Anti-seizure and Anti-Parkinson Drugs

1
Anti-seizure and Anti-Parkinson Drugs

• Nur 3704
• By Linda Self

2
Seizure Disorders

• 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

3
Seizures

• May be caused by hypoglycemia, fever, electrolyte
  imbalances, overdoses of drugs, withdrawal of
  alcohol or sedative-hypnotic drugs or as a result
  of epilepsy

4
Epilepsy

• 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

5
Epilepsy

• 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

6
Different Kinds of Seizures

• Partialbegin in a specific area of the brain.
  Movements may be automatic, repetitive or
  aversive. Behavior may be bizarre.
• Generalizedbilateral 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.

7
Seizures cont.

• Absenceabrupt alterations in consciousness that
  last only seconds
• Status Epilepticuslife-threatening, generalized
  tonic-clonic convulsions lasting for several
  minutes or at close intervals. Hypotension,
  hypoxia and cardiac dysrhythmias may occur.

8
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

9
Indications

• 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

10
Contraindications/Precautions

• 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

11
Antiseizure Drugs

• 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.

12
Dilantin (phenytoin)

• 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

13
Cerebyx (fosphenytoin)

• 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.

14
Tegretol (carbamazepine)

• 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.

15
Valium (diazepam)

• 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)

16
Phenobarbital

• 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

17
Neurontin (gabapentin)

• 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

18
Other AEDs

• 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)

19
Other AEDs

• 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.

20
Keppra (levetiracetam)

• 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

21
General considerations in AEDs

• 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

22
General considerations cont.

• 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

23
General considerations cont.

• 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

24
Monitoring AED therapy

• 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

25
Monitoring AED therapy

• Poor control of seizureslook 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

26
Parkinsons Disease

• Is a chronic, progressive, degenerative disorder
  of the CNS
• Results from destruction or degenerative changes
  in dopamine-producing nerve cells in the
  substantia nigra
• Cause is unclear
• Occurs equally in men and women between 50-80
  years

27
Parkinsons Disease

• Early onset parkinsonism is felt to have genetic
  component (in those less than 45yo)
• Phenothiazines can cause drug-induced
  parkinsonism
• Is characterized by tremors, bradykinesia, joint
  and muscular rigidity

28
Neurotransmitter Imbalance

• Basal ganglia normally contains balance of
  dopamine and acetylcholine
• Balance necessary to regulate posture, muscle
  tone and voluntary movement
• In Parkinsons, lack inhibitory dopamine and thus
  an increase in excitatory acetylcholine

29
Anti-Parkinson drugs

• Drugs used in tx increased levels of dopamine or
  to inhibit the actions of acetylcholine in the
  brain

30
Dopaminergic Drugs

• Levodopa is mainstay of drug therapy for
  idiopathic parkinsonism
• Serves as the prototype
• Increases dopamine concentrations in the brain
• Dopamine cannot penetrate blood-brain barrier but
  levodopa can. Is then converted to dopamine by
  enzyme AADC.

31
Levodopa

• 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.

32
Levidopa/Carbidopa

• 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 Parkinsons as
  body develops tolerance and loses effectiveness
  over time.

33
Anticholinergics

• 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)

34
Others

• 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

35
Parlodel and Permax

• 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

36
Mirapex (pramipexole) and Requip (ropinirole)

• Are newer dopamine receptor stimulants
• Approved for both beginning and advanced stages
• Renal insufficiency affects excretion of Mirapex

37
Eldepryl (selegiline)

• 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

38
Drug Selection

• 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

39
Drug Selection cont.

• 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

40
Drug Selection cont.

• Reserve levodopam/carbidopam as eventually loses
  its efficacy

41
Drug Dosage

• 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