11: Corticosteroids

Zones of the adrenal cortex

• Zona glomerulosa

• Zona fasciculata

• Zona reticularis

Adrenal zones that produce mineralocorticoids

Zona glomerulosa

Adrenal zones that produce glucocorticoids

Zona fasciculata and reticularis

How does stress cause the release of steroids

Stress → stimulates hypothalamus → CRH → stimulates AP → ACTH → stimulates adrenal cortex

Function of aldosterone

Na retention and K excretion

Function of cortisol

Anti-inflammatory and modulates metabolism

Negative feedback on the HPAA

Cortisol down regulates pituitary activity

Type of receptor that is used by steroids

Nuclear receptors

Contraindications for mineralocorticoid administration

Patient with heart failure (fluid shift would be bad!)

Actions of glucocorticoids on metabolism

• Increases gluconeogenesis

• Decreases glucose use in peripheral organs

• Increases glycogenesis

• Increases lipolysis and protein breakdown

Contraindications for glucocorticoid administration

Patient with diabetes (functional hyperglycemia due to decreased peripheral use)

Systemic actions of glucocorticoids

• Decreased leukocyte count and function

• Reduces inflammation

• Positive chronotropic and inotropic agent

How do glucocorticoids reduce inflammation

Inhibits PLA₂ → no release of arachidonic acid → decreased production of inflammatory mediators (PG, thromboxane, and leukotriene)

How do glucocorticoids inhibit PLA₂

Increases expression of a protein called lipocortin, which binds to and inhibits PLA₂

How do glucocorticoids decrease scarring

Increases collagenase activity and inhibits fibroblast activity

Why is the use of corticosteroids a double edged sword

They are highly effective but have lots of side effects

How do most corticosteroids exist in the body

Bound to a transport protein (transcortin)

Site of corticosteroid metabolism

Mostly in the liver, some in the kidneys

Considerations when deciding what corticosteroid to use

• Degree of glucocorticoid v mineralocorticoid activity

• Time of onset and duration

• Formulation and route of administration

• Species differences

Changing what chemical characteristic of corticosteroids changes activity

Cholesterol backbone

How do glucocorticoid and mineralocorticoid activity relate for a given corticosteroid

They are inversely related: if a corticosteroid has high glucocorticoid activity, it will have poor mineralocorticoid activity

Which type of activity in a corticosteroid is responsible for HPAA suppression

Glucocorticoid

Corticosteroid that should NOT be given to horses and cats (it would be them…)

Prednisone

How is prednisone unique from other corticosteroids

It is a prodrug that is converted in the liver to prednisolone

Route of corticosteroid administration that is associated with reduced HPAA suppression

Topical

Corticosteroid formulations that are suitable for IV administration

[Fill in the blank} sodium phosphate and [fill in the blank] sodium succinate → they are highly water soluble!

Which of the prior formulations is more rapid acting

[Fill in the blank] sodium succinate

Corticosteroid formulations that are suitable for IM and intra-articular administration

[Fill in the blank] acetate → water insoluble, slower absorption

Indications for corticosteroid use

• Physiologic replacement (hypoadrenocorticism)

• Anti-inflammation

• Anti-allergic

• Chronic palliative therapy

• Immune suppression

Why do we have to wean patients off of a short-term treatment with corticosteroids

Their body needs time for the feedback loops to recover and for the adrenal glands power back on, so we wean to prevent iatrogenic hypoadrenocorticism

Why do we have patients on long-term corticosteroids on alternate day therapy

Forces the HPAA and adrenal glands to function every other day

Within what time frame are corticosteroids potent and effective for CNS trauma

<8 hrs post injury

Why is it controversial to use steroids for septic shock (esp with endotoxemic shock)

The anti-inflammatory effects are paired with immune suppression, and then the patient can’t fight off the G- bacteria that are producing the endotoxin. The use of corticosteroids for endotoxemia needs to be paired with antibiotics

Common toxicity/side effect of corticosteroids

• PU/PD

• Iatrogenic hypoadrenocorticism

• Mineralocorticoid effects (bad for heart failure!)

• Immune suppression

• Muscle wasting

• Polyphagia

Mechanism of corticosteroid-induced PU/PD

Inhibition or atrophy of pituitary gland → reduced ACTH → reduced ADH release → reduced water retention

Principles to avoid adrenal atrophy while using corticosteroids

• Keep treatments short

• Taper off

• Treat every other day if you have to do long term treatment

Modifications made to treatment plans when doing long term every other day treatment

Double the daily dose of an intermediate acting steroid and give it every other day

Contraindications for corticosteroid use

• Patients with infections (immune suppression not great here)

• Diabetics and equine metabolic syndrome (functional hyperglycemia)

• Corneal ulcers (increased collagenase activity)

• Heart failure (fluid retention)