Drugs for Degenerative Diseases of the Nervous System (NURS 3220)

What is the most common degenerative disease

Parkinson Disease

What causes Parkinson Disease

Progressive loss of dopamine

• Degeneration and destruction of dopamine-producing neurons (within the substantia nigra portion of the brain)

• Corpus striatum also affected (normally controls unconscious muscle movement)

  • Disruption in the balance between acetylcholine and dopamine (less dopamine more AcH)

What are the symptoms of PD 

• Tremors and pill rolling 

• Muscle rigidity 

• Postural instability 

• Affective flattening 

Bradykinesia 

Slowness of movement 

Tremors and pill rolling

Involuntary movement of fingers and hands (looks like you’re rolling a pill)

Muscle rigidity 

Increased muscle tone, stiffness, and resistance to movement

Postural instability

Difficulty balancing (increase risk of falling)

Other health issues associated with PD

• Anxiety

• Depression

• Sleep disturbances

• Dementia

• Autonomic nervous system disturbances (difficulty urinating)

Extrapyramidal side effects

Drug-induced movement disorders commonly associated with antipsychotic medications (should be avoided for someone with PD)

These medications block dopamine receptors

Dopaminergic drugs

• Increase dopamine and reduce the amount of acetylcholine

• Help ambulation and appetite

Wearing-off period (PD drugs) 

Symptoms worsen because the concentration of the drug has fallen below therapeutic level (patient experiences tremors and eye twitching)

• Dose needs to be increased/adjusted 

• Dose intervals need to be changes 

• Add a medication 

Dopamine-enhancing drugs

• Restore balance of dopamine and acetylcholine

• Levodopa, Amantadine (Symmetrel), Apomorphine (Apokyn), Bromocriptine (Parlodel)

Mechanism of action of tolcapone (Tasmar) 

inhibits enzymes the breakdown dopamine (dopamine-enhancing drug) 

Mechanism of ropinirole (Requip)

Activate dopamine receptors (dopamine agonists) (dopamine-enhancing drug)

Mechanism of amantadine (Symmetrel) 

Cause dopamine release from nerve terminals (dopamine-enhancing drug) 

Catechol-O-Methyl Transferase (COMT) Inhibitors 

• Reduce requirement for levodopa-carbidopa 

• Increase concentration of existing dopamine in nerve terminals; improve motor fluctuations

Staleveo

Entacapone in combination with carbidopa and levodopa

Side effects of COMT inhibitors 

mental confusion, N+V, headache, diarrhea, possible liver damage

Levodopa/Carbidopa/Entacapone (Stalevo)

• Dopamine precursor and COMT inhibitor 

• Parkinson’s disease (bradykinesia, tremor, rigidity) 

• Restores dopamine levels in the brain

How long does it take to see the therapeutic effects of Stalevo 

Several months 

Why is levodopa combined with carbidopa and entacapone in Stalevo

Carbidopa and entacapone prevent the enzymatic breakdown of Levodopa

Nursing considerations for Stalevo

• Do not stop abruptly, monitor for toxicity (muscle twitching, spasmodic winking)

• Avoid high-protein meals

• Assess for psychosis

Why should Stalevo be used with caution with antacids 

• Increased absorption: antacids containing magnesium, calcium, or sodium bicarbonate can increase the absorption of levodopa → raising serum drug levels and creating risk for toxicity 

  • Altered pharmacokinetics: changing gastric pH and gastric emptying, antacids can unpredictably affect how quickly levodopa reaches the bloodstream, which may worsen “on-off” fluctuations → alternating periods of motor functioning 

Key side effects of Stalevo

• Dyskinesia

• N+V

• Orthostatic hypotension

• Psychosis

• Hallucinations

When should you NOT give patient Stalevo

• Narrow-angle glaucoma

• Suspicious pigmented lesions

• History of melanoma

• Acute psychoses/psychoneurosis as a result of taking MAOIs

How to treat overdose of Stalevo 

Gastric lavage, IV fluids, adequate airway maintained

Anticholinergic drugs for PD

• Centrally acting, block acetylcholine (inhibit overactivity in the brain)

• Not as effective as dopaminergics

• Used in early stages of PD

When are anticholinergic drugs most beneficial

When primary symptom in PD is tremor

Prominent autonomic effects of anticholinergic drugs 

Dry mouth, blurred vision, tachycardia, urinary retention, constipation

Examples of anticholinergic drugs to treat PD

Benztropine (Cogentin)

Biperiden (Akineton)

Trihexyphenidyl (Artane)

Benztropine (Cogentin)

• Anti-parkinson drug

• Centrally acting cholinergic receptor

• Blocks excess cholinergic stimulation of neurons in the corpus striatum

• Suppresses tremors but not effective in relieving tardive dyskinesia

Adverse effects of Benztopine (Cogentin)

Sedation, drowsiness, dizziness, restlessness, irritability, nervousness, and insomnia 

When to NOT use Benztropine

Narrow-angle glaucoma, myasthenia gravis, blockage of urinary tract, severe dry mouth, hiatal hernia, severe constipation, enlarged prostate, and liver disease

Treat overdose of Benztropine with ….

Physostigmine

Causes of structural damage in brain (that contributes to dementia) 

• Amyloid plaques 

• Neurofibrillary tangles

Both cause damage to surrounding neurons within hippocampus -memory and learning (loss of function and decrease in number) 

Causes of dementia

• Multiple cerebral infarcts, severe infections, and toxins

Possible causes of AD

• Genetics (chromosome 1, 14, or 21)

• Chronic inflammation, oxidative cellular damage, excess free radicals

• Environmental factors

• Immunologic factors

• Nutritional factors

• Viruses

What is the second most common degenerative disease 

Alzheimer Disease

• Progressive loss of brain function (memory loss, confusion, dementia, cannot communicate/think effectively, change in behavior)

• Probability to affect 50% of population over 85 

Symptoms of AD

• Impaired memory and judgment

• Confusion and disorientation

• Inability to recognize family and friends

• Aggressive behavior

• Depression

• Psychoses (paranoia and delusions)

• Anxiety

What is used to manage agitation associated with AD

Atypical antipsychotic drugs (risperidone and olanzapine)

Conventional antipsychotics (haloperidol)

What is used to address the anxiety and depression associated with AD 

• Anxiolytics (buspirone, benzodiazepines)

• Mood stabilizers (sertraline, citalopram, or fluoxetine)

  • Citalopram could have adverse effects on client’s status 

Mild AD (early stage) 

May function independently. He or she may still drive, work and be part
of social activities.
• Despite this, the person may feel as if he or she is having memory
lapses, such as forgetting familiar words or the location of everyday
objects.
• Friends, family or others close to the individual notice difficulties.
• Problems coming up with the right word or name
• Trouble remembering names when introduced to new people
• Challenges performing tasks in social or work settings.
• Forgetting material that one has just read
• Losing or misplacing a valuable object
• Increasing trouble with planning or organizing

Moderate AD (middle stage)

typically the longest stage and can last for many years.
• As the disease progresses, the person with AD will
require a greater level of care.
• Difficulty with ADL’s
• Anxiety, agitation, suspiciousness
• Sleep disturbances
• Wandering, pacing
• Difficulty recognizing family/friend
Confusion about where they are or what day it is
• The need for help choosing proper clothing for the
season or the occasion
• Trouble controlling bladder and bowels in some
individuals
• Changes in sleep patterns, such as sleeping during the
day and becoming restless at night
You may notice the person with Alzheimer's
confusing words, getting frustrated or angry, or
acting in unexpected ways, such as refusing to
bathe.
• Damage to nerve cells in the brain can make it
difficult to express thoughts and perform routine
tasks. Forgetfulness of events or about one's own
personal history
• Feeling moody or withdrawn, especially in socially or
mentally challenging situations
• Being unable to recall their own address or
telephone number or the high school or college from
which they graduated

Severe AD (late stage) 

In the final stage of this disease, individuals lose
the ability to respond to their environment
• To carry on a conversation –loss of speech
• Eventually, to control movement-total dependence
on caregiver
• Loss of appetite-weight loss-inability to swallow
• Loss of bowel and bladder control

When do the symptoms of AD begin

• After the age of 65 (could appear as early as age 40)

• Most early symptom commonly memory difficulties

Typical life expectancy of someone with AD 

4-8 years (could be 20 or more years)

Efficacy of drug therapy for AD

• No cure

• intensify effect of AcH at cholinergic receptor

• Ineffective in late stages

Class and indication of amantadine (symmetrel)

Dopamine releaser / antiviral

Treats early PD, dyskinesias

Common side effects of amantadine (symmetrel)

confusion, dizziness, hallucinations, livedo reticularis (purple-ish discoloration of the skin)

Nursing considerations for Amantadine (symmetrel) 

Monitor mental status, caution in elderly, benefits may be more short-term 

Class and indication of Apomorphine (Apokyn)

Dopamine agonist

Advanced PD (off episodes)

Side effects of apomorphine (Apokyn)

Severe nausea/vomiting, hypotension, yawning, drowsiness

Nursing considerations for apomorphine

Pre-treat with antiemetic, avoid 5-HT3 antagonists (ondansetron) due to hypotension risk 

Ropinirole (Requip)

Dopamine agonist

PD, restless leg syndrome

Side effects of Ripinirole (Requip) and nursing considerations

Somnolence (excessive drowsiness), dizziness, hallucinations, impulse-control disorders

Warn patients about sudden sleep onset,
monitor for behavioral changes

Tolcapone (Tasmar) class and indication

COMT inhibitor

Adjunct for PD 

Common side effects of tolcapone (Tasmar) 

Diarrhea, liver failure, dyskinesias 

Nursing considerations for tolcapone (Tasmar)

Monitor liver function tests, use when other treatments fail

Entacapone (in Stalevo) Class and Indication

COMT inhibitor

Adjunct for PD with levodopa

Entacapone side effects

Diarrhea, orange-colored urine, dyskinesias

Nursing considerations for entacapone

Safer than tolcapone, often combine with levodopa/carbidopa

Class and indication Benztropine (Cogentin)

• Anticholinergic 

• PD (tremor), EPS caused by antipsychotics 

Side effects of Benztropine (Cogentin)

Dry mouth, blurred vision, constipation, urinary retention, tachycardia 

Nursing considerations for Benztropine

Avoid in elderly

Contraindicated in glaucoma 

Monitor bowel/bladder function 

Biperiden (Akineton) class and indication

Anticholinergic

PD (tremor)

Common side effects for Biperiden 

dry mouth, blurred vision, urinary retention, confusion

Nursing considerations for Biperiden 

Not commonly used in US, monitor cognition 

Trihexyphenidyl (Artane) class and indications

Anticholinergic

PD (tremor)

Side effects of trihexyphenidyl

Dry mouth, confusion, constipation 

Nursing considerations for trihexyphenidyl (Artane)

Caution in elderly, monitor cognition

Major side effects of cholinesterase inhibitors 

GI issues (N+V, diarrhea) 

Weight loss 

Process for discontinuing cholinesterase inhibitors 

Do so gradually 

Mechanism of action of cholinesterase inhibitors

• Prevents the breakdown of acetylcholine by acetylcholinesterase (enzyme that naturally degrades acetylcholine in synapses)

• Enhances transmission of AcH in cholinergic neurons

Examples of Cholinesterase Inhibitors

• Donepezil (Aricept)

• Galantamine (Razadyne, Reminyl)

• Rivastigmine (Exelon)

Donepezil (Aricept) class and indication

Cholinesterase inhibitor

Mild to moderate AD

5mg - white, 10 mg - yellow, 23mg - red

Side effects of Donepezil (Aricept) 

Nausea, diarrhea, insomnia, muscle cramps, bradycardia 

Nursing considerations for donepezil

Give at bedtime, monitor HR, may take weeks to see improvement, not curative

Effects are modest and typically short-lived 

Also can be given as transdermal patch (less likely to have GI side effects as compared to taking it orally) 

Give regularly at bedtime

When should you NOT given donepezil

To patients with GI bleeding and jaundice

How to treat donepezil overdose 

Anticholinergics such as atropine

Rivastigmine (Exelon) class and indication

Cholinesterase inhibitor

Mild to moderate AD

Dementia associated with PD

Side effects of rivastigmine 

Nausea, vomiting, weight loss, dizziness

Nursing considerations for rivastigmine (Exelon)

Available oral and patch, rotate sites, monitor weight

Galantamine (razadyne) class and indication

Cholinesterase inhibitor

Mild to moderate AD

Side effects of Galantamine (Razadyne) 

Nausea, vomiting, anorexia, dizziness 

Nursing considerations for galantamine

Give with food, monitor weight and hydration

Class and indication for memantine (Namenda)

NMDA receptor agonist (binds to NMDA receptor and this causes Ca+ to enter neurons and have excitatory effect) 

• Reduces high glutamate levels 

Moderate to severe AD

How can memantine be combined with donepezil

Once-daily dosing of 2 drugs in single capsule (fixed-dose)

Side effects of memantine (Namenda)

Dizziness, headache, constipation, confusion

Nursing considerations for memantine 

Can be combined with donepezil, monitor cognition and bowel habits 

Why would antioxidants such as vitamin E be used to treat AD

Because some neuronal damage can be caused by oxidative cellular damage

Food medication for AD patients

Caprylidene (Axona) is metabolized into ketone bodies which the brain can use for energy when ability to process glucose is impaired

Adverse effects of donepezil

Hepatotoxicity, renal toxicity, bradycardia, heart block, extreme weight loss

What decreases the absorption of levodopa 

High-protein meals or high consumption of vitamin B6 (pyridoxine) 

Patient teaching for neurodegenerative diseases

• Get assistance prior to getting out of bed

• Improvement in symptoms is gradual

• Increasing symptoms or difficulty in performing activities should be reported to

Amnesia 

Loss of memories 

Anomia

unable to recall names of everyday objects

Apraxia

unable to perform tasks of movement

Agnosia 

inability to process sensory information 

Aphasia

disruption with ability to communicate

Aducanumab

Amyloid beta-directed antibody, used to treat the progression of AD