Anticonvulsants

Question 1

what is the goal of antiepileptic therapy?

Answer 1

to reduce the frequency and/or severity of seizures satisfactorily without adverse affects to the life of the patient
prevention status epilepticus is a key goal

Question 2

what are the most common anticonvulsant/antiepileptic drugs used today?

Answer 2

phenobarbital
potassium bromide
zonisamide
levetiracetam
benzodiazepines
pentobarbital/propofol

Question 3

what are some benzodiazepines?

Answer 3

diazepam
midazolam

Question 4

what are the general actions of anticonvulsants/antiepileptics?

Answer 4

decrease onset or initialization of seizure focus
decrease spread from seizure focus
do not disrupt normal function
suppress nerve conduction
stabilize neurons
enhance and potentiate action of GABA- major inhibitory neurotransmitter

Question 5

how does a drug decrease onset or initialization of seizure focus?

Answer 5

limit repetitive discharge from abnormal neurons
decrease electrical excitement of abnormal neurons without disrupting normal neurons

Question 6

what does calcium influx in the CNS stimulate?

Answer 6

neurotransmitter exocytosis

Question 7

what is the most important inhibitory neurotransmitter?

Answer 7

GABA

Question 8

what does activation of GABAa lead to?

Answer 8

influx of chloride into the post-synaptic neuron, causing hyperpolarization

Question 9

what drugs decrease seizure onset by enhancing GABA-activated chloride conductance?

Answer 9

phenobarbital
bromide
diazepam
imepitoin
topiramate

Question 10

what drugs work by decreasing seizure spread?

Answer 10

phenobarbital
zonisamide
gabapentin
levetiracetam

Question 11

what are the general pharmacokinetics of anticonvulsant/antiepileptic drugs?

Answer 11

lipophilic to enter brain
pharmacokinetic and therapeutic concentration highly variable
seizures can occur whenever drug is below therapeutic range
maintenance in therapeutic range over the dosing interval is very important

Question 12

what are the general adverse effects of anticonvulsants?

Answer 12

sedation
ataxia
loss of cognitive function
behavior changes
hepatic damage rare, more likely with multiple at once

Question 13

what is the anticonvulsant drug of choice in dogs and cats?

Answer 13

phenobarbital

Question 14

is phenobarbital approved for dogs and cats in the US?

Answer 14

no

Question 15

what is the mechanism of action for phenobarbital?

Answer 15

potentiates GABA actions
decreases onset and spread
has anticonvulsant effects at concentrations below those that produce sedation and anesthesia

Question 16

what is the clinical efficacy of phenobarbital?

Answer 16

60-70% as monotherapy

Question 17

what does GABAa do?

Answer 17

increases chloride conductance

Question 18

what does GABAb do?

Answer 18

decreases calcium influx

Question 19

what does a barbiturate or benzodiazepine do to GABAa?

Answer 19

enhances influx of chloride into post-synaptic neuron, causing hyperpolarization

Question 20

do barbiturates and benzodiazepines bind to the GABA binding site?

Answer 20

no

Question 21

what are the pharmacokinetics of phenobarbital?

Answer 21

moderately lipophilic
15-20 minutes to diffuse into brain after IV
cytochrome P450 in liver does most of metabolization
induces cytochrome P450, so kinetics change in first few days (metabolic tolerance)

Question 22

what is the half-life of phenobarbital?

Answer 22

highly variable

Question 23

why does it matter that the half-life of phenobarbital is highly variable?

Answer 23

considerable variations in the serum concentration for any specific dose
variability in serum concentrations at which seizures are controlled
therapeutic drug monitoring commonly used
loading dose can be used to rapidly achieve therapeutic drug concentrations

Question 24

what is the full therapeutic range of phenobarbital in dogs?

Answer 24

15-40 micrograms/ml

Question 25

what drug does not cause hepatic necrosis of the anticonvulsants?

Answer 25

Potassium bromide

Question 26

what anticonvulsants can we not use in cats?

Answer 26

potassium bromide: pneumonitis
diazepam: hepatic necrosis
propofol: heinz bodies, malaise