids for the Prevention of Post-Herpetic Neuralgia. http://www.thennt.com/nnt/corticosteroids-for-preventing-post-herpetic-neuralgia/ - He L, Zhang D, Zhou M, Zhu C. Corticosteroids for preventing postherpetic neuralgia. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD005582 PMID: 18254083
  20. The NNT: Corticosteroids for Acute Pharyngitis. http://www.thennt.com/nnt/steroids-for-pharyngitis/ - Hayward G et al Corticosteroids for pain relief in sore throat: Systematic review and meta-analysis. BMJ 2009 Aug 6; 339:b2976 PMID: 19661138 http://dx.doi.org/10.1136/bmj.b2976 - Little P. Sore throat in primary care. BMJ 2009 Aug 6; 339:b2476 PMID: 19661137 http://dx.doi.org/10.1136/bmj.b2476 - Hayward G, Thompson MJ, Perera R, Corticosteroids as standalone or add-on treatment for sore throat. Cochrane Database Syst Rev. 2012 Oct 17;10:CD008268 PMID: 23076943
  21. The NNT: Systemic Steroids for Acute COPD Exacerbations http://www.thennt.com/nnt/steroids-for-copd-exacerbation/ - Walters JA, Gibson PG, Wood-Baker R, Hannay M, Walters EH. Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD001288. PMID: 19160195
  22. The NNT: Glucocorticoids (Steroids) for Croup http://www.thennt.com/nnt/steroids-for-croup/ - Russell KF, Liang Y, O'Gorman K, Johnson DW, Klassen TP. Glucocorticoids for croup. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD001955 PMID: 21249651
  23. The NNT: Glucocorticoid Steroids for Bacterial Meningitis. http://www.thennt.com/nnt/steroids-for-meningitis/ - Brouwer MC, McIntyre P, Prasad K, van de Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2013 Jun 4;6:CD004405 PMID: 23733364
  24. The NNT: Systemic Steroids for Pneumocystis Pneumonia (PCP,PJ) http://www.thennt.com/nnt/steroids-for-pcppj-pneumonia/ - Briel M, Bucher HC, Boscacci R, Furrer H. Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV-infection. Cochrane Database Syst Rev. 2006 Jul 19;(3):CD006150. PMID: 16856118
  25. The NNT: Systemic Corticosteroids for Bell's Palsy http://www.thennt.com/nnt/steroids-for-bells-palsy/ - Salinas RA, Alvarez G, Daly F, Ferreira J. Corticosteroids for Bell's palsy (idiopathic facial paralysis). Cochrane Database Syst Rev. 2010 Mar 17;(3):CD001942 PMID: 20238317 - Gronseth GS and Paduga R Evidence-based guideline update: Steroids and antivirals for Bell palsy. Report of the Guideline Development Subcommittee of the American Academy of Neurology Neurology. November 7, 2012 PMID: 23136264 http://www.neurology.org/content/early/2012/11/07/WNL.0b013e318275978c.abstract
  26. The NNT: Steroids (Dexamethasone) for Prevention of Migraine Recurrence. http://www.thennt.com/nnt/steroids-for-prevention-of-migraine-recurrence/ - Colman I, Friedman BW, Brown MD et al Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence. BMJ. 2008 Jun 14;336(7657):1359-61 PMID: 18541610 - Singh A, Alter HJ, Zaia B. Does the addition of dexamethasone to standard therapy for acute migraine headache decrease the incidence of recurrent headache for patients treated in the emergency department? A meta-analysis and systematic review of the literature. Acad Emerg Med. 2008 Dec;15(12):1223-33. PMID: 18976336
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Component-of

antibiotic-glucocorticoid combination