How to use glucocorticoids

What role has cortisol evolved to have in mammals?

defence against stress

levels become very high to protect against starvation and disease (things that make us unwell)

What factors cause variation in how much cortisol an individual makes?

age, sex, breed, activity

external temperature, exercise

subclinical disease

How much more potent is prednisolone than cortisol?

5x more potent

What are the effects of cortisol?

metabolism

water and electrolyte homeostasis

immunity and inflammation

What are the effects on blood glucose metabolism?

increased gluconeogenesis

inhibit glycogen synthesis

decrease peripheral blood glucose utilization

point is to preserve glucose for your brain

What specific metabolisms does it effect?

fat metabolism- lipolysis, inhibits leptin secretion

protein metabolism- proteolysis

calcium metabolism- mobilizes calcium from bone, increases calcium excretion

bone, muscle, and CNS metabolism

What is the effect of glucocorticoids on electrolytes?

increase sodium re-absorption

increase potassium secretion

type 2 receptor (GR) effects

want to increase water retention

What is the effect on water?

if you said increase water retention, you’re a stupid head!!! I know the last card said increase water retention but forget that!

it actually increases GFR so increases flushing out of abnormalities to protect from disease

increased ANF (atrial natriuretic factor) receptors

What immunity and inflammation cells do they effect?

white blood cells- affect distribution and function, lymphocyte apoptosis

cytokines- suppression, NFkappaB

Should you vaccinate while on steroids?

YES!

they need it more now because they are immunocompromised

What are the steps in the genomic mechanism of action?

What is different about the non-genomic mechanisms of action?

cytoplasmic receptors- direct changes in metabolism

membrane receptors

direct interactions with cell membranes

it’s very fast

Which mechanism of action explains why the changes can be permanent?

chromosomal

deacetylation of histone

but this is slow

What determines the duration of action?

which esters, carriers, and prodrugs are added

Which steroid can’t cats have?

they can’t convert prednisone to prednisolone

Plasma levels of prednisolone is a waste of time, so what is a more effective way to measure the anti-inflammatory effect?

you can measure how much HPA suppression which is relative to the anti-inflammatory affect

For prednisolone, what diseases should you use a reduced dose?

if the patient has hypoalbuminemia

liver problems

maybe consider if you should be using it all

You should have a plan! What elements should be included?

starting dose

length of initial course (2 weeks is good starting point)

recheck points

method (parameters) on monitoring

likely dose reductions

What is important to tell clients before starting steroids?

why you are using it (disease and why it will work)

expected improvements

side effects (if the drug is working, they will have them)

time course

need for rechecks

What is the starting course for maintenance (ie for Addison’s)?

prednisolone 0.08 mg/kg/day

What is the starting course for an anti-inflammatory disease ie atopic dermatitis?

0.5-1.0 mg/kg q 24 h PO

What is a starting course for an immunosuppressive disease ie IMHA?

2 mg/kg q24h PO

cats double?

What is a starting course for anti-neosplastic ie cutaneous lymphoma?

20-40mg/m² q24 PO

What is a starting dose for anti-insulin ie insulinoma?

0.5-1.0 mg/kg q24h PO

What is the risk when doing a longer course of steroids?

can become dependent after 4 weeks

HPA is suppressed → dependent on steroids, if you take away → addison’s

also adrenals will atrophy after 6 months on steroids

If at first you don’t succeed, try, try again, right?

NO! stope, think, try something new

if it does not work in 5 days, change the drug, change the dose, try something else

When should you reduce doses?

for some diseases you can do direct observations ie measure platelets for IMTP (immune mediated thrombocytopenia)

for others you have to use surrogate markers ie measure CRP (c-reactive protein) for inflammation for SRMA (steroid- responsive meningitis-arteritis)

very hard for pemphigus

bottom line is adjust according to objective parameters such as PCV, platelet counts and acute phase proteins but if you can’t then you should adopt the ALARA principle (as low as reasonably achievable)

What should you do if you need to stop suddenly ie you need to take the patient to sx?

put on prednisolone 0.1 mg/kg a24h PO

There are some slides that talk about ADST, aka alternate day steroid treatment. He talked about some doses, I don’t know if we need to know it. Technically he said this whole lecture would be difficult to test on so could be a waste of time

I think his point was there isn’t proof that it’s effective? And that it’s not ‘safer’ to the adrenals

Alright, what are the golden rules of steroid therapy?

1. use enough, but no more, to control clinical signs

2. if not working soon, try something else

3. once signs controlled, start tapering doses

4. only switch to ADST when signs controlled

5. use other treatments to help reduce doses

6. monitor the animal individually

7. do not use as ‘preventative’ or ‘speculative’ treatment

8. do no use in ‘shock’, IVD prolapse, etc