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CNS Drugs - Part 3 – Page 1
Mennonite College of Nursing
At
Illinois State University
Pharmacotherapeutics for Advanced Practice Nursing 433
Drugs that Act on the Central Nervous System – Part 3
Drugs for Movement Disorders
Parkinson’s disease (PD) is a chronic, progressive, degenerative disorder affecting the
dopamine-producing neurons in the brain.
Normal balance of acetylcholine and dopamine in the CNS:
ACh______________________________ Dopamine

In Parkinson’s disease, a decrease in dopamine results in an imbalance:
ACh

Dopamine
Drugs therapy in Parkinson’s disease is aimed at correcting the imbalance between ACh
and dopamine. This can be accomplished by either:
1.
increasing the supply of dopamine OR
2.
blocking or lowering ACh levels
2.  ACh______________________________ 1.  Dopamine

Classic Parkinsonian Symptoms
 bradykinesia = slowness of movement
 rigidity = “cogwheel” rigidity, resistance to passive movement
 tremor
o pill-rolling: tremor of the thumb against the forefinger, seen mostly at rest
o is less severe during voluntary activity
o usually starts on one side, then progresses to the other
o is the presenting sign in 70% of the cases
 postural instability = danger of falling, hesitation in gait as patient starts or stops
walking
CNS Drugs - Part 3 – Page 2
Antiparkinsonian Agents
Drug Category
Neuroprotective agents
Dopaminergic agents
Agents
Selegiline (Eldepryl)
Levodopa
Leodopa-carbidopa (Sinemet) replacement
Amantadine (Symmetrel) – indirect acting
Bromocriptine (Parlodel) – direct acting
Pramipexole (Mirapex) – direct acting
Ropinirole (Requip) – direct acting
Anticholinergic agents
Benztropine (Cogentin)
Trihexyphenidyl (Artane)
Neuroprotective Therapy
 treatment to slow the progression of PD
 50-60% of patients show (+) response
 Selegiline – a very potent, irreversible MAO-B inhibitor derived from
amphetamine
o As an MAO – B inhibitor, selegiline does not elicit the classic “cheese”
effect at doses of < /= 10 mg/day
o Used in conjunction with levodopa therapy in treatment of PD
o Take in AM (mild amphetamine effect can  sleeplessness otherwise)
Dopaminergic Agents
 Because in PD little or no dopamine is produced, ACh is left as the predominant
neurotransmitter.
 Dopaminergic agents are used to help replace the lost dopamine or enhance the
function of the few neurons that are left to produce their own.
 Levodopa and carbidopa
o Directly replace dopamine
o Levodopa can pass through blood-brain barrier to get to site of action in
the brain; dopamine cannot
o Carbidopa does not cross blood-brain barrier; prevents levodopa
breakdown in periphery
o Can cause palpitations, orthostatic hypotension, agitation, anxiety,
psychotic and suicidal episodes, involuntary movements, headache and
blurred vision, hemolytic anemia, agranulocytosis
o Often started at a low dose because of the increased sensitivity of the aged
patient to these meds.
CNS Drugs - Part 3 – Page 3



Amantadine
o Indirect acting: causes release of dopamine from storage sites in nerve
ending and prevents reuptake
o Can cause impaired concentration, dizziness, increased irritability,
nervousness, blurred vision, anorexia, N&V, constipation, dryness of
mouth/nose/throat, increased weakness, purple-red skin spots
Bromocriptine, pramipexole (Mirapex), ropinirole (Requip)
o Direct acting: directly stimulate dopamine receptors (dopamine receptor
agonist)
o Can cause hypotension, drowsiness, headaches, depression, confusion,
hallucinations, uncontrolled movements, nausea, diarrhea/constipation,
abdominal cramps, anorexia
Dopaminergic drug interactions
o Hydantoins  increase levadopa metabolism   levadopa effects
o Haloperidol or phenothiazines  block dopamine receptors in brain 
 levadopa effects
 MAO inhibitors  inhibit metabolism  hypertensive crisis
 Pyridoxine (vitamin B6)  promotes levodopa breakdown  reversal of
levodopa effects (carbidopa may prevent this)
o Avoid taking vitamin B6 supplements and eating vitamin-fortified
foods
o Take with juice and low-protein snack or after meals to prevent
interactions with pyridoxine in food
Anticholinergic drugs
 Anticholinergics, by blocking ACh effects, are sometimes useful in treatment
of muscle tremors and muscle rigidity associated with PD
 Drug interactions
o Alcohol, CNS depressants, amantadine and antihistamines,
phenothiazines, tricyclic antidepressants, and antacids all cause an
additive effect, resulting in enhanced CNS depressant effects and
reduced absorption/decreased therapeutic effect of anticholinergic
 Adverse effects
o CNS: drowsiness, confusion, disorientation, hallucinations
o GI: constipation, N, V
o GU: urinary retention, pain on urination
o Other: blurred vision, dilated pupils (mydriasis), sensitivity to the
sun (photophobia), dry skin, dry mouth/decreased salivation
 Contraindicated in patients with narrow-angle glaucoma or with a history of
urinary retention
 Some aged patients taking anticholinergic agents experience paradoxical
reactions, such as excitement, confusion, or irritability.
CNS Drugs - Part 3 – Page 4
COMT (catelchol-O-methyl transferase) inhibitors
 Levodopa is routinely given with a decarboxylase inhibitors (carbidopa) to inhibit
peripheral conversion to dopamine
 But levodopa is also converted by peripheral COMT to inert metabolites
o Because of this, only about 10% of a levodopa dose actually reaches the
brain
 Adding a COMT inhibitor increases the half-life of levodopa by 50%, allowing
more continuous and stable stimulation of dopamine receptors.
 Examples: entacapone (Comtan), tolcapone (Tasmar)
o Comtan is the preferred COMT inhibitor due to liver toxicity associated
with Tasmar
 Side effects: dyskinesia (due to increased dopamine), N & V, hypotension,
neuropsychiatric problems. (If occur, reduce the dose of levodopa by 15-30%)
o Can also cause diarrhea and discoloration of the urine
CNS Drugs - Part 3 – Page 5
Anticonvulsants/Antiepileptics
Epilepsy
o not a specific disease
o it is a disorder of the brain that is a symptom of a disease
Seizure = brief episode of abnormal electrical activity in the nerve cells of the brain
Convulsion = spasmodic contractions of involuntary muscles
Hydantoins
Barbiturates
Succinimides
Benzodiazepines
Miscellaneous
Chemical Classification of Antiseizure Drugs
Phenytoin (Dilantin)
Phenobarbital (Luminal)
Ethosuxmide (Zarontin)
Diazepam (Valium)
Clonazepam (Klonopin)
Clorazepate (Tranxene)
Lorazepam (Ativan)
Primidone (Mysoline)
Valproic acid (Depakene)
Divalproex (Depakote)
Carbamazepine (Tegretol)
Levetiracetam (Keppra)
Lamotrigine (Lamictal)
Gabapentin (Neurontin)
Topiramate (Topamax)
Felbamate (Felbatol)
Antiepileptic Drugs of Choice: See “Comparison of Antiepileptic Drugs”
Partial Seizures
Simple Complex
First Choice
CBZ
CBZ
PHB
PHB
PHT
PHT
PMD
PMD
VPA
VPA
Second Choice
CNZ
CNZ
CRZ
CRZ
GTC
CBZ
PHB
PHT
PMD
VPA
CZM
CZP
Generalized Seizures
Absence Myoclonic Clonic
Tonic
ESX
PHB
VPA
CNZ
Atonic
VPA
VPA
VPA
VPA
CNZ
CNZ
CBZ
CNZ
PHT
CNZ
CBZ = carbamazepine; CNZ = clonazepam; CRZ = clorazepate;
ESX = ethosuximide; GTC = generalized tonic-clonic; PHB = Phenobarbital; PHT =
phenytoin; PMD = primidone; VPA = valproic acid
CNS Drugs - Part 3 – Page 6
Side Effects:
Watch for CNS effects (drowsiness, etc.), GI (N & V), skin rashes (and StevensJohnson syndrome), bone marrow suppression (especially with carbamazepine and
hydantoins), endocrine abnormalities with valproic acid and felbamate (irregular menses,
secondary amenorrhea, galactorrhea, rare breast enlargement, etc.)
* Angle-closure glaucoma possible with Topamax
Drug Interactions:
Bone marrow depressants with carbamazepine or succinimiades  additive
effects  increased bone marrow toxicity
Carbamazepine alters metabolism of doxycycline, phenytoin, theophylline,
warfarin  significant decrease in their half-lives
Valproic acid + barbiturates  additive effect  increased CNS depression
Hydantoin + disulfiram [Antabuse], isoniazid, valproic acid  inhibit hepatic
enzymes  increased hydantoin levels
Gabapentin (Neurontin) – structurally similar to GABA but does not mimic it or interact
with GABA receptors
Lamotrigine (Lamictal) – inhibits excessive release of excitatory neurotransmitters (has
also been used for trigeminal neuralgia)