First, they are only effective for a short time requiring frequent administration to maintain adequate serum levels. They can also be useful as temporary therapy when seizures can be predicted, such as seizures precipitated by stress or sleep deprivation. Long term use of any benzodiazepine may prevent effective use of diazepam to treat emergency seizures. Second, long term use of this category of drug reduces its effectiveness in controlling seizures. These medications are all part of the benzodiazepines and are potent anti-seizure drugs, but they all have characteristics that limit their use for maintenance of seizures in dogs. These drugs are effective for the emergency treatment of status epilepticus or cluster seizures.
Diazepam (Valium), Clonazepan, Lorazepam and Clorazepate.
Zonisamide seems to be an effective "second-line" drug in dogs, based on limited clinical experience. It's elimination half-life is 15-20 hours in dogs, so it is usually given twice daily. So far, side effects in dogs seem rare. In the dog, zonisamide (Zonegran) we use 10 mg/kg every 12 hours and is metabolized by the liver, with an elimination half-life of 15 hours. It's expensive.
OTHER MEDICATIONS Valproic Acid.
Thomas answer:. Zonegran caught my attention and I wondered how this AED is metabolized? Dr.
In 4 dogs, response to the drug was no better than response to phenobarbital alone. Clinical evaluation of gamma-vinyl-gamma-aminobutyric acid for control of epilepsy in dogs.J.Amer.Vet.Mec.Assoc.1991, 198:. In 2 dogs, seizure control improved, but gamma-vinyl-gamma-aminobutyric acid was withdrawn because of development of haemolytic anemia. For various reasons, the therapeutic effect in the remaining 4 dogs could not be evaluated. Speciale-J, et al. WB Thomas DVM, MS Dipl.ACVIM(Neurology) University of Tennessee Knoxville, TN. Excerpt from abstract: The drug was administered to 14 dogs in conjunction with other anticonvulsants, in an attempt to control refractory epilepsy. Vigabatrin has been evaluated in a small number of dogs with idiopathic epilepsy. Four of these dogs had clinically relevant evidence of decreased seizure frequency. Results were not very encouraging and several dogs developed hemolytic anemia that required stopping the drug.
William Thomas, DVM, MS. Vigabatrin Written by Dr.
I'm not aware of any clinical or long-term safety studies in dogs. William Thomas, DVM, MS Keppra (levetiracetam) is approved in the US for people with focal seizures refractory to other anti-seizure drugs. Keppra (Levetiracetam) Written by Dr. The elimination half-life in dogs is about 3.6 hours. I have used it in a few dogs with epilepsy refractory to other medication, but experience is still too limited to l if this will prove to be a useful drug for dogs. WB Thomas DVM,MS Dipl.ACVIM(Neurology) University of Tennessee. This compares to 7-10 hours in people.
Written by Dr. William Thomas, DVM, MS on Valproic Acid:.
Thomas' Answer: I'm not aware of any studies using this drug in dogs with epilepsy. The elimination half-life is approximay 4 hours. Has it been used on K-9's yet? It is made by Novartis. However, it has been studied in normal laboratory dogs. During continued treatment for 8 days, plasma concentrations showed a pronounced decline from day 3, and the half-life decreased to 1 hour. WB Thomas DVM, MS Dipl.ACVIM(Neurology) University of Tennessee Knoxville, TN. 1996 Feb; 19(1): 27-31. Schicht-S; Wigger-D; Frey-HH J-Vet-Pharmacol-Ther. Dr. It says monitoring of hepatic enzymes or hematologic tests is not required. William Thomas: I am interested in the new drug Trileptal. It doesn't effect the kidneys or the liver. This is considered to be the result of oxcarbazepine inducing its own metabolism. Trileptal (Oxcarbarepine) Question for Dr. The very short half-life suggests oxcarbazepine is probably unsuitable as antiseizure medication in dogs. Sounds like the perfect drug to me for HUMANS. Pharmacokinetics of oxcarbazepine in the dog.
William Thomas, DVM, MS Dipl. Zonisamide (Zonegran) Written by Dr. ACVIM (Neurology) University of Tennessee.
Although valproate-induced liver disease has not been documented in dogs, there are no large, long-term studies of this drug in dogs with epilepsy. WB Thomas DVM,MS Dipl.ACVIM(Neurology) University of Tennessee. Drowsiness and sedation can occur, especially at higher doses or when valproate is combined with other antiseizure drugs. The elimination half-life in dogs is fairly short (approximay 3 hours) compared to people (5 to 15 hours). Nafe LA. Side effects: Nausea and vomiting. However, these blood levels may still be sufficient in dogs, since lower protein binding of valproate in dogs gives rise to higher brain concentrations, compared to people. Plasma levels of valproic acid and its metabolites during continued treatment in dogs. Loscher W. These can usually be avoided by giving valproate with or soon after meals. It is used primarily in dogs whose seizures are not well controlled with phenobarbital or bromide. Sodium valproate: A preliminary clinical trial in epileptic dogs Journal of the American Animal Hospital Association17:131-133,1981. Hair loss has been observed in dogs and people. Valproate (valproic acid, Depekene) is considered a second line drug for the treatment of epilepsy in dogs. When used in conjunction with other anti-seizure drugs (mostly phenobarbital or primidone), valproate was successful in reducing seizure frequency by at least 50% in 21 of 41 dogs (51%). Because of the lack of long term studies and concerns about the rapid metabolism in dogs, valproate is currently considered a second line drug for the treatment of canine epilepsy. In one short-term study, treatment with valproate alone was effective in reducing seizure frequency by 50% or more in 7 out of 16 dogs (44%) with idiopathic epilepsy. Liver disease has been reported in about 1 in 3700 people (1 in 500 young children) treated with valproate. Thus, unless very high doses are used, blood levels of valproate in dogs are less than concentrations known to be therapeutic in people. Journal of Veterinary Pharmacology and Therapeutics 4:111-119,1981.
Tegretol (Carbamazepine) Written by Dr. Frey HH; Loscher W. Pharmacokinetics of carbamazepine in the dog. Unfortunay, this drug is eliminated very quickly in dogs, with a half-life of only 1-2 hours (compared to 5-25 hours in people). Successful long term treatment of a dog with psychomotor seizures using carbamazepine. Clinical experience suggests it is not very effective in dogs, probably because of the difficulty in maintaining adequate blood levels. William Thomas, DVM, MS Carbamazepine (trade name; Tegretol) is one of the most widely used antiseizure drugs in people. 1980 ; 243(2): 180-91 Holland CT. I'm not aware of any clinical trials of carbamazepine in dogs, although there is a single case report of successful use in a dog with psychomotor seizures (a form of focal seizures). Arch-Int-Pharmacodyn-Ther. Aust-Vet-J. WB Thomas DVM, MS Dipl.ACVIM(Neurology) University of Tennessee Knoxville, TN. 1988 Dec; 65(12): 389-92. With long term use, the half-life becomes even shorter because of increased liver metabolism.
Question on Zonegran for Dr. Thomas:.
In 8 of these dogs, it was possible with decrease the dose or withdraw concurrent anti-seizure drugs. From the annual ACVIM forum in Charlotte, NC: Curtis Dewey presented an abstract on using zonisamide (Zonegran) in 12 dogs with epilepsy refractory to other drugs (mostly phenobarbital and bromide). Side effects were very mild. Seven dogs (58%) had a decrease in the number of seizures after starting zonisamide, with a mean decrease in seizure frequency of 81%.
Although Dilantin is extremely effective in treating human epilepsy, dogs metabolize this drug too quickly to maintain adequate blood levels. In one clinical study only 1 in 77 epileptic dogs could be controlled with this drug.
Potential side effects include loss of hair and liver disease. Valproic Acid is primarily used in combination with other drugs such as Phenobarbital. This medication is effective in humans with all types of seizures; however, it is metabolized very quickly in dogs and therefore its use is limited.
Effects of a 44-day administration of phenobarbital on disposition of clorazepate in dogs. It is used mostly as add-on therapy in people. Brown SA, Forrester SD. Coadministration of phenobarbital with clorazepate results in lowered blood levels of clorazepate. After oral administration, clorazepate is converted to nordiazepam (also called N-desmethyldiazepam), in the stomach. Clorazepate (Tranxene) Written by Dr. Disposition of clorazepate in dogs after single- and multiple-dose oral administration. William Thomas, DVM, MS Clorazepate (Tranxene) was introduced in the United States in 1981. Nordiazepam provides all of the antiseizure effect. Forrester SD, et al. American Journal of Veterinary Research 51:, 1990. Sustained release tablets (Tranxene SD) offer no pharmacokinetic advantages over regular-release tablets in dogs. Scherkl R, et al. Epilepsy Research 3:144-150,1989. The elimination half-life is 2 to 5 hours, tending to be slightly longer with long term administration. Serum disposition of oral clorazepate from regular-release and sustained-delivery tablets in dogs. It is sometimes used as add-on therapy in dogs unresponsive to first line drugs. 14:426-429,1991. Dilantin (Phenytoin). Clorazepate in dogs: tolerance to the anticonvulsant effect and signs of physical dependence. A dose of 2 mg/kg every 8 or 12 hours has been suggested. American Journal of Veterinary Research 54:, 1993. Journal of Veterinary Pharmacology and Therapeutics. Forrester SD, et al. Tolerance (reduction in anti-seizure effects with long-term use) can occur with clorazepate, as with most other benzodiazepines.
Medicine for epilepsy in dogs