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Phenobarbital and Other Seizure control Medication used in dogs
Dietary protein and phenobarbital
Potassium Bromide
Phenobarbital levels and difficulty standing in St Bernard
Epilepsy and phenobarbital
Phenobarbital
Phenobarbital levels
also see Epilepsy
also see Seizure
Dietary protein and phenobarbitalQuestion: I have a five year old yellow lab mix, who was abandoned at four weeks old.
She had four grand mal seizures on 6/11, 7/10, 7/31 and 8/1. After the
second seizure, the vet suggested Hill's L/d dog food, as it has a lower
protein content than other dog foods. He advised me to stop adding chicken
or any other sort of protein to her dog food. After the fourth seizure,
she was put on 64.8 mg of Phenobarbital twice a day. She seemed to
tolerate both the drug and the change in diet really well. On 9/23 she had
her rabies vaccination. The next day she could barely walk, and had to be
carried up and down the stairs to go outside. She was still eating the dry
L/d, but vomited most of it up on 9/28. The vet recommended switching to
Hill's I/d, as it is easier on the digestive system. She loved the canned
Hill's I/d, and did really well on it. I was concerned about the higher
protein content, and began to reintroduce some dry L/d along with the
canned. After eight days she vomited again. Tried the same process and
ten days later she vomited. So I went back to straight Hill's canned I/d.
She was fine on two cans per day. When I began substituting some dry I/d
for the canned, she became sick again. After each vomiting episode, she's
off food for twenty-four hours, and then, over a period of days, returns to
normal eating.
I guess I have two questions: What do you think is going on? What is the
relationship between a diet high in protein and her seizures?
Thank you for your help.
Sally-
Answer: Dietary protein levels have some effect on the half-life of phenobarbital,
with a lower half-life of the medication reported in dogs on protein or
protein and fat reduced diets (Journal of the American Veterinary Medical
Association, Sept 2000, MacQuire, et.al.) but I don't think that really has
much clinical impact on the average patient being treated with
phenobarbital. It is just something to consider when phenobarbital isn't
working adequately in a patient.There is a dietary approach to seizure control in humans that is referred
to as a ketogenic diet. In this diet, a patient is kept off food for
several days to induce a ketoacidotic state (a situation in which fats are
being broken down and producing more acidity in the blood than normal).
After this state has been induced it is maintained by feeding a high fat,
low carbohydrate diet. I think that protein levels are usually higher with
this sort of diet than normal, not lower, though. This diet is not
utilized much in dogs because it is hard to induce a ketoacidotic state in
dogs by withholding food so it is questionable whether it is possible to
get any benefit from the diet, in dogs.There are dogs that are reported to have improvements in seizure control
when fed diets that contain novel proteins (diets meant to rule out food
allergies) and the new hypoallergenic diets with hydrolyzed proteins (HA
(tm) and z/d (tm)) may be helpful in this situation. I am not sure these
claims have ever really been proven, since that is hard to do because of
natural variations in seizure activity. In a dog that also seems to show
sensitivity to foods by vomiting or diarrhea, it really seems worthwhile to
consider trying one of these foods, just to see if food sensitivity does
play a role in the seizure activity or digestive problems. Truthfully,
this approach hasn't produced much benefit in our patients, that I can
remember, but it doesn't hurt to try.The only other reason that I can think of to control dietary protein in a
pet with seizures is to control seizures associated with liver disease.
Reduction of dietary protein is a really important part of treatment for
seizures and other central nervous system disorders associated with an
inability of the liver, for whatever reason, to process ammonia properly.
If this is part of the problem with your dog's seizures, then restriction
of dietary protein is important.It is important to try to rule out treatable causes of seizure activity. It
is sometimes possible to find a cause for seizures through a general blood
panel or other more specific testing suggested by the lab work. If a good
physical exam or the medical history suggest a possible central nervous
system cause, an MRI or CT scan might be helpful in identifying a cause for
seizure activity, but most patients will have normal appearing brain
anatomy on these scans.Mike Richards, DVM
11/19/2000
Question: Dear Dr. Richards,
I found your letter very informative and timely for us.But I have a few
questions regarding Potassium Bromide.
I have a 65 lbs. Chocolate Lab. 18 months old, who suffers from Epilepsy
since about 10 months. My vet tried the conventional medications that your
have in your letter, and the combination of Diazepam and Phenobarbital seem
to work for a while, but he took a cluster of seizures that really took us
by surprise. So I contacted other Vets including the PEI Veterenirian
College for more info on other forms of treatments. I gathered that
Potassium bromide could be a good choice. However my Vet. was dead set
against it on the onset, but I supplied him with much info that I had
gathered both on the Net and other sources and we finally found a pharmacist
in Halifax NS who carries it. He ordered the drug and we have him on 3cc of
Potassium bromide twice daily,(6am & 6pm) in combination with Phenobarbital
30 mg twice daily, (9am & 9pm). But he is very limited on it's use and
knowledge of the drug, so I hope that you can help us in answering the
following questions:
Is my dog destined to take these drugs for his life time?
And should or could the dosage change (for either drugs)?
What are the side effects of the Potassium bromide?
What are the danger (to us in handling the product and to my dog, and my
other dogs) of this Potassium bromide?
Is Potassium bromide addictive?
Do having a male neutered stop the seizures? I'm lead to believe that it
does, but others say it only works with females if they are spayed. True or
False/
How often should I have his blood analized? And what are they looking for?
Should there also be a Liver function test done? How often? What does it
involve?
Should the Potassium bromide be given to him on an empty stomach of after a
meal?
And finally do you think that the dosage that we have him on is too much or
not enough?
Sincerely,
JohnAnswer: John-
I am not sure if potassium bromide is addictive. I have not seen anything
that says that it is, but it is recommended that withdrawal of the
medication be done slowly in a couple of sources I have seen, so that makes
me think it is possible. Slow withdrawal is recommended for anti-seizure
medications due to the increased possibility of seizures as control
medications are withdrawn, though. So it is hard to be sure. I don't think
this is a major worry, though.I do not know of any information that suggests that seizures can be
controlled by spaying or neutering routinely, although there may be some
cases in which this has happened. There is some evidence that coming into
heat can make seizure activity worse in female dogs, so perhaps that is
what you are referring to. I think this is thought to be due to stress but
I am not certain of that.I don't think it matters if potassium bromide is given with food or not but
our clients that have used potassium bromide have mixed it with the food
and it was well tolerated. It can cause gastrointestinal upset, which might
be a little less likely when mixed with food.The recommended dosage range of potassium bromide is 20 to 80mg/kg/day,
usually given as a single dosage per day but sometimes split into two
doses. There are two reasons for the wide dose range. The first is that the
lower dosage range is usually used when combining potassium bromide with
phenobarbital and the second is that the dosage has to be adjusted over
time based on serum bromide levels. This is also true for phenobarbital.The usual recommended therapeutic dosage range for potassium bromide is 0.5
to 2 mg/ml (50 to 200 mg/dl -- some labs report in these values) but some
dogs require levels as high as 2.5 mg/ml in the serum to have control of
seizures and most dogs probably do fine in the 0.5 to 1.5 mg/ml range,
especially if combined with phenobarbital. It is usually recommended that
serum levels be checked after a month, then again at four months (when a
more steady state level has been achieved) and then at an interval that you
and your vet are comfortable with. So the dose of this medication is
adjusted based on how well an individual dog absorbs it and gets it into
the serum. If the serum levels are low, the dose is increased, if they are
high, the dose is decreased.The therapeutic serum levels for phenobarbital are reported to be between
20 and 40 ug/ml. There are a lot of recommendations as to when to check
these levels. In the "Handbook of Small Animal Practice" by Rhea Morgan,
the recommendation is to test on the 14th, 45th and 90th days after
starting phenobarbital and then every 6 months. The test should be done at
a time that should be the low point for the day --- so as long after the
morning pill as possible (at least 8 hours later). The dosage of
phenobarbital appears to be low, as 1 to 2mg per pound of body weight, or
more, is usually necessary to achieve therapeutic doses, but if serum
levels have been OK with this dose, it would not be advisable to increase
the dosage.The usual recommendation is to check a serum chemistry panel, including
liver enzymes, after 30 to 45 days and then at six month intervals when
using phenobarbital.There are no significant dangers that I am aware of from administering
potassium bromide or phenobarbital, as long as you don't take the
medications yourself.Potassium bromide can cause increased drinking, increased urination,
increased hunger, sleepiness, lethargy, loss of balance, hind leg weakness
and depression. Usually the only effects that are chronic are the first
three, but it may take several weeks for lethargy and balance problems to
disappear.It is very possible that your dog will require anti-seizure therapy for
life. Some dogs do stop having seizures, though. If there are no seizures
for a year, it is reasonable to taper off the medications and see what
happens.Hope this helps.
Mike Richards, DVM
9/13/2000
Phenobarbital levels and difficulty standing in St Bernard
Question: Dr. Mike-
I have a recue St. Bernard, 9 years, we have had him for 3.5 years, and he
has epilepsy that responds well to phenobarb and KBr, he is on 2 pills TID
and 10ml KBr in the am.He had been on 20ml of KBr for quite some time then we noticed that he was
dopeyier than usual and staggered and ran blood on him to find out that his
levels were too high so we reduced his KBr to 10ml. That was last year
about this time.He now is having problems with the ability to stand or urinate, he sags in
in back end until he is down to the ground, when up and walking he weaves some
and has an exagerated high step. I realize that his age may be a factor but
he runs and gets up with no problem, could this inability to stand fairly
stable be a result from once again to high levels of KBr?We did not give him his KBr this am. do you know what the withdrawel time
is for this get out of system? and how should we measure it. The vet that
admin. the pheno and the KBr is not my vet and is far away. My vet is
willing to try most anything but has limited experience with Potassium
Bromide and it affects.to date if my dog has any seizure activity it is basically he gets a little
dopey then may lay down and have a very short seizure then get up and be
fine. we have not had any episodes for well over 3 months, he usually
urinates so we can tell if he when he is wet.Is there any clinical work or info we can find to read on Potassium
Bromide.
thanks, C.
Answer: C.-
There is definitely a chance that the potassium bromide, or the
phenobarbital levels, may be high enough to produce the weakness and
wobbliness you are seeing now. There is also a good chance that a herniated
disc, lumbosacral instability or even degenerative myelopathy could be
causing the signs. In addition there would be some chance of liver damage
due to phenobarbital contributing to this clinical sign. Your vet can help
sort through these problems with a good physical exam, a blood chemistry
test to check on liver and kidney function and checking serum levels of
phenobarbital and potassium bromide.Potassium bromide (KBr) has a "half life" of about 24 days. This means that
in an overdosage situation it is sometimes necessary to use intravenous
saline or at least added salt in the diet to help get rid of the KBr since
it will stay at high levels for a long time. On the other hand, it also
means that once a stable dosage has been established that it will usually
stay about where it is since it takes a long time to get much change. It
also means that it doesn't matter much what time during the day blood
samples are taken to evaluate the bromide level.Phenobarbital levels should also be tested. Recent studies indicate that
timing of the blood test for phenobarbital levels isn't critical, either.
(Levitski as reported in ACVIM research abstracts in "DVM Magazine".The mechanism of action of potassium bromide is still unknown. It is used
fairly often in combination with phenobarbital and can be used alone with
good success in a number of dogs. The serum level that is usually
considered to be useful to control seizures is 1000-2000 ug/mL.I really think a good physical exam and general blood chemistry exam are
important, too. The other problems mentioned are probably just as likely as
a problem with KBr or phenobarbital.Hope this helps.
Mike Richards, DVM
11/5/99
Q: Dr. Mike--My questions are about epilepsy. My 28 month old Lhasa, Zak, has been having
seizures for the last 9 months. They were grand mal seizures and he had them one at a time
every two to three weeks. Our vet put Zak on Primidone. Zak continued to have grand mal
seizures but then started to cluster also. Our vet was reluctent to try anything else, he just
changed the dosage. So we went for a second opinion on June 1st and the new vet wanted to
try Phenobarb, which we started with 1/2 grain, twice a day. Then on June 13th Zak had one
seizure and then about midnight June 15th Zak started to having seizures one right after
another and continued non-stop, totaling 20-30 seizures, for about two hours until we got him
60 miles away to the closest animal emergency hospital. He was given valium that night and I
took him to the vet the next day and the vet increased the Phenobarb to 1 grain, three times a
day and a valium protocol when he had seizures. Zak continued to have seizurers on and off
for three more days. This all really took a toll on Zak but he has eventually made a total
comeback. Since this episode we had Zak tested for low thryoid function and he does have
low thyroid and now he also takes 0.3mg of Thyrozine two times a day. Zak went the entire
month on July without a seizure and then had two seizurers, (no cluster) two weeks apart in
August. We gave him liquid and then oral valium and he came right out of it. And then in
September he had a seizure on the 10th and another on the 13th. These seizurers were so mild
that he really fought us when we tried to give him the liquid valium (rectally). Now I have all
these questions--It has been brought to my attention that this is alot of Phenobarb to be giving
to a dog Zak's size, he weighs about 28lbs. I have had his Phenobarb levels tested and the was
41.1, which I was told was a very good level but what about liver damage with this much
Phenobarb? I've heard about adding Potassium Bromide? If he takes Potassium Bromide can
he take less Phenobarb? And how about the herbal milkthistle? Does it help protect the liver
from damage? And should it be taken before there is any damage or wait until there is a
problem? And what about the problems we are having giving Zak the liquid valium, it really
does help keep him from clustering but if the seizurers are so mild and he stays so allert he just
won't let us give it to him, is there anything else we can do? Sorry there are so many questions
but this is all totally new to us and we want to the best we can for Zak. Any input you might
have would be greatly appreciated--Thank you C. C. and Zak
A: Cathy-
I'll try not to miss a question, but if I do, feel free to write again.
The phenobarbital dosage is producing a serum phenobarbital level in the high end of the therapeutic dosage range, which is good considering the experience with seizures in the past. It is OK to give higher than normal dosages of phenobarbital if that is what it takes to get the blood values in the range necessary to control seizures. It is best to keep it below 45 micrograms/ml. In some dogs, it is necessary to give phenobarbital at dosages as high as 8mg/lb of body weight per day to control seizures.
There are several medications that can be used in conjunction with phenobarbital to control seizures but diazepam (Valium Rx) and potassium bromide are two of the more common ones. It is often the goal to reduce the need for high phenobarbital dosages when combining potassium bromide and phenobarbital and this can work. In some dogs it is even possible to switch to potassium bromide alone but I don't think you could count on that in Zak's case due to the severity of the seizure history.
We will dispense injectable diazepam, in some circumstances, for seizure control (same liquid, you just give it in the muscle by injection instead of rectally). If the seizure activity is mild enough that you can give diazepam orally by pill that would be OK, too.
Phenobarbital causes liver damage in some dogs. It is not predictable when this will happen and I don't think that preventative medications are useful in that circumstance so I guess I wouldn't recommend using milk thistle or any other liver medication unless problems occurred.
Phenobarbital is generally considered to be less likely to cause liver problems than primidone, so it was good to switch medications, especially considering the dosage necessary to control Zak's seizures.
It may be worth asking for referral to a veterinary neurologist for help with this problem. They have the most experience with dogs resistant to seizure control. Your vet seems to be doing a good job and so I don't think this is absolutely necessary but it can sometimes be helpful.
It is a good idea to check the phenobarbital serum levels periodically, especially when you are having to use high dosages.
Mike Richards, DVM
9/24/99
Phenobarbital, seizure, excessive drinking and urination
Q: Dear Dr. Mike,
Our 6 year old German Shepherd started around Thanksgiving with increased
thirst, two weeks later she had a grand mal seizures lasting about 3
minutes. Our vet did blood work and a urinalysis. All were normal.One week later she had two grand mal seizures about 1 hour apart. She was
hospitalized and had several more tests including an ultra sound to check
for tumors. She was also started on Phenobarbitol 1 gram.She continues to have cluster seizures every three weeks. Each episode is
more severe and contains more seizures. The last one was 16 seizures in a
24 hours period with 8 of them being very severe grand mal seizures. She
is now on 3 grains of Pheno BID and 6 cc potassium bromide SID. She has
been on this dose about 3 weeks and was very unsteady the first week. Then
she adapted to it and was doing quite good.About 1 week ago she started drinking literally gallons of water and
leaking urine constantly. Also she has also started being very unsteady
particularily on her left rear leg. All blood work and another urinalysis
were again normal.Our vet is treating it as diabetes insipidus hoping to get the water
intake and leakage under control. He doesn't feel that these things are
connected.I am very afraid that we might be looking at some kind of brain tumor. Do
you have any suggestions or ideas. We have already decided that we will
not have a cat scan and spinal done on her.Judy A
A: Judy-
We have seen excessive drinking and urination as a side effect of
phenobarbital administration in a few dogs. It can be very difficult to
figure out if there is a problem because of the phenobarbital or in
addition to the original problem of seizures. Since the increase in
drinking seems to slightly predate the seizures it does seem likely that it
may be a problem in its own right, though.There is a very high probability of a brain tumor or brain injury in a dog
that develops seizures after it is five years old. The MRI and CT scans are
the best way to look for tumors but sometimes there are other identifiable
signs of damage to the brain that can help identify the presence of a
tumor, such as head pressing, circling, balance problems or changes in
behavior or mentition. When seizures do not respond to medication there is
also a high correlation with brain tumors. I know that both of those
prognostic signs are bad.It is often possible to control diabetes insipidus even when it is
occurring in conjunction with other diseases. It makes it a lot easier to
handle the other problems when constant drinking and urinating are under
control.If there is a veterinary neurologist in your area it may be worth getting
an opinion from him or her even if you do not wish to have further
diagnostic tests. Neurologists are often better at discerning very subtle
signs of neurologic dysfunction than general practitioners and may be able
to give you a better idea of the prognosis.I don't know of a better combination of medications than phenobarbital and
potassium bromide.I wish that I could help more with this.
Mike Richards, DVM
4/14/99
Phenobarbital levels - seizure control
Q: My Lhasa Apso is 9 years old and has had 3 seizures in 9 months. She lies
down and convulses (not too hard) for a short time, gets up, seems
disorientated and after a short time becomes herself again. My vet started her on 15
mg. of pheno twice a day. She was a little tire for the first few days and that has
leveled off, but she is very thirsty, drinks a lot, urinates quite frequently now and
has developed a large appetite. When I asked my vet if this would level off as
the listlesness did, he advised me to take her off the medication for a week to
see if the symptoms disappeared and then resume at half the dosage. If the symptoms
recur then we know it is from the medication. She had blood tests in May and
everything was normal. He suggested blood tests again, but as much as my
dog is part of my family as my husband and daughter, I hesitate to spend
$165.00 so soon again. What do you think. Also my dog weighs 14 lbs.
A: Dear SM-
Increased drinking and urinating can be associated with the use of
phenobarbital. It also occurs as a natural consequence of diabetes, kidney
failure, hyperadrenocorticism and several other conditions. Sometimes an
increased appetite does also occur. So there is a good chance that the
signs you are seeing are due to the medication.I do think that testing the serum phenobarbital levels is the best approach
to monitoring the dosage of phenobarbital and that it should be a routine
part of the management of seizure disorders with phenobarbital. The amount
of phenobarbital that must be administered orally in order to achieve
proper blood levels varies a lot from dog to dog. It takes a couple of
weeks for phenobarbital levels to stabilize, though, so the testing should
be done after the medication has been used for that time. It is also a good
idea to check the liver enzyme levels in the serum on a routine basis (once
or twice a year, at least) when using phenobarbital.If the phenobarbital causes side effects that are difficult to live with it
is worth evaluating the need for seizure control against these side
effects. My dog seizures three or four times a year and I do not medicate
her to control the seizures because I think that the seizures are less of a
problem than the medications to control them, at that level of seizure
activity. You might want to discuss the need for the medications with your
vet again.Good luck with this.
Mike Richards, DVM
Last edited 08/30/02
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