anti epileptic drugs

Question 1

Actions of anti epilepsy drugs

Answer 1

1. Prevent spread of the seizure focus
2. Increase (raise) the seizure threshold
3. Decrease electrical excitement of abnormal neurons without disrupting normal function

Question 2

3 categories of anti epileptic drugs

Answer 2

1. Enhancement of inhibitory processes via facilitated action of gamma amino-butyric acid (GABA)
2. Reduction of excitatory transmission
3. Modulation of membrane cation (Na or Ca) conductance

Question 3

Phenobarbital (Epiphen)

Answer 3

• barbituate
• controlled substance
• low dose get anticonvulsant and higher dose get sedation
• increases seizure threshold and decreases the electrical activity of the seizure focus
• enhances GABA
• decrease calcium influx into nerves cells, decreasing release of NTs
• gastric absorption (weak acid)(slow)
• Widely distributed, low lipid solubility tho (less CNS entry)
• liver metabolism
• inducer of microsomal P-450 enzymes (enhances biotransformation of drugs = decreasd pharmologic effect)(not in cats tho)
• drug of choice for chronic tx of seizure disorders in dogs and cats.
• concurrent KBr therapy.

Question 4

Phenobarbitol adverse effects

Answer 4

-sedation, polyphasia, PUPD, behavioral changes (depressed, drowsy or ataxic)
pharmokinetic/pharmodynamic changes
-blood dyscrasias
-hepatotoxicosis (impt) (associated with high ALP and high ALT and low drug serum concentrations with the same dose)
-thyroid effects (decrease serum T4 and increase serum TSH concentration)
-Superficial necrolytic dermatitis(hyperkeratosis, crusting and erythema)

Question 5

Potassium bromide (K-BroVet)

Answer 5

• oldest and simplest anticonvulsant
• used as a second anticonvulsant drug to PB
• compounded in canada
• stabilizes neuronal cell membranes by interfering with Cl transport across cell membranes (hyper polarizing membrane) thus potentiating effects of GABA.
• synergistically with other GABA-ergic drugs like barbiturates
• well absorbed from GI
• 4 months to achieve steady state kinetics
• keep diet steady… high Cl intake increases the bromide elimination rate
• CONTRAINDICATED in advanced renal failure patients

Question 6

Potassium bromide adverse effects

Answer 6

-more frequent adverse effects than PB but more mild dose dependent and reversible
-sedation, incoordination and pelvic limb weakness or stiffness (most common signs of toxicity)(not osteoarthritis)
….continues to quadriplegia and motor unit disease resembling myasthenia gravis
-treat severe toxicity signs by chloride (salt) loading the patient
-pancretitis, skin reactions, pruiritis, behavioural change

Question 7

Diazepam

Answer 7

Valium

• its is a benzodiazepine
• rapidly distributed to the CNS after IV administration
• hyperpolarizes neurons and suppresses neuronal activity by binding to a specific GABA-binding site (modifies GABA binding site to increase GABA action on nerve cells.
• benzodiazepines act to suppress presynatpic transmission of seizure activity (anticonvulsant activity)
• high first pass effect (low oral bioavailability)…but effective when take metabolites into account. Decent per rectal availability.

Question 8

Diazepam uses

Answer 8

• anticonvulsant of choice for dogs presenting status epileptics
• efficacy because of ability to cross BBB after IV admin.
• nasal or rectally administered in emergency situations
• can be used to treat anxiety, aggression and behavioural disorders in small animals
• preanesthetics in dogs, cats, horses, ruminants and swine (horses and swine may become recumbent)
• cats don’t get tolerance so it is second to PB for long term control as anticonvulsant.

Question 9

Adverse of diazepam

Answer 9

• fulminant hepatic necrosis in cats (oral)(lethargy, ataxia and anorexia)(monitor cats liver enz on oral diazepam therapy)
• drug interactions (microsomal enzyme inhibitors decrease its metabolism and get excessive sedation)
• tolerance with 1-2 weeks of continuous therapy (feedback or decrease synthesis of GABA)