-10% of adrenal gland
-secretes epinephrine and norepinephrine
-zona glomerulosa (15% of cortex), secretes aldosterone
-zona fasciculata (60% of cortex), secretes cortisol
-zona reticularis (25% of cortex), secretes testosterone
What is the function of aldosterone?
-retains sodium and water to maintain BP
When do you dose corticosteroids?
-peaks around 8am so dose in morning
What are the metabolic effects of corticosteroids?
-carbohydrate and protein metabolism: protein catabolism, increase hepatic glycogen, gluconeogenesis, lipolysis
-lipid metabolism: redistribution of body fat (neck and abdomen)
What are the immunologic effects of corticosteroids?
-inhibit leukocyte migration, suppress cytokine, impair cell mediated immunity
What are the mineralocorticoid effects of corticosteroids?
-electrolyte and water balance (aldosterone)
What other effects do corticosteroids have?
-formed elements of blood
What are replacement therapy uses for glucocorticoids?
What are rheumatologic uses?
-ankylosing spondylitis -polymyalgia rheumatica
What are gastrointestinal uses?
What are dermatoligic uses?
-pemphigus -bullous dermatitis herpetiform
-erythema multiforme -mycosis fundgoides
-seborrheic dermatitis -angioedema
-contact dermatitis -atopic dermatitis
What are opthamic uses?
-herpes zoster opthalmitis
What are allergic uses?
What are respiratory uses?
-asthma -fulminating TB
-COPD -aspiration pneumonitis
-sarcoidosis -allergic rhinitis
How do you choose a glucocorticoid?
-depends on: pt factors, reason for use, anti-inflammatory activity and potency
-best approach is to use lowest dose for the shortest time
-may use local therapy (IA, PR, otic, inhaled, topical, nasal) whenever possible to decrease adverse effects
What corticosteroid should be used in kidney disease, CHF, or someone with HTN?
-use methylprednisolone or triamcinolone
What is the effect of long duration steroid use on the HPA axis?
-long duration steroids have increase HPA axis suppression
When should you avoid prodrugs (cortisone, prednisone)?
-in liver disease.
-use hydrocortisone or prednisolone
What is the ACUTE dosing regimen?
-<14 days use
-regimens: "physiologic" 5mg/day of prednisone
low dose 5-15 mg/day of prednisone
moderate dose 0.5 mg/kg/day of prednisone
high dose 1-3 mg/kg/day of prednisone
What is the CHRONIC dosing regimen?
->14 days of use
-taper to lowest effective dose
-may try alternate day dosing to reduce total daily steroid use
-AVOID long acting agents- esp if tapering
What is alternate day dosing?
-decreases total daily steroid dose
-used to minimize side effects (decreases degree of HPA axis suppression and growth suppression in children, may decrease cushingnoid effects)
-avoid using long acting steroids with alternate dosing schedules
How do you taper?
-taper to lowest effective dosage- sometimes no drug
-once "physiologic" dose is reached and pt is stable do the following: discontinue steroid if possible, test HPA axis with cosyntropin stimulation test (rare)
What are the goals of tapering?
-allow HPA axis function to recover
-prevent relapse of disease
-prevent withdrawal symptoms
What are the doses for an acute taper?
-prednisone 10 mg tablets #31
-take 4 tablets po x 3 days
-take 3 tablets po x 3 days
-take 2 tablets po x 3 days
-take 1 tablet po x 3 days
-take 1/2 tab po x 2 dyas
How do you do a chronic taper?
-decrease daily dose by 10% every 7 days (2.5-5mg/week)
-may have to taper slower as you approach physiologic (5mg prednisone)
-consider discontinue steroid if taking <5mg/day
-may perform cosyntropin test
What should the cosyntropin test read?
-8 am fasting cortisol should be >10ug/dl
-give 0.25 mg cosyntropin, measure cortisol 30-60 min later (should be >6ug/dl; if >20ug/dl you can d/c steroid)
What are the doses of a chronic taper?
-12.5 mg/day x 7 days
-10 mg/day x 7 days
-7.5 mg/day x 7 days
-5 mg/day x 7 days
-2.5 mg/day x 7 days
What do you need to monitor with glucocorticoids?
-vital signs and electrolytes (BMP and CBC)
-eye exams (cataracts)
-Pt education: HPA suppression and consequences, compliance, adverse effects and ways to minmize them, close follow-up, carry an identification badge
-if fever think infection
What are the adverse effects of ACUTE moderate to Hign doses?
-mood changes: insomnia, nervouseness, elevate mood, psychosis
-electrolyte disturbances: hypokalemia
What are the withdrawal symptoms?
-fatigue, fever, headache, orthostatic hypotension, hypoglycemia
-may take up to 1 year for HPA axis to recover once steroids have been stopped
What are the metabolic effects of steroids?
-muscle: myopathy (weakness), delayed wound healing
-fat: lypolysis, central redistribution (cushingnoid)
-glucose: gluconeogenesis (hyperglycemia, hyperinsulinemia)
What are the renal effects?
-salt and water retention
-hypertension: can be induced. Could switch to methylprednisolone or triamcinolone
What are the GI effects?
-nausea, vomiting,anorexia, or stimulation of appetite, constipation, diarrhea
-ulcerogenic: usually other risk factors (cirrhosis, nephrotic syndrome, NSAIDS)
So steroids cause osteoporosis?
-30-50% of pts on chronic glucocorticoid therapy will develop
-majority of bone loss occurs within first 3-12 months
-prednisone doses >7.5 mg/day at greatest risk
-possibly due to direct inhibition of osteoblast activity, decrease in calcium absorption, increased osteoclast activity due to increase parathyroid hormone secretion
How do you prevent osteoporosis?
-best therapy is to prevent unnecessary use of steroids
-prevention and treatment: wt bearing exercise, adequate calcium and vit D, estrogen replacement in postmenopausal females, alendronate and risedronate preserve bone mass
What are the central nervous system effects of steroids?
-pseudotumor cerebri (intercranial HTN)
What are the hematologic effects?
-leukocytosis (increased PMN's) <14 days
-immunosuppressive (decreased lymphocytes, eosinophils, basophils, monocytes) >14 days
What are the dermatological effects?
-thinning of skin
-hirsutism or alopecia
-impaired wound healing
What are the infectious effects?
-immunosuppression increases risk of: bacterial (reactive TB, staph), viral (varicella, herpes zoster, CMV), fungal (candida, aspergillus), parasitic (PCP, toxoplasmosis)
What are the miscellaneous effects?
-ophthalmic: cataracts, glaucoma
-growth retardation in children
How do you minimize side effects?
-use lowest dose possible
-administer as single daily dose in morning
-use short or intermediate duration agents with minimal or no mineralocorticoid activity
-use topical or local route of administration
-use steroid sparing therapies (colchicine, methotrexate)
-address other risk factors
-consider converting to alternate day dosing
What are the symptoms of addison's disease?
-weakness, wt loss, fatigue, anorexia, hyperpigmentation, hypotension, hypoglycemia
What is addisonian crisis?
-myalgias, malaise, anorexia, vomiting, fever, hypotension, shock, hyponatremia, hypoglycemia, death
What are the primary and secondary causes of addison's disease?
-primary: idiopathic, tb, cancer, bacterial infection, fungal infection, trauma, hemorrhage, congenital, autoimmune
-secondary: glucocorticoid therapy
What is the treatment for addison's disease?
-chronic steroid replacement. Hydrocortisone 20-30 mg/day
-addisonian crisis: hydrocortisone 100 mg iv q8 hrs
What are the symptoms of cushing's disease?
-obesity, HTN, moon facies, buffalo hump, hyperglycemia, menstrual irregularities, hirsutism, striae, myopathy, weakness, osteoporosis, psychosis