Talk:Glucocorticoid

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Much of the article's text has been incorporated from the article Immunosuppressive drug and should be revised. --Eleassar my talk 12:19, 27 July 2005 (UTC)

[edit] why sentence was deleted

Hi. Just wondered if you could give an example of glucocorticoid replacement therapy where the dose is not given in descending amounts (i.e. half in the morning, third at noon and potent. also sixth in the evening). AFAIK this is the usual way of administration, but I'll be glad if you point me to any sources disproving this.

I also wonder why depression would not belong on the list of side effects.

I'm relatively new to Wikipedia, so I'll be glad to learn why my contributions were deleted, and hey, I may learn something new about my job on the way.

Janek78 09:05, 12 November 2005 (UTC)

Answer: I reverted the following sentence:

Glucocorticoids in replacement therapy are usually given in two doses (1-1/2-0) to reflect the natural levels.

The sentence contained an impressive 3 errors and one unclarity in two brief clauses: (a) the number of doses for replacement is variable, from 1 to 4 or more, (b) dosing reflects the kinetics of the specific steroid used rather than the "natural levels", and (c) unlike for example thyroid replacement we do not use "natural levels" as a guide to glucocorticoid replacement. And I had no idea what 1-1/2-0 was intended to mean and didnt think anyone else would either.

Depression is a rare but possible side effect of high dose glucocorticoid therapy, although there are other terms that reflect the transient mental effects of high dose steroids more accurately with fewer misleading implications (e.g., mood changes, steroid psychosis are more commonly used terms for the two main types of effects). However, in the context of potential differences in side effect profiles of non-glucocorticoid vs glucocorticoid substitutes, I don't think we know enough yet to exclude mood or mental effects from the substitutes; those were not recognized as steroid effects until there was far more experience with use than we have with the substitutes.

Janek78, please don't stop contributing; we have all put facts in an article that someone else has corrected. Best regards. alteripse 12:24, 12 November 2005 (UTC)

[edit] Replacement therapy

Thanks for the answer, I admit that my formulation was not clear and looking back, I would have deleted what I wrote anyway. :)

But you should notice that I wrote "usually", that does not exclude 1-4 doses, I wanted to give the most common dosing regime. I also have to insist that replacement therapy in adrenal insufficiency reflects the "normal" levels, not the kinetics of the drug. This is what they taught us at school, this is what the Merck Manual says, this is what Lüllmann's pharmacology says, and all other books I have checked. Cortisol production is highest in the morning, then decreases to the lowest level around midnight. Replacement therapy is trying to simulate this by giving the largest dose in the morning, and the rest either in one (or two, or three) lower dose(s). The dose in the evening should be low in order to prevent sleep disorders. This is what all my books say, this is how all my patients (granted, I've only had two or three Addisons so far) took their medication.

I admit that rather than just "depression", it would have been better to say "mania/depression" or "mood changes", as you suggest.

I do not intend to stop contributing, I'm glad we can discus this and hopefully reach a conclusion/consensus. With regards. Janek78 13:04, 12 November 2005 (UTC)

Sorry, it is erroneous "to insist that replacement therapy in adrenal insufficiency reflects the "normal" levels, not the kinetics of the drug." I hope they did not teach you that in school and it is not what the Merck manual says. Steroid replacement is actually based on trying to match natural production rates, not "levels". Levels are what we measure in the blood, like T4, described in units of concentration like mcg/dL, whereas production rates are amounts per unit of time, like mg per 24 hours. We do not measure blood steroid levels as a guide to replacement. Because they fluctuate so much, the phrase "natural level" doesn't even mean anything useful as a description of physiology. We use the production rates as a crude first approximation to replaceent dosing, not levels. The dosing interval has nothing to do with natural levels or natural production; it is primarily determined by the kinetics of the glucocorticoid used. Hydrocortisone is usually given as 2 or 3 doses a day by mouth, but often q4-6 hours by IV. If prednisone is used for replacement, it is given in 1 or 2 doses a day by mouth. If dexamethasone is used for replacement, it given as a single dose a day. Do you see that all these dosing intervals depend on the kinetics of the steroid used and not on "natural levels".? If you intended to explain that the distribution of the doses throughout the day are sometimes intended to imitate the morning cortisol peak you should have said so and I would not have disagreed; I had no idea that is what you meant (and it is by no means a universally accepted necessity anyway). You may be doing the right thing by your patients, but your description of it needs to be more accurate. alteripse 19:14, 12 November 2005 (UTC)

If we are to split hair here, we should talk about secretion, not production; and secretion, in my opinion, leads to change in levels (see cortisol curve). So arguing about production/levels is IMHO irrelevant. But I don't want to push this point; I guess the whole argument was caused by my bad use of English (which you might have noticed is not my first language). Indeed, what I wanted to say was that the dose is distributed unevenly throughout the day, with most of the dose given in the morning (which is true for hydrocortison, prednison, and dexamethasone). I may not be "a universally accepted necessity anyway", but it is accepted enough to be included in the prescribing information of these drugs. My point was aimed at the chronic use of substitution, i.e. not including any IV administration. But again, I see your point now, I think that we actually agree with each other, it was just my unclear formulation that did not say what I wanted to say. I'll have to pay more attention to what I write. :) So what would be a suiting formulation? "In substitution therapy, a larger proportion of the dose is usually given in the morning to reflect the circadian changes in cortisol secretion" ?? Janek78 09:07, 13 November 2005 (UTC)

In terms of linguistic precision, you are correct that secretion is more precise than production, though you will often hear American endocrinologists refer to the "cortisol production rate" in this context. You are also correct that all my criticisms were aimed what you said, not what you know. But honing your language use hones your thinking, and I doubt your professors would let you get away with saying it that way (I wouldn't have). Your final sentence is fine and I would not have changed it.

Final nitpicks: (1) you referred to replacement and did not distinguish between acute and chronic; we do give IV replacement for short periods of time for a number of circumstances, (2) I do not understand how you could give oral dexamethasone with most of the dose in the morning, since its effects last about 24 hours and even the smallest single mg pill is a replacement for most adults. alteripse 11:51, 13 November 2005 (UTC)

Ad (2) - OK, in most people you would use only a single dose of dexamethasone, but in cases requiring higher doses, you would again give a higher dose in the morning, would you not? That was my point. But never mind that, I think we have clarified our views now. :) Thanks for your effort. Janek78 13:54, 13 November 2005 (UTC)

[edit] references

My father is a medical specialist (Nephrology), and has been prescribing (and doing research on) prednison and prednisolon. He claims t 1/2 to be about 3 to 3.5 hours for these drugs. He uses "5 times t 1/2" as the rule-of-thumb for little of the drug to be left (about 3%). The table in the article lists a significantly higher T 1/2, similar to the "nothing left" number my father quotes.

So, where did those numbers come from? Did someone swap a "very little left" number and a T 1/2 ?

-- rewolff