Neuropharmacology

Question 1

anti-epileptic drugs

Answer 1

• traditional
  
  • diazepam
  • phenobarb
  • bromide (K or Na)
  • Gabapentin
• newer
  
  • zonisamide
  • levetiracetam
  • pregabalin
  • imepitoin

Question 2

indications for anticonvulsants

Answer 2

• absolute
  
  • cluster seizures
  • status epilepticus
  • neurologic deficits or suspicion of structural disease
  • aggression pre- or post-ictal

Question 3

status epilepticus

Answer 3

• rapidly recurring seizures with incomplete recovery between episodes
  
  • more likely in large breed dogs
  • toxins
  • metabolic
  • sudden drug withdrawal; ineffective drugs
  • progressive disease

Question 4

when to load

Answer 4

• any clustering
  
  • if >2 seizures in 24 hours
• progressive seizures over time
• suspicion of structural brain dz and active seizures

Question 5

diazepam

Answer 5

• emergency
• IV, IN, per rectum
• give up to 3 times
• anticonvulsant effects ~20 min
• no oral diazepam in cat!

Question 6

phenobarbital

Answer 6

• long acting barbiturate
• T 1/2 ~40 hrs
• loading
• hepatic metabolism
• IV ~20 minutes to effect in brain
• reaches steady state in 10-14 days

Question 7

phenobarb monitoring

Answer 7

• check levels two weeks after starting therapy
• every six months thereafter
• chemistry panel q 6mo
  
  • if concerns, bile acids definitive function test
• will interfere with TT4 and fT4 but does not make them clinically hypothyroid
• will increase ALP
• transient sedation, paraparesis, ataxia
• hepatotoxicity

Question 8

potassium bromide

Answer 8

• T 1/2 : ~21 days (15-40)
• maintenance and loading doses
• reaches steady state at about 3 mo
• monitoring levels q6-12 mo
• dietary restrictions (Cl-)
• side effects: bromism
• fatal asthma in cats****

Question 9

gabapentin

Answer 9

• poor anticonvulsant (except for rabbits)
• AED dose and pain dose
• main side effect is sedation

Question 11

novel anticonvulsants

Answer 11

• 20-30% epileptic dogs refractory to PB +/- bromide
• Keppra, zonisamide, topiramate

Question 12

Keppra (levetiracetam)

Answer 12

• calcium channel blocker, binds SV2a
• T1/2: ~3h
• metabolism: all tissues in the body
• no known significant side effects to date

Question 13

zonisamide

Answer 13

• sulfonamide, multiple MOAs
• T1/2 ~15 hours
• reaches steady state in 3-4 days
• hepatically metabolized
• PB increases clearance, so higher doses required
• chem panel and serum level q6h
• side effects
• cats and dogs

Question 14

pregabalin

Answer 14

• neuronal voltage-gated Ca channel blocker
• theorectically more effective than gaba
• no PK studies in the dog

Question 15

Topamax

Answer 15

• topiramate
• t1/2: ~3-30h
• third line drug
• less expensive

Question 16

felbamate

Answer 16

• t1/2: 5-6 hrs
• hepatotoxicity, especially when combined with other potentially hepatotoxic drugs (PB, Zon)

Question 17

drug for control within 24 hours

Answer 17

phenobarbital load, Keppra, bromide IV load

Question 18

drug for control within 1 week

Answer 18

• phenobarb, zonisamide, Keppra

Question 19

drugs for control within 1 month

Answer 19

phenobarbital, zonisamide, Keppra, +/- bromide oral load

Question 20

cluster seizures

Answer 20

• >2 seizures in 24 hours
  
  • period of normalcy in between episodes
• reliable pattern of multiple seizures at each event
• doesn’t matter if generalized or partial seizures
• usually require >2 meds for adequate control

Question 21

neurogenic pulmonary edema

Answer 21

• non-cardiogenic
  
  • seizures, upper airway obstruction, electrocution
• loss of autonomic vascular tone
• NOT responsive to diuretics
• treat underlying cause-stop the seizures
• oxygen support

Question 22

blood-brain barrier

Answer 22

• continuous tight junctions between endothelial cells
• perivascular astrocyte feet
• small pores
• small, lipophyllic compounds can pass

Question 23

infectious organisms

Answer 23

• E. coli
• Streptococcus
• Staphylococcus
• Klebsiella
• Pasteurella
• Nocardia
• Actinomyces
• Cryptococcus
• Toxoplasma
• Neospora

Question 24

chemotherapeutics

Answer 24

• cyclosporine
• mycophenolate mofetil
• leflonumide
• cytosine arabinoside
• procarbazine
• lomustine CCNU
• L-asparaginase

Question 25

corticosteroids

Answer 25

• physiologic vs anti-inflam vs immunosuppressive
• short-acting T1/2 <12h
  
  • cortisone, hydrocortisone
• intermediate T1/2 12-36h
  
  • prednisone, methylprednisone, triamcinolone
• long-acting T1/2 >48h
  
  • paramethasone, flumethasone, dexamethasone, betamethasone

Question 26

types of steroids

Answer 26

• effects modified based on ester form
• highly soluble esters (Solu-Medrol, Decadron)
  
  • absorption over minutes to hrs
• moderately insoluble esters (Depo-Medrol)
  
  • absorption over days to weeks
• poorly soluble esters (Vetalog, Gentocin otic)
  
  • released over weeks to months

Question 27

neuroprotective corticosteroids

Answer 27

• methylprednisolone sodium succinate
  
  • Solu-Medrol: only corticosteroid to potentially improve outcome in acute spinal cord injury
  • must be given w/in 8 hrs of event
  • side effects!
  • not standard of care

Question 28

reasons for high-dose steroids

Answer 28

• prevention of secondary injury
  
  • for acute spinal cord injury
  • ischemia, vasospasm, ionic changes, free radical prod, inflam, apoptosis
  • MPSS only
• immunosuppression
  
  • for definitively diagnosed CNS inflam disease (GME, other myelitis…)
  • corticosteroids +/- other immunomodulants