Does Phenobarbital Cause Liver Damage?

Should dogs with epilepsy still be vaccinated?

My dog started medications for seizures. What side effects are tolerable before I need to start worrying?

Potassium bromide (KBr) is causing my dog to have digestive problems. Is there an alternative medication anti-epileptic medicine that, like Potassium bromide, won't harm the liver?

Do seizures always get worse over time?

Is it safe to leave my dog alone or should he/she always have someone present in case of a seizure?

Can seizures cause brain damage?

What should I do when my dog has a seizure?

What is kindling?

What is a spinal tap?

Can my epileptic dog still compete in field or agility?

Does the term "cluster seizure" only pertain to generalized seizures?

Are focal seizures as stressful on my dogs body and organs as generalized tonic-clonic seizures?

Can Potassium Bromide cause Megaesophagus?

Can Lorazepam be used instead of valium for cluster seizures?

What are the signs of liver disease?

Does the Ketogenic Diet help control seizures in Dogs?

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Q. Does Phenobarbital Cause Liver Damage?

A. Ned Patterson DVM (Canine Epilepsy Network, University of Missouri's College of Veterinary Medicine) says that about 20% of dogs eventually develop some liver damage from phenobarbital therapy.

There is only one way to protect your dog's liver from possible damage: have necessary tests run frequently. This means having a chemistry panel with the liver enzymes Alt, GGT and Alkaline Phosphatase done every 3 to 4  months.  If these levels are more than slightly elevated, a urine bile acid or a pre and post bile acid will show if there is actual liver damage.

It is also important to be aware of the signs of liver damage, although not all dogs exhibit signs before significant damage is already done. Signs can include: weight loss, abdominal pain, orange urine, yellow cast to skin and eyes, GI upsets (loss of appetite, vomiting, diarrhea, or constipation), swollen belly, pale gray feces, increased drinking and urinating, depression/lethargy, neurological signs (behavioral changes, seizures, aimless pacing/circling or head pressing).

If your dog is on phenobarbital and has any of these signs, take him/her to the vet immediately. Your dog does not necessarily have to be on phenobarbital for a long time, or at a high dosage, for damage to occur. If damage is caught early, it is often reversible. If it is not caught early, it can be fatal.


Q. Should dogs with epilepsy still be vaccinated?

A. Vaccinations are not necessary for dogs who already have sufficient protection, and most vaccines given today offer many years of protection (at least three years, and up to fifteen years). A simple "titer" test of blood drawn from your dog can indicate whether your dog's protection against disease is adequate.

Why not just go ahead and vaccinate, "just to be safe"? The answer is that vaccinations are neither totally harmless, nor totally safe, especially for dogs whose immune systems are already compromised, as happens in epileptic dogs. Vaccinations, especially when used in excess of what is needed, are suspected of causing many serious problems in dogs: seizures, pancreatitis, inflammatory bowel disease, encephalitis, and even the very diseases they are supposed to protect your dog against!

Whereas ten years ago it was standard practice to vaccinate dogs every year with a wide variety of vaccinations, all at once, vaccination protocols are changing. Annual vaccination is in fact completely arbitrary, unsupported by science. Many clinics now recommend vaccination only every three years and limit the number of vaccinations they advise for all dogs, as well as the number of antigens they will introduce during one visit.

Even if your dog in the past has had no discernible negative response to vaccinations, each time you vaccinate unnecessarily, you put your dog at greater and greater risk, since each vaccination is yet another assault on your dog's immune system. Dogs who are ill, as epileptics certainly are, already have major challenges to their immune system, just dealing with epilepsy. They are therefore more susceptible to an adverse reaction to vaccinations, which further compromise an already compromised immune system.

Talk with your vet about options to annual vaccinations, and to the use of "polyvalent" (multiple) vaccinations, which have a record of many more complications than single vaccinations administered several weeks apart. Find out which diseases your dog may reasonably be exposed to in your area, and which diseases are not at all prevalent. Some vaccinations are only advisable or required if your dog is to be boarded. Others, like the one for kennel cough, have a history of causing more harm than good (dogs vaccinated for kennel cough are more likely to get the disease than those who are not vaccinated for it); others, like the one for corona virus, are given against a disease so rare that one vet termed this "a vaccine looking for a disease." Still others, like the one for Leptospirosis, is often ineffective: the bacterial disease of Leptospirosis has at least 200 subgroups that vary from region to region, and unless your dog is vaccinated against the precise subgroup he/she encounters, the vaccination (which contains only two of the subgroups) will offer no protection. Others, like the canine hepatitis vaccine and the distemper vaccine, should not be given at the same time, to avoid serious potential reactions.

The only vaccine required by law is the one for rabies. Unfortunately, this vaccine is the one that has been implicated in the most serious side effects... among other things, seizures may develop or be worsened by this vaccine. It is always advisable, if you absolutely must get this vaccine for your dog, that it be given alone, at least 4-6 weeks before or after any other vaccine.

Your options other than annual vaccination are many: have titers done to test your dog's immunity and only vaccinate when immunity has dropped; discuss with your veterinarian what vaccinations you may be able to safely omit for your dog; insist that vaccinations be given one at a time to avoid increasing their risks; ask your veterinarian to sign a waiver so that your dog does not need to get the rabies vaccine, especially if you have seen a reaction to this vaccine in the past.

Only you and your vet can decide which vaccinations are necessary for your dog and which are not. For an epileptic dog, however, it is always advisable to avoid vaccinations if your dog already has adequate protection.

(Main source and suggested reading: "Vaccine Guide for Dogs & Cats: What Every Pet Lover Should Know" by Catherine J. M. Diodati.)



Q.  My dog started medications for seizures. What side effects are tolerable before I need to start worrying?

A.  First, if your dog is having problems, always inform your veterinarian. Keep a log of problems you see and dates when you see them. Any time your dog has a change in anti-epileptic medication or dosing, it is always wise to double-check your dog's dosage to make sure you correctly understand the dosing and that there was no mistake made. Even a correct start-up dose can simply be too strong for certain dogs, since there is wide variation in how dogs metabolize their medications.

If your dog is just starting medication or increasing the dosage of a current medication, more side effects can be expected in the beginning. Side effects for anti-epileptic drugs (AEDs) can include ataxia (difficulty walking/standing), increased appetite, increased thirst, and increased urination. It will normally take a while for your dog's body to adjust to a new medication or higher dose. Normally, you will begin to see this adjustment gradually in your log. Generally speaking, though, a dog should not be so sedated that he/she cannot get up and go outside without help. Stairs are an exception: dogs on AEDs should always be monitored and on-leash on stairs. If your dog is heavily sedated and can't function, you should discuss this with your vet. A dosage reduction may be needed. Be sure to have the blood level of any new medication checked after it has reached its full potency in the bloodstream. The amount of time this takes varies from medication to medication: ask your vet.  Usually Phenobarbital levels are drawn 2 to 4 weeks after starting medication.  Potassium Bromide levels are usually 4 to 6 weeks after starting medication.

On a continuing drug therapy, the only way to know if your dog's medication is within (and not below or beyond) therapeutic range is to have the blood level of the medication checked. Blood levels that are too high can cause side effects. Checking the blood levels of anti-epileptic medications should be done regularly-- every 6 months for the duration of the therapy. If your dog has been on the same medication for some time and suddenly begins to develop side effects, it is time to have the blood levels of the medication re-checked, even if it is sooner than 6 months since the last test.

Q.  Potassium bromide (KBr) is causing my dog to have digestive problems. Is there an alternative medication anti-epileptic medicine that, like Potassium bromide, won't harm the liver?

A.  Sodium bromide (NaBr) can be used to control seizures and works exactly like Potassium bromide does, but is much less likely to cause difficulties for a dog's GI system. If a dog gets good seizure control from Potassium bromide, but has continual or intermittent GI troubles, Sodium bromide is an excellent alternative since it is the potassium that may give some dogs stomach upset. Neither Sodium bromide nor Potassium bromide will harm the liver.

The information on our website about Potassium bromide discusses possible side effects of Potassium bromide and describes the reasons Sodium bromide may be used as an alternative to Potassium bromide. Information about Sodium bromide is in the third paragraph of the section titled "Side Effects." The link for that article is:

Q.  Do seizures always get worse over time?

A.  Seizures do not necessarily get worse over time. It is important, however, to do everything possible to keep the number of seizures at a minimum, since it is theorized that the more seizures a dog has, the more likely he/she is going to have more seizures. This theory, which proposes that each time the brain has a seizure it "learns better" how to have the next seizure, is called "kindling."

There are a number of things you can do to help lengthen the intervals between seizures. You can start medicating your dog if the seizures are frequent and your dog is not yet on medication. You can have titers done to avoid vaccinations, which can further compromise your dog's immune system and be a trigger for seizures. You can make sure your dog's food is the highest quality you can afford and does not contain BHT, BHA, or Ethoxyquin--home cooking is best, if you have the time and the budget for it. It is very important to make sure your dog has had a current 6-panel thyroid test that is interpreted by Dr. Jean Dodds, one of this country's leading experts on thyroid disease. Low thyroid function or hypothyroidism can cause seizures. Annual retesting is crucial, since thyroid problems can develop at any time. For more information on the connection between seizures and hypothyroidism, go to:


Q: Is it safe to leave my dog alone or should he/she always have someone present in case of a seizure?

A: Most people do not have someone to watch their dog 24 hours a day. If you do, that is wonderful, but not necessary in most cases. What is important is to "seizure proof" your home so that it is safer for your dog when you are not there.

It is important to keep your dog in a space where he/she can have a seizure safely. Make sure nothing can fall onto your dog, or that your dog can not hurt him/herself by banging into something. Usually a kitchen is a safe space, but make sure that the countertops do not have anything sitting near the edge, in case your dog hits the cupboards during a seizure. Regardless what room you choose, make sure that if your dog bumps into something like a coffee table, desk, or bookcase, nothing on it will tumble onto your dog.

Keep your dog securely enclosed away from stairs, which he/she can fall down during a seizure. It is also important to guard against leaving your dog in a space where a flailing leg can get caught between thin rails, for example, or where your dog or one of his/her legs can get wedged into a space and not be able to get out. Leaving your dog in the bedroom, if he/she can get under the bed, is not a good idea: a seizure under the bed can cause harm from metal springs or the frame of the box springs. If possible, floors in the room chosen should be padded with carpeting or blankets.

It is also important that your dog does not wear a collar that can, if caught on something during a seizure, hang your dog up or choke him/her. Make sure there is nothing that can snag your dog's collar; or simply remove your dog's collar if your dog is micro chipped or secure from escape from your home.

If you have other dogs in the house, it is safest to confine your epileptic dog away from all other dogs. Even if your other dogs have never been aggressive toward your epileptic dog during a seizure, you can not predict what will happen every time you are not present. It is better to be safe than to come home to something you never imagined could happen.

If possible, have a friend, neighbor, or relative come over to check on your dog if you are gone more than a few hours.

There are usually telltale signs if your dog has had a seizure while you are away. If you come home to find urine and/or feces and your dog is housetrained, that may be an indication that your dog has had a seizure. Your dog may be in an agitated or spacey post-ictal (after seizure) state. Feel around your dog's neck to see if it is damp: dogs may drool during a seizure. Blood in or around the mouth may also be a sign.


Q: Can seizures cause brain damage?

A:. Normally seizures do not cause brain damage. Most dogs go through a whole life having seizures without any brain damage. Severe clusters of multiple seizures in a short period of time may cause slight brain damage, but this is usually temporary. For example, your dog may forget commands or his/her name for a short period of time after severe cluster seizures.

There are situations that should be considered emergencies, though, since these can (but do not necessarily) cause brain damage or be life-threatening.
Take your dog to the vet as soon as possible if your dog does not recover between seizures or continues to have multiple seizures within a short period of time (despite the valium protocol, if you have it); or if his/her breathing is heavily labored or stops; or if his/her temperature is abnormally high (greater than 107 F or 41.5 C--but do not take the temperature while your dog is having a seizure: the thermometer could break).


Q:  What should I do when my dog has a seizure?

A.  The most important thing you can do when your dog has a seizure is STAY CALM.  Most seizures are very brief. Although they seem like hours, the average seizure is less than two minutes.  First be certain that your dog is safe, that he won't fall down stairs, bang into a sharp edge on furniture, get tangled in an electrical cord or otherwise injure himself.  Lifting your dog may be very difficult because of the thrashing, so do so with extreme caution.

Do not try to open your dog's mouth to pull the tongue out.  It is extremely rare for a dog to "swallow his tongue" and obstruct the airway, and the strength of your dog's jaws will probably prohibit any attempts you make to open the mouth.  In addition your dog may accidentally bite you.

If you have other pets in the house, be sure to restrain them if they act aggressively towards your seizing dog.

It may be helpful to gently talk to your dog.  Try to turn off any loud music or other stimuli, such as flashing lights.   It may also be helpful to dim all lights.  Ask other family members to stay calm and talk softly.

Your veterinarian may have recommended giving oral valium, rectal valium or oral Phenobarbital if your dog has a seizure.  When giving oral medications, be sure your dog is awake enough to swallow and aware enough not to bite you.  Rectal valium is easiest to administer when your dog is no longer thrashing but not fully recovered.

Be sure to update your log of seizures now.  Don't rely on your memory.  By observing exactly what your dog does before, during and after the seizure, you may be able to provide your veterinarian with important clues to what is going on.

You can read personal experiences from the Guardian Angels', at the following link, about things they do while their dog is having seizures. Included here are things like what to do for your epi-dog during seizures; keeping phone numbers and logs handy and updated and step-by-step actions to take that have proven effective for the Guardian Angels themselves in dealing with their epis’ seizures over time.



Q.  What is kindling?

A.  Kindling is the experimental phenomenon whereby repeated stimulation of the brain can eventually induce a chronic epileptic state that persists after the stimulation is stopped.

The underlying mechanisms of kindling are incompletely understood but involve changes in the electrical behavior of a group of brain cells.  This may be related to alterations of chemical receptors (specifically what are called NMDA subtype of glutamate receptors) and changes in how these brain cells connect with each other through structures called synapses.

In a sense, by having repeated seizure the brain "learns" how to have seizures.  Think about how a young child learning to write their name has to concentrate when printing each letter.  After doing this over and over, we become able to quickly write our name without even thinking about the intricate hand movements involved.  Obviously there is some change in our brain that allows this to happen, but it does not have to be a structural lesion.

I think of kindling as something similar.  The brain is doing what it is designed to do...learn.  It is just learning to do something harmful like have a seizure.

WB Thomas, DVM
Dipl. ACVIM (Neurology)
University of Tennessee
Knoxville, TN



Q.  What is a spinal tap?

A.  A spinal tap is a procedure where spinal fluid is collected from the space surrounding the spinal cord, either in the neck, just behind the head, or in the lower back.  General anesthesia is necessary because the dog must be perfectly still and the procedure itself is painful.  The hair over the collection site is clipped and the skin disinfected.  A needle is placed through the skin and muscle, into the space surrounding the spinal cord.  The spinal fluid is allowed to flow out into a collection tube.  Usually about 5 ml (1 teaspoon) of fluid is collected.  The body will replace this fluid in about 1 hour.

The most substantial risk associated with a spinal tap is the anesthesia.  The risk of anesthetic complications in a healthy dog are very low.  However, dogs that need spinal taps often have neurological disease, which may increase the risk.  The risks of general anesthesia in a dog with idiopathic epilepsy is very low.

The other risk is the potential for damage to the nervous system as the needle is placed.  This risk can be reduced, but not completely eliminated, by having the procedure performed by a veterinarian with experience in performing spinal taps.

The vast majority of dogs seem to feel fine once they recover from the anesthesia.  Headaches occur in about 30% of people with spinal taps, but this doesn't seem to be a problem in dogs.

The collected fluid is examined under a microscope to detect any abnormal cells and the protein content is analyzed.  These results are usually available within 24 hours.  Depending on these results, other tests, such as cultures and antibody levels, may be performed on the fluid.  These additional tests may take a week or more to before the results are available.



Q.  Does the term "cluster seizure" only pertain to generalized seizures?

A.  We asked this question of Dr. Thomas and here is his reply:

"No.  Although generalized seizures are the most common in dogs, and the most common to occur in clusters, you can see clusters of any type of seizure.



Q.  Are focal seizures as stressful on my dogs body and organs as generalized tonic-clonic seizures?

A.  We asked this question of Dr. Thomas and here is his reply:

"In general no, especially if there is no, or only mild convulsive muscle activity."



Q.  Can Potassium Bromide cause Megaesophagus?

A.  We asked Dr. Thomas this question:

I'm aware of several dogs that developed megaesophagus while taking bromide.  Whether this represents a true cause-and-effect relationship or a coincidence is not clear.  I would be reluctant to state that this is a known side effect of bromide therapy until we have more information.


WB Thomas DVM
Dipl.ACVIM (Neurology)
University of Tennessee
Knoxville, TN

The following is some information about this condition:

Megaesophagus is the enlargement of the esophagus, caused by paralysis of the esophageal musculature.  With Megaesophagus, esophageal mobility is decreased or absent resulting in accumulation and retention of food and liquid within the esophagus.  Rather than a single disease entity, megaesophagus refers to esophageal dilation and hypomotility which may present as a primary disorder or secondary to esophageal obstruction or neuromuscular dysfunction.

Megaesophagus can be congenital and is heritable in Wirehared Fox Terriers and Miniature Schnauzers.  Familial predispositions have been reported in the German Shepherd, Newfoundland, Great Dane, Irish Setter, Shar Pei, Pug, and Greyhounds.

History relating to megaesophagus may include regurgitation of food and water, weight loss or poor growth, salivation and a gurgling sound.  With congenital megaesophagus regurgitation of liquids through the nostrils and a poor hair coat may be seen.

Physical Examination Findings include regurgitation, general physical wasting and malnutrition, ausculation of retained fluid and food in the esophagus, halitosis,  excessive salivation, bulging of the esophagus at the thoracic inlet and pain associated with palpitation of the cervical esophagus.

Ref:  The 5 Minute Veterinary Consult; Larry P. Tilley, Francis W. K. Smith Jr.



Q.  Can Lorazepam be used instead of valium for cluster seizures?

A.  From the annual ACVIM forum in Charlotte, NC:

Christopher Mariani presented an abstract on the pharmacology of intranasal lorazepam in normal dogs. Lorazepam is a benzodiazepine that is normally administered by vein. It doesn’t work well when given rectally because the liver inactivates most of the drug. They found that giving the drug into the nose bypasses the liver and obtains good blood levels. So this may prove to be an effective emergency treatment for seizures in situations where intravenous administration is not possible, such as treatment at home.



Q.  What are the signs of liver disease?


Some or all of the following symptoms may be present:

1.  Intermittent, recurrent abdominal or gastrointestinal upsets.  Loss of appetite, vomiting, diarrhea, constipation.

2.  Progressive depression or lethargy.

3.  Swollen belly with a fluid-filled look.  This is known as "ascites" and is actually fluid accumulation in the belly due to circulation alterations in the abdomen.

4.  Pale gray feces.  Bile pigments are what give feces its characteristic brown color. 

5.  Orange urine.  The improper processing of bile results in the excretion of bilirubin in the urine which gives it an orange color.

6.  Jaundice, also known as "icterus."  When biliary pigments accumulate in the blood, any pale or white skin or tissue takes on a yellow cast.  Usually visible on the stomach and eyes.

7.  Hepatic encephalopathy, or severe neurological signs, such as behavioral changes, seizures, aimless pacing or circling and head pressing.

8.  Pain associated with the abdomen.

9.  Chronic weight loss.

10.  Increased water consumption and urination.



Q. Does the Ketogenic Diet help control seizures in Dogs?

A.  The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet used to treat seizures in people, mostly children. The diet is carefully and individually calculated and rigidly controlled. The ketogenic diet gets its name because the high fat content of the diet results in conversion of fat to ketones that are utilized as an energy source in place of carbohydrates. However, canines are more resistant to ketosis induced by starvation compared to people, therefore the diet has not been effective in controlling seizures in canines. Because many inquire about the Ketogenic Diet's use in dogs, below is the history and findings of the Ketogenic Diet written by Dr. William Thomas, DVM, MS, Dipl.ACVIM(Neurology):


Fasting has been a treatment for epilepsy since biblical times. In 1921, the American pediatrician Rawle Geylin, reported the successful use of fasting to treat epilepsy in children. The antiseizure effects of starvation were attributed to the ketosis and acidosis resulting from starvation. When there is no ready supply of carbohydrates in the diet, the body utilizes other available stores of energy instead. In people, this results in the production of ketones, such as acetone, acetic acid, and p-hydroxybutyric acid. Accumulation of these substances in the body is referred to as
ketoacidosis or ketosis.

In 1921, Wilder proposed that the antiseizure effects of fasting could be obtained if ketosis was produced by feeding a diet very low in carbohydrates and high in fats. The Mayo Clinic (Rochester, MN, USA) developed such a diet and subsequent reports found that the diet improved seizure control in about 60% of children with epilepsy.

Throughout the 1930's the ketogenic diet was widely used, since available drugs, namely bromide and phenobarbital, were sometimes ineffective or had serious side effects. When phenytoin was discovered in 1938, the ketogenic diet fell by the wayside. However, a few centers continued to use the ketogenic diet, most notably the Epilepsy Center at Johns Hopkins. Recently, there has been renewed interest in the diet.

Mechanism of antiseizure effects

Exactly how the ketogenic diet acts to inhibit seizures is not known precisely. Antiseizure effects may be mediated by a decrease in pH (acidosis) or the effects of ketones on the brain. Acidosis may reduce brain cell excitability and prevent seizure discharges.

Effectiveness in human epilepsy

Most of the early studies of ketogenic diets in people with epilepsy were retrospective or suffered from other limitations. A recent prospective study evaluated one type of ketogenic diet in children (ages 1 to 8 years) with epilepsy unresponsive to at least two drugs.(1) Seizure control improved in 67% of patients, while 37% of patients discontinued the diet because they continued to suffer seizures or could not tolerate the diet. Other studies have shown similar results. The diet appears to be less effective in adults.


There are several specific ketogenic diets used in people. In the 3:1 ketogenic diet, 87% of calories are from fat, 6% from carbohydrates, and 7% from protein. In the medium-chain triglyceride diet, 60% of calories are from medium-chain triglycerides, 11% from fat, 19% from carbohydrates, and 10% from protein. This diet is more palatable and does not increase blood cholesterol as much as the 3:1 diet. Patients are typically fasted for several days before being gradually introduced to the diet.

It is important to realize that these diets must be rigidly controlled by specially trained dieticians and require extensive education of the patient and parent. Even the amount of sugar in a children's vitamin pill must be accounted for.

Is the ketogenic diet useful in dogs with epilepsy?

Several years ago, one of the dog food manufacturers formulated an experimental ketogenic diet for dogs with epilepsy. The diet was tested in dogs with naturally occurring epilepsy. I heard last week at a meeting that the study has been stopped because there was no benefit in seizure control.

There are several potential limitations: Dogs are more resistant to ketosis induced by starvation, compared to people. As carnivores, dogs are adapted to relatively long periods of time between meals. Therefore, diets that induce ketosis in people may not do so in dogs. The type of epilepsies that dogs suffer may not be the same as those in people that respond to the diet. The safety of these diets has never been assessed in dogs. Pancreatitis (inflammation of the pancreas) is a fairly common and serious disease in dogs and may be precipitated by high levels of dietary fat.

I am aware of several attempts at similar diets in dogs with epilepsy. In most cases, the client is simply adding a source of fat (such as cream) to the diet without severely restricting carbohydrates. It is important to realize that the total amount of dietary fat is not as important as the ration of fat to carbohydrates.

In summary, based on the above considerations and the lack of clinical trials, we do not currently recommend a ketogenic diet in dogs with epilepsy.

WB Thomas DVM, MS
University of Tennessee