anticonvulsants Flashcards
focal seizures treatment
first line: carbamazepine, lamotrigine
second line: oxcarbazepine, valproate, levetiracetam
adjunct: combinations + gabapentin, topiramate
tonic clonic seizures treatment
first line: valproate (not WCBA), lamotrigine
second line: carbamazepine, oxcarbazepine
adjunct: combinations + levetiracetam, topiramate, clobazam
absence seizure treatment
first line: valproate (not WBCA), ethosuximide
second line: lamotrigine
adjunct: combinations + specialist advice
WCBA
women who are of child bearing age
mechanisms of anticonvulsants
calcium channel inhibition
GABAergic potentiation
-receptor potentiation
-uptake inhibition
-metabolism inhibition
sodium channel inhibition
phenytoin
stabilises voltage-gated sodium channels in inactivated state
effective against tonic clonic and partial seizures
can worsen absence and myoclonic seizures
phenytoin side effects
teratogenic
increased lupus risk
cerebellar atrophy
acne, hirsuitism
gingival overgrowth
gingival overgrowth
gums start to grow
carbamazepine mechanism
blocks voltage-gated sodium channels
may have secondary actions on GABA A receptors
uses of carbamazepine
focal seizures
useful for tonic-clonic seizures
mood stabiliser
to treat neuropathic pain
drugs related to carbamazepine
oxcarbazepine and eslicarbazepine
similar mechanisms, better side effect profile, fewer interactions
carbamazepine pharmacokinetics
auto-induces CYP3A4
-CYP3A4 metabolises carbamazepine so as people take more of the drug they produce more of this enzyme
-can take a while for the drug to reach a plateau
-means other drugs will be metabolised much more quickly, so must be careful with drug interactions
what inhibits enzyme CYP3A4
a component of grapefruit juice
side effects of carbamazepine
teratogenic
risk of lupus
worsens JME, absence seizures
cognitive problems
mood changes
psychosis in some people
mechanism of lamotrigine
sodium channel blocker
uses of lamotrigine
first line tonic clonic
second line absence
(can make myoclonic seizures worse at higher doses)
mood stabiliser- bipolar
can be asses to antipsychotic drugs for the treatment of schizophrenia
side effects of lamotrigine
not as bad as carbamazepine and phenytoin
sedation
sleep disturbances
rash
binds to eye pigment
steven-Johnsons syndrome (rare)
mechanism of benzodiazepines
potentiate actions of GABA A receptors by binding to allosteric sites on the receptor
clobazam
adjunct meditation
also used to treat anxiety
benzodiazepine
clonazepam
treat refractory epilepsy
benzodiazepine
also acts on calcium channels
only prescribed by specialists/ only on types of epilepsy not treatable by other drugs
diazepam
only really used for status epilepticus
acute serious situations, long term use = dependence
benzodiazepine side effects
sedation
tolerance and dependence build up very quickly
some cases: seizures on withdrawal
barbiturates as anticonvulsants
allosteric potentiators of GABA A receptors
side effects far worse, can directly activate the receptor making them dangerous in overdose
only prescribed by a specialist in difficulty situations
tiagabine mechanism
GAT1 inhibitor - increases the synaptic concentration of GABA as it cannot be taken up into the presynaptic nerve terminal
increasing inhibitory signals
what is tiagabine used for?
adjunct medication for focal seizures
panic attacks?
neuropathic pain?
tiagabine side effects
sedation
dizziness
paraesthesia
provokes seizures in non epileptic patients
tiagabine overdose
very sedating
causes seizures, amnesia and confusion
Vigabatrin mechanism
irreversible GABA transaminase inhibitor (short half life doesn’t matter as it will covalently modify enzyme)
increases presynaptic GABA concentration by stopping metabolism of GABA to SSA
uses of vigabatrin
adjunct medication
addictions?
panic attacks?
vigabatrin side effects
visual disturbances
depression
psychosis
sedation
teratogenic actions?
three forms of sodium valproate
sodium valproate, valproic acid and valproate semisodium (mixture of the two)
mechanism of sodium valproate
unclear
most likely GABA transaminase inhibitor (increasing GABA synthesis)
enhance post synaptic GABA function?
inhibit sodium channels?
inhibit calcium channels?
uses of sodium valporate
treat epilepsy
treat bipolar disorder
treat migraines
sometimes add on treatment for schizophrenia
side effects of valproate
Liver toxicity (can be sudden onset)
Teratogenic
Cognitive changes/brain structure changes with long term use (debatable/?reversible when drug is withdrawn ).
what teratogenic side effects are associated with valproate?
Increased risk of: anencephaly, spina bifida (20 fold increased risk), autistic spectrum disorders, cleft palate, limb defects + many others…
presentation of foetal valproate syndrome
high forehead
flat nasal bridge
broad base of nose
shallow philtrum
long upper lip
gabapentinoids
gabapentin and pregablin
believed action of gabapentin and pregabalin
act on alpha 2 - delta subunit of calcium channel
when this site is bound by natural ligands (leucine and isoleucine?) calcium channel complex transported to the cell surface
if a gabapentinoids bind this site, the calcium channel is retained within the cell and broken down
decreases the number of calcium channels at the cell surface
pregabalin secondary effect
increases glutamate decarboxylase (GAD) levels
therefore
increases synthesis of GABA
uses of gabapentinoids
Gabapentin and pregabalin: adjunct medication for focal seizures, neuropathic pain
pregabalin: monotherapy and licenced for anxiety treatment
gabapentinoid side effects
Sedation/dizziness
Suicidal thoughts
Abuse potential
(when you put these two together very worrying)
Seizures upon withdrawal
-precipitate return of epilepsy or even seizures you didn’t have before
-particular problem for this drug
ethosuximide mechanism
blocks T type calcium channels
use of Ethosuximide
first choice drug for absence seizures, rarely used for other types of epilepsy (can exacerbate them)
what may ethosuximide be preferred to valproate?
lacks the liver toxicity
there is an increased risk of birth defects, however this is less than with valproate
how does valproate produce teratogenic side effects?
at least partly by acting as a folic acid antagonist
side effects of ethosuximide
increased risk of birth defects
sedation
nausea
mood changes
use of levetiracetam
can be used to treat focal, myoclonic and tonic-clonic seizures
mechanism of levetiracetam
inhibits presynaptic calcium channels?
binds to SV2A?
reduces neurotransmitter release
side effects of levetiracetam
Psychiatric
common: depression, agitation, aggression
rarer: suicide ideation, psychosis
Steven Johnson syndrome- rarer
Steven Johnsons syndrome
some sort of immune reaction against the medication or a virus the patient has
More serious form: toxic epidermal necrolysis
potential mechanism of topiramate
potentiation of GABAA receptors
block of AMPA and kainate receptors
block of sodium channels
block of calcium channels
inhibition of carbonic anhydrase
when is topiramate used?
an adjunct treatment for focal seizures and tonic-clonic seizures
sometimes used in the treatment of migraines, bipolar disorder and alcoholism.
topiramate side effects
sedating
can cause cognitive problems and have psychiatric side effects
known to be teratogenic
what percentage of people are antiepileptic drugs successful for?
70%
what is suggested when antiepileptic drugs do not work
ketogenic diet
-classic diet: 90% calories from fat therefore need professional dietician
about 50% of children on it see a decrease in the number of seizures, some become seizure free
epilepsy surgery
localise the area of tissue generating the seizure and remove it or destroy it
benefits often outweigh issues that may arise from surgery
corpus callosotomy
used for intractable epilepsy
sever white matter tract, preventing seizures spreading from one hemisphere to the other
side effects corpus callosotomy
cognitive impairments
difficulty with language
alien hand syndrome
