Glucocoricoids

Question 1

Which parts of the adrenal gland produce glucocorticoids?

Answer 1

Zona fasciculata and reticularis

Question 2

Exogenous glucocorticoids

Answer 2

Clinical application
Negative long feedback loop (HPPA)
Strong inhibitor of hypothal.
Leads to adenohypertrophy

Question 3

Examples of prodrugs

Answer 3

Cortisone, prednisone, methylprednisone

Question 4

Aqueous solutions

Answer 4

Soluble esters- Na phosphate or Na- succinate
Given IM/IV in large doses for emergencies

Question 5

Suspensions

Answer 5

Insoluble esters with opaque consistency- salts
Given Sc or IM, slow onset

Question 6

Short-acting glucocorticoids (<24 hours)

Answer 6

Cortisol (hydrocortisone) - 1 gluco, ++ mineralo
Cortisone (prodrug)- 0.8, ++
Prednisone- 4, +
Prednisolone- 4, +
Methylprednisolone- 5, +
^^ alternate-day therapy possible

Question 7

Intermediate-acting (24-48 hrs)

Answer 7

Triamcinolone- 5, 0
Triamcinolone acetonide- 35, 0

Question 8

Long-acting (>48 hours)

Answer 8

Flumethasone- 15, 0
Dexamethasone- 30, 0
Betamethasone- 30, 0
^^ produce glucocorticoid effects

Question 9

What drugs produce mineralocorticoid effects?

Answer 9

Aldosterone + fludrocortisone

Question 10

Mineralocorticoids

Answer 10

Maintains electrolyte homeostasis
Trigger wound healing

Question 11

Glucocorticoids

Answer 11

Carb, protein and lipid metabolism
Immune and stress response

Question 12

Major endogenous glucocorticoid is ___________ and mineralocorticoid is _________

Answer 12

1. Cortisol
2. Aldosterone

Question 13

Strength of binding determines _________

Answer 13

Potency and duration

Question 14

Glucose metabolism

Answer 14

↑ gluconeogenesis and glycogenolysis (hyperglycemia)
↓ glucose uptake in peripheral tissues
Insulin resistance

Question 15

Protein and lipid metabolism

Answer 15

↓ protein synthesis (anabolism)
↑ protein catabolism and lipolysis

Question 16

Anti-inflammatory effects

Answer 16

Stimulates lipocortin production
Inhibits PL A2 activity
↓ vascular permeability
COX and LOX affected
↓ induced histamine formation
Antagonize toxins and kinins

Question 17

Immunosuppression

Answer 17

Inducing apoptosis (lymphoids)
Inhibits clonal expression of T and b cells and interferon synthesis
↓ igG and complement, leukocyte accum.

Question 18

When is Immunosuppression seen?

Answer 18

When medium to high doses are used (treating life threatening conditions)

Question 19

What does glucocorticoids do to water and electrolyte balance?

Answer 19

Prednisolone and methylprednisolone enhances K+ excretion and Na+ retention

Question 20

How do Glucocorticoids affect the kidney

Answer 20

↑ renal excretion
↓ intestinal absorption of Ca causing hypocalcemia

Question 21

How do Glucocorticoids affect bones

Answer 21

Inhibits osteoblasts, stimulates osteoclasts, ↑ parathyroid secretion affecting bone healing

Question 22

How does Glucocorticoids affect the endocrine system?

Answer 22

Suppression of ACTH, GH and TSH

Question 23

Glucocorticoids PK

Answer 23

~90% of cortisol reversibly bound to plasma proteins
Bound to albumin
Excreted in urine

Question 24

Physiological replacement therapy

Answer 24

Adrenalectomized and addisonian dogs and cats
In moderate stress (2-5 times), severe (5-20)
Hydrocortisone or cortisone
Prednisolone or prednisone

Question 25

Intensive short-term and shock therapy

Answer 25

Improve survival in hemorrhagic and septic shock Use high dose, water soluble

Question 26

Antiinflammatory and antiallergic therapy

Answer 26

Pruritic dermatoses Allergic pulmonary disease Allergic gastroenteritis Prednisolone or prednisone (small animals) Dexamethasone (large animals)

Question 27

_________ only used in cats

Answer 27

Prednisolone

Question 28

Immunosuppressive therapy for autoimmune diseases

Answer 28

Immune-mediated thrombocytopenia Autoimmune hemolytic anemia Prednisolone and dexamethasone for induction

Question 29

Chronic palliative therapy

Answer 29

Used when NSAID therapy not working Chronic arthritis Hip dysplasia in dogs

Question 30

Alternate-day therapy

Answer 30

Allows HPAA to recover on "off" days Prednisolone (short-duration) Less practical for large animals

Question 31

Special uses

Answer 31

Topical and intralesional usage Dermatitis HPAA suppression Lymphoma

Question 32

Acute dermatitis

Answer 32

Hydrocortisone or prednisolone

Question 33

Chronic dermatitis

Answer 33

Dexamethasone, betamethasone, triamicinolone

Question 34

Intraarticular administration

Answer 34

Horses to manage joint pain and inflammation (arthritis and bursitis) Triamcinolone acetonide (osteoarthritis)

Question 35

Ophthalmic applications

Answer 35

Treating retinitis, choroditis, optic neuritis, orbital cellulitis Contraindicated in corneal ulcers

Question 36

Neurological applications

Answer 36

Acute spinal/CNS trauma Acute cervical pain Peripheral neuropathies

Question 37

What syndrome does Glucocorticoids cause?

Answer 37

Cushing's → PU/PD, symmetric alopecia, ↑ susceptibility to infection, peripheral myopathy, muscle atrophy, body fat redistribution

Question 38

Adverse effects

Answer 38

Diabetes mellitus Iatrogenic secondary hypoadrenocorticism Glycogen accumulation in liver Slow turnover of enterocytes Inhibits protective PG ↓ collagen synthesis Mood/ behavior changes

Question 39

High doses in horses cause ________

Answer 39

Laminitis