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.