Anticovalent Drugs

Question 1

Convulsion

Answer 1

Abnormal and sudden attack of involuntary muscular contractions and relaxations (motor activity)

Question 2

Seizures

Answer 2

Episodes of neurological dysfunction from abnormal synchronous activity of neurons

Question 3

Epilepsy

Answer 3

A group of recurrent CNS disorders: paroxysmal cerebral dysarrythmia
Signs: seizures, convulsions or fits

Question 4

What is required for a animals to have epilepsy?

Answer 4

Abnormal, physical, sensory and autonomic activity
At least 2 unprovoked seizures
Unconsciousness

Question 5

Intracranial causes of epilepsy

Answer 5

Neoplasm, inflammation, hydrocephalus, malformation, trauma

Question 6

Extracranial causes of epilepsy

Answer 6

Hepatic/renal failure, hypoxia, toxicity, hypoglycemia, hypocalcemia

Question 7

Seizures in vet med

Answer 7

Dogs: epilepsy inherited affected 0.5-6% population
In cats and other pets it’s rare

Question 8

Higher incidence of epilepsy in ____________

Answer 8

Belgian Shepherd

Question 9

Therapeutic success

Answer 9

Balance between efficacy and safety

Question 10

Therapeutic considerations of anticonvulsants

Answer 10

Eradication not reasonable
Life-time therapy
Increased risk

Question 11

When do you start anticonvulsant drugs?

Answer 11

Seizures more than 3 minutes
Cluster seizures
More than 1 month
Worsening seizure pattern

Question 12

Excitatory NT

Answer 12

Hypopolarize
ACh
Glutamate **
Catecholamines

Question 13

Inhibitory NT

Answer 13

Hyperpolarize
Gamma amino butyric acid*
Glycine

Question 14

General cellular mechanisms of seizures

Answer 14

Altered membrane function: hypoxia and hypoglycemia
Altered mem. permeability: hypoxia, inflammation and tumors
Altered ECF electrolytes: increased K, decreased Ca
NT: increased excitatory

Question 15

General mechanisms of seizures

Answer 15

Inappropriate neuronal discharge (inititation)
Recruitment
Synchronization
Propagation

Question 16

What drugs enhance GABA inhibition

Answer 16

Increases GABAergic transmission
Barbiturates and Benzodiazepine

Question 17

Important Barbiturates

Answer 17

Phenobarbital (luminal)
Primidone (Mysoline)

Question 18

Important benzodiazepine drugs

Answer 18

Diazepam (valium)
Clonazepam (klonopin)

Question 19

Phenobarbital

Answer 19

Historic 1st choice chronic management
Increase GABA, decrease glutamine and Ca
Attenuates initiation, decreased progagation
100% F with long half life

Question 20

Phenobarbital drug interactions

Answer 20

Potent induction of CYP 450
Decreased clearance
Auto-induction in 2-4 weeks

Question 21

Phenobarbital behavioral side effects

Answer 21

Polyphagia, polydipsia, polyuria
Sedation (ataxia and grogginess)

Question 22

Phenobarbital in the bone marrow

Answer 22

Type B (allergic)- leukopenia
Requires 10-14 days or previous exposure

Question 23

Phenobarbital hepatotxocity

Answer 23

Type A (dose and duration dependent)
Limits maximum therapeutic range
Increased serum alk phos and bile acids
Decreased albumin and BUN

Question 24

Primidone (Mysoline)

Answer 24

Partial and generalized seizures

Question 25

Bromide

Answer 25

1st add-on Common 1st choice for chronic conditions

Question 26

Diazepam

Answer 26

Historic 1st choice acute management t 1/2= 2-4 hours in dogs Treats status epilepticus/ emergency use Given in bolus, rectum or infusion Decreases spinal reflexes

Question 27

Diazepam in cats

Answer 27

For maintenance in cats but can cause hepatic necrosis

Question 28

Levetiracetam

Answer 28

New add-on against refractory epilepsy in dogs and cats Prevents postoperative serizures in protosystemic shunt surgery in dogs

Question 29

PK of Levetiracetam

Answer 29

100% absorption and <10% protein binding Cats t1/2= 3 h, dogs t1/2=3- 4.5

Question 30

Which bensodiazepine drugs are approved for long-term treatment?

Answer 30

Clonazepam (myclonic, atonic and absence seizures) and clorazepate (partial seizures)

Question 31

Na+ channel inhibitors

Answer 31

Anti-seizure drug Blocks voltage-gated Na channels by selectively binding to channel in the inactive state and slowing the rate of recovery

Question 32

Phenytoin (Dilantin, Phenytek)

Answer 32

Occ. in horses for muscle disorders/ antiarrhythmic agent Limited in vet use due to side effects and variable PK

Question 33

Valproic Acid (Depankene)

Answer 33

Increases GABA production and GABA metabolism Dogs when refractory to other meds

Question 34

Valproic Acid PK

Answer 34

100% bioavailability T 1/2 = 1-2.8 hours dogs

Question 35

T calcium channel

Answer 35

Found in heart and neurons Short, small and low threshold

Question 36

L calcium channel

Answer 36

Muscle, neurons, endocrine cells, bone Long, large and high threshold

Question 37

Gabapentin (neurontin)

Answer 37

Selective inhibition of v-g N type and T-type Ca2+ channels Add on therapy in dogs and cats t 1/2 = 2-4 hours in dogs and cats

Question 38

Pregabalin (lyrica)

Answer 38

Selective inhibition of v-g N type and T-type Ca2+ channels Add on for partial and secondarily generalized seizures Neuropathic pain, fibromyalgia in equine, canines and felines

Question 39

Felbamate

Answer 39

Add-on in dogs with t1/2 of 5-6 hours Blocks voltage dependent Na+ channels Inhibits Ca2+ channels

Question 40

What does Felbamate compete with

Answer 40

Glycone- binding site on NMDA glutamate receptor

Question 41

Bromide therapy

Answer 41

Liver disease (sole anticonvulsant) t1/2 in dogs 25 days

Question 42

Bromide toxicosis in dogs and cats

Answer 42

CNS depression, weakness, ataxia, decreased proprioception Polyphagia, PU/PD and behavior change in dogs Respiratory signs (asthma)- cats

Question 43

Impact of short half-life compared to dosing interval

Answer 43

Fluctuation during dosing interval No accumulation (shortens interval) Clearing out quickly

Question 44

Impact of long half-life compared to dosing interval

Answer 44

Minimal fluctuation during dose interval Protected against breakthrough seizures Accumulation dramatic (steady-state in therapeutic range)