Corticosteroids

Glucocorticoids

Functions:
 Promote intermediary metabolism – it’s a stress hormone, so it will increase serum
glucose to help the body fight stress
 Decreases the following cells by sending them to lymph tissues:
o Eosinophils and basophils
o Monocytes
o Lymphocytes
  Increases the following cells:
o RBCs
o Platelets
o Neutrophils – inhibits adhesion
 Anti-inflammatory effects:
o Lower lymphocytes
o Inhibit the ability of WBCs and macrophages to respond to mitogens and
antigens
o Inhibits phospholipase A2 – blocks synthesis of arachidonic acid, the precursor to
many pro-inflammatory PGs and LTs
o Stabilize mast cell and basophil membranes – prevent histamine release

Therapeutic uses:
 Replacement therapy for Addison’s disease – hydrocortisone used
o Hydrocortisone’s dose is divided into a morning 2/3rd and an afternoon 1/3rd to
mimic the body’s natural pattern of cortisol release
o Fludrocortisone (mineralocorticoid) also given to replace lost aldosterone
 Replacement therapy for secondary/tertiary adrenal insufficiency – caused by low ACTH
or CRH – hydrocortisone used
 Diagnosis of Cushing’s syndrome – dexamethasone suppression test
 Replacement therapy in CAH
o Suppress ACTH production and androgen release – this helps treating virilization
in women
 Relief of inflammatory symptoms
o Reduce manifestations of inflammation in rheumatoid arthritis and inflammatory
skin conditions
o Help in symptom control in persistent asthma
o Used in inflammatory bowel disease
 Treatment of allergies
o Allergic rhinitis
o Serum, drug, and transfusion allergic reactions
 For asthma and allergic rhinitis, topical administration via an inhaler is done to reduce
side-effects. An example is fluticasone.
 Betamethasone or dexamethasone can be given IM to a mother within 48 hours before
a preterm delivery to accelerate fetal lung maturation

Pharmacokinetics:
 Metabolized by the liver and the products are excreted by the kidney
 Hepatic dysfunction can increase half-life considerably
  Pregnancy:
o Prednisone preferred because it cannot be converted to the active form
prednisolone by the fetal liver
o Also, any prednisolone made by maternal liver is inactivated by the placenta
back to prednisone

AEs:
 Osteoporosis – most common AE
o Glucocorticoids suppress calcium absorption from the intestine
o Also inhibit bone formation
o Also inhibit sex hormone synthesis
o Advise patients to take calcium and vitamin D supplements
 Cushing syndrome – if excess corticosteroids given
 Cataracts if long-term therapy
 Hyperglycemia and possible DM
 Increased appetite – reason why prednisone is used in cancer patients
Taper these drugs slowly – sudden withdrawal can lead to acute adrenal insufficiency due to
suppressed ACTH production

Inhibitors of adrenocorticoid synthesis/function

Ketoconazole:
 Antifungal
 Inhibit all gonadal and adrenal steroid hormone synthesis
 Used in Cushing syndrome treatment

Spironolactone:
 Competes for mineralocorticoid receptors
 Can also antagonize testosterone synthesis
 Uses:
o Hyperaldosteronism
o HTN
o Heart failure with reduced EF
o Hirsutism in women – interferes with the androgen receptor at the hair follicle
 AEs:
o Hyperkalemia
o Gynecomastia
o Menstrual irregularities
o Skin rashes
Eplerenone:
 Binds to mineralocorticoid receptor and acts as an aldosterone antagonist
 Specific so no gynecomastia seen
 Uses:
o Hypertension
o HF with reduced EF