Corticosteroid Therapy

"Na+ retaining"

• increase Na+ = increase H2O = increase volume
• decrease K+

• Endogenous = Aldosterone
• Synthetic = fludrocortisone, oral (Florinef); deoxycorticosterone, IM

"Glucose retaining"

• 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

• 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

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.

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.

• General
• 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

• Treatment
• 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+

Med-ID alert.

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.

• General
• 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.

• Immunosuppressive
• 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

• GI
• routine use of antacids, PPI’s and H2 antagonists not recommended for ulcer prevention
• N/V; diarrhea/constipation; take with food

• Cardiovascular
• BP, lipids, fluids, electrolytes

• CNS
• vertigo; insomnia; depression

• Dermatological
• skin atrophy; ecchymosis

• Endocrine
• hyperglycemia

• Musculoskeletal
• aseptic necrosis; myalgias; weakness
• Steroid withdrawal syndrome
• Probably related to abrupt change in levels

• Ophthalmic
• ­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