Adrenal Steroids

Question 0

Intermediate-acting GCs with less MC effects.

Answer 0

Prednisone

Question 1

Short acting GC with MC effects also

Answer 1

Hydrocortisone

Question 2

Long acting GC with least MC effects

Answer 2

Dexamethasone

Question 3

The clinically useful MC drug

Answer 3

Fludrocortisone

Question 4

Mineralcorticoid antagonist with some endocrine uses

Answer 4

Spironolactone

Question 5

T/F: GC inhibit all components of inflammation-redness, swelling, heat, pain?

Answer 5

True

Question 6

Antinflammatory mechanisms of GC

Answer 6

• Enhance vasoconstriction and decrease vascular permeability, which decrease redness and swelling.
• Inhibit formation of arachidonic acid metabolites such as prostaglandins and leukotrienes that cause fever and pain, including inhibition of PLA2 and COX2.
• Complex effects on white blood cells that decrease both inflammation and immune cell defense mechanisms.
• Alter synthesis and release of numerous cytokines and other inflammatory mediators.

Question 7

GC and MC are highly bound ind in blood, to corticosteroid binding globulin and albumin. Knowing this, what contributes to higher potency of dexamethasone and some other drugs?

Answer 7

The lack of protein binding.

Question 8

T/F: Protein bound hormone crosses cell membrane and binds to intracellular receptors that are nuclear transcription factors.

Answer 8

False: Free hormone does this (not protein-bound).
-Hormone receptor complex binds to specific “GC response elements” (GREs) on DNA to enhance transcription of specific genes leading to synthesis of specific proteins.

Question 9

Separate receptors for GCs and MCs (and drug forms), causing their different effects. What are these effects?

Answer 9

• GC: primarily metabolic effects, esp. glucose metabolism. Primary endogenous GC is cortosol, which also has MC effects. Analogs for anti-inflammatory effects.
• MC- Control body fluid and electrolyte levels. Primary endogenous MC is aldosterone, which has almost no GC effect.

Question 10

The biologic half life of hydrocortisone is longer than plasma half-life. Explain

Answer 10

Because of tissue sequestration of the drugs and their mechanism of action (increasing mRNA and protein.

Question 11

Hydrocortisone is effective for what type of inflammation?

Answer 11

Mild- Significant MC side effects prevent use of these drugs at high enough concentrations to treat severe inflammation.

Question 12

MC receptor effects:

Answer 12

• Water retention, HTN, edema.

- Hypernatremia, hypokalemia, alkalosis

Question 13

GC receptor effects:

Answer 13

• All serious, and all directly proportional to anti-inflammatory effects.
  1) Muscle wasting, weakness
  2) Skin thinning, easy bruising
  3) Fat redistribution, trunk obesity
  4) Osteoporosis
  5) Peptic ulcer
  6) Diabetes or insulin resistance
  7) Weight gain
  8) Inhibition of growth in children
  9) CNS disturbances-euphoria, insomnia, restlessness, psychosis
  10) Cataracts, glaucoma
  11) Poor wound healing
  12) Increase risk of infection
  13) Decreased ability to respond to stress
• Contraindications: VERY cautious use in patients with heart disease, HTN, Diabetes, peptic ulcer, infections, osteoporosis, glaucoma, psychoses

Question 14

Replacement therapy in adrenal insufficiency: Primary (Addison’s)

Answer 14

Due to defective adrenal function. Low cortisol and aldosterone in spite of high ACTH

Question 15

Replacement therapy in adrenal insufficiency: Secondary

Answer 15

Due to defective pituitary or hypothalamic function. Decreased cortisol with inappropriate ACTH. Aldosterone usually normal.

Question 16

Replacement therapy in adrenal insufficiency: Acute

Answer 16

Due to abrupt withdrawal of GCs or with stress in H-P-A compromised patient. Replacement therapy with hydrocortisone.

• Because both GC and MC effects may be needed.
• Can supplement with fludrocortisone for additional MC effect if needed.
• Replacement therapy often uses prednisone also: Longer half-life, many pts dont need MC effects.
• TOXICITY not a limiting factor in endocrine replacement therapy.

Question 17

What is used to stimulate surfactant production and lung maturation prior to delivery in premature infants.

Answer 17

Betamethasone

Question 18

What is used in some cancer therapy regimens because of cytotoxic effects on immune cells?

Answer 18

Prednisone

Question 19

What is used following brain surgery to minimize postoperative cerebral edema?

Answer 19

Dexamethasone

Question 20

Additional uses of GCs

Answer 20

• Useful effects in myasthenia gravis, MS, spinal cord injury.
• Calcium suppressive effects of GCs are useful in treating hypercalcemic conditions.

Question 21

What is also used to decrease MC effects from endocrine disorders and aldosterone-secreting tumors? Some androgen receptor blockade and some progesterone-like action.

Answer 21

Spironolactone