Anti-Epileptic Drugs

Question 1

Seizures are excessive synchronous neural activity usually occuring in the _______. They are complex and incompletely understood

Answer 1

Cerebral Cortex

Question 2

Seizure causes:

Answer 2

1) Intracranial lesion (symptomatic)
2) Extracranial insult (reactive)
3) Primary disorder (idiopathic)

Question 3

What are the 7 traits of the ideal anti-epileptic drug (AED)

Answer 3

1) effective –> broad spectrum
2) Safe –> risk vs benefit
3) limited drug-drug interactions
4) Long half life (SID or BID dosing)
5) Anti-epileptogenic effects
6) enteral and parenteral formulations
7) affordable/sustainable for long term

Question 4

What are the two “Old AEDs”

Answer 4

1) Phenobarbital

2) Bromide

Question 5

Phenobarb

• ROA
• Class
• MoA

Answer 5

Oral and IV

• Most common first line AED for chronic therapy
• Class: Barbiturate (long acting) - drug class IV
• MoA: classic barbiturate mechanism: GABA-A agonist/potentiator; potentiates the inhibitory effects of GABA by binding and prolonging opening of Cl- channels

Question 6

Phenobarbital Pharmacokinetics

Answer 6

• Crosses BBB
• Good oral bioavailability (~90%), wide distribution
• Extensively plasma protein (albumin) bound
• Metabolized by liver –> potent inducer of hepatic microsomal enzymes, and is metabolized through that system (P450).

Question 7

Is tolerance more likely to develop in bromide or phenobarbital?

Answer 7

phenobarbital

Question 8

Precautions/Adverse Effects of Phenobarb

Answer 8

PU/PD/PP

• Sedation (transient)
• Elevated liver enzymes (induced alkaline phosphatase- ALP)
• Less commonly: paradoxical hyperexcitability, hepatoxicity, pancytopenia (reversible)

Question 9

Bromide

• RoA
• Use
• Class

Answer 9

• Oral Only
• 1’ add on anticonvulsant for dogs NOT CATS
• Class: anticonvulsant: Salt/Chemical powder - alters chloride transport across neuronal cell membranes

Question 10

Bromide pharmacokinetics

Answer 10

• Good oral absorption, excreted unchanged by kidneys
• changes in serum chloride ion concentration can significantly interfere with bromide levels –> keep salt intake from diet stable

Question 11

Bromide Precautions/Adverse Effects

Answer 11

• Interferes with chloride on serum chemistry -> reads falsely high (bromide recognized as Cl-)
• GI upset (vomiting), sedation (can be severe during loading)
• 25-50% of cat may show asthma-like pulmonary changes (CONTRAINDICATED)
• Toxicity with overdose is termed “bromism- severe sedation and neurological signs (tx with.9% NaCl to promote bromine excretion)
• Pancreatitis is also possible -> range of GI signs from vomit, regurg, GI ulcers, abdominal pain, inappetence

Question 12

Name the 3 New AEDs

Answer 12

1) Levetiracetam (Kepra)
2) Zonisamide
3) Imeption