Antiepileptic Drugs AEDs

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Antiepileptic Drugs(AEDs)

• NUR 125
• Mendocino College Nursing Program
• Melissa Hladek NP, MS, RN
• October 2, 2007

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What are seizures?

• Episodes of abnormal electrical activity in the
  brain causing involuntary movement, sensations or
  thoughts
• Recurrent seizures without any proximal cause are
  seen in patients with epilepsy
• Accompanied by characteristic changes in the
  electroencephalogram (EEG)

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Neurobiology of Seizures

• Seizures are caused by synchronous neuronal
  discharges within a seizure focus
• Once initiated, the abnormal discharges may
  spread
• The mechanism(s) that initiates a seizure is
  unknown but may be mediated by excessive
  glutamatergic neurotransmission

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Causes of Seizures

• head trauma,
• stroke,
• fever,
• alcohol withdrawal
• or others

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Types of Seizures

• There are two categories of seizures
• 1. Partial (focal) seizures
• -simple
• -complex
• 2. Generalized seizures
• -tonic-clonic
• -myoclonic
• -absence
• -atonic

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EEG monitoring
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Special Epileptic Syndromes

• Status epilepticus
• Medical emergency
• Seizure repeated continuously
• Tonic clonic hypoxia could develop if muscle
  contraction is lengthened. Also hypoglycemia,
  acidosis, hypothermia, brain damage, death
• IV administration of antiepileptics
• Maintain airway patency
• Febrile seizures
• Tonic-clonic motor activity X 1-2 min
• During illness
• Children 3 mos- 5 yrs
• Prevention!

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General Pharmacological Considerations

• Choice of drug depends on
• type of seizure
• Medical history
• Diagnostic studies
• Start at low dosage
• Gradually increase until seizure control or side
  effect threshold
• Second medication?
• Start low and gradually decrease first medication
• Never abruptly stop medications
• Can precipitate a seizure

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Mechanism of Action of all AEDs

• Basic principal
• control electrolytes and neurotransmitters across
  neuronal membrane
• Goal
• suppress neuronal activity just enough to prevent
  abnormal or repetitive firing
• Mechanisms of action
• Sodium channel blockade
• Calcium channel blockade
• Glutamate antagonism
• GABA potentiation
• Carbonic anhydrase inhibition

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Synapse
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Where Do They Work?
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GABA

• Gamma-aminobutyric acid (GABA)
• Primary inhibitory neurotransmitter
• Associated with an influx of chloride ion
• Influx of chloride ion SUPPRESSES neuronal
  activity
• Results in CNS depression

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Drug Classes that potentiate GABA

• Barbituates
• Benzodiazepines
• Misc agents

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Barbituates

• Low margin of safety
• Respiratory depression, sedation
• Habit forming
• Caution with hepatic or renal dysfunction
• Contraindicated with pregnancy (Cat. D) breast
  feeding
• ? effectiveness of OCPs
• No alcohol
• Cause accelerated metabolism depletion Vit. D
  Vit. K

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Barbituates -barbital

• Phenobarbital (Luminal)
• Indicated for seizures, status epilepticus
• PO, IV, IM
• Less side effects than other in class
• Amobarbital (Amytal)
• Intermediate acting
• Given IM/IV to terminate status epilepticus

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Benzodiazepines

• Intensify effect of GABA in the brain by binding
  to GABA receptor site
• Tolerance develops after few months, dosage must
  be adjusted
• Used as
• adjuncts for short term seizure control
• Considerations
• Pregnancy cat D ?effectiveness of OCPs
• Contraindicated Narrow-angle glaucoma
• Caution Liver/kidney impairment, EtOH, tobacco,
  driving, digoxin (potentiates action raising dig
  levels)

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Benzodiazepines -zepams

• Diazepam (Valium) IM/IV
• Terminate status epilepticus
• Clonazepam (Klonopin) PO
• Lorazepam (Ativan) IV
• Terminate status epilepticus
• Clorazepate (Tranxene) PO
• IV
• Hypotension, tachycardia, arrhythmia, muscular
  weakness, BP, HR
• Do not give mix with other drugs or IV fluid
  additives

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Drugs that potentiate GABAMisc Agents

• Gabapentin (Neurontin)
• similar structural relationship to GABA
• does not act on the GABA receptor
• may alter GABA metabolism or alter reuptake by
  presynaptic GABA transporters
• Topiramate (Topamax)
• blocks voltage-sensitive NA channels
• augments GABA activation of GABAA receptor
• blocks kainate and AMPA glutamate receptors

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Drugs that potentiate GABAMisc Agents

• Primidone (Mysoline)
• Tiagabine (Gabitril)

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Ion Channel Blockers

• At rest, neurons surrounded by ? extracellular
  concentrations of
• Sodium
• Calcium
• Chloride ion
• (K is higher inside the cell)
• Influx of sodium or calcium ENHANCES neuronal
  activity
• Influx of chloride ion SUPPRESSES activity (GABA)

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Drugs that Suppress Sodium Influx

• Dampens CNS activity by delaying an influx of
  sodium across neuronal membranes into
  intracellular spaces
• No abuse potential or CNS depression
• Hydantoins
• Phenytoin-like Drugs

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Hydantoins

• Fosphenytoin (Cerebyx) IV
• Phenytoin (Dilantin) PO
• Toxicity
• Dizziness, ataxia, diplopia, lethargy
• Effect Vit. K metabolism blood dyscrasias,
  bleeding
• May increase serum glucose
• Caution in hepatic/renal disease
• ? effectiveness of OCPs
• Contraindications heart block

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Phenytoin (Dilantin)

• PO, IV formulations
• Metabolization of drug varies per patient
• Dosages highly patient dependent
• Careful monitoring very narrow therapeutic range
• Often used in Status Epilecticus
• Side Effects
• Known to cause dysrhythmias
• Gingival hyperplasia
• Numerous Interactions
• Pregnancy category D
• Still a good choice!

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Phenytoin-like Drugs

• Carbamazepine (Tegretol) PO
• Drug of choice for tonic-clonic parital
  seizures
• Low side effects
• Felbamate (Felbatol) PO (preg. Cat. C)
• Lamotrigine (Lamictal) PO (preg. Cat. C)
• blocks voltage-sensitive NA channels and has
  another mechanism of action (inhibits the release
  of excitatory amino acids such as glutamate?)
• Valproic acid (Depakote, Depakene) PO, IV
• Zonisamide (Zonegran) PO

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Valproic Acid (Depakote)

• Long term management
• Drug of choice for absence seizures
• Use with clonazepam may induce absence seizure
• Numerous PO formulas interactions
• Considerations
• Caution in liver disease
• GI irritant
• Drowsiness during induction
• Capsules as sprinkle for kids
• Pregnancy category D

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Drugs that Suppress Calcium Influx

• Succinimides
• Suppress seizures by delaying calcium channel
  influx into neurons
• Absence seizures only
• Considerations
• Caution in hepatic/renal impairment
• Preg cat C
• May alter effectiveness of other antiepileptics
• Side Effects drowsiness, dizziness, N/V/D, wt
  loss, abd pain life threatening depression
  with SI, Stevens-Johnson syndrome, blood
  dyscrasias

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Succinimides -ximides

• Ethosuximide (Zarontin) PO
• A drug of choice for absence seizures
• Methsuximide (Celontin) PO
• Phensuximide (Milontin) PO

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Effects of Drugs
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Therapeutic choices

• Seizure type 1st choice alternative or add-on
• Tonic-clonic carbamazepine Benzodiazapine
• phenytoin lamotrigine
• valproic acid topiramate
• Absence ethosuximide Benzodiazapine
• valproic acid lamotrigine
• topiramate
• Partial (simple carbamazepine Benzodiazapine
• or complex) phenytoin lamotrigine
• valproic acid
• phenobarbital

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Antiepileptic Drugs of Choice
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Drugs for Status Epilepticus

• Benzodiazepam (Valium) GABA mediated
• Phenytoin voltage-sensitive Na channels
• Phenobarbital if necessary
• General anesthesia

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Drug Interactions

• Many antiepileptic drugs interact with other
  medications
• Carbamazepine and phenytoin induce cytochrome
  P450 enzymes
• Phenytoin plasma protein bound
• Valproate inhibits the metabolism of
  phenobarbital, phenytoin, carbamazepine and
  ethosuximide

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General Management Principles

• Start therapy with low dose of single drug
• Increase dose to attain serum concentration
• Single drug not effective, substitute or add a
  second
• Discontinue drug use slowly
• Monitor serum levels to ensure adequate dosage
  (toxicity, therapeutic failure or non-compliance)

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Additional Uses of Category

• Carbamazepine
• mania, , bipolar, trigeminal neuralgia (possibly
  behavioral disturbances in dementia)
• Gabapentin
• neuropathic pain (possibly mania)
• Lamotrigine
• (possibly mania, migraine, schizophrenia)
• Phenytoin
• (possibly neuropathic pain, trigeminal neuralgia)
• Valproic acid
• Mania, bipolar, migraine (possibly behavioural
  disturbances in dementia)

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Nursing Considerations

• Monitor symptoms
• Teaching Points/Side Effects
• Serum Drug Levels
• Signs of Toxicity
• Effects on childbearing