Potassium Bromide Handout
Like sodium chloride, potassium bromide is a salt. It is an very old anticonvulsant, which was used in the 1800's as both an anticonvulsant and sedative. Its mechanism of action is not fully understood, but presumably it competes for and replaces chloride in the cell (and the neuron), thus increasing the electro negativity of the cell and hyperpolarizing it. The potassium does not appear to disassociate. The therapeutic range for potassium bromide in dogs has not been well established, but there are some published reports that offer guidelines. Generally, our laboratory uses 1.0 to 2.5 mg/ml if the animal is receiving phenobarbital; and 2.0 to 3.5 if not concurrently receiving phenobarbital. The latter range is less well established.
The half-life of potassium bromide in dogs is probably about 24 days. Since it takes any drug 3 to 5 half-lifes to reach steady state, that means that the efficacy of a particular potassium bromide dose should not be evaluated until 3 to 4 months have elapsed in a patient receiving that dose. There are also other idiosyncrasies regarding potassium bromide because of its long half- life. First, if the dose has to be manipulated (decreased or increased), 3 to 4 months must elapse before the desired effect is realized. Second, if toxicity occurs, administration of sodium chloride will increase its elimination from the kidney, since chloride will be conserved at the cost of bromide. Third, if a patient misses a dose, or a week of doses, there is not likely to be any adverse effect. Simply have the owner make up those missed doses over the next week (ie, double dose for a week). Alternatively, if the patient is about to seizure, adding an extra dose will be of no benefit, since the total amount of drug in the animal's body represents approximately 3 months worth or 90 doses. A single dose will not appreciably change plasma drug concentrations. In fact, a pet owner could administer this drug once a week with no adverse effects. Twice daily dosing is probably recommended because some animals can not tolerate that much salt in their gastrointestinal tract at once (imagine eating a tablespoon of sodium chloride). However, if the pet will tolerate it, and the client won't consistently forget, once daily dosing is frequent enough. Finally, because of the long half-life, plasma bromide concentrations change very little during a single 24 hour dosing interval (remember, it takes 24 days for plasma drug concentrations to drop by 50%). Thus, when monitoring, a single sample can be collected at any time. We recommend trough samples, particularly if you are also measuring phenobarbital, simply for consistency's sake.
Because of the long half-life, it is necessary to wait several months before the maximum anticonvulsant effects of this drug are realized. To avoid this wait (which simply is not tolerable in some seizuring dogs), a loading dose is administered to dogs starting potassium bromide, or dogs whose potassium bromide concentrations are too low (if the patient is seizuring). The loading dose is intended to rapidly achieve therapeutic concentrations and is based on patient volume of distribution of potassium bromide (0.3 l/kg) and the target concentration (1.5 mg/ml or 1.5 gm/l). Thus the loading dose is 1.5 gm/l X 0.3 l/kg or 0.450 gm/kg (450 mg/kg). We divide this 450 mg/kg dose over 5 days (90 mg/kg/day) and add it to a maintenance dose of 20 to 40 mg/kg (average of 30 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 30 mg/kg per day. We strongly recommend collecting a single sample within a week of the loading dose to see how close you came to therapeutic levels with this loading dose.. We then recommend another sample at 1 month to see if your maintenance dose is sufficient to maintain the concentrations established by the loading dose. We modify the maintenance dose if the 1 month sample is not the same as the post-loading sample. Finally, we recommend retesting at 6 month intervals once the patient's seizures are controlled. Several labs in the US run bromide tests. Our lab runs these tests every Monday and Thursday at a cost of $18 per sample. (Contact us for our complete submission protocol.)
Side effects of potassium bromide therapy are limited to sedation, ataxia, increased urination and rare skin disorders. We tend to see these signs in patients whose potassium bromide concentrations are greater than 2.5 mg/ml. Decreasing phenobarbital doses may be preferred to decreasing potassium bromide concentrations in a patient whose seizures are controlled, yet is too groggy. We encourage monitoring prior to any dose change in a controlled animal (in order to establish the target if seizures begin again). If a patient continues to seizure after receiving potassium bromide, we recommend monitoring and modifying the dose based upon actual concentrations. Again, we recommend loading the patient. Rather than loading with 450 mg/kg, we will load with a fraction of 450 mg/kg depending upon how far away the patient is from 1.5 (the first target). Thus, if the patient is 1.0 mg/ml, we will load with 450 mg x ([1.5-1]/1.5) or 0.5 X 450 or 150 mg/kg. We will also increase the daily maintenance by the same fraction ([1.5- 1]/1.5). If the patient is already at 1.5 mg/ml and continues to seizure, our next target is 2.0. We use the same approach in loading, and we always recommend collecting a monitoring sample after loading. Care should be taken that the animal receiving potassium bromide be maintained on the same diet, or a diet with similar salt content. Since chloride competes with bromide for absorption, high salt diets can increase the elimination of bromide and thus decrease plasma drug concentrations. Note also that most clinical pathology tests can not distinguish between the chloride ion and the bromide ion. Thus, chloride concentrations may "max out" (ie, greater than 200 meq/l).
Potassium bromide is not approved in any form in the United States (although it is in Europe). Current sources are as follows:
- Chemical companies such as Aldrich (1001 West Saint Paul Avenue, Milwaukee, WI, 53233; Phone 800 558 9160) or Sigma (PO Box 14508, St. Louis, MO 63178; Phone 800 325 3010). Chemical companies may refuse to sell potassium bromide for medicinal purposes without an investigational new animal drug application (INADA). However, this should no longer be necessary, since the Food and Drug Administration (Division of Drug Compliance; phone number 301-594-1785) will grant regulatory discretion.
- Several compounding pharmacies in the United States make and sell this drug. Examples: a.) Island Pharmacy Service, Woodruff, WI 54568 (800) 328-7060. b.) B&B Pharmacy, 10244 Rosecrans Avenue, Bellflower, CA 90706 (800) 231-8905. c.) BCP Veterinary Pharmacy, 8323 Southwest Freeway # 620, Houston, TX 77074, (713) 771-1144.
- Several, but not all, veterinary college pharmacies in the country will sell the prepared form of the drug to you. Numbers of the colleges can be obtained in the AVMA directory. I would call the Dean's office of the respective school and ask for the number of the pharmacy.
The FDA realizes the need for KBr in our profession and has made it more legal to obtain the drug without the need for an Investigational New Animal Drug designation. You can obtain regulatory discretion from the FDA (giving you permission to purchase and buy the drug from a chemical company) by contacting the Division of Compliance at the Center for Veterinary Medicine, FDA at 301 594 1785. With this permission, prosecution by the FDA is unlikely unless you fail to meet their guidelines (ie, establish a VPC relationship) or you compound for profit by selling the drug to animals that are not your patients. We make the drug in water, at a concentration of 250 mg/ml. Any convenient concentration can be used. For our study, we put the dose in gelatin capsules. Finally, sodium bromide can be used in lieu of potassium bromide. However, the drug may not mix as well, and the concentration of bromide per mg of NaBr is higher since sodium weighs less than potassium (22 versus 39 MW). For instance, to obtain the same concentration levels of bromide, KBr would be mixed at a concentration of 250 mg to each ml of water, while NaBr should be mixed at a ratio of 215 mg/ml of water.
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