Corticosteroids

Question 1

What is the role of corticosteroids?

Answer 1

• Glucocorticoids - immunosuppressant effects

- Mineralocorticoids - role is to deal with water balance

Question 2

What is the general effect of exogenous corticosteroids?

Answer 2

Disrupt normal phys, treat symptoms but not will treat the underlying problem

Question 3

How are glucocorticoids released?

Answer 3

Circadian rhythm. Nocturnal animals will have a peak during the night and diurnal animals will have a peak during the day.

Question 4

What is the mechanism of action of corticosteroids?

Answer 4

• Highly protein bound
  1. Binds to cell and moves into nucleus
  2. Alters the mRNA strand therefore interrupting protein synthesis by inhibiting or stimulating certain protein production

Question 5

Give examples of proteins induced by corticosteroids

Answer 5

Angiotensin converting enyme
B2 - adrenoceptor
Lipocortin 1

Question 6

Give examples of proteins inhibited by corticosteroids

Answer 6

Ctokines
Cyclo-oxygenase (COX)
Collagenase
Inducible NOS

Question 7

What is the mechanism of action of glucocorticoids?

Answer 7

Metabolic, systemic, anti-inflammatory, immune suppressive

Question 8

Give examples of short acting glucocortcoids

Answer 8

Prednisolone, prednisone, methyprednisolone (<24hrs)

Question 9

GIve examples of long acting glucocorticoids

Answer 9

Dexamethasone, betamethasone, triamcinolone (>24hrs)

Question 10

How do combination with water soluble salts aid the formulation of corticosteroids?

Answer 10

• ideal for IV administration
• readily absorbed and eliminated within 8-24hrs
• high conc reached rapidly
• sodium phosphate sals and soluble esters e.g. succinate
• useful for shock and allergy

Question 11

How do combination with insoluble esters aid formulation of corticosteroids?

Answer 11

• useful for more sustained therapy
• longer acting e.g. joints
• SC or IM
• slow release from injection site

Question 12

What are the different routes of adminstering corticosteroids?

Answer 12

• topically - skin problems; allergy, inflammation. Pro-drug, metabolised to active compound
• inhalation - specifically target the lungs
• intra-articular injection - joints

Question 13

What are the general principles of corticosteroid therapy?

Answer 13

• minimal activity is preferred
• use as low a dose as possible, start with low dose then increase if required
• withdraw treatment gradually, esp if given systemically
• greater risk of toxicity with longer acting compounds
• need to treat the underlying cause of the problem

Question 14

Why do corticosteroids need to be withdrawn gradually?

Answer 14

Exogenous corticosteroids have a negative feedback effect causing suppression of ACTH followed by atrophy o the adrenal gland. Adrenal gland can no longer produce endogenous corticosteroid. So sudden termination of exogenous corticosteroid can result in a life threatening situation.

Question 15

What are the side effects of corticosteroids?

Answer 15

• Gastric and corneal ulceration (inhibition of epithelium renewal)
• Suppression of immune system
• Muscle and cutaneous atrophy
• Hyperglycaemia
• Osteoporotic effect (increase Ca excretion)
• Na and water retention (blood pressure), loss of K
• Polyuria and polydypsia
• Iatrogenic Cushing’s
• Suppression of HPA leading to Addison’s disease on drug withdrawal
• Laminitis

Question 16

Name 2 disease casued by abnormal functioning of the adrenal gland and HPA axis

Answer 16

Addison’s disease and Cushing’s disease

Question 17

What is Addison’s disease?

Answer 17

• Deficiency of adrenocortical steroid production
• Mineralocorticoid and glucocorticoid deficiency
• Underlying pathology usually immune mediated destruction of adrenal cortices
• Central hyoadrenocorticism is most commonly iatrogenic

Question 18

What are the clinical signs of Addison’s disease?

Answer 18

Anorexia, vomiting, diarrhoea, weakness, exercise intolerance, polydypsia, polyurea. May be precipated by a stressful event.

Question 19

How is addison’s diagnosed?

Answer 19

Circulating ACTH conc elevated in primary addison’s

Question 20

How is Addison’s treated?

Answer 20

Permanent mineralocorticoid therapy

Question 21

What is Cushing’s disease?

Answer 21

Overproduction of glucocorticoids due to a pituitary adenoma (ACTH increase) or to an adrenal tumour (ACTH v low).
Iatrogenic Cushing’s can result from prolonged treatment with glucocorticoids

Question 22

What are the clinical signs of Cushing’s?

Answer 22

Polydypsia, polyurea, polyphagia, elevated liver enzymes, pot belly (redistibution of fat), thin skin, coat chnages, muscle wastage

Question 23

How is Cushing’s diagnosed?

Answer 23

• ACTH test - elevated corticosteroid before ACTH and rise after administration
• Low dose dexamethasone suppression test - won’t suppress cortisol
• High dose dexamethasone suppression test - sometimes used to differentiate between pituitary and adrenal probelm. If pituitary, high dose will not suppress cortisol production
• X-ray or ultrasound

Question 24

How can Cushing’s be treated?

Answer 24

• Trilostane
• Ketoconazone - interferes with synthesis of adrenal steroids
• Mitotane - cytotoxic - removes layers of adrenal cortex to reduce corticosteroid production, adrenal tumours