Adrenal medication

Question 1

What causes canine adrenocorticism?

Answer 1

Chronic exposure to excessive glucocorticoids:
- iatrogenic
- functional adrenal tumor
- pituitary tumor producing excess ACTH

Question 2

Mechanism of action of Trilostane?

Answer 2

Steroid analogue & competitive inhibitor of 3 beta-hydroxysteroid dehydrogenases in adrenal cortex:
- 3 beta-hydroxysteroid dehydrogenase important for cortisol synthesis
- blocks glucocorticoid production with less effects on other steroids

Question 3

What can Trilostane affect?

Answer 3

• increase in steroid precursor
• affects hypothalamic-pituitary axis
• affect renin-aldosterone axis

Question 4

Indication of Trilostane

Answer 4

• treatment for canine & equine hyperadrenocorticism
• Alopecia X in Malamute
• less effective treatment of feline hyperadrenocorticism
• can decrease insulin requirements in diabetic cats

Question 5

What is important to tell owners when giving Trilostane?

Answer 5

• teratogenic
• do not open capsule when giving medication

Question 6

Special characteristics of Trilostane

Answer 6

• highly lipophilic (erratic absorption)
• absorption increases with food
• current recommended dosage is lower than than labelled dose & original literature
• accumulates in the adrenal gland
• metabolized by hydroxylation & glucuronidation in liver

Question 7

Monitoring protocol for animals on Trilostane

Answer 7

Monitor by doing ACTH stim test to evaluate adrenal function:
Start 2 weeks after initial treatment
- test at 2-6 hr after the AM trilostane with food
- do not adjust dose if the cortisol level is higher than desired (some fall slower)
Second monitoring at 1 month:
- dose adjustment
Retest 10-14days following dose change
Monitor every 4-6 months after

Question 8

Adverse effect of Trilostane

Answer 8

• most common: diarrhea, vomiting, lethargy/dullness, poor appetite, lameness 7 worsening DJD
• occasional but serious effects: severe depression, hemorrhagic diarrhea, collapse, adrenal necrosis

Question 9

Why is Trilostane contraindicated in pregnant animals?

Answer 9

inhibit progesterone synthesis

Question 10

What issue can Trilostane cause?

Answer 10

Corticosteroid withdrawal syndrome (~10d after treatment)

Question 11

What to do when Corticosteroid withdrawal syndrome occurs when giving trilostane?

Answer 11

temporarily pausing the treatment and restarting at a lower dose

Question 12

What do we need to do when we suspect Trilostane is causing Corticosteroid withdrawal syndrome?

Answer 12

need to measure serum electrolyte and do ACTH stimulate test

Question 13

How does Mitotane work?

Answer 13

• cytotoxic to zona fasciculate and zona reticularis
• inhibit steroid production

Question 14

What is mitotane indicated for?

Answer 14

hyperadrenocorticism

Question 15

Pharmacokinetics of mitotane

Answer 15

• poor bioavailability
• but higher availability in animals with pituitary-dependent hyperadrenocorticism
• high volume of distribution

Question 16

Monitoring protocol for Mitotane

Answer 16

ACTH stimulation test every 7-10 days until the right dose

Question 17

Adverse effects of Mitotane

Answer 17

• GI upset (can lead to hypoadrenocorticism with mineralocorticoid & glucocorticoid)

Question 18

What to do when hypoadrenocorticism occurs with mitotane?

Answer 18

discontinue treatment and continue with a supplemental glucocorticoid

Question 19

How does ketoconazole treat hyperadrenocorticism?

Answer 19

inhibition of P450 enzymes involved in steroidogenesis

Question 20

How to increase ketoconazole absorption?

Answer 20

give with food since there is an increased ionized form due to the secretion of acids into the stomach

Question 21

Adverse effects of ketoconazole

Answer 21

• common: anorexia, vomiting, diarrhea
• hepatotoxicity

Question 22

What species is ketoconazole contraindicated in?

Answer 22

cats (do not absorb well)