The natural endogenous glucocorticoid
Hyrdocortisone (Cortisol)
The equivalent dose of 20mg of hydrocortisone
5mg of prednisolone
Metabolism and excretion of glucocorticoids
Metabolism is by the liver by microsomal oxidizing enzymes→ metabolites are conjugated to glucuronic acid or sulfate and excretion is by the kidney
The glucocorticoid prefered in pregnancy + why
Prednisone is preferred in pregnancy because it minimizes steroid effects on the fetus. It is a prodrug that is not converted to the active compound( prednisolone) in the fetal liver.
Mechanism of action of glucocoricoids
Corticosteroids bind first to cell surface receptors then to
cytoplasmic receptors (carriers), then transported to the
nucleus, where it interacts with many DNA receptors (steroid
response elements) acts as a transcription factor to turn genes
on (coactivators) or off (corepressors), depending on the
tissue and affect their function.
Anti-inflammatory and anti-immunological effects of glucocorticoids
1) inhibit B cell function →↓antigen-antibody reaction
2) inhibit T cell functions →↓inflammatory mediators and cytokine release
3) inhibit macrophage activity and stabilize lysosomal membranes
4) inhibit mast cells→↓ histamine release and capillary permeability
5) inhibit phospholipase A2 enzyme→↓ synthesis of PGs & LTs
Effects of glucocorticoids on CVS
Hypertension due to:
o Na+& water retention
o Increase sensitivity catecholamines of BV and heart to circulating catecholamines
The anti shock effects of glucocorticoids are due to
▪ Hypertensive and CVS effects
▪ Anti-inflammatory action
Effect of glucocorticoids on growth
Growth retardation, which is not prevented by growth hormone
Effect of glucocorticoids on bone
↓ intestinal Ca2+ absorption, inhibit bone formation, and ↓ sex
hormone synthesis→ osteoporosis
Used after brain surgery to minimize inflammatoru edema associated with tissue injury
Dexamethasone
For acute hypercalcemia
Glucocorticoids to enhance Ca+ secretion
Managment of acute adrenocortical insufficiency (acute addisonian crisis)
i. i.v.fluids (saline).
ii. Hydrocortisone 100 mg i.v./8h until the patient is stable.
iii. ACTH: 0.5 mg i.m.
Given to reduce the incidence of respiratory distress syndrome in infants + why
Betamethasone, it is chosen because its maternal protein binding is
less than other steroids, allowing increased transfer across the
placenta to the fetus.
Iatrogenic cushing syndrome occurs if…
If doses up to 100mg hydrocortisone are used daily for > 2 weeks
Peptic ulcers might occur from prolonged use of glucortoids due to
Due to prolonged inhibtion of gastroprotective PGs
↑ IOP (Glaucoma) might occur from prolonged use of glucortoids due to…
Due to ↓aqueous humor drainage
Side effects that might occur after prolonged topical use of glucocorticoids
Skin atrophy& hypopigmentation
Sudden withdrawal after prolonged administration of glucocorticoids can cause…
Acuet addisonian crisis
Contraindictations of glucocorticoids
1) Presence of infections: especially viral infection and TB.
2) DM.
3) Hypertension & heart failure: they cause salt and water retention
4) Peptic ulcer: they ↓ synthesis of PGE2 and I2 that protect the stomach
5) In early pregnancy: may cause cleft palate
6) Psychoses
7) Peptic ulcer
8) Osteoporosis
Natural mineralocorticoids include
Aldosterone
Physiological actions of aldosterone
It binds to specific intracellular receptors in the DCT to inhibit Na+ excretion (hypernatremia) and stimulates K+ and H+ excretion (hypokalemia)
Synthetic mineraocorticoids include
Deoxy corticosterone acetate (DOCA)
&
Fluodrocortisone
