Seizures are the clinical manifestation of excessive hypersynchronous electrical activity of neurons within the cerebral cortex. This is a result of inappropriate neuronal inhibition, increased neuronal excitation or a combination of these. The majority of our antiepileptic drugs work by enhancing neuronal inhibition, often by potentiating gamma-aminobutyric acid (GABA, the major inhibitory neurotransmitter in the brain) or antagonizing glutamate (major excitatory neurotransmitter in the brain). The remainder of this article will provide a quick review of the anticonvulsants used more commonly in veterinary medicine.
Medication:
Phenobarbital
Mechanism of action: Potentiates GABA, antagonizes glutamate, decreases neuronal Ca2+ influx
Time to reach steady state: 10-15 days
Dose: 2-5mg/kg BID PO, IM or IV
Loading: 16-22mg/kg either as a single dose or divided into 2-4 doses within 24 hours.
Side effects: The most common side effects include sedation, pelvic limb weakness and ataxia, PU/PD and polyphagia. Less common side effects include hepatic dysfunction, bone marrow suppression, facial pruritus in cats.
Monitoring: Serum phenobarbital level should be checked 2 weeks after initiating therapy and 2 weeks after any dose adjustment. It may be helpful to check a level in a patient that was previously well controlled with a recent increase in seizure activity. The therapeutic range varies from 15-20ug/ml at the low end to 35-45ug/ml at the high end. In a patient that is poorly controlled, I will typically continue to increase the phenobarbital dose until a level of 30-35ug/ml is reached as long as the side effects are tolerable before adding another anticonvulsant. Serum chemistry and complete blood count should be monitored every 6 months. It is common for phenobarbital to cause an elevation of liver enzymes and does not always indicate hepatic dysfunction. Bile acids may be helpful if hepatic dysfunction is suspected.
Facts:
- Increases microsomal enzyme activity, which will alter the metabolism of itself and other drugs. It is common to increase the dose of this medication over time to maintain consistent serum levels.
- Avoid serum separator tubes as the silicone binds phenobarbital and will result in artifactually lower serum levels.
- Can be used in dogs and cats.
Medication: Potassium Bromide
Mechanism of action: Hyperpolarizes neuronal membranes
Time to reach steady state: 2.5-4 months
Dose: 20-35mg/kg PO SID
Loading: 400-600mg/kg PO divided over 24 hours or 125mg/kg/day for 5 days
Side effects: Sedation, pelvic limb weakness and ataxia, PU/PD, polyphagia, GI upset are the most common. Cats can develop pneumonitis if given KBr, most neurologists recommend not giving KBr to cats.
Monitoring: Serum therapeutic range is 1-3mg/ml. If the dog is also on phenobarbital, the serum level should be 1-2mg/ml.
Facts:
- Bromide will be measured as chloride so when checking electrolytes, Cl- may be falsely elevated.
- Bromide is excreted by the kidneys, therefore altering dietary salt intake or fluid diuresis can affect serum bromide concentration.
Medication: Levetiracetam (keppra)
Mechanism of action: binding synaptic vesicle protein 2A, preventing the release of glutamate.
Time to reach steady state: 20 hours
Dose: 20-40mg/kg PO, IM or IV TID
Loading: Not needed
Side effects: Side effects are uncommon but can include sedation or GI upset. This medication is considered very safe.
Monitoring: Serum levels can be monitored, however the therapeutic range is taken from human medicine and the relevance in veterinary medicine is not known.
Facts:
- ~80% excreted by the kidneys, the remainder is metabolized by the liver.
- Can be used in cats
- An extended release formulation is available for BID dosing.
Medication: Zonisamide
Mechanism of action: Blocks voltage gated Na+ channels, blocks calcium channels, antagonizes glutamate
Time to reach steady state: 2-3 days
Dose: 5-10mg/kg BID
Loading: Not needed
Side effects: Mild sedation, ataxia, vomiting. Rare reports of hepatotoxicity, myelosuppression or renal tubular acidosis.
Monitoring: Serum levels can be monitored, however the therapeutic range is taken from human medicine and the relevance in veterinary medicine is not known.
Facts:
- Zonisamide is partially metabolized by the liver, therefore if the dog is also on phenobarbital, it should be dosed at 10mg/kg BID.
- Zonisamide is a sulfonamide, use caution in patients sensitive to sulfonamides.
Medication: Felbamate
Mechanism of action: interferes with voltage gated Na+ channels, antagonizes glutamate receptors (NMDA), GABA agonist
Time to reach steady state: 25-30 hours
Dose: 15mg/kg PO TID
Loading: Not needed
Side effects: Hepatotoxicity, myelosuppression, KCS, tremors
Monitoring: Serum levels can be monitored, however the therapeutic range is taken from human medicine and the relevance in veterinary medicine is not known. Serum chemistry and complete blood count should be monitored every 4-6 months.
Facts:
- Felbamate can increase phenobarbital serum levels.
Medication: Topiramate
Mechanism of action: Blocks voltage gated Na+ channels, antagonizes glutamate, GABA agonist, blocks Ca2+ channels
Time to reach steady state: 10-20 hours
Dose: 5mg/kg PO BID
Loading: Not needed
Side effects: Sedation, possible urinary calculi
Monitoring: Therapeutic range unknown
Facts:
- May be prohibitively expensive for some clients.
Medication: Gabapentin
Mechanism of action: Inhibition of voltage gated Ca2+ channels
Time to reach steady state: 15-20 hours
Dose: 25-60mg/kg PO divided into TID or QID doses
Loading: Not needed
Side effects: Sedation, pelvic limb weakness and ataxia, increased appetite
Monitoring: Serum levels are rarely pursued
Facts:
- Clinically thought to have poor anticonvulsant effects.
When it comes to anticonvulsants, there isn't a "one size fits all" medication. The key to successful seizure control relies on good client communication in regards to their expectations, side effects and monitoring. If you have a tricky case or just have questions about which anticonvulsant to use, don't hesitate to call and ask one of the Neurologists at VCA Alameda East Veterinary Hospital.
References:
- Dewey, CW. 2008. Seizures and Narcolepsy, p.237-253. In C. Dewey A Practical Guide to Canine and Feline Neurology. Blackwell, Iowa.
- Rossmeisl, JH. Alternative Anticonvulsants for Dogs and Cats. NAVC Clinician's Brief. 2011,(October)63-66.
- Plumb, Donald C. 2011. Veterinary Drug Handbook. 7th ed; Wiley-Blackwell, Iowa.
Welcome to the New Year! This year marks our 45th anniversary; Alameda East was founded in 1971 by Dr. Robert Taylor. For this very special year we have chosen to aim for greatness and visible forward progress in our hospital. This is a large feat and I know there will be bumps along the road, however we will persist, learn from our mistakes and keep moving forward toward our goals. We are grateful for your support and to be part of such a wonderful community; we look forward to sharing the next year with you!
