Anticovalent Drugs Flashcards
Convulsion
Abnormal and sudden attack of involuntary muscular contractions and relaxations (motor activity)
Seizures
Episodes of neurological dysfunction from abnormal synchronous activity of neurons
Epilepsy
A group of recurrent CNS disorders: paroxysmal cerebral dysarrythmia
Signs: seizures, convulsions or fits
What is required for a animals to have epilepsy?
Abnormal, physical, sensory and autonomic activity
At least 2 unprovoked seizures
Unconsciousness
Intracranial causes of epilepsy
Neoplasm, inflammation, hydrocephalus, malformation, trauma
Extracranial causes of epilepsy
Hepatic/renal failure, hypoxia, toxicity, hypoglycemia, hypocalcemia
Seizures in vet med
Dogs: epilepsy inherited affected 0.5-6% population
In cats and other pets it’s rare
Higher incidence of epilepsy in ____________
Belgian Shepherd
Therapeutic success
Balance between efficacy and safety
Therapeutic considerations of anticonvulsants
Eradication not reasonable
Life-time therapy
Increased risk
When do you start anticonvulsant drugs?
Seizures more than 3 minutes
Cluster seizures
More than 1 month
Worsening seizure pattern
Excitatory NT
Hypopolarize
ACh
Glutamate **
Catecholamines
Inhibitory NT
Hyperpolarize
Gamma amino butyric acid*
Glycine
General cellular mechanisms of seizures
Altered membrane function: hypoxia and hypoglycemia
Altered mem. permeability: hypoxia, inflammation and tumors
Altered ECF electrolytes: increased K, decreased Ca
NT: increased excitatory
General mechanisms of seizures
Inappropriate neuronal discharge (inititation)
Recruitment
Synchronization
Propagation
What drugs enhance GABA inhibition
Increases GABAergic transmission
Barbiturates and Benzodiazepine
Important Barbiturates
Phenobarbital (luminal)
Primidone (Mysoline)
Important benzodiazepine drugs
Diazepam (valium)
Clonazepam (klonopin)
Phenobarbital
Historic 1st choice chronic management
Increase GABA, decrease glutamine and Ca
Attenuates initiation, decreased progagation
100% F with long half life
Phenobarbital drug interactions
Potent induction of CYP 450
Decreased clearance
Auto-induction in 2-4 weeks
Phenobarbital behavioral side effects
Polyphagia, polydipsia, polyuria
Sedation (ataxia and grogginess)
Phenobarbital in the bone marrow
Type B (allergic)- leukopenia
Requires 10-14 days or previous exposure
Phenobarbital hepatotxocity
Type A (dose and duration dependent)
Limits maximum therapeutic range
Increased serum alk phos and bile acids
Decreased albumin and BUN
Primidone (Mysoline)
Partial and generalized seizures
Bromide
1st add-on
Common 1st choice for chronic conditions
Diazepam
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
Diazepam in cats
For maintenance in cats but can cause hepatic necrosis
Levetiracetam
New add-on against refractory epilepsy in dogs and cats
Prevents postoperative serizures in protosystemic shunt surgery in dogs
PK of Levetiracetam
100% absorption and <10% protein binding
Cats t1/2= 3 h, dogs t1/2=3- 4.5
Which bensodiazepine drugs are approved for long-term treatment?
Clonazepam (myclonic, atonic and absence seizures) and clorazepate (partial seizures)
Na+ channel inhibitors
Anti-seizure drug
Blocks voltage-gated Na channels by selectively binding to channel in the inactive state and slowing the rate of recovery
Phenytoin (Dilantin, Phenytek)
Occ. in horses for muscle disorders/ antiarrhythmic agent
Limited in vet use due to side effects and variable PK
Valproic Acid (Depankene)
Increases GABA production and GABA metabolism
Dogs when refractory to other meds
Valproic Acid PK
100% bioavailability
T 1/2 = 1-2.8 hours dogs
T calcium channel
Found in heart and neurons
Short, small and low threshold
L calcium channel
Muscle, neurons, endocrine cells, bone
Long, large and high threshold
Gabapentin (neurontin)
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
Pregabalin (lyrica)
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
Felbamate
Add-on in dogs with t1/2 of 5-6 hours
Blocks voltage dependent Na+ channels
Inhibits Ca2+ channels
What does Felbamate compete with
Glycone- binding site on NMDA glutamate receptor
Bromide therapy
Liver disease (sole anticonvulsant)
t1/2 in dogs 25 days
Bromide toxicosis in dogs and cats
CNS depression, weakness, ataxia, decreased proprioception
Polyphagia, PU/PD and behavior change in dogs
Respiratory signs (asthma)- cats
Impact of short half-life compared to dosing interval
Fluctuation during dosing interval
No accumulation (shortens interval)
Clearing out quickly
Impact of long half-life compared to dosing interval
Minimal fluctuation during dose interval
Protected against breakthrough seizures
Accumulation dramatic (steady-state in therapeutic range)
