Classes of Glucocorticoid Usage

Question 1

What is the natural function of glucocorticoids? In what 3 ways does it do this?

Answer 1

protects glucose-dependent cerebral function by…

1. stimulating the formation of glucose by the liver
2. decreasing the peripheral utilization of glucose
3. promoting glucose storage as glycogen

Question 2

How is the natural effect of glucocorticoids observed? Why?

Answer 2

muscle wasting, delayed wound healing, thinning of skin

body is working to protect glucose in important tissues, like the brain and heart

Question 3

What are the 3 physiological effects of glucocorticoids?

Answer 3

1. increase gluconeogenesis from amino acids and glycerol
2. decrease protein synthesis
3. increase lipolysis to release glycerol from FFAs

Question 4

What do glucocorticoids do during fasting?

Answer 4

maintains glucose concentrations by increasing the release of glucose by the liver and gluconeogenesis by glycogen synthase

Question 5

What is the pharmacological effect of glucocorticoids in the near-term fetus? What happens when neonates mature before their adrenal axis?

Answer 5

stimulates the synthesis of surfactant proteins (GR knockouts do not survive long due to lung atelectasis)

neonatal respiratory distress syndrome

Question 6

What are the 3 major effects of glucocorticoids on energy metabolism?

Answer 6

1. antagonize effects of insulin - increase glucose production from amino acids (gluconeogenesis)
2. enhance lipolysis - redistributes fat and stimulates appetite to stimulate hyperinsulinemia
3. inhibits bone formation - inhibits osteoblast proliferation and the synthesis of bone matrix, stimulates osteoclasts

Question 7

What cardiorespiratory effect do glucocorticoids have?

Answer 7

direct positive chronotropic and inotropic effects by increasing the number and affinity of β1-adrenergic receptors and α-adrenergic receptors in vascular smooth muscle (hypertension)

Question 8

How do glucocorticoids affect water and electrolyte balance?

Answer 8

invariably leads to PU/PD by inhibiting ADH release and increases glomerular filtration

Question 9

What effect do pharmacological doses of glucocorticoids have on the stomach? In what patients should these be used very carefully?

Answer 9

stimulates excessive production of acid and pepsin

• patients under stress
• those already on drugs that contribute to GI damage (NSAIDs)

Question 10

How do glucocorticoids affect nutrient absorption? Liver function?

Answer 10

facilitates fat absorption and antagonizes the effect of vitamin D and calcium absorption

hepatomegaly and elevated liver enzymes (slowly reversible 1-1.5 months after discontinuation of therapy)

Question 11

How do glucocorticoids affect the immune system?

Answer 11

• alters concentration, distribution, and function of peripheral leukocytes (apoptosis of normal lymphoid cells)
• inhibits antibody production at high doses of long-term therapy
• inhibits virus-induced IFN synthesis
• inhibits monocyte differentiation into macrophages

Question 12

What is the purpose of most glucocorticoid therapy? How can clinicians judge the efficacy of treatment?

Answer 12

suppress clinical signs

define specific therapeutic objectives - raise hematocrit, suppress allergic reactions

Question 13

How are glucocorticoids used for physiologic replacement therapy? What 2 common conditions are treated this way? What medications are used?

Answer 13

use glucocorticoids in amounts like those naturally made (cortisol) in the adrenal gland

1. adrenalectomized animals
2. Addisons disease
   - rarely indicated in large animals

hydrocortisone/cortisone and prednisolone/prednisone**

Question 14

In what cases may intensive short-term doses of glucocorticoids increase survival? What should this therapy also include?

Answer 14

hemorrhagic and septic shock

• fluid therapy
• broad spectrum antimicrobial for endotoxic shock

Question 15

In what case is short-term (shock therapy) glucocorticoid usage contraindicated?

Answer 15

chronic sepsis - immunosuppressive effects

Question 16

What is the main concern for glucocorticoid usage as anti-inflammatory and anti-allergic therapy? For what 3 conditions may they be used?

Answer 16

such diseases are difficult to definitively diagnose and misuse of glucocorticoids is not uncommon

1. symptomatic treatment of pruritic dermatoses
2. allergic pulmonary disease
3. allergic gastroenteritis

Question 17

What is the preferred glucocorticoid for the treatment of inflammatory and allergies in small animals?

Answer 17

prednisolone or prednisone

Question 18

What is the main disadvantage to depot glucocorticoid usage for inflammatory and allelrgic therapy? What are 3 common long-acting injectable products work this way?

Answer 18

drug dosage cannot be reduced/stopped once its given, even if it’s incorrect

1. prednisolone acetate
2. dexamethasone in propylene glycol
3. triamcinolone

Question 19

What are the 2 most common causes of immune dysregulation?

Answer 19

1. genetics
2. environment - infectious agents, drugs, vaccines, neoplasia

Question 20

What are 2 common causes of lymphocyte dysfunction? What are common inappropriate responses to immunosuppressive therapy?

Answer 20

1. failure of lymphocyte selection
2. antibody or self-antigen generation

tissue destruction and clinical disease

Question 21

What are 4 common inflammatory diseases with an immune-mediated etiology in dogs and cats that can be treated with glucocorticoids? What is the goal to this treatment?

Answer 21

1. inflammatory bowel disease (IBD)
2. immune-mediated hemolytic anemia (IMHA)
3. immune-mediated thrombocytopenia (IMT)
4. immune-mediated polyarthritis (IMPA)

induce disease remission by inhibiting inflammation and modulating lymphocyte function while minimizing adverse drug effects

Question 22

What is the first-line treatment of inflammatory and immune diseases? What 4 immunosuppressants are also used?

Answer 22

glucocorticoids

1. cyclosporine
2. azathioprine
3. chlorambucil
4. mycophenolate

Question 23

How are glucocorticoids used with acute illness caused by immune-mediated disease?

Answer 23

highest immunosuppressive recommended dose until clinical signs decline and taper slowly

Question 24

When can glucocorticoid usage be discontinued for autoimmune disease? What can be used for incomplete remission?

Answer 24

once disease is in remission for 2-3 months

add other immunosuppressants, like cyclophosphamide (alkylating agent)

Question 25

What commonly happens with glucocorticoid therapy lasting longer than 2 weeks in dogs?

Answer 25

loss of adrenal functional reserve —> typically takes 2 weeks to normalize cortisol secretion

(more than 2 week treatment is considered chronic therapy)

Question 26

How does the cellular effect of glucocorticoids compare are anti-inflammatory and immunosuppressive doses?

Answer 26

inhibit phospholipase A2 and the release of pro-inflammatory cytokines

target macrophage function by downregulating Fc receptor expression and decreasing responsiveness to antibody-sensitized cells and antigen processing

Question 27

How does prednisone compare to prednisolone? How does pharmacokinetics compare in cats?

Answer 27

prednisone is a prodrug that becomes prednisolone

cats achieve higher plasma concentrations when administered oral prednisolone vs. prednisone (may lack enzymes)

Question 28

What 3 glucocorticoids can be used for immunosuppressive therapy?

Answer 28

1. prednisone/prednisolone
2. dexamethasone - lacks mineralocorticoid activity
3. budesonide - soft corticoid with low absorption and distribution, which allows it to avoid systemic adverse effects but must be administered to the site where its action takes place

Question 29

At what dose is immunosuppressing effects achieved with glucocorticoids?

Answer 29

high doses —> 2-4 mg/kg, observe patient and change dose accordingly

Question 30

When is every other day dosage recommended for glucocorticoid immunosuppressive therapy? What is the purpose of this therapy? What types of glucocorticoids cannot be used this way?

Answer 30

intermediate-acting drugs (12-36 hours)

reach immunosuppression while minimizing (but not preventing) adrenal atrophy

long duration activity glucocorticoids

Question 31

What are 7 possible side effects of immunosuppressive therapy glucocorticoid usage?

Answer 31

1. iatrogenic hyperadrenocorticism
2. adrenal gland suppression
3. GI ulceration and colon perforation
4. insulin resistance
5. muscle catabolism
6. delayed wound healing
7. opportunistic infections (esp. urinary)

Question 32

When are close monitoring and clinical vigilance with glucocorticoid especially important?

Answer 32

• intolerable or life-threatening side effects
• lack any clinically significant response to steroids with 7-14 days of treatment

(alternative immunosuppressive drugs need consideration)

Question 33

What 4 situations of minor stress may benefit with glucocorticoid supplementation? What severely stressful situation? What drug is used?

Answer 33

1. minor surgery
2. general anesthesia
3. minor illness
4. visit to vet

major surgery including adrenalectomy

prednisolone or prednisone (acetate)

Question 34

What are the effects of the different doses of glucocorticoids?

Answer 34

• ANTI-INFLAMMATORY: 10x physiologic dose
• IMMUNOSUPPRESSIVE: 2x anti-inflammatory dose
• SHOCK: 5-10x immunosuppressive dose