Corticosteroids

Question 1

What is a corticosteroid and what does it do?

Answer 1

Steroid that increases gluconeogenesis and increases fat redistribution

Question 2

What is a mineralocorticoid and what does it do?

Answer 2

Steroid that helps the kidneys and colon with electrolyte and water balance

Question 3

What is an example of naturally produced mineralocorticoid:

Answer 3

Aldosterone and Deoxycortisone

Question 4

Do high anti-inflammatory, immunosuppressant activity and effects on carb and protein metabolism correlate more with glucocorticoid or mineralocorticoid activity?

Answer 4

Glucocorticoid activity

Question 5

What is the predominant action of glucocorticoids on intermediary metabolism?

Answer 5

Increase the breakdown of proteins and lipids (gluconeogenesis)

Question 6

T/F Corticosteroids also cause an increase in glycogenolysis

Answer 6

FALSE; they do not change glycogenolysis

Question 7

What is the predominant action of corticosteroids on CNS?

Answer 7

Glucocorticoids: excitation and euphoria

Mineralocorticoids: decrease excitability by decreasing K in the ECF/ICF –> Hyperpolarization –> decreased excitability

Question 8

What effects does glucocorticoids have on the lymphoid tissues and immune responses?

Answer 8

Increase PMNs, monocytes, and platelets, while decreasing lymphocytes, eosinophils, and basophils

Decreases the production of IL 1 and 2

Increases immunosuppresive cytokine production

Question 9

What can the use of glucocorticoids lead to in regards to immune and lymphoid tissues/

Answer 9

Increases circulating RBC, neutrophils, and platelets

Decreases circulating lymphocytes, and basophils

Can also decrease size of LNs and thymus

Question 10

Why would you use glucocorticoids in a lymphoid tissue setting?

Answer 10

Can supplement the treatment of lymphoma or mast cell tumors
Can be used to control excessive humoral or cellular reactions

Question 11

Glucocorticoids can have what effect on RBCs?

Answer 11

Increases RBCs leading to polycythemia

Question 12

Glucocorticoids have what effect on inflammatory processes?

Answer 12

Anti-inflammatory due to suppression of immune system

DOES NOT suppress the underlying issue

Question 13

What effects do glucocorticoids have on skeletal muscle function? Mineralocorticoids?

Answer 13

Deficiency can cause weakness due to hypoglycemia and poor circulation

Excess M: hypokalemia which causes weakness in muscles

Question 14

What effects do glucocorticoids have on electrolyte and water balance? Mineralocorticoids?

Answer 14

G: Incerase the cardiac output leads to increase GFR; after while can lead to PU/PD

M: Increase Na and HCO3 retention and increase H, Cl, and K excretion

Question 15

What effects does glucocorticoids have on the respiratory tract?

Answer 15

Increases the expression of Beta-2: bronchodilation
Increase expresion of alpha-2: vasoconstriction
Helps with anti-inflammatory

Question 16

What effects does M&G have on cardiovascular system?

Answer 16

Increases the vasomotor responses and myocardial contraction.
M: Increases Na in ECF = increased BP
M: Decreases K in ECF = increases myocardial Ca

G: increase the expression of A-adrenergic receptors in BVs and Beta-adrenergic receptors in heart

Question 17

What are the clinical signs of hyperadrenocorticism? How do these relate to the actions of the steroids?

Answer 17

PU/PD: diurect effect from excretion of glucose and ions
Polyphagia: trying to eat more glucose so they don’t have to bkdown their body
Potbelly: weakness of abdominal muscles
Muscle weakness: breakdown of muscle
Recurrent UTI: Lots of glucose and ions in the urine for bacT and the immune system is suppressed
Dermatologic conditions: not enough energy to grow hair

Question 18

What are the clinical signs of hypoadrenocorticism? How do these relate to the actions of the steroids?

Answer 18

Dehydrated: body isn’t retaining Na or glucose so water flows out of the body
Hypotension: dehydrated
Bradycardia: dehydrated
Renal failure: no aldosterone produced; losing Na and water –> medullary washout
Circulation collapse: dehydration

Question 19

How does an animal get hyperadrenocorticism from steroid treatment?

Answer 19

Vet continually keeps the animal on steroid treatment

Question 20

How does an animal get hypoadrenocorticism from steroid use?

Answer 20

Had them on corticosteroids, adrenal crotex atrophies, and then takes them off the corticosteroids

Question 21

How does mineralocorticoid affect electrolyte transport in the kidney?

Answer 21

Increases Na and HCO3 and decreases K, H, and Cl in the distal tubules and collecting duct
Aldosterone increases Na absorption, which incrases AIP –> increases Na/K ATPase pump –> increased Na/ decreased K

Question 22

Why would a mineralocorticoid such as DOC increase myocardial contractility?

Answer 22

Hypokalemia = increase in myocardial Ca = increased contractility

Question 23

Why would you not use DOC with digoxin?

Answer 23

They essentially both do the same thing; Cardiac arrythmias

Question 24

What are the genomic mechanism of actions for corticosteroids?

Answer 24

Increases mRNA synthesis for enzymes that breakdown bradykinin and enzymes for gluconeogenesis

Decreases mRNA synthesis of cytokines and their receptors

Inhibits expression of chemicals responsible for inflammation while expressing ones that are anti-inflammatiory

Question 25

What are some examples of the nongenomic actions of corticosteroids/

Answer 25

BP and Hr can increase within 10 minutes Activation of plasma membrane receptors or ion channels

Question 26

Know key differences between Cortisol, DOC, and Dexamethasone and why that affects their activity

Answer 26

All has to do with carbon binding

Question 27

Cortisol, dexmethasome, and DOC: discuss the structure activity relationship of these glucocorticoids

Answer 27

Cortisol: most prevalent GC in mammals DOC: Loses both 11-OH and 17-OH = NO GC activity but good MC activity Dexamethasone: CH3 on C16 to protect 17OH enhances GC activity

Question 28

Rank the glucocorticoid potency in animals of: cortisone, cortisol, prednisolone, prednisone, methylprednisolone, fluoroprednisolone, dexamethasone, DOC, Aldosterone

Answer 28

``` Dex: (G=25) Fluoroprenisolone (G=20) Methylprednisolone (G=5) Prednisolone (G=4) Cortisol (G=1) Aldosterone (G=.3) DOC (G=0) Prednisone and cortisone (No activity) ```

Question 29

Rank the mineralocorticoid activity of aldosterone, DOC, and cortisol

Answer 29

Aldosterone (M=3000) DOC (M=100) Cortisol (M=1)

Question 30

What are some corticosteroids that are naturally produced by animals?

Answer 30

Cortisol, corticosterone

Question 31

Would you want to administer these naturally occuring corticosteroids to animals? Why or why not?

Answer 31

NO; they are subject to 1st pass effect. Most of the drug will be deactivated and flushed out

Question 32

Do corticosteroids cure disease and remove the underlying condition?

Answer 32

NO, they simply help with the symptoms and make the animal feel better

Question 33

What is the advantage of alternate day therapy? What corticosteroids would be good for this use?

Answer 33

There is less atrophy of the pituitary gland because the drug is given less frequently Prednisolon, triamcinolone

Question 34

Why are Gs used as part of chemotherapy regimens? What kind of cancer patients would respond best to glucocorticoid tx? What are the adverse effects?

Answer 34

Used against lymphoma and mast cell tumors; apoptosis of lymphocytes and decreases size of LNs and thymus Administration of exogenous glucocorticoids can cause the dog to have hyperadrenocorticism

Question 35

If you need to administer an immediate acting glucocorticoid orally to cats or horses, would you use prednisone?

Answer 35

NO; conversion of prednisone to prednisolone is impaired in cats and horse

Question 36

Which corticosteroid injectable preparations can be given in a safe manner?

Answer 36

Only water soluble forms: phosphate, succinate salts, or polyethylene glycol DO NOT give IV suspensions = embolism

Question 37

Which synthetic corticosteroid is the preferred drug for the control of hypoadrenocorticism? Why?

Answer 37

Fludrocortisone: high GC and MC activity

Question 38

What are the two major types of adverse reactions associated with the corticosteroid therapy?

Answer 38

Iatrogenic hypoadrenocorticsim Toxic effects (Extension of pharmacological effects)

Question 39

Are the adverse effects of corticosteroids qualitatively different from the physiological and pharmacological actions of the compounds?

Answer 39

No they are usually just extension of the pharmacologic effects

Question 40

List at least ten of the adverse effects of the corticosteroids

Answer 40

``` Decreased wound healing Increased susceptibility to infection Epidural steroid could induce pathogens Fluid and electrolyte imbalance Thrombosis Myopathy Osteoporosis Glaucoma ```

Question 41

Why would the long-term use of glucocorticoid cause bone fracture?

Answer 41

Causes a negative Calcium imbalance. Increased PTH will increase osteoclastic activity to reabsorb bone Apoptosis of osteoblasts will lead to decreased bone collagen synthesis and bone formation

Question 42

Least at least 5 contraindications to the use of corticosteroids

Answer 42

``` Uncontrolled infections DM Corneal ulcers Cardiac disorders Burns Late pregnancy ```

Question 43

Why should you not use glucocorticoids for the tx of corneal ulcers?

Answer 43

G will suppress the maintenance of corneal epithelium, which will cause perforation of cornea

Question 44

Why should you be extra careful in selecting the dosages of GCs in birds, rodents, and cats?

Answer 44

Corticosterone is the endogenous corticosteroid of birds, rodents, and cats; 30% more potent than cortisol Should use short acting, alternate day therapy. NEVER use long acting GC

Question 45

Differentiate the effects of ACTH and an individual GC or MC

Answer 45

ACTH stimulates adrenal cortex to release corticosteroids; will get GC and MC actions both Does not have specific effect

Question 46

Why is ACTH not used therapeutically?

Answer 46

Half-life is so short and ACTH is not specific Used more to diagnose

Question 47

What is an adrenal cytotoxic agent?

Answer 47

Mitotane

Question 48

Which zones of the adrenal cortex does Mitotane destroy?

Answer 48

Zona fasiculata and reticularis Does not affect the Zona glomerulosa (aldosterone)

Question 49

How do ketoconazole, trilostane, bromocriptine, and selegiline affect corticosteroid secretion?

Answer 49

ketoconazole: inhibits steroidogenesis by inactivating cytochrome P450 Selegiline: Inhibits ACTH secretion by increasing DA Trilostane: inhibitor of 3Beta-hydroxysteroid dehydrogenase

Question 50

Ketoconazole, trilostane, bromocriptine and selegiline; which can cause repro failures as a side effect?

Answer 50

Trilostane Ketoconazole

Question 51

What drug is best for treating hyperadrenocorticism?

Answer 51

Trilostane

Question 52

What are some naturally occuring minarolcorticoids?

Answer 52

Aldosterone and DOC