Anticonvulsants

Question 1

Felbamate

Answer 1

• Anticonvulsant
• MOA: directly blocks NMDA receptor and excitatory amino acids. Blocks Na/Ca channels and potentiates GABA mediated inhibition. Renal eliminations.
• SE: decreased appetite (dogs). Black box warning in people due to aplastic anemia and acute hepatoxocity. Will increase phennobarbital concentrations/other p450.
• 20mg/kg PO q8hr

Papich/Rushing

Question 2

Bromide (Potassium and Sodium Bromide)

Answer 2

• Anticonvulsant
• MOA: uncertain, but increase chloride conductance via GABA receptors. Not metabolized, renal elimination.
• SE: related to high levels of bromide- CNS depression, ataxia, sedation. Dermatopathy. Nausea/panceatitis (maybe)/GI-dogs. DO NOT USE IN CATS- Pneumonitis. PU/PD/PP.
• Monitor plasma concenetration when changing diets, as increasing chloride concentration will shorten the half-life.
• False elevation of chloride on bloodwork
• 30-40mg/kg/day. Load 100mg/kg/day x 5 days

Question 3

Levetiracetam (Keppra)

Answer 3

• Anticonvulsant
• MOA is uncertain/complex and does not involve inhibitory neurotransmitters (GABA agonism and Na/Ca chnnel antagonism). Renal clearance.
• SE: mild sedation
• Honeymoon effect - increase in seizure activity after ~ 6months of therapy
• 20mg/kg q8hr or 30mg/kg q12hr (XR)

Papich/Rushing

Question 4

Pregabalin

Answer 4

• Anticonvulsant, Anesthesia
• MOA: complex/poorly understood. Renal elimination.
• SE: mild sedation
• 5-10mg/kg q8-12hr

Rushing

Question 5

Zonisamide

Answer 5

• Anticonvulsant
• Complex/uncertain MOA- Na/Ca channel blocker, GABA agonism (potentiate), Glutamate blocker. Renal and hepatic elimination.
• SE: uncommon, but ataxia, GI reported, sedation, KCS

*Resembles sulfonamides in structure- use with caution in sensative breeds

-5-10mg/kg PO q12hr (higher dose with pheno -or other p450 inducers- because of increased elimination and increase pheno by 25%)

Papich/Rusing

Question 6

Gabapentin

Answer 6

• Anticonvulsant, Analgesic
• MOA uncertain/unclear- analog of the inhibitory neurotransmitter GABA. May bind to voltage-sensative calcium changels in neuronal tisse and inhibit administration. Renal clearance (30% liver in dogs)
• SE: sedation, ataxia. Careful with xylitol sweeter. Antiacids will decrease oral absorption.
• 30-60mg/kg/day

Papich/Rushing

Question 7

Phenobarbital Sodium

Answer 7

• Anticonvulsant
• Long acting barbiturate. Stabalizes neurons by increased chloride conductance via GABA mediated channels
• SE: dose related. Sedation, ataxia, polyphagia. LE (ALKP) elevation which may not be associated with liver pathology (more likely hepatotoxic at higher doses). Cytopenia (possible pancytopenia) reported idiosuncratic reaction- may recover after pheno stopped. Superfical necrolytic dermatitis (dog). Lowers thyroid levels. Caution to dogs with liver disease.
• Will increase clearance of other drugs with hepatic clearance (increased activity of p450)
• Naive dog 2-3mg/kg q12h. Load 4mg/kg/dose x 4 over 24 hr (2 mg/kg/dose cats)
• Receck blood levels in 2-3 weeks, then q6months: Theraputic range 15-45mcg/ml (aim 30-35)

Papich/Rushing

Question 8

Topiramate

Answer 8

1-3 reduce neuronal excitation

Class: anticonvulsant and nerve pain medication

MOA:

1) Voltage gaited Na channel blocker
2) Glutamate receptor inhibitor
3) Reduction of voltage sensative calcium current

4) Gaba agonist
5) carbonic anhydrase inhibitor
6) increased K conductance

Jung