Difficult epileptic

RE: Difficult epileptic

Anthony Todd — Sat, 10 Dec 2016 19:29:38 GMT

[quote user="robloxley"]I think this comment says more about you than anyone giving you one star![/quote]

You actually prove my point; by your reasoned, sensible response, so I'd be surprised if you were the one-starrer.....

However, looking at your all embracing all singing all-dancing put-down and review; getting to KBr we get to this summary:

Evaluation of bromide monotherapy efficacy was found in only a single study[34] in which 73.9% (17/23) of dogs had > 50% seizure reduction and 52% (12/23 dogs) were seizure- free during the 6-month treatment period. The remaining studies focused on the efficacy of potassium bromide as an additional drug with phenobarbital, primidone, or both.[31, 32, 34, 38-40]

with no mention whatsoever of:

In a retrospective study, at least 10% of dogs receiving potassium bromide/phenobarbital combination therapy, compared with 0.3% of dogs receiving phenobarbital monotherapy, had probable pancreatitis. Pancreatitis may be a more frequent and more serious adverse effect of potassium bromide/phenobarbital combination therapy than has been reported previously.

from: Pancreatitis associated with potassium bromide/phenobarbital combination therapy in epileptic dogs Can Vet J Volume 41, July 2000

which does distract from the reference, more than somewhat....

Whereas PB has a lot of emphasis on blood levels and the serious effects on the liver [even if that may be idiosyncratic and totally independent of dose and probably totally idiosyncratic if this is to be credited...

Effects of Long-Term Phenobarbital Treatment on the Liver in Dogs

http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2000.tb02231.x/abstract

Returning to the original citation:

The cumulative success rate of >50% seizure reduction to improve seizure control was 82% (258/311 dogs), with a cumulative seizure-free rate of 31% (93/311) and failure rate (no improvement) of 15% (48/311).

I've got absolutely no way of proving this, but my recollection is of either 100% control or no control, even at semi GA levels, when euthanasia was performed. The rest were "normal", fit free, if gaining weight usually..... 15% of "no improvement" sounds about right, unfortunately.

I can only cite the two alsatians sacrificed because of the dodgy price rise via the VMD after a long period of high-dose PB and no fits.

But then we weren't shackled by following some anecdotal maximal blood value. and just tried to reduce the dose to the minimum which stopped the fits which is prehistoric, I know, but seemed to work.

RE: Difficult epileptic

Rob Loxley — Sat, 10 Dec 2016 17:18:15 GMT

[quote user="Anthony Todd"]modvet approach to a dog that's just had a fit or in status epilepticus[/quote]

You could start with the 2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs: http://onlinelibrary.wiley.com/doi/10.1111/jvim.13841/full

[quote user="Anthony Todd"]you say "we must establish a pattern, it might never occur again"[/quote]

Consider whether your 'perfectly' controlled from day one, with no trouble, 'epileptic' dogs might never have had another fit in spite of, not because of, your treatment?

[quote user="Anthony Todd"]One star just shows a lack of scientific acumen or just something personal, nah, must be personal, because you will have got stratospheric A levels.... but common sense or logic isn't an A level subject unfortunately[/quote]

I think this comment says more about you than anyone giving you one star!

RE: Difficult epileptic

Anthony Todd — Sat, 10 Dec 2016 16:55:11 GMT

Ok, bleeding one-starrer, tell me your modvet approach to a dog that's just had a fit or in status epilepticus, with a semi-hysterical owner telling you to do something.

"Do nothing" you say "we must establish a pattern, it might never occur again"

One star just shows a lack of scientific acumen or just something personal, nah, must be personal, because you will have got stratospheric A levels.... but common sense or logic isn't an A level subject unfortunately.

RE: Difficult epileptic

Anthony Todd — Sat, 10 Dec 2016 16:27:16 GMT

[quote user="Lucy Fleming"]I think the approach also depends a lot on the frequency of fits at presentation [/quote]

Back in the day almost all clients rushed the dog to us, either during[!], or after the first fit, so we had no way of knowing whether it was a one-off, continuous status, or part of a sequence at intervals so it was high doses of PB to start I'm afraid.

RE: Difficult epileptic

Lucy Fleming — Fri, 09 Dec 2016 12:36:18 GMT

I think the approach also depends a lot on the frequency of fits at presentation - I would deal with (for example) a status dog or a dog showing cluster seizures very differently to the more common/ typical case in which fits are often only occurring/ observed once a month or even less frequently. It takes a while in those cases to know what your reduction in seizure frequency is (hopefully 100%) as you kind of have to wait until the dog is 'due' to fit anyway. In cases like that I would start on a dose rate that I would expect to stop seizure activity and then increase if needed (like most others, I've tended to find it often isn't).

RE: Difficult epileptic

Anthony Todd — Fri, 09 Dec 2016 11:34:17 GMT

[quote user="robloxley"] but you will see significant sedation, and in many (most?) cases will be unnecessary.[/quote]

Almost certainly but trouble is, as I've been at pains to point out, the main object of the client's visit is because the dog is fitting.

The first important thing, both for the dog and the client is to stop the fits with an adequate dose, which probably, in future, will be excessive.

As both the oral dose and the blood level are not set in stone it is vital that the dose chosen will stop the fits, and ASAP. The dose can then be adjusted as [I have just noticed] my most vociferous antagonist has previously advised in a personal case, depending on the demeanor or the patient with or without the modern mandatory blood test.

As an aside, but of relevance when clients complain that the dog is dopey, PB is an addictive drug in humans because the effects of an "overdose", in some people, gives a nice feeling; it is possible that the dog quite likes the effect of the overdose, certainly it is preferable to a fit.

RE: Difficult epileptic

Rob Loxley — Fri, 09 Dec 2016 09:58:07 GMT

[quote user="Anthony Todd"]

the dose should not be increase the full effect of the medication does not appear for two weeks and doses should not be increased during this time, for the fitting to be controlled?

Just made it bold for emphasis 'cos it's just so sad.....

Many clients in my day would have either, had the dog put down, or sought another, quicker medication regime!!

[/quote]

The pharmacokinetics of oral pb in the dog are well established. Yes you could load the dog to get serum pb level up quicker - e.g. when giving i/v phenobarb - but you will see significant sedation, and in many (most?) cases will be unnecessary.

RE: Difficult epileptic

Anthony Todd — Wed, 07 Dec 2016 12:21:27 GMT

[quote user="Lucy Fleming"]Lets hope so - and perhaps the wobbliness will be transient as well. Fingers crossed.[/quote]

Should be able to adjust the dose easier than PB as:

Imepitoin is rapidly cleared from blood (Cl = 260 to 568 ml/hours/kg) with an elimination half-life of approximately 1.5 to 2 hours.[!!]

c/f PB

From their website.

RE: Difficult epileptic

Lucy Fleming — Wed, 07 Dec 2016 10:24:01 GMT

[quote user="Joyce Whitehead"]It would be lovely if he didn't fit this time when he is due, we shall see. [/quote]

Lets hope so - and perhaps the wobbliness will be transient as well. Fingers crossed.

RE: Difficult epileptic

Thomas Johnson — Tue, 06 Dec 2016 17:53:53 GMT

[quote user="Anthony Todd"]

Found this which sounds significant:

The elimination of primidone, phenylethylmalonamide, and phenobarbital (administered IV) was studied in dogs . The elimination half-lives were primidone, 1.85 +/- 0.3 (SEM) hours; phenylethylmalonamide, 7.1 +/- 1.45 hours; and phenobarbital, 40.9 +/- 4.96 hours.

from

Am J Vet Res. 1980 Oct;41(10):1643-5.

Serum concentrations of primidone and its metabolites, phenylethylmalonamide and phenobarbital, in the dog.

Yet I think most advice is twice daily, orally I admit but??

[/quote]

I'm think the only relevance of this is that the long half life of phenobarbital at around 40 hours is the reason that it takes a couple of weeks for serum levels to reach a plateau when the dose is changed. It doesn't help with knowing what level of drug will be therapeutic or will cause adverse effects.

RE: Difficult epileptic

Anthony Todd — Tue, 06 Dec 2016 17:16:41 GMT

Found this which sounds significant:

from

Am J Vet Res. 1980 Oct;41(10):1643-5.

Serum concentrations of primidone and its metabolites, phenylethylmalonamide and phenobarbital, in the dog.

Yet I think most advice is twice daily, orally I admit but??

RE: Difficult epileptic

Anthony Todd — Tue, 06 Dec 2016 17:02:10 GMT

I'll have a go.

Did you look back at the other "40" I found before?

RE: Difficult epileptic

Thomas Johnson — Tue, 06 Dec 2016 16:50:44 GMT

[quote user="Anthony Todd"]

Yeah, 40 mg/L has been quoted in another thing I found too

[/quote]

But this isn't quoting it, this is saying that they found this to be the toxic dose in the research they did for this paper.

[quote user="Anthony Todd"]

the abstract sounds weird because they talk of "during an enforced drowsy period to establish upper limits of desirable serum concentrations of the drug." No idea what that means??

[/quote]

I imagine it means that they chose to give the dogs a high dose that made them drowsy so they could assess the side-effects of the high dose and see how high the serum concentrations were. I assume the full paper would give you the details.

[quote user="Anthony Todd"]

They don't say what the "side effects" were either.....

[/quote]

It's just an abstract, I'm sure they do in the full paper. If you've got the time you could contact the Journal of the American Veterinary Medical Association and see if they could send you a copy of the full paper, I'd be interested to read it if you do get hold of it.

RE: Difficult epileptic

Anthony Todd — Tue, 06 Dec 2016 16:34:49 GMT

[quote user="Thomas Johnson"] I can only access the abstract:[/quote]

Yeah, 40 mg/L has been quoted in another thing I found too and the abstract sounds weird because they talk of "during an enforced drowsy period to establish upper limits of desirable serum concentrations of the drug." No idea what that means??

They don't say what the "side effects" were either.....

Wasn't primadone sold by ICI called "Mysoline" used to come in a nice metal screw topped thingy, ah, the memories just flood back...

Found it:

https://www.ncbi.nlm.nih.gov/pubmed/1748613 and i commented at the time with some caveats.

RE: Difficult epileptic

Thomas Johnson — Tue, 06 Dec 2016 15:17:18 GMT

I think I've found where the risk of toxicity if serum concentration of phenobarbital is over 40mg/L has come from, though I can only access the abstract:

https://www.ncbi.nlm.nih.gov/pubmed/6863121

RE: Difficult epileptic

Thomas Johnson — Tue, 06 Dec 2016 14:46:02 GMT

[quote user="Anthony Todd"]

Just to say if money's tight and the alternative is euthanasia, try what I've been on about

It has worked for me and other dinovets for a long time and many fitting dogs...

[/quote]

I don't think anyone would withhold treatment if the client could afford the tablets but not the blood tests. As long as the client is aware that there are some risks involved then I would start phenobarb as normal and adjust the dose as necessary.

RE: Difficult epileptic

Joyce Whitehead — Tue, 06 Dec 2016 14:40:03 GMT

Hi Lucy, thanks, he's a bit close to home this boy. Pexion has now been added in by the neurologist, and he's back on pulsed Levetiracetam too, and I think this with his already high phenobarb dose is why he is so wobbly. It would be lovely if he didn't fit this time when he is due, we shall see.

RE: Difficult epileptic

Anthony Todd — Tue, 06 Dec 2016 13:30:02 GMT

[quote user="Thomas Johnson"]I'm going to try one more time.[/quote]

I was going to reply and this is absolutely true!

I composed the reply, the usual effective rebuttal etc., hit "Post" and the cursor started random motions and a strange message appeared, something about "don't shut down" so finally I turned the thing off, lost my reply so thought "I'm being sent a message....."

Just to say if money's tight and the alternative is euthanasia, try what I've been on about

It has worked for me and other dinovets for a long time and many fitting dogs...

RE: Difficult epileptic

Lucy Fleming — Tue, 06 Dec 2016 12:42:10 GMT

[quote user="Joyce Whitehead"]Believe me, I've tried. And tried. As it belongs to one of my best friends, and I walk with her and the dog a couple of times a week, euthanasia is something I certainly don't look forward to having to undertake. [/quote]

I'm very sorry to hear this Joyce, it sounds like a very difficult case for all sorts of reasons. Did the neurologist say if they thought adding in Pexion would be useful at all? I can't imagine it necessarily would, and I'm aware it isn't licensed for clusters, but I suppose if the owners wanted to know they had tried everything then it's an option (forgive me if it's something already tried or mentioned and I missed it in the thread)

RE: Difficult epileptic

Thomas Johnson — Tue, 06 Dec 2016 09:06:47 GMT

[quote user="Anthony Todd"]We would have a dog fitting-free within 12 hours, probably before you had the first blood level back..... and your's would be a low dose unlikely to stop fitting [see above][/quote]

I'm going to try one more time. In my experience most dogs with idiopathic epilepsy have one or two seizures a week. Often the starting dose of phenobarb will stop the dog having any further seizures, if it doesn't it usually reduces the frequency of seizures and the dog will have another seizure perhaps 3-4 weeks after starting the phenobarb. At that point I've probably already done the blood tests, so I know that it's safe to increase the phenobarb dose, then I wait and see, and usually the dog has no further seizures. I'll probably see it 3 month later for a check-up.

RE: Difficult epileptic

Anthony Todd — Mon, 05 Dec 2016 23:00:51 GMT

[quote user="Joyce Whitehead"]Anthony, I'm probably going to bow out of this thread even though I started it, as it is raising my blood pressure.[/quote]

This may be helpful, if you haven't already seen it:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348850/

RE: Difficult epileptic

Anthony Todd — Mon, 05 Dec 2016 20:41:02 GMT

[quote user="Joyce Whitehead"]Anthony, as you keep repeating the mantra of how in your time you would have sorted this dog in a day.[/quote]

Sorry Joyce, you're paraphrasing and misinterpreting what I have said.

What I have quoted, challenged, logically and humanely I think, is the supplier's advice which some have even said is legally binding...

I never said, nor would I say I "would have sorted this dog in a day". I did say I would have stopped the dog fitting in a day but also said that if the dog continues to fit on an "ataxic" dose, rather than a certain high blood level, then the prognosis would be grave and this, sadly, may be one of those cases.

I suppose there isn't a date/time pattern in the seizures so you could pulse dose also Aine's posts re salt and drugs may be worth trying before making any terminal decisions?

RE: Difficult epileptic

Joyce Whitehead — Mon, 05 Dec 2016 19:56:17 GMT

Anthony, I'm probably going to bow out of this thread even though I started it, as it is raising my blood pressure. In your ideal world when you practiced it seems everything recovered immediately and you never had difficult cases. As we have severally pointed out, most "standard" epileptics will be controlled well with phenobarbitone, and we can adjust the dose if needed. No one is saying we start at a ridiculously low dose. Unfortunately as I pointed out, this dog is a cluster seizure dog, so he only fits every 3-4 weeks, and then fits at least 3 times in 24 hours. So this is not an easy dog to control. With every increase in drug dose, or additional drug, we might get him to nearer 4 weeks, or to having 2 rather than 4 seizures, but he then deteriorates again.

At the moment, with his increased meds from the neurologist, he is very ataxic and woozy. The owners are willing to persist for now, and he will be due to fit in the next 10 days or so, but if the side effect persist or he is no better on these meds I think they will decide to euthanase him.

Please don't feel I'm being unnecessarily rude, but I really don't think you are being particularly helpful here Anthony, as you keep repeating the mantra of how in your time you would have sorted this dog in a day. Believe me, I've tried. And tried. As it belongs to one of my best friends, and I walk with her and the dog a couple of times a week, euthanasia is something I certainly don't look forward to having to undertake.

RE: Difficult epileptic

Anthony Todd — Mon, 05 Dec 2016 19:41:03 GMT

[quote user="Thomas Johnson"]I think to put the dog through that level of side-effects is completely unacceptable[/quote]

What, and having the dog continue to fit for 2 weeks before the dose is gradually increased as below....??? Not to me it ain't!

Dogs should be dosed orally, starting with a dose of 2–5 mg per kg bodyweight per day. The dose should be divided and administered twice daily.

Steady state serum concentrations are not reached until 1–2 weeks after treatment is initiated. The full effect of the medication does not appear for two weeks and doses should not be increased during this time.

[from the suddenly revised suppliers' site...]

Actually 2-5mg/Kg is the dose rate in NOAH 2009 so I would have started at around 5mg/Kg and increased it after 12 hours if still fits. [I suspect the much higher dose rate was a error somewhere, somebody]

We never seemed to have any resistance from owners providing the dog was not fitting and , as I said, this wore off and/or we lowered or raised the dose if the fits continued or the dog was too dopey, but we could do this by instructing the owner and/or a phone call.

We never waited two days, let alone 2 weeks!

All I have been banging on about is the reliance on blood values which are "approximate", as far as fitting control is concerned, [and not defined at all, as are,say antibiotics], rather than stopping the dog's fitting with, initially a larger, but definitely effective dose, and reducing it progressively whilst continuing to suppress fits.

We would have a dog fitting-free within 12 hours, probably before you had the first blood level back..... and your's would be a low dose unlikely to stop fitting [see above]

I'm sure manipulating the doses and the drugs nowadays allows fine tuning although they seem to have their serious side effects.

RE: Difficult epileptic

Thomas Johnson — Mon, 05 Dec 2016 18:09:17 GMT

[quote user="Anthony Todd"]The dose would be what used to be in NOAH and I think was up to 40 mg/Kg [dose rates have disappeared] which almost always made the fitting stop BUT the animal a zombie although this lessened over a week or so. If the fitting didn't stop with obvious sedation then the prognosis was grim![/quote]

I think to put the dog through that level of side-effects is completely unacceptable, a seizure is generally not a welfare issue for the dog, it is completely unaware of what is happening, though obviously some dogs will have some distress in the post-ictal phase. I have a dog that has been seizure free on Pexion for a couple of years, it has started to have seizures again about once a month, I increased the Pexion dose but there was no improvement so I added in phenobarb, there has been some improvement but the dog was very lethargic, and seeing the dog like that all day upset the owner far more than seeing it have a seizure, dropping the Pexion dose has greatly improved the dogs demeanor and we are gradually increasing the phenobarb dose and reducing the Pexion dose.