Transcript Drugs Treating Seizure Disorders

DRUGS TREATING
SEIZURE
DISORDERS
WHAT IS A SEIZURE?
Joshua’s Epilepsy
https://www.youtube.com/watch?v=TDAOqKXOO24
Hannah’s Seizure
https://www.youtube.com/watch?v=c4t8lyWSH4s
Newborn Seizure
https://www.youtube.com/watch?v=aaxOSfw1UwI
EPILEPSY
Epilepsy is a disorder of electrical activity in the
brain.
Seizures are loss of consciousness with:
• Generalized muscle twitching,
• Mild alterations in consciousness, and/or
• Repetitive blinking.
What are Seizures? Educational Video:
https://www.youtube.com/watch?v=S9SPxikmf9E
PHYSIOLOGY
 Action potentials within neurons are initiated
by an influx of sodium into the cell.
 Then an calcium follows sodium into cells to
create an action potential.
 When the cell fires, there is a flood of
neurotransmitters into the neuronal synapse.
 The neurotransmitter glutamate produces
excitation.
 GABA is a counterbalance to glutamate,
preventing hyper-excitation and producing a
calming effect.
PATHOPHYSIOLOGY
 When a group of neurons exhibits
coordinated, high-frequency discharge, it is
termed a focus.
 The causes of a focus include head trauma,
tumor growth, hypoxia, and inherited birth
defects.
 When the activity from a focus spreads to
other areas of the brain, causing other
neurons to join in the hyperactivity, seizures
result.
EPILEPSY
The three main ways that antiepileptic drugs
work are by:
• Decreasing the rate at which sodium flows into
the cell thus slowing neuronal depolarization.
• Inhibiting calcium flow rate into the cell through
specific channels also slowing neuronal
depolarization.
• Increasing the effect of the inhibitory
neurotransmitter gamma-aminobutyric acid
(GABA) which makes the neurons less reactive
to stimulation.
PATHOPHYSIOLOGY
Seizures may result from either high levels of glutamate
or low levels of GABA.
Partial seizures occur when focus activity is limited to an
area of the brain.
When the focus activity is within both hemispheres,
generalized seizure symptoms occur.
Types of Seizures:
http://www.youtube.com/watch?v=6zXFUIjY5xU
PHARMACOLOGY OF ANTIEPILEPTIC
DRUGS (AEDS)
PHARMACOLOGY OF ANTIEPILEPTICS
Various antiepileptic drugs work on
different stages in the action potential of
the neuron
• Sodium influx
• Calcium influx
• Reducing Glutamate excitation effects
• Improving GABA inhibitory effects
PROTOTYPE: VALPROIC ACID
(DEPAKOTE, DEPAKOTE ER)
Pharmacodynamics:
Blockade of sodium channels and increased
brain levels of gamma-aminobutyric acid (GABA)
Pharmacotherapeutics:
Complex partial seizures
Absence seizures
Migraine headache prevention
Mania associated with Bipolar disorder
VALPROIC ACID (DEPAKOTE,
DEPAKOTE ER)
Side Effects: Sedation and hunger, Nausea
Adverse Effects:
Nausea, somnolence, dizziness, vomiting,
asthenia, abdominal pain, dyspepsia, rash,
diarrhea, increased appetite, tremor, weight
gain
Black Box Warnings:
• Hepato-toxicity
• Pancreatitis
• Fetal risk for neural tube defects
VALPROIC ACID (DEPAKOTE,
DEPAKOTE ER)
Maximizing therapeutic effects
• Monitor drug levels at the start of therapy
and when changing dosage.
Minimizing adverse effects
• Assess CBC and LFT.
• Serum amylase if pancreatitis is suspected.
• Taper dose gradually if need to discontinue
the drug.
PHENYTOIN (DILANTIN): CORE DRUG
KNOWLEDGE
Pharmacotherapeutics
• One of the earliest antiepileptic drugs
• Used to control partial and generalized seizures
Pharmacokinetics
• Peak 1.5 to 3 hours. At low doses, the half-life is less than
at the therapeutic dose. Highly protein bound.
Pharmacodynamics
• Reversibly binds to sodium channels while they are in the
inactive state
PHENYTOIN: CORE DRUG
KNOWLEDGE (CONT.)
Contraindications and precautions
• Bradycardia and heart block
Adverse effects
• Nystagmus, ataxia, dysarthria, slurred speech,
mental confusion, tremor, and gingival hyperplasia
Drug interactions
• Numerous drugs interact with phenytoin
GINGIVAL HYPERPLASIA
PHENYTOIN: PLANNING AND
INTERVENTIONS
Maximizing therapeutic effects
• Monitor blood levels of the drug.
• Titrate the dose upward gradually.
Minimizing adverse effects
• Monitor blood levels—narrow therapeutic range.
• Administer IV push phenytoin no faster than 50
mg/minute in adults or 1 to 3 mg/kg/minute in
neonates.
• Pregnancy Category D (fetal risk)
LEVETIRACETAM (KEPPRA)
Pharmacotherapeutics:
• Partial seizures
• Pregnancy Category C
Pharmacodynamics:
Inhibits presynaptic calcium channels reducing
neurotransmitter release and acting as a
neuromodulator
LEVETIRACETAM (KEPPRA)
Common side effects
• Somnolence and Fatigue
• Weakness and dizziness
Serious adverse events
• Psychiatric reactions
• Suicidal Behavior And Ideation
• Dermatologic Reactions
• Hematologic Abnormalities
CARBAMAZEPINE (TEGRETOL)
Pharmacodynamics:
Stabilizes the inactivated state of sodium
channels, making fewer of these channels
available to subsequently open and potentiate
GABA receptors.
Pharmacotherapeutics:
• Partial seizures
• Generalized tonic-clonic seizures
• Mania associated with Bipolar disorder
• Trigeminal neuralgia
CARBAMAZEPINE (TEGRETOL)
Common adverse effects:
• Drowsiness, dizziness, headaches, nausea,
vomiting and/or constipation (generally well
tolerated)
Serious adverse events:
• Loss of blood cells or platelets. In rare cases can
cause aplastic anemia or agranulocytosis (white
blood cell loss).
• In rare cases, the loss of platelets may become
life-threatening.
Pregnancy Category D: Fetal malformation risk
CARBAMAZEPINE (TEGRETOL)
Maximizing therapeutic effects
• Monitor drug levels at the start of therapy and
when changing dosage.
Minimizing adverse effects
• Assess CBC in particular WBC
• Get STAT labs if patient develops signs of
infection, URI
• Taper dose gradually if need to discontinue the
drug.
TOPIRAMATE (TOPAMAX)
Pharmacodynamics
Topiramate is a sulfamate-substituted
monosaccharide, related to fructose, an unusual
chemical structure for an anticonvulsant.
Blockage of voltage-dependent sodium channels,
an augmentation of gamma-aminobutyric acid
activity
Indications
• Epilepsy
• Migraine headache prevention (off label)
• Weight loss (off label)
TOPIRAMATE (TOPAMAX)
Common Side Effects
• Dizziness, Weight loss, Paraesthesia,
Somnolence, Nausea, Diarrhea, Fatigue
• Cognitive clouding “stupa-max”
• No laboratory monitoring needed
Serious Adverse Events
• Rare
Pregnancy Category D (risk for cleft palate)
LAMOTRIGINE (LAMICTAL)
Pharmacodynamics
Acts presynaptically on voltage-gated
sodium channels to decrease glutamate
release
Indications
• Epilepsy
• Maintenance stage of treating Bipolar
disorder
LAMOTRIGINE (LAMICTAL)
Common adverse effects
• Dizziness and lack of coordination, drowsiness,
insomnia, anxiety
• Pregnancy Category C
Serious adverse events
Black Box Warning:
• Stevens-Johnson Syndrome in 1:1000 patients
• Toxic epidermal necrolysis
• Watch for rash, fever, and fatigue preceding
necrolysis of skin
STEVENS-JOHNSON SYNDROME
GABAPENTIN (NEURONTIN)
Pharmacodynamics
Interacts with voltage-sensitive calcium
channels in cortical neurons
Indications
• Focal and partial seizures
• Post-herpetic (herpes) neuralgia e.g.
Shingles
• Neuropathic pain (off-label)
GABAPENTIN (NEURONTIN)
Common side effects
• Dizziness, fatigue, weight gain, drowsiness,
and peripheral edema (elderly)
• Pregnancy Category C
Serious adverse events
• Very minimal
• Patients who overdosed manifested
drowsiness, blurred vision, slurred speech
and somnolence or coma
CONGRATULATIONS!
You have completed the lecture
component of B261 !!
Your Final Exam will now be opened in
Canvas. This 50 point, open-book
examination (Due on 5/4 at 9:00 am) will be
over the four areas of Intracranial Regulation
just reviewed:
• Mood, Depression and Bipolar
• Anxiety and Sleep
• Dementia, Delirium and Psychosis
• Seizures