Glucocorticoids Flashcards
What is the effect on glucocorticoids on plasma glucose levels?
Increased plasma glucose due to increased gluconeogenesis
What is a negative consequence of the increased plasma glucose?
Diabetes mellitus
How do glucocorticoids effect glycogenolysis?
They don’t!
What is the effect of glucocorticoids on protein metabolism?
Increased protein breakdown –> increased amino acids
What are the effects of glucocorticoids on lipid metabolism?
- Increase in bile production
2. Increase in fat redistribution
What are the effects of mineralocorticoids on electrolyte and water balance?
Increase Na+ and HCO3- retention while decreasing retention of H+, Cl-, and K+
How do glucocorticoids cause PU/PD?
Decreased ADH secretion
Glucocorticoids increase C.V. –> increase GFR –> increase Na+ and H2O excretion
How do glucocorticoids cause osteoporosis?
Decrease gut absorption and renal reabsorption of Ca2+ –> decreased plasma Ca2+ –> increased PTH –> increased bone resorption
What is the effect of glucocorticoids on osteoblasts?
Increases apoptosis of osteoblasts
What is the effect of glucocorticoids on osteoclasts?
Increases the life span of osteoclasts
Glucocorticoids (increase or decrease) excitation?
Increase
Mineralocorticoids (increase or decrease) excitation?
Decrease
What are the 2 major cardiovascular effects of glucocorticoids and mineralocorticoids?
- Increased vasomotor response
2. Increased myocardial contraction
How do mineralocorticoids effect blood pressure?
Increase blood pressure by increasing Na+ in ECF
How do mineralocorticoids increase myocardial contractility?
Decrease of K+ in ECF leads to increase in myocardial Ca2+
Mineralocorticoids induce hypokalemia. Hypokalemia + digitalis = ___?___
Cardiac arrhythmia
Glucocorticoids and mineralocorticoids both increase vasomotor response and myocardial contractions. How do glucocorticoids do this?
Increase epi, NE –> increase expression of alpha-1 and beta adrenergic receptors –> increase angiotensinogen –> increase ACE –> decrease bradykinin –> vasoconstriction –> decreases capillary permeability –> decreases edema
Describe the effects of glucocorticoids on the following: RBCs, neutrophils, eosinophils, lymphocytes, WBCs, platelets, lymph nodes, thymus.
RBCs - increased
Neutrophils - increased
Eosinophils - decreased
Lymphocytes - decreased
WBCs - decreased function
Platelets - increased
Lymph node - decreased in size
Thymus - decreased in size
What is the T1/2 of short acting corticosteroids?
What is the T1/2 of intermediate acting corticosteroids?
12-36 hours
What is the T1/2 of long-acting corticosteroids?
36-72 hours
In which species is conversion of prednisone to prednisolone impaired?
Cats
Horses
What is the glucocorticoid potency of short-acting glucocorticoids?
What is the glucocorticoid potency of intermediate-acting glucocorticoids?
4-5
What is the glucocorticoid activity of long-acting glucocorticoids?
> 10
Which 2 configurations are important for corticosteroid activity?
- 3-keto
2. 4,5 delta
Which 2 configurations are important for glucocorticoid activity?
- 11 beta-OH
2. 17 alpha-OH
What is the purpose of 1,2-delta?
Strengthens 4,5-delta
What is the purpose of 16-OH, CH3?
Protects 17-OH
What is the purpose of 6-, 9-fluoro, 6-CH3?
Protect 11-OH and 4,5-delta
How would you administer a water soluble corticosteroid?
IV
How would you administer a water insoluble corticosteroid?
IM or SQ
Which two plasma proteins are involved in the binding of cortisol in the plasma?
- Corticosteroid-binding globulin (CBG)
2. Albumin
What are the adverse effects associated with glucocorticoids?
- Decreased wound healing
- Increased susceptibility to infection
- Thrombosis
- Myopahty
- Osteoporosis
- GI ulcers
- Hepatotoxicity
- Diabetes
- Glaucoma
- CHF in cats
- Laminitis
- Abortion
What are the 6 general contraindications for steroid use?
- Late pregnancy
- Burns
- Diabetes mellitus
- Corneal ulcer
- Cardiac disorders
- Uncontrolled infections
Dopamine (D2) receptors (increase or decrease) ACTH secretion?
Decrease
Primary hypoadrenocorticism = increased or decreased ACTH?
Increased ACTH
Secondary hypoadrenocorticism = increased or decreased ACTH?
Decreased ACTH
Can ACTH be used therapeutically?
No
Which of the following are reversible and which are irreversible: Ketoconazole, Trilostane, Selegiline, Mitotane.
Irreversible : Mitotane
Reversible : Ketoconazole, Trilostane, Selegiline
Which layers of the adrenal cortex are affected by Mitotane?
Mitotane destroys (1) zona reticularis and (2) zona fasciculata
What are the 2 adverse effects associated with Mitotane?
- Hypoadrenocorticism
2. Hepatotoxicity
What is the mode of action of Trilostane?
Inhibits 3 beta-hydroxysteroid dehydrogenase (this enzyme forms the 3-keto group, and without that keto group, there is no corticosteroid activity)
What are the 2 adverse effects associated with Trilostane?
- Adrenal gland necrosis (although rare)
2. GI and reproductive disturbances (inhibits the synthesis of sex steroids)
What is the mode of action of Ketoconazole?
Inhibits steroidogenesis by inactivating cytochrome P450
What are the 3 adverse effects associated with Ketoconazole?
- Hepatotoxicity
- GI and reproductive disturbances
- Drug interactions due to enzyme inhibition
What is the mode of action of Selegiline?
Inhibits ACTH secretion by increasing dopamine (dopamine decreases ACTH secretion)
What are the 4 D2-receptor agonists?
- Bromocriptine
- Cabergoline
- Pergolide
- Apomorphine
Which of the following is used to treat pituitary-dependent hyperadrenocorticism: Mitotane, Ketoconazole, Selegiline, or Trilostane?
Selegiline
