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- increase Na+ = increase H2O = increase volume
- decrease K+
- Endogenous = Aldosterone
- Synthetic = fludrocortisone, oral (Florinef); deoxycorticosterone, IM
- Endogenous = Cortisol (by circadian rhythm and stress
- Regulation of fat, carbohydrate and protein metabolism
- Naturally occurring = Hydrocortisone and Cortisone
- Synthetics differ by duration, MC, and anti-inflammatory potency
Pharmacologic Doses of GC
and Immune Response by:
- Inhibiting macrophage accumulation in inflamed areas
- Decreasing capillary permeability and edema formation
- Antagonize histamine activity
- Decrease immune globulins and passage of immune complexes through basement membrane
- Prevent release of destructive acid hydrolases from leukocytes
Most require hepatic conversion: prednisone metabolized into prednisolone, cortisone metabolized into hydrocortisone
Glucocorticoid Equivalencies, Potencies and T 1/2
Short Acting, T 1/2 8-12hrs: Cortisone, Hydrocortisone
Intermediate Acting, T 1/2 18-36hrs: Prednisone:Prednisolone (1:1 equivalency), Triamcinolone, Methylprednisolone
- Long Acting, T 1/2 36-60hrs: Dexamethasone, Betamethasone.
- No sodium retaining properties.
- Most postent anti-inflammatory steroids.
- Useful for fetal organ Maturation.
- Prednisone Equivalents
- Hydrocortisone 20mg = Prednisone & Prednisolone 5mg, Triamcinolone & Methylpred 4mg, Dexamethasone & Betamethasone 0.75mg.
Therapeutic Uses for Corticosteroids
Primary: Addison's Disease
Secondary: Defficiency of ACTH due to gland suppression; usually caused by overuse of exogenous GC.
- Never curative, only decrease sx.
- Does not affect progression of dz.
- Use lowest dose for shortest time.
- Taper usually not necessary if duration of use < 2wks.
- For anti-inflammatory and immunosuppressive effects, use synthetic GC with minimal MC potency.
- Usually asymptomatic until loss of > 90% of adrenal cortex.
- 50% usually involve clinical disorder of another hormonal system.
- Usually minimal effect on catecholamines (medulla).
- Common Symptoms
- Decrease BP, decrease glucose, hyperpigmentation, vitiligo, electrolyte abnormalities
ACTH stimulation test: abnormal response
- Physiologic doses of corticosteroids.
- 10-20mg QD cortisol equivalent
- GC: 2/3 AM and 1/3 PM to try to mimic circadian rhythm. Use Hydrocortisone.
- Usually double dose during febrile illness.
- MC: Fluodrocortisone QD
- Monitoring Goals of Therapy
- Normalization of BP, glucose, K+, Na+
Corticosteroid Use Precautions
Risk of adrenal suppression: Can last 6-12 months after long-term, high dose use.
Infections: doses > 1 mg/kg/day of pred-equivalent.
Pregnancy: amenorrhea with high doses; possible fetal effects.
Pediatrics: avoid long-term use; goal of QOD dosing, growth suppression, cataracts.
Corticosteroid Adverse Effects
- Increased duration of use + increase dose = increased risk of adrenal suppression [>7.5mg prednisone for >3wks].
- Suppression unlikely with short term use of high doses.
- Cosyntropin test (ACTH stimulation test)
- Measure to Avoid Suppression
- QOD dosing.
- Low dose, short acting, short term.
- Use route other than systemic.
- Usually > 1mg/kg/day of prednisone-equivalent
- Decreased inflammation by inhibiting mediators and movement of WBCs
- Post transplant use low doses with "steroid sparing" immunosuppressive agents
- routine use of antacids, PPI’s and H2 antagonists not recommended for ulcer prevention
- N/V; diarrhea/constipation; take with food
- BP, lipids, fluids, electrolytes
- vertigo; insomnia; depression
- skin atrophy; ecchymosis
- aseptic necrosis; myalgias; weakness
- Steroid withdrawal syndrome
- Probably related to abrupt change in levels
- increased IOP; cataracts [risk highest in peds and RA pts]
- Osteoporosis [OP]
- most serious AE!!
- Has to do with Ca2+ balance
- Cumulative dose of 10 gm pred-equiv
- 50% of pts on > 7.5mg pred-equiv for > 1 yr have 4x increased vertebral fractures and double risk of hip fractures
- inhibits osteoblasts; decreases intestinal absorption of Ca++
- bisphosphonates now recommended for prevention and treatment of GC-induced OP