What are systemic corticosteroids and how do they work?

Corticosteroid

any of a group of steroid hormones produced in the adrenal cortex or made synthetically. There are two kinds: glucocorticoids and mineralocorticoids. They have various metabolic functions and some are used to treat inflammation.

Systemic corticosteroids

 Systemic corticosteroids refer to corticosteroids that are given orally or by injection and distribute throughout the body. It does not include corticosteroids used in the eyes, ears, or nose, on the skin or that are inhaled, although small amounts of these corticosteroids can be absorbed into the body.

 Naturally occurring corticosteroids

 Naturally occurring corticosteroids, hydrocortisone (Cortef) and Cortisone, are produced by the outer portion of the Adrenal Gland known as the Cortex (hence the name, corticosteroid). Corticosteroids are classified as either:

1. glucocorticoids (anti-inflammatory) which suppress inflammation and immunity and assist in the breakdown of Fats, Carbohydrates, and proteins, or as
2. mineralocorticoids (salt retaining) that regulate the balance of salt and water in the body.

Mechanism of action

1. enter cells where they combine with steroid receptors in cytoplasm.
2. combination enters nucleus where it controls synthesis of protein, including enzymes that regulate vital cell activities over a wide range of metabolic functions including all aspects of inflammation.
3. formation of a protein that inhibits the enzyme phospholipase A₂ which is needed to allow the supply of arachidonic acid. Latter is essential for the formation of inflammatory mediators.
4. also act on cell membranes to alter ion permeability.
5. also modify the production of neurohormones.

Mineralocorticoid

1. Na retention by renal tubule.
2. increased K excretion in urine.

Glucocorticoid

1. CHO metabolism: increased gluconeogenesis, � peripheral glucose uptake may be decreased with resultant hyperglycaemia � glycosuria
2. protein metabolism: anabolism is decreased but catabolism continues unabated or is increased resulting in negative N balance and muscle wasting. Osteoporosis occurs, growth slows in children, skin atrophies (together with increased capillary fragility leads to bruising and striae), healing and fibrosis delayed
3. fat deposition: increased on shoulders, face and abdomen
4. inflammatory response depressed
5. allergic response depressed
6. antibody production reduced by large doses
7. lymphoid tissue reduced (including leukaemic lymphocytes)
8. decreased eosinophils
9. renal urate excretion increased
10. euphoria or psychotic states may occur. ? due to CNS electrolyte changes
11. anti-vitamin D action
12. reduction of hypercalcaemia (chiefly where this is due to increased absorption from gut: vit D intoxication, sarcoidosis)
13. increased urinary Ca excretion. Renal stones may form
14. growth reduction where new cells are being added (eg in children) but not where they are replacing cells as in adult tissues
15. suppression of HPA axis. NB steroid suppressed adrenal continues to secrete aldosterone