Transcript Anti-seizure and Anti-Parkinson Drugs

Anti-seizure and AntiParkinson Drugs
Seizure Disorders
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Seizures involve a brief episode of
abnormal electrical activity in nerve
cells of the brain that may be
accompanied by changes in
behavior or appearance
Convulsion is a tonic-clonic type of
seizure characterized by spasmodic
contractions of muscles
Seizures
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May be caused by hypoglycemia,
fever, electrolyte imbalances,
overdoses of drugs, withdrawal of
alcohol or sedative-hypnotic drugs
or as a result of epilepsy
Epilepsy
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Seizures occur in a chronic,
recurrent pattern
Abnormal and excessive electrical
discharges in a group of nerve cells
affecting brain function
Abnormality in neuronal plasma
membranes results in increased
permeability and responsiveness to
stimuli
Epilepsy
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Involves neuron fire with escalating
frequency and amplitude, reaches
threshold and spreads to adjacent normal
neurons
Diagnosed by clinical signs and symptoms
of seizure activity and by abnormal brain
wave patterns on the EEG
Cause is idiopathic in 60-80% of children
Different Kinds of Seizures
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Partial—begin in a specific area of the
brain. Movements may be automatic,
repetitive or aversive. Behavior may be
bizarre.
Generalized—bilateral and symmetric and
w/o discernible point of origin in the
brain. Tonic-clonic. Tonic phase is
sustained skeletal contraction, clonic
phase is rapid and rhythmic jerking
movements.
Seizures cont.
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Absence—abrupt alterations in
consciousness that last only
seconds
Status Epilepticus—life-threatening,
generalized tonic-clonic convulsions
lasting for several minutes or at
close intervals. Hypotension,
hypoxia and cardiac dysrhythmias
may occur.
Antiepileptic Drugs (AEDs)
Mechanisms of action
 Suppress seizures by decreasing
movement of ions into nerve cells,
altering the activity of neurotransmitters
(GABA and glutamate) or both.
 Actions of drugs may increase GABA
(inhibitory), decrease glutamate
(excitatory) or affect Na+ and Ca++ ions
thus decreasing responsiveness
Indications
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Maintenance treatment of epilepsy
Stop tonic-clonic seizures
Status epilepticus
Treatment of choice for status
epilepticus is Ativan then
maintenance on Dilantin or Cerebyx
AEDs also useful in bipolar disorder
and for neuropathic pain
Contraindications/Precautions
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Caution if renal or hepatic
impairment
Caution if CNS depression
History of hypersensitivity
Dilantin in patients with bradycardia
or heart block
Tegretol with bone marrow
depression
Antiseizure Drugs
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Dilantin is the prototype. Often
initial drug of choice. Careful in
switching from generic to trade
name as bioavailability may vary
(can lead to toxicity).
Monitor drug levels.
May gibe IV or orally
Pregnancy Cat. D.
Dilantin (phenytoin)
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Adverse effects include:
hypotension, bradycardia, cardiac
dysrhythmias, thrombophlebitis,
gingival hyperplasia, folic
deficiency.
Extremely irritating to veins.
Dilute, use only saline
Give no faster than 50mg/minute
Cerebyx (fosphenytoin)
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Formulation that is hydrolyzed to
dilantin. Approved for status
epilepticus and for those who
cannot take oral preparation. Less
tissue irritation than phenytoin, can
be diluted w/dextrose and can be
given more quickly than phenytoin.
Tegretol (carbamazepine)
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For partial, generalized tonic-clonic
and mixed seizures. Also useful in
treating trigeminal neuralgia and
bipolar disorder. Contraindicated in
bone marrow depression and in
patients on MAOIs. MAOIs must be
discontinued at least 14 days before
starting Tegretol. Preg. Cat. D.
Valium (diazepam)
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Indicated for acute convulsive
seizures and for status epilepticus.
Pregnancy Cat. D.
Given in repeat doses then followed
by long-acing anticonvulsant such
as phenytoin (Dilantin)
Phenobarbital
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Long acting barbiturate that is used
alone or with another AED
Causes sedation and cognitive
impairment
Long half-life taking 2-3 weeks to
reach therapeutic levels
Preg. Cat. D
Neurontin (gabapentin)
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Treatment of partial seizures, often
with other AEDs
Eliminated by kidneys
Adverse effects: dizziness,
drowsiness, fatigue, loss of muscle
coordination, tremors, nausea,
vomiting, gingivitis, pruritus
Preg. Cat. C
Other AEDs
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Zarontin (ethosuximide)—choice for
absence seizures
Lamictal (lamotrigine) used w/other
AEDs for treatment of partial
seizures. Adverse effects: skin
rashes to Stevens-Johnson
syndrome, visual changes, ataxia,
drowsiness. Caution w/co-admin. of
Depakote (valproic acid)
Other AEDs
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Topamax (topiramate)—broad
spectrum of activity. Excreted by
kidneys. Must decrease dosage if
renally impaired. Most common side
effects include: ataxia, drowsiness,
dizziness, nausea and renal stones.
Keppra (levetiracetam)
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Newer drug for tx of partial seizures
Mechanism of action is unknown
Inhibits abnormal firing w/o affecting
normal neuronal excitability
Not metabolized by liver
Low potential for drug interactions
Adverse effects: decreases in RBCs and
WBCs, lability, paresthesias, pharyngitis
General considerations in AEDs
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Take regularly to maintain serum
levels
Do not stop taking abruptly
Do not drive a car, operate
machinery which requires alertness
Ensure provider is aware of other
meds taken due to many
interactions
General considerations cont.
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Caution during pregnancy or
breastfeeding
No switching generic phenytoin to
Dilantin due to differences in
formulation
May need to take folic acid, calcium,
vitamin D or vitamin K if on Dilantin
General considerations cont.
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Meticulous oral care
If diabetic, closer monitoring of
blood sugars
Report unexplained bleeding, joint
pains, rashes, fevers, sore throat,
petechiae
Lamictal may cause photosensitivity
or serious skin rashes
Monitoring AED therapy
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Based on client response
Periodic measurements of serum
drug levels necessary
Baseline blood studies to include:
CBC, platelet ct., LFTs, renal
function tests then repeat on
periodic basis
Monitoring AED therapy
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Poor control of seizures—look at
compliance, incorrect diagnosis of
type of seizure, use of wrong drug
for type of seizure, inadequate drug
dosage, drug interactions
(theophylline), use of alcohol or
electrolyte imbalances
Parkinson’s Disease
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Is a chronic, progressive,
degenerative disorder of the CNS
Results from destruction or
degenerative changes in dopamineproducing nerve cells in the
substantia nigra
Cause is unclear
Occurs equally in men and women
between 50-80 years
Parkinson’s Disease
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Early onset parkinsonism is felt to
have genetic component (in those
less than 45yo)
Phenothiazines can cause druginduced parkinsonism
Is characterized by tremors,
bradykinesia, joint and muscular
rigidity
Neurotransmitter Imbalance
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Basal ganglia normally contains
balance of dopamine and
acetylcholine
Balance necessary to regulate
posture, muscle tone and voluntary
movement
In Parkinson’s, lack inhibitory
dopamine and thus an increase in
excitatory acetylcholine
Anti-Parkinson drugs
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Drugs used in tx increased levels of
dopamine or to inhibit the actions of
acetylcholine in the brain
Dopaminergic Drugs
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Levodopa is mainstay of drug
therapy for idiopathic parkinsonism
Serves as the prototype
Increases dopamine concentrations
in the brain
Dopamine cannot penetrate bloodbrain barrier but levodopa can. Is
then converted to dopamine by
enzyme AADC.
Levodopa
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Once converted to dopamine, then is
stored in presynaptic dopaminergic
neurons. With advanced disease, fewer
neurons allow for less storage capacity.
Thus, it has a shorter duration of action.
Large amounts of Levodopa required as it
undergoes extensive peripheral
metabolism leaving less for use in the
brain.
Levidopa/Carbidopa
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Peripheral metabolism is reduced leaving
more available for brain use when
carbidopa is added to levodopa. Adding
carbidopa “ties up” decarboxylase and
enzyme COMT. This then allows greater
utilization by the brain
Levodopa reserved for later tx of
Parkinson’s as body develops tolerance
and loses effectiveness over time.
Anticholinergics
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Centrally active agents are used
Atropine and scopolamine not used
due to side effects
Anticholinergics decrease the effects
of acetylcholine which decreases the
excess of acetylcholine to dopamine
Examples: Cogentin (benztropine)
and Benadryl (diphenhydramine)
Others
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Symmetrel (amantadine)-an
antiviral that also increases release
and inhibits the reuptake of
dopamine in the brain
Used initially, loses efficacy quickly
w/continuous usage (6-8 weeks)
Often used w/levodopa
More effective than anticholinergics
buts less so than levodopa
Parlodel and Permax
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Parlodel (bromocriptine) and
Permax (pergolide)—ergot
derivatives that directly stimulate
dopamine receptors in the brain
Used with levodopa/carbidopa to
prolong the effectiveness
Caution in CAD, can cause
pulmonary fibrosis
Mirapex (pramipexole) and Requip
(ropinirole)
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Are newer dopamine receptor
stimulants
Approved for both beginning and
advanced stages
Renal insufficiency affects excretion
of Mirapex
Eldepryl (selegiline)
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Increases dopamine in the brain by
inhibiting metabolism by MAO-B (MAO-A
acts more specifically on tyramine,
norepinephrine, epinephrine, and
serotonin which can result in severe
hypertension and stroke)
At oral doses of 10mg/day or less,
Eldepryl is selective for MAO-B, higher
doses will result in stimulation of both
MAO receptors
Drug Selection
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For drug induced parkinsonism or
EPS, an anticholinergic is drug of
choice
Early parkinsonism, anticholinergic
may be initial agent in younger than
60 years
Symmetrel useful in bradykinesia or
tremors
Drug Selection cont.
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Dopamine agonist improves
bradykinesia, rigidity, impaired
dexterity, speech, gait and tremor
In advanced disease-anticholinergic
plus levodopa/carbidopa or
Symmetrel in combination or
Dopamine agonist in combination
Drug Selection cont.
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Reserve levodopam/carbidopam as
eventually loses its efficacy
Drug Dosage
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Doses are adjusted as disease progresses
Levodopa/carbidopa must be
individualized
Will gradually have to increase the
levodopa to achieve therapeutic levels
When adding a dopaminergic, will need to
reduce dosage of levodopa/carbidopa