Anti-epileptics

Question 1

What is the benefit on the intra-nasal route of administration for anti-epileptics

Answer 1

• No need for IV access
• Allows entry of drugs through nervous pathway (olfactive and trigeminal nerves) -> no blood-brain barrier to cross
• Also high absorption in circulation since highly vascularized epithelium

Question 2

What is the therapeutic range of phenobarbital levels? When should levels be monitored?

Answer 2

Dogs: 25-35 mg/L = ~100-150 umol/L
Cats: 15-45 mg/L = 65-190 umol/L

Levels should be measured 2 weeks after starting or any change in dose, 6 weeks after starting, and then every 6 months

Question 3

Mechanism of action of phenobarbital

Answer 3

• GABA-A receptor agonist ->prolongs opening of Cl channel -> hyperpolarization
• AMPA glutamate receptor antagonist
• Voltage-gated calcium channel inhibitor

Question 4

Name 2 anticonvulsants that do not have hepatic metabolism

Answer 4

Bromide and levetiracetam (excreted unchanged in urine)

Question 5

Which anticonvulsant has minimal protein binding

Answer 5

Levetiracetam

Question 6

Mechanism of action of levetiracetam

Answer 6

Binds to synaptic vesicle proteins SV2A -> inhibits release of neurotransmitters

Question 7

Mechanism of action of bromide

Answer 7

Bromide ions move intracellularly via chloride channel -> hyperpolarization

Question 8

Mechanism of action of zonisamide

Answer 8

• Voltage-gated Na and T-type Ca channels inhibitor
• Modulation of dopaminergic activity
• GABA agonist
• Carbonic anhydrase inhibitor

Question 9

When should serum levels be monitored after initiation of pheno / bromide / zonisamide

Answer 9

• Phenobarbital: 2 weeks
• Bromide: 6-12 weeks
• Zonisamide: 2 weeks

Question 10

What are adverse effects of zonisamide

Answer 10

• Sedation, ataxia
• GI signs
• Idiosyncratic severe hepatotoxicity
• Tubular acidosis
• KCS

Question 11

Name 3 anti-epileptics whose metabolism is enhanced by phenobarbital administration

Answer 11

• Phenobarbital
• Levetiracetam
• Zonisamide

Question 12

What is the mechanism of action of CBD for its anticonvulsant effect

Answer 12

• Inhibition of glutamate via binding to transient receptor potential channels
• Activation of 5-HT1A receptors
• Inhibition of adenosine reuptake

Question 13

List adverse effects of phenobarbital

Answer 13

• Sedation, ataxia
• PUPD
• Polyphagia
• Cardiovascular and respiratory depression (loading dose)
• Bone marrow suppression
• Hepatotoxicity
• Superficial dermatitis
• Pseudolymphoma
• Altered metabolism of other drugs
• Decreased T4 (without hypothyroidism)
• Increased ALP (without liver injury)

Question 14

What are some considerations of diazepam that should be known when preparing for administration?

Answer 14

• Should not be stored in plastic syringes or infusion lines for any length of time (loses potency)
• Precoating the infusion lines with DZP before CRI administration is required
• Light sensitive
• Diluted in propylene glycol –> phlebitis and hypotension with rapid administration

Question 15

List 2 neuroprotective properties of dexemdetomidine

Answer 15

• Decreases cerebral metabolic and oxygen demand
• Decreases brain edema via vasoconstriction + maintenance of MAP

Question 16

What receptors does propofol act on?

Answer 16

• GABAa (agonist)
• Glycine (agonist)
• NMDA (antagonist)
• Calcium channels

Question 17

What is the hypothesis for magnesium mechanism of action in seizure control?

Answer 17

Magnesium may inhibit NMDA receptors and calcium channels, and increase cerebral blood flow via vasodilatation

Question 18

What anti-convulsant can cause pneumonitis in cats and should therefore be avoided?

Answer 18

Bromide

Question 19

What IV fluid should be avoided in patients receiving bromide and why?

Answer 19

NaCl 0.9% –> associated with the decreased serum concentrations and the increased renal clearance of bromide

Question 20

What electrolyte can be affected by potassium bromide?

Answer 20

Fasle elevation in Cl