PottasiumBromide in epileptic dogs

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Dr. Swarupmay Majumdar

Posted By : Dr. Swarupmay Majumdar - BVSc

Posted On : Oct 12, 2009 (Views : 4520)

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First choice Drug:

Potassium Bromide, abbreviated as Kbr, is often considered the first choice drug for any dogs with idiopathic epilepsy. It has no effect on the liver, so it is often chosen for dogs with liver damage. Unlike Phenobarbital (Pb), which is processed by the liver, bromide works by replacing chloride throughout the body and it is stored in body fluids before being eliminated unchanged by the kidneys. 

 

Expected therapeutic level:

Target range for Bromide is 2 to 3 mg/ml for dogs not on Phenobarbital

Target range for Bromide is 1.0 to 2.0 mg/ml if the dog is also receiving Phenobarbital

 

Loading dose

However, where Phenobarbital is effective almost immediately, Kbr can take up to three or four months to reach its full effect. A loading dose may be necessary for dogs with frequent seizures or when Phenobarbital must be withdrawn rapidly because of liver disease.

 

Kbr & Pb combination:

Sometimes Kbr and Pb are used together. For those dogs with epilepsy whose seizures are not well controlled by Pb alone, the addition of bromide can greatly improve seizure control.  This often allows either a decrease or total withdrawal of Phenobarbital.

 

Choosing Sodium or Potassium Bromide:

There are actually two kinds of bromide -- potassium bromide and sodium bromide -- and both are equally effective at controlling seizures. Compounded with either potassium or sodium, the bromide controls the seizures. Potassium bromide is preferred when sodium intake must be restricted (e.g., congestive heart failure). Sodium bromide is preferred when potassium intake must be restricted (e.g., hyperadrenocorticism).

Bromide is a very old anti-convulsant which was used in the 1800's as both an anti-convulsant and a sedative but seldom used in people.Pottasium bromide has been used in dogs for a long time, and has proven to be reliable and safe.



Dosage:

Both potassium bromide and sodium bromide are available in liquid and capsule form. The liquid form, which comes in flavors, is generally less expensive and it is easier to adjust the dose in liquid than in capsules. The long half life of bromide, about 24 days, means that the timing of an individual dose is much more flexible - unlike Phenobarbital (Pb), you don’t have to stick to a strict 12 hour schedule for giving the medication. Even though the dosing can be flexible, twice daily dosing is probably recommended because some animals cannot tolerate too much salt in their gastrointestinal tract at once.

 

Missed dose:

If you miss a dose or even a week of doses, there is not likely to be any adverse effect. The missed doses can simply be made up over the next week (i.e. double doses for a week).   But the long half life also means that the effectiveness of a particular dose should not be evaluated until the patient has been on the dose for three or four months, unless a loading dose is given. And if the dog is having seizures, adding an extra does will not help.

To avoid this wait, which simply is not tolerable in some seizing dogs, a loading dose can be administered to dogs starting potassium/sodium bromide, or to dogs whose potassium/sodium bromide concentrations are too low (if the patient is seizing). The loading dose is intended to rapidly achieve therapeutic concentrations.

 

Dosing:

Because absorption, distribution and speed of metabolism can vary among dogs, published dose recommendations only serve as a general guide. Most new patients are started at the lower end of the dose range; however, patients with frequent or severe seizures are often best managed by starting at the higher end of the dose range or by using a loading dose.

An average maintenance dose for potassium bromide is 20 mg to 30 mg per kg of body weight given once a day. You may divide the dose and give potassium bromide twice a day. Sodium bromide has slightly more bromide compared to an equal weight of potassium bromide, so the dose of sodium bromide is 15% lower than for potassium bromide. The dosage may be adjusted based on blood levels, seizure activity and side effects of the medication. 

 

Calculating Loading dose:

The loading dose is based on (a) patient volume of distribution of potassium bromide (0.3 l/kg) and (b) the target concentration expected (1.5 mg/ml or 1.5 gm/l). (The loading dose is 1.5 gm/l X 0.3 l/kg = 450 mg/kg. This 450 mg/kg dose is divided over 5 days (450/5=90 mg/kg/day) and added to a maintenance dose of 20 to 30 mg/kg (average of 25 mg/kg) per day.) Thus, a new patient will receive 120 mg/kg of potassium bromide each day for 5 days, and then back down to 25 mg/kg per day. 

 

 

 

Salt in food:

High chloride (salt) intake can increase the elimination of bromide, which means that if your dog's salt intake increases, you may need to adjust the bromide dose. It is not necessary for dogs taking bromide to be on a low salt diet, but it is important that the salt content of the diet not be drastically changed during treatment, as this will affect bromide levels. Ideally, it's best to keep the diet stable if you can.

 

Monitoring Therapy:

To determine the correct dose of bromide, it can be very helpful to monitor its level in the blood. Any change in dose should be made based upon the actual concentration in the blood. If you have used a loading dose, It is recommended that you collect a single sample within a week of the loading dose to see how close you came to therapeutic levels with this loading dose, and then another sample at one month to see if your maintenance dose is sufficient to maintain the concentrations established by the loading dose. The maintenance dose would be modified if the one month sample is not the same as the post-loading sample.

If you have started with a regular dosing schedule, you will want to test the bromide levels after about a month and then at six month intervals, once the blood level has reached a therapeutic range.

 

SIDE EFFECTS:

The most common side effects of bromide therapy are sedation, ataxia (hind end weakness and loss of coordination), increased urination and rare skin disorders. Increased urination, hunger and thirst are also common for dogs taking bromide alone or with Pb.

Occasionally, abnormal behavior, such as irritability or restlessness can also require a reduction in dose. Side effects are more common in patients whose potassium bromide concentrations are greater than 2.5 mg/ml and the symptoms usually go away within a week after the dose is decreased.   If the dog is too groggy and is on both Phenobarbital and bromide, it may be preferable to decrease the Phenobarbital dose, rather than the bromide. If the dose of bromide is to be decreased, we recommend monitoring of blood levels before any dose change in order to establish a target if seizures begin again.

Potassium bromide can also cause stomach upset, nausea and vomiting. If this occurs, you may wish to try giving the drug with food, or dividing the daily dosage into two or more portions; you and your may also consider switching to sodium bromide which is just as effective but doesn't cause the same stomach symptoms. And some dogs prefer the taste of sodium bromide.

Bromide should be used with caution in dogs with renal insufficiency.

Bromide toxicity is uncommon, however, it is a potential side effect of bromide use and most of the potential side effects that have been discussed on our list are from bromide toxicity. Bromide toxicity can occur in dogs with renal insufficiency or those that are on a very high dose of bromide. Signs of bromide toxicity include severe ataxia, sedation or stupor and muscle spasms. Usually, reducing the dose by 10% to 25% is sufficient to take care of these signs.

 

DISCONTINUING THERAPY:

The decision to stop therapy must be made very carefully, but is reasonable to consider in dogs that are seizure-free for one to two years. The dose is gradually tapered over a period of 6 months. The major risk of discontinuing drug therapy is seizure recurrence, which is most likely to occur during withdrawal or within several months of stopping therapy.

 

DRUG INTERACTIONS:

Bromide is eliminated from the body by the kidneys. Bromide and chloride compete for re-absorption by the kidneys. A substantial increase in dietary chloride (salt) will cause decreased re-absorption of bromide by the kidneys, resulting in more bromide being eliminated. That means that if the amount of salt in the diet increases, bromide levels will decrease, which could lead to seizures. Conversely, switching to a diet low in chloride will cause bromide levels to increase, which could cause bromide intoxication.

It is not necessary for dogs taking bromide to be on a low salt diet, but it is important that the salt content of the diet not be drastically changed during treatment, as this will affect bromide levels.

Diuretics also increase bromide excretion and can lower the level of bromide in the blood.

 

In nutshell:

1.  Potassium and sodium bromide are drugs given to control seizures in dogs. Unless you give a loading dose, it can take up to three or four months before it really begins to work.

2.  When first started, blood levels should be checked at one month and then every six months; if you have given a loading dose, then levels should be checked sooner.   

3.  The dosing schedule is more flexible than with Phenobarbital because of bromide's long half life, but please be aware of the chloride (salt) content in your dog's food and if it changes, discuss changing the dose with your veterinarian.

4. There can be side effects, most of which disappear in a few weeks. These can include excessive hunger, thirst and the need to urinate, lethargy and ataxia (loss of coordination). If the drug upsets your dog's stomach, try giving it with food or in two doses. If the problem continues, discuss switching from potassium bromide to sodium bromide.


Compiled by:

Dr Swarupmay Majumdar, B.V.Sc

The General Veterinary Clinic, Indiranagar

 



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