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3.22 Anticonvulsants
By Dr. Nichols
124
Pharmacology
Professional
03/31/2012

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Term
What is the definition of a convulsion?
Definition
sudden attack of involuntary muscular contractions and relaxations
Term
Define seizure.
Definition
Abnormal central nervous system electrical activity
Term
Define epilepsy.
Definition
A group of recurrent disorders of cerebral function characterized by both seizures and convulsions
Term
What is the prevalence of epilepsy in the US?
Definition
approximately 2.5 million people; 1%
Term
What are the causes of seizures?
Definition
genetic (autosomal dominant genes), congenital defects, severe head trauma, ischemic injury, tumor, drug abuse, idiopathic
Term
What does your EEG look like during a seizure?
Definition
pre-seizure= more activity, chaotic
Seizure= chaotic intense activity
post-seizure= very little activity, flat lining almost
Term
What is the definition of a partial seizure?
Definition
excessive electrical activity in one cerebral hemisphere; affects only part of the body
Term
What is another name for a partial seizure?
Definition
focal seizure
Term
What are the symptoms of a simple partial seizure?
Definition
person may experience a range of strange or unusual sensations= motor, sensory, autonomic
Term
What type of seizure has a key feature of preservation of conciousness?
Definition
simple partial
Term
What are the symptoms of a complex partial seizure?
Definition
loss of awareness at seizure onset; person seems dazed or confused and exhibits meaningless behaviors
Term
Where do complex partial seizures typically originate?
Definition
frontal or temporal lobes
Term
What is the definition of a generazlied seizure?
Definition
excessive electrical activity in both cerebral hemispheres, affects the whole body and loss of consciousness is common
Term
What type of seziure affects the whole body?
Definition
generalized
Term
Where do generalized seizures usually originate?
Definition
thalamus or brainstem
Term
myoclonic=
Definition
brief, shock-like muscle jerks generalized or restricted to part of one extremity
Term
atonic=
Definition
sudden loss of muscle tone
Term
tonic=
Definition
sudden stiffening of the body, arms, or legs
Term
clonic seizure=
Definition
rhythmic jerking movements of the arms and legs without a tonic component
Term
What is another name for grand mal seizures? Describe the seizure.
Definition
tonic-clonic seizure; tonic phase followed by clonic phase
Term
What are the different types of generalized seizures?
Definition
myoclonic, atonic, tonic, clonic, tonic-clonic, absence, lenox-glastaut syndrome
Term
What is another name for a petit mal seizure?
Definition
absence seizure
Term
What type of seizure presents as the person "blanking out" or "daydreaming"?
Definition
absence seizure (petit mal)
Term
What are the three types of absence seizures?
Definition
simple absence (primarily effects consciousness only), complex absence (involve change in mucle activity), atypical absence (involves physical symptoms like eye blinking or lip movement)
Term
What is lenox-glastaut syndrome?
Definition
atypical absence, atonic, and myoclonic seizures
Term
What is status epilepticus?
Definition
a seizure lasting longer than 30 minutes, or 3 seizures without a normal period in between; may be fatal, emergency intervention required
Term
How long do absence seizures last?
Definition
from a second to several minutes
Term
What are the 3 most common types of seizures?
Definition
complex partial, then tonic clonic, then simple partial
Term
Why do patients turn blue during a seizure?
Definition
breathing may cease for a few seconds
Term
Are seizures painful?
Definition
people don't feel pain during a seizure; muscles may be sore afterward
Term
What is the first thing you should think of when treating a new onset seizure?
Definition
is there an underlying cause of the seizures that needs to be treated
Term
What percent of patients with epilepsy can have their seizures controlled with medication?
Definition
80%
Term
How long do you treat someone with epilepsy syndrome?
Definition
recommended for AT LEAST two years; 6-12 months for individuals with a lower risk of occurrence
Term
Why should patients with epilepsy avoid suddenly stopping their medication?
Definition
sudden withdrawal can exacerbate seizures
Term
What are the three main types of MOA of seizure therapeutics?
Definition
1. inhibition of voltage gated Na+ channels to slow neuron firing
2. enhancement of the inhibitory effects of the neurotransmitter GABA
3.inhibition of calcium channels
Term
What are the CNS effects of antiseizure meds?
Definition
drowsiness/sedation/somnolence, depression, confusion, learning difficulties, headache, dizziness, vertigo, diplopia, nystagmus, slurred speech, ataxia, tremor
Term
What are the non-CNS side effects of anticonvulsants?
Definition
dry mouth, nausea, vomiting, anorexia, diarrhea, rash, fetal abnormalities and birth defects
Term
What percent of patients discontinue their first perscribed seizure meds due to adverse effects?
Definition
20%
Term
Name the anti-seizure meds that are Na+ channel inhibitors?
Definition
carbamazepine, phenytoin, topiramate, lamotrigine, valproate, zonisamide
Term
What types of seizures do you use phenytoin with?
Definition
first choice for partial and generalized tonic-clonic seizures; some efficacy in clonic, myoclonic, atonic, no effect on infantile spasms or absence seizures
Term
What are the drug interactions associated with phenytoin?
Definition
decreases blood levels of many medications, increases blood levels of phenobarbital and warfarin
Term
What are the adverse effects of phenytoin?
Definition
hirsutism and coarsening of facial features, acne, gingival hyperplasia (20-40%), decreased serum concentrations of folic acid, thyroxine, and vitamin K with long-term use
Term
What's a good reason of why not to perscribe phenytoin to children?
Definition
you need to brush your teeth more than 8 times per day to prevent gingival hyperplasia
Term
What are the indications for carbamazepine?
Definition
first choice for complex partial and generalized tonic-clonic seizures
Term
What are the CI of carbamazepine?
Definition
may exacerbate absence or myoclonic seizures, blood disorders, liver disorders
Term
What are the drug interactions of carbamazepine?
Definition
CBZ metabolism is affected by many drugs, and CBZ affects the metabolism of many drugs
Term
What are the adverse effects of carbamazepine?
Definition
mild leukopenia or hyponatremia; circulating concentrations of thyroid hormones may be depressed; TSH remains normal
Term
What is the difference between oxcarbazepine and carbazepine?
Definition
fewer adverse effects than CBZ, phenytoin
Term
What is oxcarbazepine used for?
Definition
complex partial seizures, primary and secondarily generalized tonic-clonic seizures, no effect on absence or myoclonic seizures
Term
What is the MOA of valproic acid?
Definition
some inhibition of T type Ca2+ channels, increases GABA production and decreases GABA metabolism, and Na+ channel inhibitor
Term
What types of seizures can be treated by valproic acid?
Definition
simple or complex partial, and primary generalized tonic clonic; also used for absence, myoclonic and atonic seizures; highly effective for photosensitive epilepsy and juvenile myoclonic epilepsy
Term
What are the contraindications for valproate?
Definition
liver disease
Term
What are the drug interactions of valproate?
Definition
affects metabolism of many drugs through liver enzyme inhibition; phenobarbital= drunkenness, clorazepam= prolonged absence seizures
Term
What are the adverse effects of valproic acid?
Definition
weight gain, bone loss, ankle swelling, dose-related tremor, transient hair loss, polycystic ovary syndrome and menstrual disturbances
Term
What is the MOA of lamotrogine?
Definition
na channel inhibitor and may inhibit synaptic release of glutamate
Term
What are the indications for lamotrigine?
Definition
adjunct therapy (ages 2 and up)= for simple and complex partial seizures and generalized seizures of lennox gastaut syndrome
monotherapy (adults)= simple and complex partial seizures
Term
What are the contraindications of lamotrigine?
Definition
may make myoclonic seizures worse
Term
What are the adverse effects of lamotrigine?
Definition
rash (10%; rarely progresses to serious systemic illness), increased alertness
Term
What is the MOA of topiramate?
Definition
enhances post-synaptic GABA(A) receptor currents, kainate receptor antagonist (blocks a certain type of glutamate channel)
Term
What are the indications of topiramate?
Definition
adjunct therapy for partial and primary generalized tonic clonic seizures in adults and children over two; decreases tonic and atonic seizures in children with Lennox-Gastaut syndrome
Term
When is topiramate contraindicated?
Definition
history of kidney stones
Term
What are the drug interactions of topiramate?
Definition
CBZ, phenytoin, phenobarbitaland primidone decrease blood levels
Term
What are the adverse effects of topiramate?
Definition
nervousness and paresthesias, psychomotor slowing, word-finding difficulty, impaired concentration interference with memory, weight loss and anorexia, metabolic acidosis
Term
What are teh MOAs of zonisamide?
Definition
Na+ channel inhibitor, inhibits T-type Ca2+ currents, binds to GABA receptors, facilitates dopaminergic and serotonergic neurotransmission
Term
What types of seizures does zonisamide treat?
Definition
approved for adjunct treatment of partial seizures in adults; appears to have a broad spectrum (myoclonic seizures, infantile spasms, generalized and atpyical absence seizures, lennox-gastaut syndrome)
Term
What are the drug interactions with zonisamide?
Definition
phenytoin and carbamazepine decrease its half-life by half
Term
What are the adverse effects of zomisamide?
Definition
weight loss, abnormal thinking, nervousness, agitation/irritability, usually well tolerated
Term
When is lidocaine used to treat epilepsy?
Definition
only when other drugs are refractory for status epilepticus
Term
Name the barbiturate drugs?
Definition
phenobarbital and primidone
Term
What is the mechanism of action of barbiturates?
Definition
increases the duration of GABA(A) activated Cl-channel opening
Term
What are the indications for phenobarbital?
Definition
second choice for partial and generalized tonic clonic seizures, status epilepticus
Term
What age group is best for phenobarbital?
Definition
rapid absorption has made it a common choice for seizures in infants, but adverse cognitive effects cause it to be used less in older children and adults
Term
What are the contraindications of phenobarbital?
Definition
absence seizures
Term
What are the indications of primidone?
Definition
adjuvant or monotherapy for partial and generalized tonic-clonic seizures; may control refractory generalized tonic-clonic seizures
Term
What are the contraindications of primidone?
Definition
history of porphyria
Term
What are the drug interactions with barbiturates?
Definition
synergy with other CNS depressants, increased metabolism of vitamin D and K; phenytoin increases the conversion of primidone to phenobarbital
Term
What are the adverse effects of barbiturates?
Definition
agitation and confusion in the elderly, worsening of pre=existing hyperactivity and aggressiveness in children, sexual side effects, physical dependence
Term
What is the mechanism of action of benzodiazepines?
Definition
increases the frequency of GABA(A)-activated Cl- channel opening
Term
Name the different benzodiazepine drugs.
Definition
clorazepate, clonazepam, diazepam, lorazepam
Term
Which benzodiazepines are approved for long term treatment?
Definition
clorazepate, clonazepam
Term
What is clorazepate used for?
Definition
incombination for partial seizures
Term
What is clonazepam used for?
Definition
lennox-gastaut syndrome, myoclonic, atonic, and absence seizures
Term
Although clonazepam can be used for long term treatment, it may not be because...
Definition
tolerance develops after about 6 months
Term
Which benzodiazepines can be used in the treatment of status epilepticus?
Definition
diazepam and lorazepam; diazepam is painful to inject however so lorazepam is more commonly used in acute treatment
Term
What is Diazepam used for?
Definition
intermittent use for control of seizure clusters
Term
Diazepam is frequently combined with what other drug?
Definition
phenytoin
Term
What are the contraindications of diazepam?
Definition
children under 9; also narrow angle glaucoma
Term
What are hte contraindications of benzodiazepines?
Definition
narrow angle glaucoma
Term
What are the adverse effects of benzodiazepines?
Definition
hypotonia, dysarthria, muscle in-coordination (clonazepam), behavioral disturbances (especially in children)= aggression, hyperactivity, irritability, and difficulty concentrating
Term
What is the MOA of tiagabine?
Definition
inhibition of GABA (GAT-1) --> reduces reuptake of GABA by neurons and glial cells
Term
When is tiagabine indicated?
Definition
approved in 1998 as an adjunct therapy for partial seizures in patients at least 12 years old
Term
What are the contraindications of tiagabine?
Definition
absence seizures
Term
name some drug interactions with tiagabine.
Definition
blood levels decreased by CBZ, phenytoin, phenobarbital and primidone
Term
What are the adverse effects of tiagabine?
Definition
asthenia and abdominal pain
Term
Name the seizures medications whose main mechanism of action is blocking calcium channels.
Definition
ethosuximide; gabapentin; pregabalin; levetiracetam
Term
What is the MOA of ethosuximide?
Definition
reduces low threshold Ca2+ currents (T currents) in the thalamic neurons
Term
What is the half-life of ethosuximide?
Definition
60 hrs in adults; 30 hours in children
Term
What are the indications of ethosuximide?
Definition
first line for absence seizures
Term
What are the contradications of ethosuximide?
Definition
may exacerbate partial and tonic-clonic seizures
Term
What are the adverse effects of ethosuximide?
Definition
psychotic behavior, blood dyscrasias, persistent headaches, anorexia, hiccups, lupus-like syndrome
Term
What are the toxicities of ethosuximide?
Definition
parkinson-like symptoms, photophobia
Term
What is the MOA of gabapentin?
Definition
originally designed to be a centrally acting GABA agonist; selective inhibition of v-g Ca2+ channels containing the alpha 2 delta 1 subunit
Term
What are the indications for using gabapentin?
Definition
adjunct therapy in adults and children with partial and secondarily generalized seizures; also effective as monotherapy
Term
What are the contraindications of gabapentin?
Definition
can exacerbate myoclonic and absence seizures
Term
What are the adverse effects of gabapentin?
Definition
weight gain with ankle edema, irritability, behavioral problems in children, has been associated with movement disorders
Term
What is the MOA of pregabalin?
Definition
selective inhibition of voltage gated calcium channels containing the alpha 2 delta 1 subunit
Term
What are the indications for pregabalin?
Definition
approved in 2005; adjunct therapy for partial and secondarily generalized seizures
Term
What are the contraindications of pregabalin?
Definition
no effect on absence, myoclonic or primary generalized tonic-clonic seizures
Term
Besides seizures, what else can pregabalin be used to treat?
Definition
neuropathic pain and fibromyalgia
Term
What is the MOA of Levetiracetam?
Definition
not exactly known; binding affinity to synaptic vesicle protein 2A correltes with its anticonvulsant activity; also blocks calcium channel N-currents, increases intracellular Ca2+ levels, modulates GABA channel currents
Term
What are the indications for levetiracetam?
Definition
approved in 1999 as an adjunct therapy for adults with partial seizures; some patients have success with monotherapy
Term
What are the contraindications of levetiracetam?
Definition
renal dysfunction
Term
What are the adverse effects of levetiracetam?
Definition
asthenia, infection, behavioral problems in children
Term
What are the uses of magnesium chloride?
Definition
used for magnesium deficiency and seizures
Term
What are teh uses of paradldehyde?
Definition
alcohol withdrawal seizures
Term
Name the seizures medications that have unknown mechanisms of action?
Definition
magnesium chloride; paraldehyde
Term
Name the DOCs for primary generalized tonic-clonic seizures?
Definition
phenytoin, carbamazepine, oxcarbazepine, valproate
Term
What the alternative drugs for primary generalized tonic-clonic seizures?
Definition
lamotrigine, topiramate, zonisamide, levetiracetam, primidone, phenobarbital, diazepam
Term
What are the drugs of choice for partial and secondarily generalized seizures?
Definition
phenytoin, carbamazepine, oxcarbazepine, valproate
Term
what are the alternative drugs for partial/secondarily generalized seizures?
Definition
lamotrigine, topiramate, zonisamide, levetiracetam, primidone, phenobarbital, gabapentin, pregabalin, tiagabine
Term
What are the drugs of choice for absence seizures?
Definition
ethosuximide, valproate
Term
What are the alternative treatments for absence seizures?
Definition
clonazepam, zonisamide
Term
What is the drug of choice for atypical absence/myoclonic and atonic seizures?
Definition
valproate
Term
What are the alternative drugs for atypical absence/myoclonic/atonic seizures?
Definition
clonazepam, topiramate, zonisamide, levetiracetam
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