Neuropharm

Question 1

Objectives

Answer 1

1. become familiar with anticonvulsant drugs
2. recognize side effects, interactions and contraindications of drugs
3. recognize drugs that penetrate CNS

Question 2

Traditional anti-epileptic drugs (4)

Answer 2

1. Diazepam
2. Phenobarb
3. Bromide - K or Na
4. Gabapentin

Question 3

New anti-epileptic drugs (4)

Answer 3

1. Zonisamide
2. Levetiracetam
3. Pregabalin
4. Imepitoin

Question 4

Phenytoin

Answer 4

Doesn’t work in dogs

Question 5

Primidone

Answer 5

Converted to pheno, just use pheno

Question 6

Oral diazepam - Cat

Answer 6

DON’T DO THIS - hepatic necrosis

Question 7

When to load (3)

Answer 7

1. Any clustering - > 2 seizures in 24 hours
2. progressive seizures over time
3. suspicion of structural brain dz and active seizures

Question 8

Phenobarbitol (8)

Answer 8

1. old faithful
2. long acting barbiturate T 1/2 = ~ 40hrs
3. Oral:
   - canine: 2.2 mg/kg BID
   - Feline: 8.1 mg BID
4. Loading: ~ 16-20 mg/kg IV bolus once (oral?!?!)
5. Metabolism: hepatic (cP450)
6. Onset action 20 min when given IV
7. Steady state in 10-14 days
8. Check levels two weeks after start then q6 months
   - chem q6 months, bile acids definitive function test

Question 9

Pheno interaction, effects, etc (3)

Answer 9

1. Increases metabolism/excretion TT4 and fT$
   - won’t make hypothyroid
2. Increases ALP (don’t care)
   - monitor ALT
3. Transient sedation, paraparesis, ataxia
4. Hepatotox - chronic high levels ( > 40 for months)
   - dec alb/BUN/gluc/cholest/inc tbili

Question 10

Potassium Bromide (6)

Answer 10

1. T 1/2 ~ 21 days
2. Dose:
   - Maintenance: 40 mg/kg/day
   - Loading: 400-600 mg/kg over 5 days PO/over 12-24 hrs IV
   - don’t load rectally - colitis
3. Steady state at 3 months - check at 1 month for 1/2 ideal
4. Dietary restrictions: Cl promotes renal Br excretion
   - limit NaCl intake
5. Don’t use in cats - fatal asthma
6. Side effects: ataxia, paresis, polyphagia, pica, psychosis, pruritis
   - worse in large breeds

Question 11

Gabapentin (3)

Answer 11

1. poor anticonvulsant
   - except rabbits
2. Dose:
   - AED: > 20 mg/kg PO q 6-8 hrs
   - Pain: > 5-10 mg/kg PO q8 h
3. Side effect: sedation

Question 12

Anticonvulsant optimization (3)

Answer 12

1. Optimize current med prior to adding another
2. PB levels stable around 25
3. KBr levels stable around 1.5-2

Question 13

Keppra (9)

Answer 13

1. Ca channel blocker
2. T 1/2 about 3 hrs
3. Metabolism: all body tissues
4. No known side effects
5. Dose
   - Injectable: > 15-20 mg/kg q8h IV, SQ, IM, Rectal
   - Oral: reg > 15-20 mg/kg PO q8h, XR > 30 mg/kg PO q8h
6. 100% bioavail IM or PO
7. Higher doses if on PB
8. Goast capsule…lol
9. Honeymoon effect?

Question 14

Zonisamide (8)

Answer 14

1. sulfonamide abx cP450
2. T 1/2 about 15 hours
3. Dose: 5 mg/kg PO q12h
4. Steady state in 3-4 days
5. PB inc clearance, need higher dose
6. Monit CBC/chem q6 months
7. Side effects
   - sedation
   - hepatopathy
   - Immune med dz: cytopenias, KCS
8. VERY SAFE CATS

Question 15

Pregablin (lyrica) (4)

Answer 15

1. Neuronal voltage-gated Ca channel blocker
2. more effect than gabapentin?!?!?!
3. No PK studies dog, 1 clin study
4. 3-4 mg/kg PO q8h

Question 16

Topamax (topiramate) (4)

Answer 16

1. PK: peak at 0.6-0.8 hrs
2. T 1/2 about 3 hours - 30?!?!?!
3. dose: 5 mg/kg PO q12h
4. Safe 3rd line drug

Question 17

Felbamate (4)

Answer 17

1. T 1/2 about 5-6 hrs
2. Dose: 12 mg/kg PO q8h
3. HEPATOTOXICITY esp w/ PB, Zon
4. Cheap, more dangerous

Question 18

Drugs for control w/in 24 hours (3)

Answer 18

1. phenobarbital load
2. Keppra
3. Bromide IV load

Question 19

Drugs for control w/in 1 week (3)

Answer 19

1. Phenobarbital
2. Zonisamide
3. Keppra

Question 20

Drugs for control w/in 1 month (4)

Answer 20

1. Phenobarbital
2. Zonisamide
3. Keppra
4. +/- bromide oral load

Question 21

Considerations drug choice

Answer 21

1. Dosing frequency (TID too much?)
2. Owner compliance - drug with longer T 1/2
3. Dietary restrictions with KBr
   - meh for dogs w/guarded prog
   - bad for ocean swimmers
   - bad for homes with small kids
4. Concurrent liver dz
   - no PB, zonisamide

Question 22

Neurogenic Pulmonary Edema (5)

Answer 22

1. non-cardiogenic: seizures, upper airway obstrctn, electrocution
2. Loss autonomic vascular tone
3. NOT RESPONSIVE to diuretics
4. Treat underlying cause - stop seizures
5. Oxygen support

Question 23

BBB (4)

Answer 23

1. Continuous tight junctions btwn endothel cells
2. Perivascular astrocyte feet
3. Small pores
4. Small, lipophyllic compounds can pass

Question 24

Infectious orgs (10)

Answer 24

1. E. Coli
2. Strep
3. Staph
4. Klebsiella
5. Pasteurella
6. Norcardia
7. Actinomyces
8. Cryptococcus
9. Toxoplasma
10. Neospora

Question 25

Chemotherapeutics (7)

Answer 25

1. Cyclosporine
2. Mycophenolate mofetil
3. Leflonumide
4. Cytosine arabinoside
5. Procarbazine
6. Lomustine CCNU
7. L-asparaginase

Question 26

Pred equivalents KNOW 4-EVA

Answer 26

Physiologic: 0.25 mg/kg/day
Anti-inflammatory: 0.5-1 mg/kg/day
Immunosuppresive: > 2 mg/kg/day

Question 27

Types of steroids

-short, intermed, long acting

Answer 27

1. short acting T 1/2 < 12 hrs
   - cortisone, hydrocortisone
2. Intermediate T 1/2 12-36 hours
   - prednisone, methylprednisone, triamcinolone
3. Long-acting T1/2 > 48 hours
   - paramethasone, flumethasone, dexamethasone, betamethasone

Question 28

Methylprednisolone sodium succinate

Answer 28

1. neuroprotective trials, not standard of care

Question 29

Reasons for high dose steroids

Answer 29

1. Prevention of secondary injury
   - ASCI
   - ischemia, vasospasm, ionic changes, free radical production, inflammation, apoptosis
   - MPSS only?!?!?!
2. Immunosuppresion
   - definitively diagnosed CNS inflammatory dz: GME, other myelitis
   - corticosteroids +/- other immunomodulants