Lecture 9: Corticosteroids I

How do corticosteroids inhibit PLA2?

activate expression of lipocortin which is a direct inhibitor of PLA2

What is the general vascular MOA for the anti-inflammatory effects of corticosteroids?

activated expression of lipocortin → inhibits PLA2 → reduction of capillary permeability and exudation → reduced inflammation

Be able to recognize a disease that will benefit from corticosteroid therapy.

• diseases involving inflammation

• auto-immune conditions (corticosteroids suppress immune system)

• hypoadrenocorticism aka addisons (replacement therapy) for primary adrenal issues, secondary pituitary issues, tertiary hypothalamic issues, or iatrogenic causes

Be able to recognize a side effect associated with corticosteroid therapy.

• PU/PD

• Iatrogenic Cushing’s syndrome

• adrenal insufficiency once tx is stopped

• fat redistribution → moon face and buffalo hump

• increased susceptibility to infection

• peptic ulcer

• diabetogenesis from increased gluconeogenesis

What are the two main corticosteroids indicated for use in cats?

prednisolone and methylprenisolone

What is the corticosteroid indicated for use against bovine ketosis?

isofluprednone

Name the drug used to replace mineralocorticoid activity.

fludrocortisone or desoxycorticosterone

How are horses and cats similar in regards to corticosteroid therapy?

they both cannot convert prednisone to prednisolone, so prednisolone is better to use

Why is depo-methylprednisolone a second choice in atopic dogs but a viable first choice in cats?

HPA axis suppression is not as concerning in cats because they are less sensitive to the side effects of corticosteroids

Which is more likely to require corticosteroid replacement therapy after receiving corticosteroid therapy- a atopic dog or a dog with pemphigus?

pemphigus because the treatment is long term, as opposed to the short term less intensive treatment of atopy

What are corticosteroids commonly used to treat in equids?

equine heaves (recurrent airway obstruction in horses, allergic rxn to particulates in straw and hay)

Name three advantages for triamcinolone.

• intra-lesional injection

• lack of mineralocorticoid acitivty

• possibly safer in renal patients

• subconjunctival for horse instead of daily eye drops

Which topical corticosteroid would be a good choice if you were especially concerned about side effects in a patient?

mometasone (much less systemic absorption b/c Bi-clorinated which inhibits passage across biomembranes?

Name two drugs that should not be used in conjunction with corticosteroids.

1. diuretics that cause hypokalemia or digitalis → can lead to arrhythmias

2. NSAIDs → synergize upon reducing gastric mucus, thus doubling chances for peptic ulcers

Name the adrenolytic drug and describes how it works.

mitotane → irreversibly destroys the zona fasciculata and reticularis

Name the six drugs that reduce corticosteroid secretion and the MOA for each.

1. trilostane: inhibits 3-B-hydroxysteroid dehydrogenase

2. ketoconazole: inhibits cytochrome p450 system involvled in steroidogenesis

3. selegiline: inhibits ACTH secretion by increasing dopamine activity at the anterior pituitary (prevents dopamine reuptake increasing dopamine at synapse which blocks ACTH release at AP cell)

4. Bromocriptine: inhibits ACTH secretion by activating dopamine receptors at anterior pituitary

5. cabergoline: same as bromocriptine

6. pergolide: same as bromocriptine

What long-term therapy will be need after adrenolytic therapy?

glucocorticoid therapy because you induce Addison’s disease

What side effect is common to trilostane and ketoconazole but not relevant for the other secretion inhibitors?

inhibition of sex steroid synthesis leading to reproductive disturbances

What were some of the therapeutic indications for the use of anabolic steroids?

stimulate appetite, promote weight gain, enhance recovery from illness, counteract muscle wasting, and treat certain anemias