Anticonvulsants Flashcards
Anticonvulsants
Anti-seizure, Anti-epileptic Drug used to treat seizures **Control signs not cause of problem**
Seizure (convulsion)
Clinical manifestation of abnormal activity in the brain
Epilepsy
Multiple seizures during long period of time
Status epilepticus
Seizure lasting 5+mins, or two or more discrete seizures without full recovery of consciousness between seizures
Anticonvulsant Causes of seizures
Primary Secondary Reactive
Primary type causes of seizure
Idiopathic epilepsy
Secondary type causes of seizure
Distemper Head/Injury Encephalitis CNS tumors
Reactive type causes of seizure
Fever/ Heatstroke Poisoning
Anticonvulsant Mechanism of action
Limit either the initialization or spread of seizure focus *PICTURE*
Anticonvulsant- Status Epilepticus At-Home treatment
Diazepam - Emergency! 1-2 mg/kg per rectum (teat cannula, rubber catheter) up to 3x within a 24 hour period -Suppositories, gel formations
Anticonvulsant- Status Epilepticus In-hospital management
ABC - airway, breathing, circulation STOP SEIZURES Treat cause Prevent further brain damage
Anticonvulsant- Status Epilepticus Stop Seizure! Treatment Name the drugs
Diazepam (IV, Rectal, CRI) Lorazepam Midazolam Clonazepam Clorazepate Phenobarbital General anesthesia (last resort)
Anticonvulsant- Status Epilepticus - Treatment Diazepam - IV
5-10 mg to effect ~= 0.5 mg/kg
Anticonvulsant- Status Epilepticus - Treatment Diazepam - Rectal
1-2 mg/kg if no IV access
Anticonvulsant- Status Epilepticus - Treatment Diazepam - CRI
0.5 mg/kg/h - absorption into plastics -If seizures recur after diazepam boluses
Anticonvulsant- Status Epilepticus - Treatment Phenobarbital
10-20 mg/kg IV increments to effect
Anticonvulsant Prevention When to start treatment?
More than one seizure per month Seizure within one week of head injury Brain lesion identified
Anticonvulsant Treatment
Drugs given long term Quality of life Reduce frequency & severity while avoiding serious side effects
Anticonvulsant - Long term treatment stats
Effective in about 33% Some control in 33% Ineffective in the rest
Anticonvulsant Benzodiazepines Used for long term treatment?
No! not for long-term
Anticonvulsant -Benzodiazepines Duration of action?
Short, frequent administration
Anticonvulsant -Benzodiazepines Cross tolerance?
No further use in status epilepticus Enzyme induction
Anticonvulsant -Benzodiazepines Oral diazepam in cats
Leads to fatal liver necrosis
Anticonvulsant - Client education
Client compliance Goals of treatment Potential side effects Missed dose Supply of medication Data log
Anticonvulsant - Drug choice criteria
Efficacy Safety Price Pharmacological information Clinical experience Single drug vs. combination
Anticonvulsant - Drug dose
Recommended doses are only a guide Lower end for new patients, (adjust upward as needed) Higher end of “loading dose” for frequent & severe seizures (then adjust downward)
Anticonvulsant - PK considerations
Loading Dose PK change over time (phenobarbital)
Anticonvulsant - PK considerations - Loading Dose
For drugs eliminated slowly (brombide & phenobarbital) No time for tolerance to sedative side effects
Anticonvulsant - Drug list
Peanut Butter Love Zone Feels Very Good Phenobarbital Brombide Levetiracetam Zonisamide Felbamate Valproate Gabapentin
Anticonvulsant Phenobarbital Length of action
Long-acting barbiturate
Anticonvulsant Phenobarbital Receptor activity
Potentiates GABAa receptor activity
Anticonvulsant Phenobarbital Drug of choice in what species
Dog & Cat
Anticonvulsant Phenobarbital Loading dose administration
Loading Dose can be given IV
Anticonvulsant Phenobarbital Target concentration
Target concentration = 15-40ug/ml
Anticonvulsant Phenobarbital Side Effects
Cytochrome p450 induction Sedation Hyperexcitability Restlessness Polyuria/Polydipsia/Polyphagia
Anticonvulsant Phenobarbital Cytochrome p450 induction
Initial T1/2 beta in dogs ~100hrs T 1/2 beta after induction ~24hrs
Anticonvulsant Phenobarbital Toxicosis
Hepatotoxicity Anorexia Sedation Ataxia Icterus Ascites
Anticonvulsant Brombide
Unknown mechanism of action
Anticonvulsant Brombide Ways it is used
Initial therapy or as add-on to phenobarbital
Anticonvulsant Brombide T 1/2
21-24 days!
Anticonvulsant Brombide Excretion
Filtered & reabsorbed in kidneys High chloride intake increases elimination
Anticonvulsant Brombide Loading dose
Use NaBr if given IV KBr - congestive heart failure NaBr- hypoadrenocorticism
Anticonvulsant Brombide Side effects
Vomiting Sedation Ataxia Weakness Polyuria/ Polydipsia/ Polyphagia Pancreatitis
Anticonvulsant Brombide Toxicosis
Blindness Ataxia Paresis Altered behavior Dysphagia Megaesophagus
Anticonvulsant Brombide Toxicosis protocol
Reduce/stop Br Diuresis (IV fluids, furosemide) Do not use in cats! Pneumonitis!
What anticonvulsant drug should not be used in cats?
Brombide! Pneumonitis!
Anticonvulsant Levetiracetam
Unknown mechanism of actio Synaptic vesicle protein GABA- & Glycine-gated currents Voltage-dependent K+ currents
Anticonvulsant Levetiracetam Half life
T 1/2= 3-4 hours (Dogs) = 3 hrs (Cats)
Anticonvulsant Levetiracetam Uses/ Combinations
Monotherapy or as add-on with phenobarbital
Anticonvulsant Levetiracetam Side effects
Sedation & decreased appetite (uncommon)
Anticonvulsant Zonisamide
Unknown mechanism Blocks voltage-gated sodium channels Blocks T-type calcium channels Potentiates GABAa receptors Enhances Glu uptake Reduces GABA uptake
Anticonvulsant Zonisamide Uses/Combination
Monotherapy or as add-on to phenobarbital
Anticonvulsant Zonisamide Half-life
T 1/2 beta = 15 hr in dogs = 35 h in cats
Anticonvulsant Zonisamide Side effects
Cytochrome P450 induction Sedation, ataxia, vomiting Metabolic acidosis
Anticonvulsant Gabapentin Mechanism of action
Blocks N-type voltage-gated calcium channels (a2 gamma subunit)
Anticonvulsant Gabapentin Metabolism/Excretion
Excreted in urine Only partially metabolized in liver to N-methyl-gabapentin
Anticonvulsant Gabapentin Half-life
T 1/2b = 2-4 hours in dogs
Anticonvulsant Gabapentin Uses/ Combination
As add-on with phenobarbital & /or bromide
Anticonvulsant Gabapentin Effect
Mild sedation & ataxia
Anticonvulsant Gabapentin Oral solution
Oral solution contains xylitol (toxic to dogs)
Which drug’s oral solution is toxic to dogs? What is the toxic chemical?
Gabapentin oral solution Contains xylitol
Anticonvulsant Felbamate Mechanism of action
Potentiates GABAa receptors Blocks voltage-dependent Na+ channels Blocks NMDA receptors
Anticonvulsant Felbamate Metabolism/Excretion
Dogs: 30% metabolized in liver Rest excreted unchanged in urine
Anticonvulsant Felbamate Half-life
T 1/2b = 5-6 hrs in dogs
Anticonvulsant Felbamate Uses/ combinations
Monotherapy or Add-on with phenobarbital
Anticonvulsant Felbamate Effects
Nervousness Mild thrombocytopenia Leucopenia Hepatic disease
Anticonvulsant Valproate Mechanism of action
Blocks voltage-gated Ca channels Potentiates GABAa receptors Reduces T-type calcium currents
Anticonvulsant Valproate Half-life
T 1/2B = 1.5-3 hr (dogs) = 8.5 hr (cats)
Anticonvulsant Valproate Uses/Combination
As add-on with phenobarbital
Anticonvulsant Valproate Effects
Alopecia Hepatotoxicity Vomiting (give with food)
Anticonvulsant Primidone
Approved in dogs Metabolized to phenobarbital Very Hepatotoxic More expensive than phenobarbital Not controlled, not recommended Just use phenobarbital!
Anticonvulsant Phenytoin
Not reliable Not recommended Hepatotoxic
Anticonvulsant Phenytoin Problem at high doses
Zero-order kinetics @ high doses
Anticonvulsant Phenytoin Half-life
T 1/2b = 2hour (dogs) = ~100hr (cats)
Anticonvulsant Phenytoin Use in horses
Azoturia & antiarrhythmic treatment
Anticonvulsant Drugs to avoid!
P-FOB Phenothiazines Fluoroquinolones (+NSAIDS) Opioid agonists Butryophenones
Anticonvulsant Stopping treatment
Seizure-free for 1-2 years -Taper dose over ~6 months -2 weeks between dose changes -Retreat if seizures return
