Synaptic Tails

Join hosts Dr Emma Hancox and Dr Mark Lowrie in this episode of Synaptic Tails as theydelve into the 'Measure' aspect of the S.M.A.R.T approach to epilepsy in veterinary practice. Focusing on phenobarbital, they discuss the importance of regular monitoring, assessing liver function, understanding drug serum concentration, variations in metabolism, and the use of other antiepileptic drugs like bromide.

Resources:
Access TVM UK Vet Resources at https://www.tvm-uk.com/registration-page/

Creators & Guests

Host
Dr. Emma Hancox
Dr Emma Hancox graduated from Bristol Vet School in 2016 and worked in first opinion practice for 6 years before joining TVM UK Ltd, in 2022 to pursue her interest in ophthalmology and neurology. She is currently the Technical Vet Advisor and the host of our new podcast Synaptic Tails.
Guest
Dr. Mark Lowrie
Mark qualified from the University of Cambridge and then worked in first opinion small animal practice. Following an internship at the Royal Veterinary College (RVC), he moved to the University of Glasgow to complete a residency in veterinary neurology. Mark worked for several years at a leading multidisciplinary veterinary centre near London, then as Clinical Director for a multidisciplinary referral centre in the East Midlands. Mark has a Master’s degree in steroid-responsive meningitis-arteritis in dogs and has a particular interest in the management of movement disorders, inflammatory brain and spinal disease and feline neurology. He is a Veterinary Consultant to the International Society of Feline Medicine (ISFM) and was awarded the prestigious national prize of “Petplan Vet of the Year” in 2022.

What is Synaptic Tails?

Welcome to the Synaptic Tails podcast, where neurology meets practical tips in veterinary care. Hosted by Dr Emma Hancox, a Technical Vet Advisor at TVM UK, a Dômes Pharma Brand, alongside Dr Mark Lowrie of Movement Referrals.

In each episode, we delve into managing neurology cases in first-opinion practice, sharing insights, tips, and tricks we've gained through our experiences.

But that's not all! Over the upcoming episodes, we'll introduce you to TVM's S.M.A.R.T. Approach To Epilepsy. What does S.M.A.R.T. stand for? Speak, Measure, Advise, Realistic, and Tailor. We'll explore how this innovative approach can be applied to real-life cases, providing practical solutions to enhance patient care.

About TVM UK:

TVM UK is more than an animal health company; we're dedicated to the well-being of pets and the support of vets and pet owners. Specialising in crucial areas such as poisoning, ophthalmology and neurology, we strive to improve the quality of life for pets in your care.

Join us on the Synaptic Tails podcast as we unravel the complexities of neurology, share stories, and empower you with knowledge. Together, let's enhance the health and happiness of our canine companions.

🌐 Learn more about TVM UK: https://www.tvm-uk.com/

If you're passionate about veterinary care, subscribe now for expert insights and engaging
conversations.

Access Vet Resources from TVM at https://www.tvm-uk.com/registration-page/

To contact TVM UK email help@tvm-uk.com

🌐 Learn more about Movement Referrals: https://www.movementvets.co.uk

Movement Referrals is an independent, specialist veterinary hospital based in the north-west of
England. Our aim is to provide high quality but efficient Specialist referral services. We concentrate
on orthopaedics and neurology, two of the most common reasons for referrals. We are able to offer
common referral procedures, such as TPLO, patellar luxation, and spinal surgery, at reasonable
prices. One of our fundamental philosophies is “getting it right first time”. We not only provide more
choice at better value but we aim to objectively demonstrate our value through measuring and
publishing our outcomes.

Dr Emma Hancox: Welcome back to the
Synaptic Tails podcast with your

hosts, Emma Hancox, TVM Technical Vet,
and Mark Lowrie, RCVS and European

Specialist in Veterinary Neurology,
and Co-director of Movement Referrals.

Hi Mark.

How are you?

Dr Mark Lowrie: Hello.

Yeah.

Welcome back everyone.

Dr Emma Hancox: As you hopefully
will remember from last time we

introduced our S.M.A.R.T Approach to
epilepsy, that's TVMs new guide for

first opinion practitioners, and we
were chatting about the importance

of speaking and how communicating
with the client is so important.

The next step of the smart
approach is going to be Measure.

So measuring is a bit of a
minefield I think out there.

What is it that you routinely measure
in your epileptic patients Mark?

Dr Mark Lowrie: So if we're thinking
about measure when a dog started

medication there are key things that
are really important to look at in

these dogs . I think there's a lot of
bad press, and I hinted this last time,

about phenobarbital and what it does.

Dr Emma Hancox: You did, you left
us on a cliffhanger last time...

Dr Mark Lowrie: Am I gonna clear it up?

Dr Emma Hancox: A spoiler...

Dr Mark Lowrie: So for me, when we're
checking bloods, it's all very easy to go

let's check bloods, send them away,
check they're okay and we're happy.

And it will be inevitable if you are
taking bloods from a dog, and I'm, using

the term bloods loosely right now, but
when you get them back, you've probably

measured a selection of liver enzymes.

And those liver enzymes are likely to
be very high because we like to look

at our reference range and we like our
values to be within the reference range.

It makes us all feel comfortable.

Dr Emma Hancox: Yep.

Dr Mark Lowrie: Now, if the dog's
been on phenobarbital for two weeks or

longer, those liver enzymes will be high.

And all I'd say at this moment in time
is I disregard liver enzymes a lot.

I don't worry too much about them.

You asked what I measure.

So the things I want to be including
on those blood tests is I want to

look at values for liver function.

Liver enzymes tell you about liver
structure and by nature of phenobarbital,

it is metabolized by liver.

It makes the liver work harder,
the liver becomes damaged.

A small bit of liver damage is fine.

So the things I look for liver
function, there are four values

I really, really want to look at

Dr Emma Hancox: Okay.

Dr Mark Lowrie: The first is glucose.

So we want to look at glucose and
the liver produces glucose, so we

wanna make sure it's not too low.

So when I'm looking at glucose
on my biochemistry, I'm

checking it's not too low.

The others are albumin,
cholesterol, and urea.

Dr Emma Hancox: Okay.

Dr Mark Lowrie: Now if any of those
are low, again, that alerts you

to the fact there could be some
kind of liver damage going on.

So if we measure those four things,
if they're at all low, I'm worried.

Now I have to add to that, that we
don't just measure them because, I

suppose we'll touch on this when we
talk about diagnosis of epilepsy,

but when you’re taking bloods, you
always want to do a fasted sample.

So you want to wait until the dog's been
starved for 12 hours, very much like

we would, when we go to the doctors,
we're told not to have breakfast.

And that's not a weight limiting strategy.

It's not a way of us dieting or the
doctors are trying to be good to us.

It's to make sure that like
our blood sugar levels are

checked when we've been starved.

Of course, the body should be able to
adapt to no intake of food by ensuring

we've got a steady glucose concentration.

So always do a fasted blood
sample to look at these things.

Now, if those four values are
within normal level, I'm quite

happy about liver function.

If you want to be really thorough or if
you've got any concern, then this is where

the bile acid stimulation test comes in.

Dr Emma Hancox: Yeah

Dr Mark Lowrie: A bile
acid stimulation test.

We do the fasted bile acids and then we
feed the dog and we do a post sample.

I do find as a reasonable screen,
a fasting bile acids is fine.

You will miss some cases.

I’ll be very honest if you don't do a
full bile acids, but actually the vast

majority of dogs, particularly when
it comes to measuring liver function,

doing a fasting bile acids is plenty.

And as long as that's
normal, we're fine too.

The only time I really start to worry
about the liver and liver enzymes,

and indeed even if bile acids start
to creep up, is when dogs are actively

showing signs of liver disease.

Dr Emma Hancox: Yeah, definitely.

Dr Mark Lowrie: So a yellow
dog, that's a concern.

Potbellied, all these things.

The other thing to say about phenobarbital
here when we're talking about measurements

is measuring those clinical signs.

Phenobarbital can do two things to liver.

The first is just its chronic
use can cause liver disease.

Now that's really, really rare.

when we're doing serum concentration
measuring, we do want to keep it at the

right level because if you are above,
35 to 40 Mgs per litre, that is when

we need to be worried that we could be
pushing the dog into a hepatotoxicity.

So we do try and keep below the
sort of 35 to 40 level on our

phenobarbital concentration to
make sure we don't go there.

If we do that's really safe.

Now the other thing that phenobarbital
can do is there's an idiosyncratic

reaction where it just causes a
really nasty acute hepatotoxicity.

Now I’ve said the chronic phenobarbital
abuse of the liver is fairly rare.

This idiosyncratic reaction is even rarer

.
Dr Emma Hancox: Okay.

Dr Mark Lowrie: These are dogs that have
gone on to phenobarbital and they, within

weeks, they develop what can only be
described as horrendous liver disease.

They go jaundiced, they become Ascitic.

They really don't look very well at all.

Dr Emma Hancox: Is this reversible?

Dr Mark Lowrie: It's not.

So when we see that, that is a real
concern, but this is so, so rare, and

what I want to pick up on here is if
you are checking your blood values

after two weeks and you’re seeing high
liver enzymes, do not worry about that.

Because I think I’ve come across
a number of situations where vets

will stop phenobarbital because
the liver enzymes are a bit high.

As we've said, that's completely normal.

we expect the liver enzymes to be high.

You could make an argument that if
they're normal, that's possibly because

the liver's already really badly damaged
And there's no more liver to destroy.

Dr Emma Hancox: Yeah.

Dr Mark Lowrie: So high liver enzymes
is actually not a bad thing, and

that makes me a lot more happy.

Dr Emma Hancox: Yeah, I'm really glad
that you've picked up on the liver

monitoring because that is, as the Tech
Vet at TVM, obviously I do get quite

a few calls about phenobarbital, for
instance, and when they've done liver

values and say, I'm just picking out
ALP is usually the perpetrator I will

say, we expect as a rough guideline
about three to five times a reference

range, but I’ve seen cases where it is
often dramatically higher than that.

And you’re so right in that
actually, I really don't worry

about it in the vast majority of
cases caveat that with of course.

But you’re right.

The first things I'm gonna be
asking them is, has the dog

actually got any clinical signs?

I'm gonna look at other, clues on bloods.

So you mentioned things
like the albumin et cetera.

But just coming back
to these liver values.

One of the ones that is
interesting to me is the AST.

Do you ever use that in practice?

Do you rely on it at all?

Dr Mark Lowrie: I'm not gonna say
this because you’re sat in opposite

me but I would say about liver
disease and phenobarbital there is

a great resource on the TVM website
and she hasn't told me to say this.

This is just me

Dr Emma Hancox: I actually haven't

Dr Mark Lowrie: I would guide you
that way to get a lot more information

because it does explain these liver
values far better and more eloquently

than I'm likely do right now.

But AST yes, it is something that
is less effected by phenobarbital,

but personally I don't use it.

I think the other measures that are
better to look at liver function, because

AST it's a measure of liver structure.

I know it's involved in muscles as well.

So you get muscle disease, AST can
increase so it's not specific to

the liver and when it is high, you
shouldn't therefore blame the liver.

You should think there
may be another cause.

But I'm, I honestly hand on heart, I
don't look at it very much but I would

also say hand on heart, I don't look at
the other liver enzymes very much either

So liver enzymes to me
aren't particularly useful.

and it's those liver function, values
that I'm looking at in more detail.

Dr Emma Hancox: Yeah.

And just picking up on what you just said,
looking for other causes, don't forget

there are other causes for ALP to go high.

So things like undiagnosed Cushing's, if
they've been on phenobarbital for years

don't rule out or forget those, steroid
use, whether that be oral or topical,

can sometimes cause that to increase.

Is that the actual drug that they're
on or is that something else?

Don't ever forget.

Those are the co-morbidities
that might be happening.

Or other treatments as well.

Dr Mark Lowrie: I think that's really
valid because you've just mentioned

the word that I don't understand.

So Cushing's, I don't
know what that means.

Dr Emma Hancox: What was that?

Again, we need a medic in the room.

Dr Mark Lowrie: No.

so I dunno what that means and that's
why I don't look at liver values 'cause

they scare me too much but in the
context of phenobarbital the other

values are far more helpful for you

Dr Emma Hancox: Yeah, I guess I don't,
this is now just for my own peace of mind

to be honest, are they not going to be
reduced later on in the disease process?

So my worry there would be actually,
if I'm looking at things like glucose

or albumin for instance, are we not
going to, have we mentioned at the

beginning, 70% or more loss of liver
kind of function at that stage?

Is that not a concern for you or?

Dr Mark Lowrie: It is.

So there's two things.

In end stage liver disease, these
products of the liver would be so

reduced that they're incredibly low.

But I'd like to think with regular
monitoring, we'd pick up on that in time.

So this is where measuring every
three to six months is a good idea.

And that way you would be able to pick
up that decline before it gets too far.

But similarly, liver enzymes
in end stage liver disease,

liver enzymes can become normal.

They can even get low because
you've got no liver left.

Yeah, So the same is
true of liver enzymes.

But they definitely go sky high before
they go anywhere close to dropping.

And hence, I don't worry.

But regular monitoring is vital.

Dr Emma Hancox: So you’re
getting that trend.

Dr Mark Lowrie: You are, and
I think that brings in the

serum concentration monitoring

Dr Emma Hancox: Yeah.

Dr Mark Lowrie: So serum
concentrations are the other

measure that we do in these dogs.

This is with phenobarbital, it's fair to
say with many of the other medications

available for epilepsy, we're not quite
as set on measuring the concentrations.

I appreciate bromide, we do.

But the other medications, we don't
really monitor them in the same way.

Now, the reason for that is
phenobarbital is metabolized by the

liver, the P450 cytochrome system.

Dr Emma Hancox: Oh goodness.

You've just given me flashbacks to uni.

Dr Mark Lowrie: I'm not gonna say it again
'cause I felt a bit scared saying it too.

It made me nervous.

Um, But this is, like an enzyme
induction where the enzymes that

break down phenobarbital work
harder and harder with time.

So you can start a dog on
phenobarbital at your standard dose.

I choose three mgs per kg twice
a day as my starting dose for

phenobarbital, and then it takes about
10 to 14 days to reach steady state.

So again, an owner would need to
understand if you started that

medication, it will be, A good
couple of weeks before it's really

at its effective working levels.

Now that doesn't mean it isn't
working after a few days, it's just

not working at its optimal, position
until that time now at two weeks.

We then measure the phenobarbital
serum concentration because every

dog, and indeed every person's liver
metabolizes things at different rates.

So there'll be some dogs.

That can metabolize
phenobarbital really effectively.

We don't like that 'cause
that not working as well.

but that would mean in those
individuals they'll need a higher dose.

I don't worry about what
I'm putting into the dog

Dr Emma Hancox: Okay.

Dr Mark Lowrie: So I'm not too
interested in the dose going in.

I'm much more interested in the serum
concentration, so if I'm measuring the

serum concentration after two weeks
and serum concentration is low, that

tells me that dog needs a higher dose
to achieve the therapeutic range.

Dr Emma Hancox: Yeah.

Dr Mark Lowrie: Therapeutic range is big

Dr Emma Hancox: It's massive, isn't it?

Dr Mark Lowrie: I would aim at going
somewhere between 25 to 30 mgs per litre.

Dr Emma Hancox: Yeah.

Why would you aim for that range?

The 25 to 30 mgs per litre?

Is that where most dogs
you find are controlled?

Dr Mark Lowrie: It is, I think when
you reach that concentration, you

know you’re getting your optimal
performance from phenobarbital.

That doesn't mean it's
a, it's gonna be perfect.

It doesn't mean you’re gonna
have to be delighted with that

performance, but that's the best
performance for that individual dog.

So that's what I aim at.

I think the range goes from
15 to 40 mgs per litre.

That worries me a bit because we have
talked about the higher end of that

being more of a risk of developing
liver problems the lower end of that,

I do consider myself, as being a bit
sub therapeutic, so I'm also aware

of dogs that may only be at 15 to 20.

And we're not getting the best out of
phenobarbital there in that individual.

So we need to aim a little bit higher.

Dr Emma Hancox: I guess if they're doing
well though, so obviously if they're

at say 17, 18 mgs per litre and the
dog's doing well, it's not having many

seizures, then I guess it's fine to leave
it there, but it's in those that aren't,

obviously we'd want to try and increase.

Is that what I'm getting from this?

Dr Mark Lowrie: Absolutely we need, so we
look at the serum concentration, but when

we come to giving advice on what to do
with the medication, we need to consider

what the seizure activity's been doing.

Of course, it depends on the
historical baseline seizure activity.

It may be this dog only has had one
fit every 12 weeks and we've chosen

to start medication with the owner's
guidance, well if you’re measuring two

weeks in and it's sub therapeutic, we've
probably not given long enough yet to

know if it's being effective or not

Dr Emma Hancox: Yeah, makes sense.

Dr Mark Lowrie: So in that circumstance,
I may not change it, but I'd let an owner

know it is below the level where we know
it can be most effective, but let's keep

an eye on it and then we can know that
we might need to increase it in time.

Dr Emma Hancox: Yeah, and I think,
are you likely to see, so say you've

got a dog that is quite happy at,
I dunno, 25 mgs per litre, I'm just

plucking this out of thin ai r.

Is it likely to stay that way?

Why do we need to keep
measuring them in the future?

Why, once we're settled on
it, can't we just stay on it?

Dr Mark Lowrie: So here's the problem, and
I think this is sometimes a mistake that's

made or there's been a misunderstanding
with it that, over time you can, you can

get a dog on a nice therapeutic range.

The seizures seem controlled and we're
all happy and we send that owner home.

Now that owner needs to understand that
things might not stay hunky dory forever.

I think we do need to keep monitoring.

Now, there's a question as to whether
we check the serum concentration

every three to six months.

Now that is a perfectly viable,
sensible thing to do, and you'll

read about that everywhere.

That's the advice that's given.

Dr Emma Hancox: Yeah.

Dr Mark Lowrie: If owners are bit
concerned with cost, or indeed, if

there's difficulty with taking bloods
from the dog, say it's a, a very nervous

dog, it's a dog that's hard to, to
bleed, then what you may consider doing

is just monitor the dog from a seizure
activity perspective and just check

the seizures aren't getting worse.

Now, what will happen with phenobarbital?

I’ve got a way of thinking about this.

This is where my alcoholic
tendencies come out.

Dr Emma Hancox: Oh goodness.

He's having a confession
now on the podcast.

Dr Mark Lowrie: Well,
so, so I like red wine

Dr Emma Hancox: Don't we all?

Dr Mark Lowrie: And so phenobarbital
well, this will work well.

I mean, it can be any red wine.

It doesn't matter if it's a
merlot or a malbac, it's red wine.

Dr Emma Hancox: you’re
talking to the right person.

Dr Mark Lowrie: Good.

Good.

So if we had never drunk red
wine before, imagine that.

I mean, the deprived life we'd of had

Dr Emma Hancox: Oh wow.

I, I can't remember that time.

Dr Mark Lowrie: But if we'd never had
wine before and we had a small glass of

red wine, It would probably give us a
little happy feeling once we've drunk

it and we'd feel that nice, fuzzy, warm
feeling that wine does for an alcoholic.

The problem is if you then keep drinking
that one small glass of wine every

night, it won't quite have that nice,
fuzzy, warm feeling in subsequent nights.

And to achieve that nice fuzzy
feeling, you have to drink

that little bit more red wine.

You can see where I'm going.

This is my life.

So night after night, if I want to achieve
that same effect, I have to drink more.

Over the period of say, six weeks,
I might have gone from being

teetotal to a raving alcoholic.

And that's because I felt, this
is on me, that I need more red

wine to achieve the same feeling.

Now, phenobarbital, there
is a reason for me...

Dr Emma Hancox: I gonna
say, where's this going?

Dr Mark Lowrie: It's suddenly
becomes something very different.

Phenobarbital is exactly the same,
that if you put a dog on a low dose

of phenobarbital on day one, six
to eight weeks later, it is very

possible the serum concentration
in that dog has steadily decreased.

That is very normal, and it's because
the liver's working harder to get

rid of the medication from the body.

So over time, and it varies with
individuals, I can't say this is

necessarily gonna happen over weeks,
months, or years, but in a dog in general,

the serum concentration will steadily
drop despite keeping the same dose,

So we're putting the same drug
in but the dose is decreasing.

So six months into management, if
you start to breakthrough seizures

or seizures become worse, the most
common reason for that would be that

you’re now at a sub therapeutic range.

So if you recheck the phenobarbital
serum concentration, you may find it is

below the level where we want it to be

Dr Emma Hancox: Right,

Dr Mark Lowrie: And you've
got scope to increase it.

Even if the dog is on a really high
dose of phenobarbital, that's fine.

And I’ve known dogs that have been
on nine mgs per kg twice a day.

That's a huge dose.

Dr Emma Hancox: That is a huge dose, yeah.

Dr Mark Lowrie: And it's not a starting
dose, but it might be a dose you end

up at in the future, provided the serum
concentration allows you to do it.

Dr Emma Hancox: So it sounds like
you don't really mind how high the

dose goes that you’re putting in.

It's all about what those
serum concentrations and

obviously how the dog is doing.

Is that right?

Dr Mark Lowrie: It's absolutely
that and It's such easy maths.

I can't do maths, but if the therapeutic
concentration we're achieving is 25

and we're on, say that's what we wanna
achieve, level 25 and our therapeutic

concentration says 12, we just double
the dose that we're giving the dog and

hopefully that gets up to about 24 or
so, which will be a nice place to be.

Dr Emma Hancox: I didn't realise
it was quite that simple maths.

Dr Mark Lowrie: Very easy.

Very easy, and if I can do it, then
everybody listening to this can because

they can clearly operate a smartphone
and load a podcast, which I can't do.

Dr Emma Hancox: So you'll never
be able to listen to this.

So it is interesting that you say
different dogs or different individuals

will metabolize it differently 'cause
then I remember back in practice,

having, being concerned that I had a
little Jack Russell dog on the same

dose as a probably fat Labrador.

Um, but that's sounds okay.

It doesn't really matter then I guess.

Dr Mark Lowrie: It doesn't matter.

And I think, it is
important in those cases.

We're doing all the other testing,
so we're looking at liver function,

we're doing the blood tests there.

Ideally when they're on the high
dose, I would be saying every

three months, then we can make
sure we're doing the right thing.

But absolutely, that's absolutely fine
to do and I'd have no concern about it.

Dr Emma Hancox: Great.

You mentioned that you could look at
seizure frequency as a way of monitoring

these patients, if we are recommending
these guys come in every three, six months

for blood samples, that can get quite
expensive alongside their treatments.

So is there a way to, as it
were, do epilepsy on a budget?

Dr Mark Lowrie: Yeah, there, there
is a question here of what are

we expecting from the medication?

Dr Emma Hancox: Yeah

Dr Mark Lowrie: And people don't talk
about this, and I find when you bring

this up with an owner, they can often be
a bit horrified by this, if I'm honest.

Now I'm gonna speak very
freely with this and

Dr Emma Hancox: Please do.

Dr Mark Lowrie: Pretend
it's not a TVM podcast.

But I think with medication in
general, part of the reason these

medications are used is we find
that they reduce seizure frequency.

Many of the drug companies have done the
testing and they know these drugs can

reduce seizure frequency by at least 50%.

Now what they've done in the trials,
and these aren't the drug companies,

these are people like myself who have
gone out and tested these medications.

That means that maybe the dog
that's had one fit every two

weeks will go onto medication.

And these studies would say that that dog
would have one seizure every four weeks

as a result of successful treatment.

Now that isn't necessarily
great news for an owner.

A seizure a day is not a good outcome.

But it would be considered successful.

So owners need to know about
that with these medications.

That's what we're aiming at.

Now doing things on a budget,
phenobarbital is a really inexpensive

medication and I think even with
a budget, it's the right first

line medication to be trying.

So blood tests aren't expensive.

If we get a dog that has one or more
seizures and the owners haven't got

very much money, I would recommend
doing very basic blood tests.

I know we're gonna talk about the blood
tests that we would consider doing

in a future podcast with diagnosing
epilepsy, but we do those blood tests.

If everything seems normal, it's
fine to start phenobarbital at the

standard starting dose of 3 Mgs
per kg twice a day and monitor.

Now if that dog's doing all right with
its seizure frequency and it's achieved

that 50% or more reduction in seizures,
we don't need to do anything more

and we can leave things well alone.

It would be advisable, and we
should always advise, checking

bloods every three to six months.

Now they may not be able to afford
that and that's fine 'cause you can

say, alright, let's do it annually.

But if you’re gonna do it annually
or if you’re not gonna do it at all,

let's be honest, the owner needs to
be aware of the risks of that entails.

And so all this discussion we've
had about liver disease, we

have to broach that with them.

There is a lot of conversation there,

I'm always trying to empower the owners
to make the right decision for them.

And as we talk about this, it's
probably becoming more and more obvious.

There isn't a right answer

Dr Emma Hancox: Yeah.

Yeah.

Dr Mark Lowrie: You try and do the
right thing for that particular pet

and the right thing takes on board all
sorts of different things, including

the owner's financial circumstances,
their living arrangements, everything,

even the age of the dog is important.

And these things help us to make the
right call, but the right call is

ultimately with the owner, not with us.

Dr Emma Hancox: Yeah, no,
that makes a lot of sense.

So we've spoken a lot about
phenobarbital and everything makes sense.

Liver monitoring, when to do it, what
we're looking for, all of those things.

Makes a lot of sense.

just thinking, obviously it's not the
only anti-epileptic drug out there, so

Dr Mark Lowrie: Others are available.

Dr Emma Hancox: Others are
available, just so you know.

Do you measure the same things in those?

What, do you measure serum
concentration for other drugs?

Like what, what would differ basically?

Dr Mark Lowrie: I think the main
drug to bring up when it comes to

serum concentration is bromide.

That is the other medication out
there that would require some

kind of monitoring, but there's
huge differences with bromide.

First is bromide takes, I want to say it
takes forever to reach a steady state.

Dr Emma Hancox: Feels like that

Dr Mark Lowrie: but it's
two, two to three months.

But yes, it would feel like that for
an owner with a dog with epilepsy,

and you start that medication, waiting
three months may not be appropriate.

So there's, it's not great.

But the main reason for bringing it up is
when you read the insert on bromide and

you see what they suggest is it actually
recommends you check blood levels after

one month and then again at three months.

Now here's another top tip and where
big mistakes happen because if we said

it takes three months to reach steady
state and we start the dog on a standard

maintenance dose, say 20 mgs per kg
once a day or divided twice a day, if

you wish, after a month, we know that
serum concentration will still be low.

It'll be higher than at the beginning, but
it won't be up to the therapeutic range.

So if we are measuring at one month as
the insert recommends we do, we're gonna

have a sub therapeutic concentration.

So very often I’ve seen dogs that
then get an increased dose into

the patient at one month, and of
course that's the wrong thing to do

because we're heading into toxicity.

I personally don't recommend
checking the serum concentration

on bromide until three months.

At three months is fairly reliably at
the level it needs to be, and we can

then make decisions based on that.

A brief bit here, if I may, about
bromide is it's a great medication

and I think there's a lot of
times when it should be used.

Actually, when I can, I try and use
it as the second line medication, not

only because it's licensed as an add-in
with phenobarbital, but also because

it's a pretty good drug long term.

It's well tolerated and seems
to manage seizures well.

But there is that issue of waiting two
to three months so you can load bromide.

So loading bromide is a
very reasonable thing to do.

The problem with loading any
anti-epileptic medication is of

course, it doesn't allow a dog to
tolerate or to get tolerant to it,

to the side effects of it quickly.

Yeah, so I’ll go back
to the alcohol thing.

if you binge drink

Dr Emma Hancox: Oh no.

Dr Mark Lowrie: three bottles of red
wine, you’re gonna be all over the place.

Whereas if you drank it steadily
over a longer period of time, I

won't specify the length, but if you
drank it steady over a long period of

time, you won't be quite as legless.

With bromide, if you did load up to
the loading dose very quickly, over

a short period of time, dogs will
become very ataxic, so drunk, they

will be falling all over the place
and they take a zombie-like state.

I’ll be honest.

Now, that's okay.

If the dog came in status epilepticus

If dog came in on status epilepticus,
it had been managed well with

phenobarbital and was on acceptable
serum concentration doses then giving

bromide as a loading dose in that
scenario is probably a good thing

because you’re facing such bad seizures
that those owners will do anything

to try and get the dog through it.

But if you've got a dog that's having a
fit once every eight weeks and you load

them with bromide and they don't even
manage to walk out the hospital after

that consultation, then owners clearly are
going to have something to say about that.

So there is a time and place to load
bromide, but it's more in those much more

severe cases where we're really worried.

You can load it steadily
over, say, six weeks.

I can say it here, the loading dose,
what I try and do is I give 600

mgs per kg over a period of time.

So traditionally when we're giving
an emergency, we do it over, say

anything between three to five days.

So we divide 600 mgs per kg over three
to five days and give that to the dog.

But over those three to five days,
we also give the maintenance dose

of 20 to 30 mgs per kg once a day.

Dr Emma Hancox: I see.

Dr Mark Lowrie: If you did it over,
say two weeks, you would put the

600 mgs per kg over the 14 day
period and divide it accordingly.

it's the way that we try and manage it
to get these dogs loaded if we need to.

And at the end of loading, we take a
blood sample to see where we are with

the serum concentration of bromide.

Dr Emma Hancox: It makes so much sense
and I think, I think bromide has a

bit of a bad press, again, a bit like
phenobarbital we was saying, but it's

seen a little bit as an old school drug.

in that giving those high
doses, those loading doses,

it might not always be needed.

If it does, just knowing that you are
gonna have those side effects and how

to manage those and warning the owners
and potentially spreading it across.

Dr Mark Lowrie: And so I think
some of the reasons it's got bad

press is it's an archaic medication
as far as human epilepsy goes.

I believe it was used as an epileptic
medication in people, but around the

time that people believed in witches too.

So, It's not, not really something
that if you mention to doctors

about bromide, they'll laugh
you out the room sort of thing.

You really give that to dogs?

Dr Emma Hancox: I actually did to
my sister, who's a GP and she was

what, you still use these drugs?

Yes we do.

So yeah, it is a pretty old
school drug and I think that's

got a bad press with it.

And I'm not sure I want to open
this can of worms, but is there

a risk of pancreatitis with
phenobarbital and bromide together?

Dr Mark Lowrie: Yeah, it's hard this one.

There's definitely an association with it
and there's papers out there that support

that and suggest it is a risk factor.

So I think I have to say yes
based on the evidence out there.

Having said that, I think you've
gotta be very careful that

you’re definitely dealing with
pancreatitis and not just vomiting.

Dr Emma Hancox: Yes.

Dr Mark Lowrie: What I mean by that
is bromide, I find specifically when

you give it, without giving it a nice
big bolus of food, It can irritate

the stomach lining and cause vomiting.

So it's quite a normal thing to have and
I know vomiting is a sign of pancreatitis.

So you could see how very
quickly you go, this must be

pancreatitis, let's avoid bromide.

Actually, for me, the solution there is
put it in a much better bolus of food so

it doesn't irritate the stomach lining.

When it then gets into the
gut, it's fine, it's absorbed

and everything's working well.

So the big top tip for bromide
when it's when does seem to trigger

vomiting is to give it in a big bowl
of food and potentially, if the dose

is big, don't be afraid to divide it
twice or even three times in the day.

So smaller amounts are given.

Dr Emma Hancox: Right, that irritates
less, I guess, it makes sense.

Dr Mark Lowrie: You did ask about serum
concentration with other medications

and all I'd want to say to finish
off that discussion is that all the

other medications we have out there,
and there's lots of them, which

the vast majority are off license.

So things like levetiracetam,
dare I say gabapentin, I don't

like it, but we should mention it.

We don't routinely measure
serum concentrations in them.

They've got a fairly standard dose that
we give, in both of those circumstances

in fact, they're medications that get
into, get up to steady state very quickly.

You can test it.

Dr Emma Hancox: I think I’ve
seen the tests available, but

Dr Mark Lowrie: Yeah, so I wouldn't
worry about doing it because I

don't think it means a huge amount.

And for me personally, I also think 'cause
it's got a short half life, the levels

can fluctuate a bit more freely than
maybe they do with other medications.

So phenobarbital, we don't worry about
the time of day that we do the serum

concentration testing, the advice
there as we try and stick with the

same time of day in the same patient.

So whether that's morning
or evening, doesn't matter,

as long as we're consistent.

But levetiracetam, because we're giving
it three times a day, I can see there

will be a bit of fluctuation there.

And that value could be wildly different
depending on the time of day you do it.

Dr Emma Hancox: So you don't care
about phenobarbital peaks and

troughs and all of those things.

Dr Mark Lowrie: No,

no, not at all.

So as long as you’re
consistent, it's fine.

So yeah, if you, last time you measured
it in the morning, well make sure you

measure it in the morning again the
next time around, just so you don't

have too much alteration in that way.

Dr Emma Hancox: That makes sense.

I just wanted to pick up on one
of the other drugs if possible.

So I’ve mentioned bromide,
levetiracetam, phenobarbital.

Imepitoin, It doesn't have the same effect
on the liver, does it, as phenobarbital?

I was under the impression that you didn't
necessarily need to monitor the liver

as much as you do for phenobarbital.

Do you need to do it at all?

Dr Mark Lowrie: It's really hard
with imepitoin because when it came

out there was limited safety data,
just what was done in the trials.

So it hasn't had that wider use yet
to know exactly what's happening.

But I think it's fair to say
there aren't any major reports of

liver disease, though it happens.

So it definitely causes liver problems
like with any chronic drug use, I

would recommend doing blood tests
every three to six months just in case.

But that goes with every
medication we ever prescribe.

So I wouldn't say you need to
be any more or less concerned.

I think just that monitoring level
is appropriate with the drug.

Dr Emma Hancox: Yeah.

Brilliant.

No, that all makes sense.

Thank you.

Thank you Mark.

I again, I think that's all we've got
time for in this episode, but it has been

really great speaking to you once again.

I’ve personally learned a lot
from this episode, so I hope

our listeners have as well.

Please tune in for our next episode
where we'll be moving on to the third

instalment of the S.M.A.R.T Approach,
which is advise, discussing three

key areas for epilepsy management.

Notice I said epilepsy
management there not treatment.

Mark, I'm learning, aren't I?

And just a reminder that this was
episode two of the S.M.A.R.T Approach.

So if you haven't already, please take a
listen to episode one where we introduce

a S.M.A.R.T Approach and discuss the
importance of owner communication.

Thanks again, Mark.

I’ll see you next time.

Dr Mark Lowrie: Thanks very much.

Bye.