Anti-Seizure Drugs Flashcards
what are the different drugs effective for generalized onset of seizures?
Valproate (first line/DOC)
Topiramate
Zonisamide
what is the first line broad-spectrum anti-seizure drug for px with generalized epilepsies?
valproate
in what population can u not give valproate?
women of childbearing age & pregnant women
what are the clinical uses of valproate?
- generalized onset tonic-clonic seizures
- generalized absence seizure
- myoclonic seizures
- atonic seizures
- focal seizures
- status epilepticus
what is the MOA of valproate?
it inhibits enzymes involved in GABA degradation -> DEC GABA degradation -> INC GABA increasing
what are other uses for valproate?
headache
mania in bipolar disorder
can valproate be taken with food?
food delays absorption so give it after meals
what are D/I of valproate?
- inhibit metabolism of other anti-seizure drugs
- INC free fraction of phenytoin -> toxicity
- INC conc of phenobardibtal -> stupor/coma
- DEC clearance of lamotrigine & rufinamide
what are the AEs of valproate?
dose-related: GIT (nausea, vomiting, abdominal pain, heartburn)
reversible: INC weight, INC appetite, hair loss
Higher levels: fine tremors
what is a rare toxic effect of valproate?
Idiosyncratic hepatotoxicity
idiosyncratic thrombocytopenia
what are C/Is of valproate?
- PLUMS: Pregnancy, Liver dis, Urea dis, Mitochondrial dis, Suspected disorders <2 yrs
- Pregnancy: @1st trim risk of NTD
what are D/I of Topiramate?
- INC clearance of contraceptives
- INC clearance of topiramate when given w/ CYP3A4 enzyme inducers
what is the MOA of Topiramate?
blocks voltage-gated Na channels –> INC GABA receptor activity -> reduce membrane depolarization by AMPA or kainate receptors
what are the clinical uses of Topamirate?
- primary generalized tonic-clonic seizures
- focal seizures
- atonic seizures
- prohylaxis in migraine
- infantile spasms in WEST SYNDROME
What are AE of Topiramate?
- cognitive impairments -> discontinued bcos of this
- DOSE-RELATED during initiation = Paresthesias
- Long term therapy = significant weight loss, Urolithiasis
- Prompt withdrawal = acute myopia, angle-closure glaucoma
- Metabolic acidosis (DEC HCO3) = rare
what is the teratogenic effect of Topiramate?
1st trimester = oral cleft formation in newborns
what is the MOA of Zonisamide?
blocks voltage-gated Na channels & T-type Ca channels
what are the clinical uses of Zonisamide?
- focal & generalized tonic-clonic seizures
- atypical absence seizures
- some myoclonic epilepsies
- infantile spasms
- adjunct therapy in tx of focal seizures w/ or w/o secondary generalization in adults
what aer AEs of Zonisamide?
- potentially serious skin rashes
- low birth weight
- weight loss
- metabolic acidosis, kidney stones, oligohydrosis (rare)
- drowsiness
- cognitive impairment
what are drugs effective for generalized onset of seizures?
Generalized motor
* valproate
* Topiramate
* Zonisamide
Generalized absence
* Valproate
* Ethosuximide
* Lamotrigine
* Trimethadione
what is the MOA of Ethosuximide?
inhibits low-voltage-activated T type Ca channel
what is the main indicationfor Ethosuximide?
- childhoos generalized absence seizures
- atypical absence seizures
- epileptic negative myoclonus (rare)
what is the main goal of Ethosuximide?
seizure conrtol with monotherapy
what are the AEs of Ethosuximide?
- Common: Gastric distress (pain, nausea, vomiting)
- Others: euphoria
what is drug for generalized onset seizures that is not used anymore?
Trimethadione –> AE: Hemeralopia (day blindness)
what are the drugs effective for seizures assoc with Lennox-Gastaut syndrome?
- Valproate: Myocolonic seizures
- Valproate + Iamotrigine + BZD: Atonic seizures
- Topiramate, Felbamate, Iamotrigine, Clobazam, Rufinamide, Valproate: Lennox-Gastaut Syndrome
- Stripentol, Cannabidiol, Fenfluramine: Dravet syndrome
- IM ACTH, oral corticosteroid or Vigabatrin: Infantile spasms in West syndrome
what is a caution to note for Lennox-Gastaut syndrome?
phenobarbital & Vigabatrin = worsens atonic seizures
Dravet syndrome/Mycolonic epilepsy = diverse generalized & focal seizure types
what is the clinical use of Clobazam?
Lennox-Gastaut syndrome
What are AEs of Clobazam?
- somnolence, dysarthria, drooling, behavioral changes
- tolerance with chronic admin
- withdrawal symptoms after abrupt discontinuation
what is the MOA of Rufinamide?
blovks voltage-gated Na channels
what is the clinical use of Rufinamide?
atonic seiures
what are important D/I of Rufinamide?
- Valproate = decrease clearance of Rufinamide
- Concomitant use requires dec in valproate dose
what are drugs effective for Dravet syndrome?
Stripentol
Fenfluramine
Cannabidiol
what is the cause of Dravet syndrome?
mutations of SCN1A gene
what are AEs of Stripentol?
sedation/drowsiness, slowing of mental function, ataxia, diplopia, nausea, DEC appetite, abdominal pain
what are AEs of Cannabidiol?
somnolence
decreased appetite
diarrhea
fatigue
liver function abnormality
what program restricts ppl form aquiring Fenfluramine?
Risk Evaluation and Mitigation Strategy program
what is the main metabolite formed in Fenfluramine that causes BBW?
Norfenfluramine -> causes valvular <3 disease & pulmonary HTN
what are drugs effective for infantile spasms in West syndrome?
Vigabatrin
Everolimus
what are the goals of treatment in cessation of seizures in infantile spasms in west syndorme?
- ACTH IM injection
- oral corticosteroids (predinosine, hydrocortisone)
- Vigabatrin
what is the MOA of Vigabatrin?
irreversible inhibits GABA transaminase -> sustained INC extracellular GABA in the brain
What aer AEs of Vigabatrin?
- most important: irreversible retinal dysfunction
- less common: psychosis, agitation, confusion,
VIGabatrin = VIsion loss & weight GAin
what drug for West syndrome treats focal seizures in Tuberous Sclerosis Complex?
Everolimus
what are the most common AEs of Everolimus?
Stomatitis
Diarrhea
Pyrexia
What are the specific drugs for seizure syndromes?
- Valproate: Juvenile Myoclonic Epilepsy
- Clobazam, Rufinamide: Lennox-Gastaut syndrome
- Stiripentol, Cannabidiol, Fenfluramine: Dravet syndrome
- Vigabatrin: Infantile spasms in west syndrome
- Vigabatrin & Everolimus: Tuberous Sclerosis Complex
What are other drugs that can be ued in managing seizures & epilepsy?
Carbonic anhyrdase inhibitors
Benzodiazepines
what is the MOA of Carbonic anhydrase inhibitors?
inhibition of CA II & CA VII –> DEC intracellular HCO3 & DEC depolarizing action
what are the 2 prototypes of Carbonic anhydrase inhibtors?
- Sulthiamine = benign focal epilepsy w/ centrotemporal spikes
- Acetazolamide = Intermittent tx of menstrual seizure exacerbations
what are the different Benzodiazepines & their clinical indications?
- Diazepam: first line for status epilepticus
- Lorazepam: status epilepticus
- Midazolam: out of hospital for status epilepticus
- Clonazepam: PO: absence, atonic, myoclonic seizures, infantile spasms
- Nitrazepam: PO: infantile spasms, myoclonic seizures
- Clorazepate dipotassium: PO: focal seizures
- Clobazam: PO: seizures assoc with LGS, focal seizures
what condition is defined as abnormally prolonged or repetitive seizures?
Status epilepticus
forms: Convulsive SE, Non-convulsive SE, Focal SE
what form of status epilepticus is a life-threatening emergency with repeated generalized tonic-clonic seizures with persistent postical depression of neuro function betw seizures?
Convulsive status epilepticus
what is the treatment for convulsive status epilepticus?
- begin when seizure duration reaches: 5 mins for gen tonic-clonic seizures, 10mins for focal seizures without impairment of cosnciousness
- IV Lorazepam or Diazepam: first line
- if it continues: IV Fosphenytoin or phenytoin, IV Valproate or Levetiracetam, IV Phenobarbital
what form of status epilepticus occurs at least 30 mins after treatment with first and 2nd therapy agents?
refractory status epilepticus
what is the tx for refractory status epilepticus?
anesthetic doses of Phenobarbital, Propofol, Midazolam or Thiopental, Ketamine
What is known as status epilepticus that continues or recurs 24 hrs after anesthesia wears off
super refractory status epilepticus
what form of status epilepticus has persistent change in behavior or mental processes with continuous eileptiform EEG w/o major motor signs?
Non-convulsive Status epilepticus
what are the tx for Non-convulsive status epilepticus?
Benzodiazepine (1st)
IV Valproate/oral NGT Ethosuximide (2nd)
what is the form of status epilepticus that has prolonged, generalized absence seizure that lasts hours/days?
Absence status epilepticus
what type of status epilepticus has or does not have altered awareness?
focal status epilepticus
what are group of seizures that occur more frequently that the px habitual freq?
acute reptitive seizures (seizure clusters)
complete recovery betw seizures
what is the tx for acute repetitive seizures?
**IV Benzodiazepines **(emergency)
Rectal diazepam (out of hospital)
Alternatives:
* Buccal midazolam
* Intranasal modazolam, diazepam, lorazepam
For how long should u** taper drug withdrawal**?
slowly over 1-3 months period or longer -> rebound status epilepticus if abrupt discontinuatoin
what are risk factors for seizure recurrence?
- abnormal neuro exam/EEG
- neurologic deficits
- longer duration of epilepsy
- seizure control
- certain epilepsy syndromes
- abrup cessation of AEDs
What anti-seizure drugs are C/I in prengnacy/teratogenic?
- Phenobarbital: cardiac effects
- Topiramate = oral cleft
- Valproate = congenital malformations
What anti-seizure drugs can penetrate through breastfeeding in relatively high conce?
Primidone
Levetiracetam
Gabapentin
Lamotrigine
Topiramate
Barbiturates & BZD = sedation of bby
What anti-seizure drugs can penetrate through breastfeeding in relatively high conce?
Primidone
Levetiracetam
Gabapentin
Lamotrigine
Topiramate
Barbiturates & BZD = sedation of bby
