34/35: Anticonvulsant Drugs Flashcards
define seizure
sudden, transient episode of brain dysfunction and altered behavior due to abnormally excessive, synchronous, and rhythmic firing of certain populations of hyper-excitable neurons in the brain
activation of motor neurons leading to involuntary contractions of skeletal muscle =
convulsions
chronic neurological disorder characterized by recurrent seizures =
epilepsy
primary/idiopathic - unknown origin
secondary - identifiable cause
describe a simple partial seizure
- minimal spread of abnormal neuronal discharge
- no loss of consciousness
- limited motor or sensory manifestations
describe a complex partial seizure
- starts in a small brain area but quickly spreads to other areas
- altered consciousness with potential automatisms
- strong emotional feelings, gradual recovery of consciousness within minutes
what are automatisms?
lip smacking, fumbling, swallowing, etc…
involve the entire brain with global EEG change and bilateral manifestations
generalized epileptic seizures
describe absence/ petit mal seizures
- sudden onset and abrupt cessation
- brief loss of consciousness
- typically in children less than 15 yo
- inducible by hyperventilation, stress or flash light
describe tonic-clonic/ grand mal seizures
- tonic spasms and major convulsions of entire body bilaterally
- loss of consciousness and profound CNS depression after seizure
what are the four phases of a tonic-clonic seizure?
- aura
- tonic (tense)
- clonic (convulsions)
- stuporous state and sleep
observe: child with sudden loss of postural tone resulting in falls or dropping of head and torso if in sitting position, may be wearing a helmet
atonic generalized seizure
recurrent myoclonic jerks of the body with sudden flexion or extension of the body and limbs
infantile spasms
what is status epilepticus?
continuous or very rapid recurrin seizures, usually of tonic-clonic type
- medical emergency requiring immediate therapy
mechanism generating epileptic seizures: 3 stages
- initiation (focal epileptogenesis)
- synchronization of surrounding
- propagation (recruitment of normal neurons)
goal of antiepileptic medications
restore normal patterns of electrical activity
inhibit seizures, partially effective as prophylaxis but not a cure
alternative treatment options for epilepsy (not meds)
- surgery (resection, particularly in temporal lobe)
- vagus nerve stimulation (for drug-resistant patients with partial seizures)
what medications would you use for partial seizures (complex or simple) with or without secondarily generalized seizures?
carbamazepine
phenytoin
valproate
what medications would you use for tonic-clonic seizures, tonic seizures, or atonic seizures?
carbamazepine
phenytoin
valporate
what medications would you use for absence seizures?
ethosuximide
valproate
what medications would you use for myoclonic seizures?
clonazepam
valproate
what medications would you use for status epilepticus?
diazepam
larazepam
phenytoin
fosphenytoin
3 major MOA for anticonvulsant medications
- decrease excitatory effects of glutamate and repetitive firing of neurons
- increase inhibitory effects of GABA
- alter neuronal activation by altering movement of ions across neuronal membrane
anti-seizure medications can bind to Na channels in the _______ and prevent conversion ______
inactive; resting state
- this prolongs Na channel inactivation and make neuronal membrane less excitable
what reduces the pacemaker current that underlies the thalamic rhythm in spikes and waves seen in absence/ petit mal seizures?
reducing the calcium influx
general side effects of anticonvulsants
- sedation
- diplopia
- nystagmus
- ataxia
- GI upset
other side effects to watch for in anticonvulsants…
- abrupt withdrawal can cause seizures
- decreased efficacy of oral contraceptives
- teratogenic
what drug is considered safest for pregnancy?
phenobarbital
what is the elimination of phenytoin look like?
dose-dependent (zero order) elimination that is different for different patients
system can become saturated and transition ot a non-linear relationship
metabolized in liver, excreted in urine
MOA phenytoin
- blocks and prolongs the inactivated state of voltage-gated Na channels
- enhances the release of GABA
- prevents seizure propagation
clinical uses for phenytoin
- grand mal
- partial seizures
- status epilepticus
gingival hyperplasia is a negative side effect of what drug?
phenytoin
what is fetal hyantoin syndrome?
teratogenic
cleft lip and palate
side effec tof phenytoin
MOA carbamazepine
*inhibition of voltage gated Na channels
also blocks high frequency firing of neurons and decreases synaptic release of glutamate
how is oxacarbazepine different than carbamazepine?
shorter half-life, but active metabolite has longer duration and fewer drug interactions
drug of choice for trigeminal neuralgia
carbamazepine
clinical uses for carbamazepine
- grand mal
- partial seizures
- trigeminal neuralgia
SIADH = ?
syndrome of inappropriate ADH secretion
side effect of carbamazepine that causes increased fluid retention and hyponatremia
what drug interactions do you need to watch for with carbaamazepine?
phenytoin
valproate
phenobarbital
MOA phenobarbital
enhances phasic GABAa receptor responses by increasing duration of Cl- channel opening
drug of choice for seizures in infants
phenobarbital
clinical use for phenobarbital
status epilepticus (and others)
metabolized by the liver to phenobarbital
primidone
drug of choice petit mal/ absence seizures
ethosuximide and valproic acid
MOA ethosuximide
blocks presynaptic t-type Ca2+ channels to stop high-freqeuncy firing of neurons
least sedating anticonvulsant
valproic acid
also chemically unrelated to other anticonvulsants
MOA valproic acid
- inhibition of presynaptic t-type Ca2+ channels to block neuronal firing
- inhibition of GABA transaminase
special adverse effects for valproic acid
hepatotoxic syndrome and spina bifida if preggers (teratogenic)
do not use less than 5 yo
preferred initial agent for status epilepticus
diazepam
how is lorazepam different than diazepam?
longer duration of action
MOA diazepam
- potentiates GABAa responses by increasing frequency of channel opening
use limitations for diazepam
sedative effects and tolerance
MOA gabapentin and pregabalin
GABA analogs that block presynaptic voltage-gated Ca2+ channels to decrease excitatory transmission
clinical uses gabapentin
- grand mal
- partial seizures
- neuropathic pain
MOA lamotrigine
blocks presynaptic voltage-gated Na and Ca channels
clinical uses for lamotrigine
- partial and generalized seizures
- petit and grand mal
adverse effect of lamotrigine
**stevens-johnson syndrome (rash)
especially if used with valproate
MOA felbamate
blcok Na channels and glutamate receptors
adverse effects felbamate
aplastic anemia, hepatic failure
specifically designed as an inhibitor of GABA uptake
tiagabine
MOA acetazolamide
carbonic anhydrase inhibitor
effect thought to be related to mild CNS acidosis
spasticity v. spasm
both are the result of hyperexcitabiliyt of the neurons or muscle cells
primarily an exaggerated muscle stretch reflex syndrome that occurs following injury to the CNS
v.
an increase in muscle tension seen after certain musculoskeletal injuries and inflammation (injury is local and not in the CNS)
goal of pharmacotherapy for muscle spasms and spasticity
normalize muscle excitability without causing a profound decrease in muscle function
centrally acting muscle relaxants (2)
diazepam
baclofen
how does diazepam act as a muscle relaxant?
works by increasing the central inhibitory actions of GABA on alpha motor neurons in the spinal cord
treat spasms with _____; treat spasticity with _______
diazepam; baclofen
MOA baclofen
GABAb receptor agonist
as effective as diazepam, but causes less sedation
