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Corticosteroid questions

ebola?

ebola?

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Hi all.
I'm not a regular in [the steroid forum, where this was originally posted], but I figured that this forum would be where I'd find those most savvy in endocrinology explicable to laypeople such as myself. :)

I have recently developed the auto-immune disorder, "Lichen Planus", and in turn have been put on 3 temporary courses of centrally administered corticosteroids (prednisone, an IM injection that the doctor fucking left unnamed, and prednisone again 8) ), along with an assortment of creams.

I have noticed two alarming trends:
1. As far as I can tell, I am rather susceptible to the effects of the centrally administered agents on mood. I would characterize the feeling as a bizarre combination of nervousness, increased social dominance, and low-grade mania that is mostly unpleasant.
2. By the third course of treatment, prednisone had ceased being effective for my condition, while still imparting unpleasant mental effects.

In short, I am wondering what, in particular, these drugs are doing to my body

Now, it is my understanding that these drugs are agonists at corticosteroid receptors which mimic the effects of cortisol. The desired main effect here is reduced immune function, which leads to a decrease in various inflammatory responses.

One thing that I don't understand well are the intracellular effects of these compounds. When we say that they diffuse across lipid bi-layers to alter gene-transcription, what is actually happening more specifically?

I also have a poor understanding of how endocrine systems adapt to maintain homeostasis in the face of exogenous cortisol-mimics. How is it, exactly, that adrenal function 'shuts down' following artificially induced corticosteroidal activity? What role does altered genetic transcription play in this process?

ebola
 
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From what I understand, (and I'm no endocrinologist) things like prednisone bind irreversably to either glucocorticosteroid receptors or mineralocorticosteroid receptor, causing it to dimerize and interact with DNA in a very ill-defined manner.

The end result of binding to the glucocorticoid receptor is usually anti-inflammatory activity, i.e. release and upregulation of anti-inflammatory proteins like Hsp90, and (with much higher doses) supression of natural horomone processes due to disruption of the normal feedback mechanisms in your pituitary-adrenal axis. Compare shutdown of the testes/gonads in anabolic steroid use.

Cortisol is a very important stress horomone, and I can definitely see why corticosteroids could make you... temperamental, or otherwise. Lichen planus seems to be correlated with stress but I think in this case the corticosteroids are best left as ultra-powerful antiinflammatories. I would discontinue IV treatment with them if your symptoms are not improving.
 
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After seeing a real dermatologist in the interim, I received a pair of topical corticosteroids that appear to have worked without doing my head in. :P I still find this topic interesting though.

ebola
 
It is interesting that you mention the relationship between prednisone and memory.

I was on long massive courses of prednisone to try and control my Crohn’s when I was in my pre-teens. During this time my mother was very very ill and almost died. I remember very vaguely my grandparents telling us that she may die this one night and then going to the hospital and to say goodbye. That and that she was on the couch for a very long time is all I really remember for about 3 years.

To this day I have always wondered why I have so few memories from this time in my life. I assumed that it was due to stress and trauma of the situation and that I was just repressing these memories, but now I wonder if the medications I was on at the time played a role.
 
I understand that the adrenal crisis / Addisons is as a result of the synthetic corticosteroids downregulating the production of natural ones. though I think it's more of a problem for people who use corticosteroids regularly longterm, like eczema or asthma sufferers. over a short course it shouldn't be an issue.
 
chasing_s said:
I understand that the adrenal crisis / Addisons is as a result of the synthetic corticosteroids downregulating the production of natural ones. though I think it's more of a problem for people who use corticosteroids regularly longterm, like eczema or asthma sufferers. over a short course it shouldn't be an issue.
Click to expand...

Not necessarily. I have adrenal crisis from a single corticosteroid injection and I've had heaps of test to explain it and no answers. I'm not allergic to the medication, just have sensitive adrenals I guess. A look on the internet and it turns out it is more common than many would have you think. Took awhile to manifest itself but it has been some of the hardest months of my life (medically anyway). Now however I can take cortisone acetate and feel heaps better, and this doesn't supress my adrenals from recovering.
 
Interesting. I unfortunately caught a respiratory virus recently, and my elevated general immune response as led to a flare up in my Lichen Planus (I talked to a friend in med school who considers this hypothesis quite plausible).

Now I'm wondering, to what degree should I worry about topical corticosteroids absorbing transdermally, causing central effects? I would like to treat my auto-immune condition, but I'd also like to continue to combat this cold deftly.

ebola
 
I haven't heard of topical corticosteroids applied reasonably (i.e. not slathering your torso in 10% cortisone every hour) causing any neurological effects aside from placebo. At least I wouldn't expect there to be.

If anything is adsorbed it will be on the order of micrograms. Most topical preparations are pretty good with localizing the drug as the skin is an excellent chemical barrier. Things like fentanyl that are active at minute concentrations and highly fat soluble are the exception however.
 
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