Epilepsy Drugs Flashcards
What are the four main pillars of epilepsy treatment?
Drugs, Diet, surgery, vagal stimulation
Define Anticolvulsant Hypersensitivity syndrome.
Life threatening ADR may occur in the first 1-8 weeks of epilepsy treatment
Fever
Rash
Viceral involvement (often liver)
What is the occurrence rate of AHS? what population has the highest risk?
1/1000,1/10,000
Most commonly Han Chinese
What class of drugs causes AHS?
Aromatic drugs:
phenobarbital, phenytoin, carbamazepine, lamotrigine
Deine refractory/intractable patients. What portion of patients achieve seizure freedom?
2/3 are drug responsive and will never get a seizure
1/3 never achieve drug control –> refractory
How do you know if a patient is intractable? refractory?
if they dont respond to an appropriate dose of a drug–> probably intractable
appropriate dose of 2 drugs–> definitely refractory
What kinds of seizures are intractable?
Complex partial seizures (also most common in adults)
West’s and Lennox-Gastaut syndromes seizures
What are common comorbidities with epilepsy?
depression, anxiety, and suicide risk (3x)
What are common side effects with AED? Is abuse an issue?
Sedation, and stomach upsets
compliance is an issue, abuse is NOT
Is polypharmacy attempted in epilepsy?
Yes if the seizures are intractable
New compounds with few drug interactions have reawakened interest in rational polypharmacy
What is the effect of valproate on other drugs?
It increases blood levels of other drugs
What are the effects of phenobarbital, phenytoin, and carbamazepine on blood levels of other drugs?
They decrease blood levels of other drugs
What class of drugs affect birth control pills?
Inducer drugs, which are the amine groups drugs: phenobarbital, carbamazepine, phenytoin, and lamotrigine
What AED interacts with warfarin?
phenytoin
what are blood levels of the drug used for?
determine if concentrations are in therapeutic range, occurrence of ADRs in liver, kidneys or blood
noncompliance
How does withdrawal of AED happen?
Withdrawal should never be done quickly
risk for rebound seizures or status epilepticus
risk for losing driver’s license if rebound seizure occurs
How does pregnancy affect treatment?
one drug is continued
Risk of seizures on the baby is higher than risks related to treatment
What is the teratogenic effect of AED during pregnancy?
Risk of teratogenicity increases with increased number of drugs
Phenytoin and valproate have the highest risk
What are the three mechanisms of AED action?
1- inhibition of voltage dependent Na channels
2- enhancing the activity of gaba-a receptor
3- inhibition of T voltage dependent Ca channels
What is the function of Na channel and what drugs inhibit it?
initiates action potentials
cycles between active, inactive, and resting states.
phenytoin and carbamazepine hold the channel a little longer in its inactive state–> lengthen the refractory period.
What drugs enhance the activity of gaba-a? how does this reduce seizures
barbituates and benzodiazepines
- increase gaba-a mediated Cl influx–> maintaining the membrane near its resting potential and reducing excitability
What is the risk associated with gaba-a mediating drugs?
sedation
paradoxical irritability especially in children
What drugs inhibit T type voltage gated Ca channels and what type of seizures are they used for?
Ethosuximide
these channels are highly important in the thalamus function–> absence seizures
What are rare side effects of ethosuximide?
Photophobia and hiccups
What drugs are used only for tonic-clonic and partial seizures?
Phenobarbital
Phenytoin
carbamazepine
levetiracetam
What patient population is phenobarbital used in?
Children (Partial seizures and tonic-clonic seizures)
What are some side effects of phenytoin?
Gingival heprplasia, hirsutism, acne
becomes zero order metabolism at therapeutic levels –> half life becomes larger
Nystagmus, ataxia
What patient population is phenytoin used in?
It is well tolerate in elderly patients
What is the mechanism of action of levetiracetam? and what is the associated risk of drug interaction
Decrease transmitter release (SV 2A binding)
very few drug interactions
What drugs are used as broad spectrum drugs to reduce seizures? what kind of seizures do they act on?
Tonic clonic, absence, and partial
Valproate, clobazam, lamotrigrine, topiramate.
What are the side effects of valproate?
Hairloss, tremor, weight gain, bruising, and bleeding
Hepatitis especially in young children
highly teratogenic
What class of drugs is clobazam? what’s the associated risk of using it?
Benzodiazepine –> gaba-a
Sedation, personality change
dependence after 6 months
What is the risk of using lamotrigine?
Some patients show a rash that develops to hypersensitivity syndrome
What are the side effects of topiramate?
Sedation
Weight loss
What drugs are used IV? what for?
Status epilepticus Benzodiazepines (lorzepam, diazepam, midazolam) Phenytoin Propofol, phenobarbital, pentobarbital Full sedation if nothing works
