Jesse just diagnosed with Cushings

[labblab]

Re: Jesse just diagnosed with Cushings

Patti, here is a February, 2009 video interview with Dr. David Bruyette in which he discusses trilostane dosing and monitoring (he's a well-known specialist in Los Angeles). You may find it interesting, because he discusses the relative merits of once vs. twice daily dosing, given the recent research study results.

If I am understanding him correctly, his clinic still recommends starting first with once daily dosing, because even though the recent studies indicate that twice daily dosing suppresses cortisol efficiently and at a lower overall daily dose, the majority of dogs appear just as "well" clinically on a once daily dose. As we have discussed here, he shifts to twice daily dosing only for the minority of dogs who do not demonstrate consistent symptom relief throughout the day.

One thing that is surprising to me is that he says that the overall daily dose tends to be lower with twice daily dosing. I thought it was just the reverse -- that in many cases, the overall daily dose needs to be increased a bit, at least when it is first split into two doses (and I think that is Dechra's recommendation). But perhaps what he is referring to is the effect over time. Anyway, here's the video:

http://veterinarymedicine.dvm360.com.../detail/567360

Marianne

[Patricia ann Wh]

Re: Jesse just diagnosed with Cushings

Hi Marianne,

So.......say Jesse was getting 90 mg. a day - if he were to get 2 doses a day
....a lower end dose would be something like 40 / 40 ?? equaling a lower dose than 90?????

Yes, I had seen that before - a month ago it didn't mean much to me ... different story now.

I think he is saying that either way - once a day or twice a day dosing - both are just as effective.

I would think because Jesse symptoms are worse at night - twice a day would be better for him.

PS Have others found the symptoms are worse at night????

(By the way - Peterson wasn't advising my vet for free)

Not that I want to start badmouthing - I need to focus my attention on making Jesse feel better - that's all I want.

Once Jesse feels better I can start throwing rocks. (or dog poop)

Thank you so much, Patti and Jesse

[labblab]

Re: Jesse just diagnosed with Cushings

Hi Marianne,
So.......say Jesse was getting 90 mg. a day - if he were to get 2 doses a day
....a lower end dose would be something like 40 / 40 ?? equaling a lower dose than 90?????

I, too, was confused by Dr. Bruyette's statement that dogs on twice daily dosing regimens require a lower daily dose than those who are given trilostane once a day. Especially since the starting example he gave was the same daily total either way (90 mg. once a day, or 45 mg. twice a day) . So I'm thinking that perhaps what he meant is, down the road -- after their endocrine systems have stabilized on the medication -- dogs who are dosed twice a day end up needing less total daily trilostane than those dosed once a day.

If that is truly the case -- that dogs on twice daily dosing end up needing less medication, then I too am even more puzzled as to why twice daily dosing isn't the "norm" rather than the "exception." But having worked in healthcare myself, I know that it is easier for most people to remember to take their medication consistently if they only have to do it once a day (rather than more times a day). So maybe part of the theory is that "simpler is always better" if you can end up with the same symptom relief either way.

But back to your original dosing question, for a dog of Jesse's weight, 90 mg. is a low, conservative starting dose for him whatever way you look at it. I'm betting that you will end up needing to adjust his total dose upward at least a bit, regardless of which dosing regimen you go with. That will be the value of the monitoring ACTH tests -- to let you know how much his dose needs to be altered as time goes on. And remember, even if your vet really wants you to start first with the trilostane once a day, you can jointly decide to make a switch at any point that Jesse's symptoms seem to warrant it. Just make sure that you order his trilostane capsules in a dosage size that will allow you to "manipulate" it (for instance, in 45 mg. capsules if you are getting compounded trilostane which you can order in any dose you want, or 30 mg. capsules if you are ordering brand-name Vetoryl which only comes in certain dosage strengths).

Marianne

[Patricia ann Wh]

Re: Jesse just diagnosed with Cushings

Marianne,

That is exactly what I"m thinking - exactly.
And - most of all - if the theory (or is it more than a theory) could mean a dog would need less trilostane - why not do it that way --UNLESS -UNLESS - and I am in complete agreement with you (it was actually my first reaction) people could possibly forget to dose twice a day.

Interesting VERRRRY interesting.

I have to go out now - but when I get back I'll tell you the latest.

Your last statement on dosing was great. It pertains to the latest story.

Patti and Jesse

[Patricia ann Wh]

Re: Jesse just diagnosed with Cushings

Hi,

As I said earlier I don't want to get into bad mouthing (well - I do - but....)
No, I can't talk to Peterson. Period.
As for the vet dealing with Peterson - I WILL NOT deal with him either.
I don't want to waste my time getting into the story behind it, but believe me - you'd do the same thing
On to another vet. Actually 2 - working together.
They did the latest ultrasound and the acth test.
They want to start him on 15 mg - yep -15 - twice a day for a few days.
Then up it to 30 twice a day. (it was compounded yesterday)
I think their thinking is because of his age. Yes, I do want to start slow - but - I need to changes - Jesse is such a good boy - he gets up every half hour to go out and pee - hes exhausted!!!!!!!!! Poor Boy.
So.......they want me to do a split dose of 15 - 15 for a few days, then go to 30 - 30.
One of the vets has never used trilostane the other has used it once. His experience was this - he gave it to a dog every other day.
I don't know - please tell me exactly what you think about this.
Is this low low dose going to do ANYTHING at all??????????????
Even the 30 - 30 a day?????????????????
Would the 15 - 15 or even the 30 - 30 make any difference in the cortisol at all??????????
I had to start him on something - its been since APRIL 1st when I first called Peterson - and we were supposed to get started immediately
Talk to me Marianne

I wish I could print this but I don't know how to get it on the screen.
I have an old cc story I kept. This guy was giving his dog 90 mg a day.
60 in the am and 30 in the pm. The pm dose was 9 hours after the first dose because it would wear off and dog was stressed before bedtime.
He said his dog was on that regime for a year and it was perfect.
I thought that was interesting.

Do you know how long it takes before a pill kicks in???
I mean how many hours???

Patti and Jesse

[labblab]

Re: Jesse just diagnosed with Cushings

Patti,

The 2007 UC Davis protocol that I've been referring to suggests starting a dog on a total daily dose as low as 1 mg. per kg. (this is a lower starting dose than Dechra recommends). If Jesse weighs 88 pounds, that translates into approx. 40 kg. So the regimen that your vets are recommending to you is pretty much consistent with the Davis protocol. And by starting this low and gradually increasing the dose, Jesse may be spared any ill feelings associated with a sudden and rapid lowering of his cortisol. The possible downside is that it may take several increases to get his dose to the appropriate level, and it may be hard to feel patient along the way.

But truthfully, after all our messages back and forth, I think you're actually right at the place that you wanted to be . Twice daily dosing at a low level with a plan for gradual increases. You should know within a week to ten days whether this dose is effective for him (both by watching his symptoms and by a monitoring ACTH test). If his first ACTH test shows very little drop in his cortisol level, then your vets will know that they can be more aggressive with increasing his dose. Given the experience of others here, I am guessing that he will need a higher dose. But every dog is different, and there is no way of knowing for certain what dose he will need without monitoring his symptoms and test results.

I can't remember the exact timing of the maximum effect of trilostane, but it is within the first few hours of ingestion (that's why the ACTH is scheduled for approx. 4 hours after dosing). It also wanes rapidly, and supposed has totally cleared the system within 24 hours. For that reason, dosing every other day makes little sense to me (even though we have had a very few members who report that there dogs have been dosed this way).

Is your compounded trilostane in pill or capsule form? And what is the dosage strength?

WHEW!!!!! You must feel very relieved to finally be launching into treatment. Here's hoping that you and Jesse will soon be feeling some relief!

Marianne

[Patricia ann Wh]

Re: Jesse just diagnosed with Cushings

Marianne, Hi,

Thanks again, yes, oh yes, I am relieved to have at least gotten started.

I'm glad you said that starting low could avoid Jesse feeling ill. That made me feel good. Thank you for that.

The vets wanted to start out really really low. They gave me 30 mgs. and told me to get it made into 15 mg. "capsules". They said to do 15 twice a day for 3 days then go to 30 twice a day and then on day 10 we would do the blood test.

I'd like your opinion on that. Is the 15 - 15 - so low it won't do anything??
Or the 30 - 30 for that matter??

I just hope it doesn't take forever for him to start drinking less and just plain feeling better.
I guess - like you said - every dog is different.

At least today I didn't sit around waiting for phone calls - that never came.
Oh, thank you for that little video - I was trying to find it the other day.

Your the best, Patti and Jesse

[labblab]

Re: Jesse just diagnosed with Cushings

I'd like your opinion on that. Is the 15 - 15 - so low it won't do anything??
Or the 30 - 30 for that matter??

I just hope it doesn't take forever for him to start drinking less and just plain feeling better.
I guess - like you said - every dog is different.

Patti, of course I am only guessing, but I would assume that if Jesse's cortisol has barely nudged downward at the time of the first ACTH test, your vets will feel as though they can significantly increase his trilostane dose. So at worst, I think you only have another ten days to wait and see. I can easily imagine how anxious you are to see some improvement for him, so that probably seems like a long time to you. But you have waited so long to get him the help that he needs -- I am hoping that the next couple of weeks will speed by for you.

Also, I just want to tell you how much I have also gained from our "conversation" today. It has helped me to clarify my own understanding of things, and corrected some misinformation that I was carrying around with me. So I am hoping that this will turn out to be a turning point for us all three -- you, me, and Jesse...especially Jesse.

Marianne

[Patricia ann Wh]

Re: Jesse just diagnosed with Cushings

Hi Marianne,

Yes, "cushings" seems to be an endless, interesting, conversation topic, to say the least.

One more thing, do you think that the "lower dose - twice a day" idea is because the larger, once a day dose would stay in the system longer, and the smaller dose just doesn't last quite as long.

I don't know - I just can't seem to figure out the fact that the drug is short acting on one hand (and I haven't read anything that contradicts that!)- but on the other hand one dose should be adequate to should last 24 hours and keep a (at least somewhat) constant cortisol level.
Bottom line - HOW LONG DOES THE TRILOSTANE LAST IN THE SYSTEM??
You don't need to answer - if there even is an answer, it just all seems really contradictory to me. That's me though. I've always been a "WHY" person.

By the way - is that a picture of your puppy, the beautiful, beautiful, yellow lab???

Sincerely, Patti

[Lulusmom]

Re: Jesse just diagnosed with Cushings

Hi Patti.

I see you've got Marianne on the case which is great because she knows her stuff when it comes to Trilostane. For what it's worth, I agree with everything she has told you.

I don't believe that dogs are any different than humans when it comes metabolizing a drug and measuring it's effects from one person to the next. The effects of Trilostane on dogs is much the same. Some dogs are more sensitive than others and some dogs metabolize it better, whether it be from physiological makeup or absorption due to diet.

It is known that Trilostane has a short half life and studies have shown that the drug starts to lose it's enzyme blocking ability any time after 8 hours. I am providing a link to an abstract of one study below. A pertinent excerpt from that abstract is:

At 3 to 4 hours and 8 to 9 hours after once-daily dosing, mean post-ACTH stimulation serum cortisol concentrations were 2.60 and 8.09 Pg/dL, respectively.

That's pretty telling huh?

http://www.find-health-articles.com/...ministered.htm

I'm not sure that Trilostane is effective for a full 24 hours in any dog but rather due to physioligical make up and/or diet, some dogs probably tend to see Trilostane's effects prolonged enough throughout the day so that overnight cortisol concentrations do not increase enough to exacerbate or see a return of symptoms.

Dr. Edward T. Siegel, Late Professor of Medicine and Chief, Endocrine Service at the School of Veterinary Medicine at the University of Pennsylvania wrote a book called Endocrine Diseases of the Dog. There is some really interesting reading on the basic chemistry of steroids but the one thing I found interesting is this excerpt:

The secretion of cortisol is not constant throughout the day. The circadian rhythm of cortisol and ACTH secretion fluctuates from one day to another. Maximal cortisol secretion occurs late in the day, with the peak level occurring between midnight and early morning. Both ACTH activity and cortisol secretion gradually decrease during the day, and by late evening cortisol secretion is at its minimum.

This would certainly explain why some dogs' symptoms are much worse in the wee hours of the morning. When do you notice Jesse's symptoms getting worse?

I think your vets prescribing 15mg BID for three days and 30mg BID for seven days is a very conservative approach and I personally like conservative dosing. I've never really heard of that protocol and when I saw your post I initially thought; "how totally weird" but after mulling it over a bit, I actually think it makes sense. A lot of dogs experience huge drops in cortisol in the first few days and experience cortisol withdrawal which makes them feel pretty bad. The 15mg doses are baby steps that will drop the cortisol but not enough to make Jesse feel bad. Hmmm? Not such a bad idea really.

Glynda

[Patricia ann Wh]

Re: Jesse just diagnosed with Cushings

Hi Glynda!!!!!!!!!

I've been wondering where you've been?????
Marianne sure does know her stuff!!!!!!!!!!
She's fantastic.

Excellent - excellent info, that's the stuff I've been wondering about for so long.
Everyday, 4:30 the panting starts, water goes up hunger goes crazy, he doesn't fall asleep till midnight. During the day - no panting - ever, the hunger is totally normal, (at night he would take your hand off) water goes through the roof starting at the same time.
He started Thurs. 15 mg twice a day.
Last week he was drinking up to 2 1/2 gallons a day(24 hours) !!!,(that just went through the roof about 2 weeks ago.)
Yesterday he walked and socialized more than he has in weeks, and he did not drink a full gallon of water in the 24 hours.!!!!!!!! (It was almost scary)
I had said to my mom that I bet he would be really sore today, in fact I made him go in the house because I knew he was doing too much.
He had a hard time getting up this a.m. - I got really really nervous though, thinking - is it a side effect, or was he up and down and walking around so much yesterday he was sore from all the exercise??!!
He slept most of the day which he usually does because he's so wound up most of the night, come 4 - 4:30 in the afternoon, he gets going.
The water intake is low again today.
Its 6:00 pm here, he was hungry for sure. His legs are still tired or weak and that has me concerned, is it a side effect or just from doing so much yesterday??????? Geez - !!!!!!!!
Oh and he was barking at everyone this am. (Sunday morning)
That was a good sign. (Not for the neighbors) But they love him and are very concerned too.
Interesting info on the number of hours its in the system, I have to go back and reread that now.
Great info Glynda. Thank you very very much.
You guys are brilliant - you know that???

Patti and Jesse

[Patricia ann Wh]

Re: Jesse just diagnosed with Cushings

Glynda - did you see this.

I wish I could print this guys story but I don't know how to get his story on this screen.
I have an old cc story I kept.
This guy was giving his dog 90 mg of trilostane a day.
60 in the am and 30 in the pm. The pm dose was 9 hours after the first dose because it would wear off and dog was stressed before bedtime.
He said his dog was on that regime for a year and it was perfect.
I thought that was interesting.

I wonder why he didn't give his dog 30 in the am and 60 in the pm ??

It sounds like he gave the first dose at - maybe - 9 am and the 2nd dose at
6 pm.

It caught my eye because it sounds like what Jesse needs.

[Lulusmom]

Re: Jesse just diagnosed with Cushings

Patti, I did see that post and I know that a few members give their dogs one mg in the am and a different in the pm. I personally prefer to achieve control of cortisol with one bottle of pills if at all possible. Just remember that there is no hard and fast rule that applies across the board. Most of us that treat or treated with Trilostane have had to tweak the doses (with vet's guidance, knowledge and/or concurrence, of course) to find that magic daily cocktail(s) for our dogs. If you're really, really lucky, the 30mg BID will be it but if you are like the vast majority of us, let the tweaking begin.

Glynda

[AlisonandMia]

Re: Jesse just diagnosed with Cushings

It would certainly be preferable to be able to control the cortisol "with one bottle of pills" as Glynda puts it and very often this works really well - that is the same dose twice a day if 2 x a day dosing is necessary.

I think the rationale for using a lower dose for one of the doses (usually the second dose) is that when you give a second dose there is still some as-yet-unmetabolized Trilo in the system even if it is not enough to have much impact on the cortisol. This means that when you give the second dose you are giving it on the "tail" of the previous dose. This happens with almost all medications - for example on a packet of Ibuprofen (human anti-inflammatory med) I have here it says: "Initial dose 2 tablets, then 1 or 2 every 4 - 6 hours as necessary.." I always need another 2 (if I need to take more) whereas my daughter (who is smaller) often gets away with only needing 1 in the subsequent dose. My husband who is larger than me also gets away with just 1 - so individual differences must be a factor here too.

What suits an individual dog and its situation seems to be quite individual and even varies over time just to make things even more interesting!

I don't know if anyone else has mentioned this to you yet but lot of people find it handy to have some 10mg caps on hand for tweaking purposes. You'd probably want to hold off forking out for 10mg caps initially (you could well never need them) but get hold of some pretty promptly if it looks like you are getting into wonderful world of tweaking doses as they can be really useful as you try to work out whether you need say, 60 in the am and 30 in the pm or whether 40 morning and night isn't going to work better.

Good luck!

Alison

[Patricia ann Wh]

Re: Jesse just diagnosed with Cushings

Oh Great! Let the tweaking begin.

Now see, I had no idea people ending up doing that.
That article I read was the only one I had seen where someone actually "tweaked"

Thanks Alison. That it true about the "second" dose, I hadn't thought about that.

So - you just kind of watch the signs and "tweak"
When symptoms are more pronounced - you may want to add - say 10 mgs??

Its like being a MAD SCIENTIST

Again, today, less than 1 a gallon of water. Incredible! I 'm still holding on to my seat. Its hard to believe. He was a little more relaxed this evening too. He napped a few hours, that was unusual. His legs were a little better too.
THANK GOD

I had printed alot of little stories from cc forum that I saved, ex.
68 lb dog, 15 mg 2X day (see- why start really high) you never know
80 lb dog 40 2X day 78 lb dog 60 every other day.
pony 120 mg once a day - yes a pony
toy poodle 90 once a day.
little tiny dog 4 mg once a day
And all doing great for a few yrs. I might add
I've read stories where people stop dosing for whatever reason and the cushings symptoms don't come back

Its just crazy. But - to me - it doesn't make sense to start high, because if there IS a bad reaction you need to stop and wait 5 to 7 days, and so now not only have you made your poor dog sick , you've also wasted time.

Maybe alot of people aren't like us and can't be bothered watching and tweaking and being concerned with our babies health and happiness.

Anyway, thank you all again,

Patti and Jesse (Border Collie #1)