Anti-seizure_and_Anti-Parkinson_Drugs PHARMACOLOGY

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
 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.

7. Seizures cont.
 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.

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 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

26. Parkinson’s 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. Parkinson’s 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 Parkinson’s, 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
Parkinson’s 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