CORTICOSTEROIDS

mechanism of action
Structure

·      hydrocortisone (cortisol) is principal corticosteroid of adrenal cortex

·      produced by hydroxylation of cortisone

·      prednisone is synthetic analog of cortisone

·      prednisone similarly hydroxylated  to form active prednisolone

Plasma levels

·      plasma cortisol maintained at 5-25 ug/ml by hypothalamic-pituitary-adrenal feedback loop

·      transport

·      80% bound to transcortin

·      10% bound to albumin

·      10% provides biological activity

Receptors

·      receptor proteins found in cytoplasm of corticosteroid-responsive tissues

·      receptor and cortisol bind and move to nucleus

·      results in production of mRNA

Protein synthesis

·      main corticosteroid effect is increased protein synthesis

·      esp. lipocortin

·      lipocortin inhibits phospholipase A2

·      thus inhibits formation of many proinflammatory products

·      prostaglandins

·      leukotrienes

·      cytokines (esp. interleukins)

Lymphocyte function

·      in vivo effects not clear

adverse reactions
Metabolic

Obesity

·      increase fat deposition

·      induce alteration of fat distribution

·      Cushingoid moon face and buffalo hump

Glucose/protein metabolism

·      hyperglycaemia and insulin resistance

·      protein catabolism in muscle and bone

Electrolyte imbalance

·      sodium retention

·      potassium loss

Predisposition to infection

·      esp. S. Aureus, G -ve and TB

Musculoskeletal

Osteoporosis

·      principally loss of trabecular bone

·      greatest in spine

·      less in proximal femur

Osteonecrosis

·      increased risk of AVN

Growth retardation

·      inhibits linear bone growth

·      causes delayed epiphyseal closure

Steroid arthropathy

·      follows repeated intra-articular steroid injections in joints damaged by rheumatoid arthritis or osteoarthritis

·      usual slow progression of joint destruction accelerated

·      rapidly progressive but relatively painless collapse

·      similar to neuropathic arthritis

·      thought to be due to

·      unappreciated osteochondral fractures

·      diminution of normal protective pain responses

·      also may exist with excessive use of analgesics

Others

·      myopathy

·      tendon rupture

Gastrointestinal

·      peptic ulcer disease

Dermatological

·      acne

·      striae

·      alopecia

·      bruising

·      skin atrophy

CNS

·      depression

·      psychosis

Ophthalmic

·      cataract

·      glaucoma

HPA axis

·      suppresses H-P-A axis