3 Adrenocoticoids and adrenocortical antagonists

Synthesized under the control of ACTH (Adrenocorticotropic hormone)

Natural adrenocortical steroids

– the predominant glucocorticoid in humans

Cortisol (hydrocortisone)

– the major mineralocorticoid of the adrenal cortex

Aldosterone

an aldosterone precursor, has both mineralocorticoid and glucocorticoid activity

11-Deoxycorticosterone,

Control water and electrolytes

Mineralocorticoid

Homeostasis

Glucorticoid

 A wide array of steroid compounds with various ratios of mineralocorticoid to glucocorticoid properties

Synthetic adrenocortical steroids

effects are mediated by two separate and specific intracellular receptors, the MR (mineralocorticoid receptor) and GR (glucocorticoid receptor)

Synthetic adrenocortical steroids MOA

Both the [] interact with these receptors resulting to complexes that modulate the transcription rate of specific genes and lead to an increase or decrease in the levels of specific proteins.

natural and synthetic steroids

Oral Adrenocortical Steroids

Anti inflamm and Sodium Retainin

Agent Table

Topical Adrenocortical Steroids

Potency

Potency Agent

Agents with the longest half-life tend to be the most potent

Corticosteroids

 Short-acting: Corticosteroids

: Cortisol (8-12 hours)

Intermediate-acting Corticosteroids

Prednisolone (12-36 hours)

Long-acting Corticosteroids

Dexamethasone (39-54 hours)

Corticosteroids Routes

PO, IV, IM, SQ, Inhalation, otic, rectal, topical

Corticosteroids

may relieve the clinical manifestations of the disease state while causing less severe suppression of the adrenal-hypothalamic-pituitary axis

Alternate-day therapy

Corticosteroids

Patients must be weaned off the drug over several days before discontinuation by using

progressively lower doses

used in replacement therapy for primary or secondary insufficiency (Addison’s Disease)

Glucocorticoids

also called adrenal insufficiency, is an uncommon disorder that occurs when your body doesn't produce enough of certain hormones. The adrenal glands, produce too little cortisol and, often, too little aldosterone

Addison's disease

Addison’s Disease This replacement therapy requires the use of both

mineralocorticoid and a glucocorticoid.

Addison’s Disease Symptoms

● The unique manifestation of Addison’s Disease is the skin discoloration. There is bronze pigmentation of the skin

● Hypoglycemia and Low Blood Pressure

● Profound/Chronic Fatigue

● Weight Loss

● Dehydration

● Craving for Salty Food

Inflammation and Immunosuppression

Glucocorticoids

 Used to treat RA, SLE, and other autoimmune diseases

Also used in hypersensitivity and allergic reactions

 Can reduce organ or graft rejection

Glucocorticoids

This test measures the suppression of plasma cortisol following the administration of dexamethasone.

3. Diagnosis of Cushing syndrome (Dexamethasone Suppression Test)

Failure to suppress cortisol may indicate

primary Cushing syndrome.

Other Indicaitons:

Sarcoidosis, dermatologic disorders, idiopathic nephrosis of children, neuromuscular disorders such as Bell’s Palsy, shock, adrenocortical hyperplasia, stimulation of surfactant production and acceleration of lung maturation in a preterm fetus, and neoplastic diseases including adult and childhood leukemia

Glucocorticoids

is a disorder that occurs when your body makes too much of the hormone cortisol over a long period of time.

Cushing syndrome.

is sometimes called the “stress hormone” because it helps your body respond to stress.

also helps maintain blood pressure. regulate blood glucose, also called blood sugar

Cortisol

Cushing syndrome symptoms

● The opposite of Addison’s Disease

● When our body is always in a state, it triggers the body to produce and release too much cortisol

● The unique manifestation of cushing syndrome is Buffalo Hump wherein there is a fatty pads in the neck

● Striae or Abdominal Stretch Marks

● Pendulus Abdomen

● Bruise Easily

● Proportion of the body. In the middle part of the body, fat is concentrated compared to the arms and legs

primarily affect the kidney, regulating salt and water balance and increasing sodium retention and potassium loss.

Mineralocorticoids

agent of choice for long term mineralocorticoid replacement

Mineralocorticoids

Fludrocortisone

used in replacement therapy to maintain electrolyte and fluid balance in hypoadrenalism

Mineralocorticoids

Fludrocortisone

Mineralocorticoids

Fludrocortisone AEs

Sodium retention, hypokalemia, edema, hypertension

An adrenolytic agent

 Suppresses the adrenal cortex and causes selective atrophy of the zona fasciculata and zona reticularis

 Can reduce plasma cortisol levels in Cushing syndrome produced by adrenal carcinoma

Mitotane

adrenocortical carcinoma

Mitotane

Mitotane AEs

GI distress, confusion, lethargy, rash

 blocks the activity of 11-hydroxylase, reducing cortisol production

 Used diagnostically to assess adrenal and pituitary function

Metyrapone

 An antifungal agent

 At high doses, a potent inhibitor of several P450 enzymes involved in steroidogenesis in the adrenals and gonads

 Can be used for Cushing syndrome

Ketoconazole