Parkinson's Disease Flashcards
A slowly progressive neurodegenerative disorder that affects movement, muscle control, & balance
- Part of dz process develops as cells are destroyed in certain parts of the brain
- Cells release essential neurotransmitters (dopamine) that help control movement & coordination
Primary is idiopathic
Secondary may be seen w/parkinsonian sx’s as a s/e of antipsychotic drugs or tumors
Normally, the ___ ___ neurons produce the neurotransmitter dopamine which acts to inhibit neurons from firing
substantia nigra
___ is a neurotransmitter that excites neurons & fires to stimulate motor neurons
The 2 neurotransmitters work together to maintain a balance in neuronal excitation & the person has control over movement & balance
Acetylcholine (Ach)
In PD, the substantia nigra neurons die & no longer produce dopamine
Acetylcholine’s effects on neuronal excitation goes unopposed
There’s no longer the balance of dopamine to slow impulses
Therefore, purposeful movement, coordination, & balance are impaired
Pts w/PD have difficulty controlling & initiating movement
Dopamine is also responsible for assisting the body to respond to stress & prepare it for the fight-or-flight response
Also appears to be important for efficient info processing, & deficiencies may also be responsible for problems in memory & concentration that occur in many pts
Approx 80% of the 20,000 dopamine-producing neurons in the substantia nigra have died by the time PD motor sx’s have developed
Etiology & Risk: Genetic
- Specific genetic factors appear to play a strong role in early-onset PD, an uncommon form of the dz
- Recent research suggests that multiple genetic factors may also be involved in some cases of late-onset PD; have been @ least 5-10 genetic locations id’d
Environmental
- May trigger the condition in genetically-susceptible people
- Some evidence implicates pesticides & herbicides
- Higher incidence in those living in rural areas; those who drink private well water or are agricultural workers
Dopaminergic neurons produce a protein called ____ that’s normally degraded by enzymes
If not degraded, build-up of this protein in the dopaminergic neurons causes toxic fibrils called Lewy bodies
Too many Lewy bodies are assoc w/neuron death in the substantia nigra
Pesticides & herbicides may interfere w/enzymes that degrade this protein
alpha-synuclein
Age
- > 40 & more than likely 60 & over are @ higher risk
Low estrogen
- @ neuronal synapses, estrogen inc the conc of neurotransmitters such as serotonin, dopamine, & norepinephrine
- It affects their release, re-uptake, & enzymatic inactivation; also inc the # of receptors for these neurotransmitters
Repeated head trauma
- Greater than 2 episodes of LOC
Stages of PD
- Stages I-V
Stage ___
→ Complete dependence
V
Stage ___
→ Postural instability
→ Inc gait disturbances
III
Stage ___
→ Akinesia
→ Rigidity
IV
Stage ___
→ Bilateral limb involvement
→ Mask-like face
→ Slow, shuffling gait
II
Stage ___
→ Unilateral limb involvement
→ Minimal weakness
→ Hand & arm trembling
I
Assessment: Motor Symptoms
► on-off phenomenon
► resting tremor
► pill rolling
► micrographia
► cogwheel rigidity - resistance to passive movement
► bradykinesia/akinesia
► postural instability - a dec or change in motor & muscle movements that leads to unsteadiness & hesitation in movement & gait when the individual starts or stops walking
► loss of balance
- Non-motor sx’s occur earlier than motor sx’s
- Orthostatic hypotension r/t dec SNS influence on heart & blood vessels
Assessment: Non-motor Symptoms
◄ dementia
◄ impaired memory
◄ depression/emotionally labile
◄ urinary problems & constipation
◄ difficulty speaking/nightmares
◄ orthostatic hypotension
◄ difficulty swallowing
◄ difficulty in speaking/soft voice/echolalia
◄ chewing difficulties
◄ loss of sense of smell
Dysphagia
- Persistent coughing >swallow
- Regular choking on liquids
- Difficulty maintaining wt
- Inc eating time
- Worsening tongue control
- Chronic slow or delayed food passage
- Significant loss of appetite
Dietary Suggestions for Dysphagia: Tips & Precautions
- Don’t eat when fatigued
- Sit erect
- Emphasize soft, moist foods
- Don’t talk while eating
- Take smaller bites
- High calorie, high protein foods to maintain wt
Pureed Diet
► Thicken liquids to honey consistency
► Cooked cereals, whipped potatoes & squash
► Strained fruits, applesauce, mashed bananas
► Strained meat, soft scrambled egg
► Strained & whipped vegetables; thickening material avail @ drugstores incl Thick-It, Nutra Thickt, ThickenUp
Mechanical Soft Diet
► Thickened liquids if necessary
► Cooked or ready-to-eat cereal, soft bread
► Well cooked vegetables
► Cut-up canned fruit without tough membrane
► Tender cuts of meat w/extra sauce or gravy
► Eggs, cheese, macaroni, moist casserole
Interventions
- Allow pt extra time to respond & for ADLs
- Schedule activity during “on” time
- Admin meds in timely manner to maintain blood lvls
- PT, OT, & SLP consults
- Monitor s/e & toxicity of meds (e.g., delirium [acute confusion], cog impairment, hallucinations)
- Drug toxicity or tolerance incl a drug holiday - removal of rx’s for about 10 days
- Minimize complications of immobility
- SLP for diet & communication
- Assess depression & sleep patterns
Non-Surgical Interventions: Medications
Anticholinergic agents
- Block receptors for ACh
Dopaminergic agents
- Directly or indirectly activate dopamine receptors
Dopamine Receptor Agonists: Indirect Acting
MAO-B selective inhibitors
- selegiline (Eldepryl, Zelapar)
- rasagiline (Azilect)
Pre-synpatic dopamine release enhancer
- amantadine (Symmetrel)
COMT inhibitors
- tolcapone (Tasmar)
- entacapone (Comtan)
MAO inhibitors
- MAO’s primary role is to breakdown catecholamines
- Inc the lvls of dopaminergic stimulation
- Selegiline extends the effectiveness of levadopa 1.8x than levadopa alone
! Contraindicated w/demerol (delirium, muscle rigidity, high fever, hyper-irritability or serotonin synd) & non-selective MAOIs
! Interaction w/tyramine foods (cheese, red wine, beer, yogurt)
- Azilect can be used as monotherapy
- s/e: dizziness, dyskinesias, nausea, syncope
Pre-synaptic dopamine release enhancer
- Releases dopamine & other catecholamines from their vesicles in the pre-synaptic fibers of nerve cells in the basal ganglia that have not yet been destroyed by PD
- Also blocks the re-uptake of dopamine thereby inc dopamine in synapses
- s/e: dizziness, insomnia, nausea
Catechol-o-methyltransferase (COMT) inhibitors
- Also breaks down catecholamines so inhibitors block the break down of dopamine
- s/e: GI upset, dyskinesias, urine discoloration
- Tolcapone used as last resort d/t risk of severe liver failure
Dopamine Receptor Agonists: Direct Acting
Non-dopamine dopamine receptor agonists
Ergot - bromocriptine (Parlodel)
Non-ergot
- pramipexole (Mirapex)
- ropinirole (Requip)
MoA
- Stimulate pre-synaptic and/or post-synaptic dopamine receptors in the brain to produce more dopamine
! Bromocriptine s/e
- ataxia, confusion
- dizziness, depression, drowsiness
- GI upset, visual changes
! Pramipexole & ropinirole s/e
- leg edema, fatigue, syncope
- dizziness, GI upset, viral infection (presumed unk immunosuppressant effect)
- assoc w/orthostatic hypotension, hallucinations, sleepiness, & drowsiness
Dopamine Replacement Drugs
- carbidopa (Lydosin)
- carbidopa-levodopa (Sinemet, Parcopa)
- Levodopa is a biologic precursor of dopamine; is the only form of dopamine that can cross the blood brain barrier
- Carbidopa helps to keep the breakdown of levodopa in the periphery vs centrally; therefore, less levodopa is req’d
! Give w/meals to inc absorption
s/e
- cardiac dysrhythmias
- hypotension (change position slowly)
- chorea (a neurological disorder characterized by spasmodic involuntary movements of the limbs or facial muscles)
- muscle cramps, GI distress, drowsiness, sleepiness
- Controlled release Sinemet - inc “on” time & dec “off” time
- Elderly are @ inc risk for confusion, loss of appetite, & orthostatic hypotension
- Often started at low doses b/c of the inc sensitivity of older pts to these meds & the need to save higher dosages for a later time during treatment
! Do not stop abruptly → Parkinsonian crisis → NMS
! Contraindicated for acute angle glaucoma
! Activates melanoma → check skin
Anticholinergic Drugs
- benzotropine (Cogentin)
- trihexyphenidyl (Artane)
MoA
- Blocks the effects of the neurotransmitter acetylcholine @ cholinergic receptors in the brain as well as systemically
- Help w/tremors, pill rolling, rigidity, salivation, lacrimation, urination, diarrhea, GI motility, & emesis
! Doesn’t help w/bradykinesia
- Anti-secretory effects - dry mouth/urinary retention/constipation/dilated pupils (mydriasis)/smooth muscle relaxation
- Avoid in older adults → can cause acute confusion & anti-secretory effects
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A gradual worsening of PD symptoms as a pt’s medications begin to lose their effectiveness, despite maximal dosing w/a variety of meds
Wearing off phenomenon
Iggy: 3-5 yrs
Lilly: 5-10 yrs
On-Off Phenomenon
A common experience of pts taking medication for PD in which they experience periods of greater symptomatic control (“on” time) alternating w/periods of lesser symptomatic control (“off” time)
Surgical Management
► Stereotactic pallidotomy
► Thalamotomy
► Deep brain stimulation
► Stem cell transplant
Pallidotomy & thalamotomy
✔ Are effective in alleviating many PD sx’s
✔ Pts eligible for these are those who have had an inadequate response to meds
✔ Purpose of these is to interrupt nerve pathways & thereby alleviate tremor or rigidity
! Both destroy parts of the brain
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Destroys the ventrolateral portion of the thalamus
Thalamotomy
Both the thalamus and pallidus control movement
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Is done by inserting a wire probe into the globus pallidus in the corpus striatum; then, radio waves are transmitted & heat the surrounding tissue
Pallidotomy
Deep brain stimulation
- An electrode is placed in the thalamus & subthalamus which is attached to a pulse generator implanted under the skin in the chest
- An impulse to this area impairs the neurons producing tremors
- May dec the dose of meds in order to limit PD sx’s
Stem cell transplant
- Fetal pig or human tissue of the substantia nigra tissue is transplanted into the caudate nucleus of the brain; PD sx’s usually have improved
