Anticonvulsants Flashcards
What is a seizure?
Seizure: an abnormal, disorderly discharging of the brain’s nerve cells, resulting in a temporary disturbance of motor, sensory, and mental function.
What are symptoms of seizures in dogs?
What is epilepsy in dogs? When may epilepsy diagnosis be considered?
How are anticonvulsant drugs used?
These drugs are used to block seizure initiation and propagation by blocking either
abnormal events in a single neuron or the synchronization of related neurons
What is the goal of therapy with anticonvulsants? What is the mechanism of action overall for these drugs?
Goal of therapy: reduction in the firing frequency of neurons
MOA: Inhibit neurotransmitters
Why is their few anticonvulsants that can be used for humans as well as dogs and cats?
Only a few of the anticonvulsant drugs available for human use have been
approved for clinical use in dogs and cats
* Some of the drugs are too rapidly metabolized in dogs to be effective, even in high dosages
* Cats metabolize drugs more slowly and poorly than dogs
TRUE OR FALSE: Cats rapidly metabolize anticonvulsant drugs and it is too fast for it to be effective, even in high dosages. Dogs on the other hand metabolize drugs slower and much poorer than cats.
FALSE:
Some of the drugs are too rapidly metabolized in dogs to be effective, even in high dosages * Cats metabolize drugs more slowly and poorly than dogs
What is the MOA of anticonvulsant drugs?
Stabilization of the neuronal membranes evoking hyperpolarization.
How do anticonvulsant drugs evoke hyperpolarization?
- They activate GABA-gated Cl- channels * They bind to GABAA receptor and facilitate its action (agonist) * Inactivating Na+ and Ca++ conductance
What is rapid cessation? Why is that problematic?
When drugs are rapidly metabolized by the liver. This requires more dosages, which can increase the possibility for toxicity.
What is the therapeutic uses of anticonvulsants?
Therapeutic Uses:
Reduction of incidence, severity, and duration of seizures
What are adverse effects of anticonvulsant drugs?
Adverse Effects:
* Rapid cessation effect of administration of these drugs
* Liver and serum enzymes induction
* Hepatotoxicity in dogs
What are the different categories of Anticonvulsant drugs? What do they all cause?
- Barbituates
- Benzodiazapines
- Hydantoins
- Valproic Acid
- Unconventional drugs like gabapentin, keppra, felbamate, zonisamide.
- all of these will cause membrane hyper-polarization and inhibiting the section of neuron transduction
What is Gaba? What is it considered ? Where is it produced? What is it used for ? What is its role?
▪ GABA is the major inhibitory NT in the CNS
▪ GABA is considered our natural “Valium-like” NT
▪ GABA is produced mostly in the brain from glutamic acid/glutamate (needs Vitamin B6 for its synthesis)
▪ GABA plays an important role in behavior, cognition, and the
body response to stress. GABA controls fear and anxiety
▪ The role of GABA is to inhibit or reduce the activity of the neurons
* gaba can be found in food, exogenous forms of gaba, synthesized by gut microbes, ect.
* If you have anxiety you can increase gaba intake and it may help.
How does activation of Gaba gated cl channels work? What is the result of gaba a antagonists?
- chloride channels allowing cl ions to flow into cell allowing for cell hyper polarization
- Each receptor consists of 5 subunits that form channel
- When gaba like compounds bind to receptor, channel opens, and allows charged cl ions to pass through.
- cumulative neural inhibition caused by gaba binding to too many cells will result in sedation
- Compounds that enhance the gaba receptor activity cause increased neural inhibition
- gaba a antagonists cause excitation of the signal.
What is the method of action for barbituates?
MOA: activation of GABA-gated Cl- channels
What is unique about phenobarbital? What is its therapeutic uses? What is its adverse effects? When are peak levels ?
Phenobarbital: Is unique in that it usually produces anticonvulsant effect at lower doses
than those necessary to cause pronounced CNS depression (sedation)
Therapeutic uses:
* For long-term control of seizures
* Administered orally
* It is not useful for terminating an ongoing seizure b/c the time span from administration until the onset of effect is too long (~ 20 min)
* When given orally, its GI absorption is practically complete in all animals
Peak levels occur in 4-8 hr after oral dosing in dogs
Adverse effects:
* Sedation, polydipsia, polyuria, and polyphagia
* Dogs develop a tolerance to the sedative effects after 1-2 weeks
Why is phenobarbital not an ideal choice to terminate an ongoing seizure?
- It is not useful for terminating an ongoing seizure b/c the time span from administration until the onset of effect is too long (~ 20 min)
What is primidone? What is the important pharmacokinetics of primidone? What are uses of this drug?
Primidone: is a deoxybarbiturate * Slow absorption after oral administration in dogs
* PK: primidone is rapidly metabolized by the liver to Phenobarbital (85% of its anticonvulsant activity is attributable to its conversion to phenobarbital)
* In cats, the metabolism to phenobarbital is slow
(do not use in cats
- Not active drug -> pro drug which is metabolized by liver to make phenobarbital
Uses: preanesthetic, migraines ect. Not used a-lot for seizures
What animal should you not use primidone in? Why
In cats, the metabolism to phenobarbital is slow
(do not use in cats)
What are adverse effects of primidone?
Adverse Effects: * Prolonged use in dogs may lead to decreased serum albumin and
elevated serum concentrations of liver enzymes * Occasionally, serious liver damage
What are adverse effects of primidone?
Adverse Effects: * Prolonged use in dogs may lead to decreased serum albumin and
elevated serum concentrations of liver enzymes * Occasionally, serious liver damage
What are the therapeutic uses for pentobarbitol? What is it used for specifically? What is beneficial about pentobarbitol?
Therapeutic uses:
* Will terminate seizures at a dose that produces anesthesia
* Used for status epilepticus*
* It has rapid onset (< 1 min) after IV injection and short duration of action
What is the adverse effects of pentobarbital?
Adverse effects:
* CNS depressant
* May cause excitement during recovery from anesthesia
* Irritating when administered perivascularly
What is the therapeutic uses for midazolam? What are its adverse effects?
What are the therapeutic uses of clonazepam? What is its adverse effects?
Used for status epilepticus, muscle relaxant, tranquilizer, and appetite stimulant the
same way as diazepam
What are the therapeutic uses of lorazepam? What is its adverse effects?
What are hydantoins? What is the MOA? What is its therapeutic uses?
What is Valproic acid? What is its MOA?
What is the therapeutic uses of valproic acid? What is its adverse effects?
What is potassium bromide? What is its MOA? What is its therapeutic uses?
What are the adverse effects of potassium bromide?
What is gabapentin? What is its MOA?
What are the therapeutic uses of gabapentin? Adverse effects?
What is the MOA of Levetiracetam?
What is the therapeutic uses of levetiracetam? What are the adverse effects that can be seen?
What is felbamates MOA? What is its therapeutic uses?
What is the adverse effects that can be seen with Felbamate?
What is the MOA of Zonisamide?
What is the MOA of Felbamate?
What is the MOA of Potassium Bromide?
What is the MOA of Hydantoins?
What is the therapeutic uses of zonisamide?
What are the adverse effects associated with zonisamide?
Why may canine owners be less likely to use zonisamide unrelated to medical reasons? what about cats?
