what are the risk factors for Parkinson’s?
- increased age (typically over 60)
- white
- men
what are the signs and symptoms of Parkinson’s?
- speech difficulties
- shuffling gait
- bradykinesia
- muscle rigidity
- frozen face
- tremors
- pilling rolling
what are neurotransmitters like with Parkinson’s?
- low dopamine (inhibitory)
- high acetylcholine (excitatory - tremors)
what part of the brain isn’t functioning right with Parkinson’s?
- substantia nigra - where dopamine is produced
- basal ganglia - smooth muscle movements and houses the substantia nigra
what % of neurons need to be lost for Parkinson’s symptoms to present?
70-80%
what is needed for a Parkinson’s diagnosis?
2 out of the 4 cardinal symptoms
- tremors at rest
- rigidity
- bradykinesia
- postural instability
what other symptoms are associated with Parkinson’s besides motor issues?
- depression
- drooling
- impotence
- cold intolerance
- orthostatic hypotension
what 2 broad types of medications are needed for Parkinson’s?
dopaminergic and anticholinergic
what are the overall effects of an anticholinergic drug (not directly related to Parkinson’s)?
- control smooth muscle
- decrease heart rate
- vasodilate
- increase body secretion
what are 2 examples of dopamine receptor agonists?
- levodopa/carbidopa (Sinemet)
- carbidopa
what is the purpose of levodopa and carbidopa being prescribed together?
together it increases the concentration of dopamine that crosses the blood-brain barrier
- levodopa mostly ends up outside the brain because it metabolized fast but carbidopa helps prevent the breakdown outside of the brain
what is the action of levodopa specifically? what is the action of carbidopa specifically?
- levodopa - increases dopamine
- carbidopa - increase the amount of levodopa that gets to the brain
when do the benefits of levodopa/carbidopa (Sinemet) typically diminish?
2-5 years
what are the benefits of levodopa/carbidopa (Sinemet)?
- highly effective, but benefits diminish over time
- most effective treatment for PD
what route is levodopa/carbidopa (Sinemet) given?
PO - rapid absorption by the small intestine
what foods should be avoided with levodopa/carbidopa (Sinemet)?
avoid a protein-rich diet and high acidic foods
what are the adverse effects of levodopa/carbidopa (Sinemet)?
- POSTURAL HYPOTENSION (stay hydrated)
- nausea and vomiting
- chest pain
- anxiety
- increased heart rate
- increased involuntary movement
- prolongation of QRS
what is the on-off effect?
levodopa/carbidopa (Sinemet) can stop working
what teaching is needed with levodopa/carbidopa (Sinemet)?
it is time-critical - don’t miss a dose or the s/s will return
what is the use of a dopamine agonist?
first-line for mild to moderate PD
- direct activation of dopamine receptors in the striatum
what is an example of a dopamine agonist?
pramipexole (Mirapex) -ole
when is pramipexole (Mirapex) used?
used aline in early PD or with levodopa in advancing PD
what are the benefits of pramipexole (Mirapex)?
- less likely to cause movement disorders or akinesia than Sinemet
- less response failure than levodopa
what teaching is needed with pramipexole (Mirapex)?
maximal benefits take several weeks and it takes several weeks for pramipexole (Mirapex) to be completely out of the system
what are the adverse effects of dopamine agonists - pramipexole (Mirapex)?
- N/V
- dizziness
- weakness
- sleepiness through day
- insomnia at night
- hallucinationS
what is a major concern with dopamine agonists - pramipexole (Mirapex)?
impulse control like pathologic gambling due to increased dopamine
what is an example of COMT inhibitors (-capone)?
entacapone
entacapone is useless without what?
levodopa - adjunct therapy
what are the side effects of entacapone?
- orange colored urine
- dyskinesia
- impulse control
- sleep issues
what is the action of entacapone?
inhibits COMT to prevent levodopa breakdown
- enhances levodopa
what are 2 examples of MAO-B inhibitors?
selegiline (Eldepryl) and rasagiline (Azilect)
-giline
what is the action of MAO-B inhibitors?
prevent the breakdown of natural dopamine
what is an adverse effect of MAO-B inhibitors?
insomnia
what drugs are contraindicated with MAO-B inhibitors?
- SSRIs - serotonin syndrome
- Demerol - decreased respiration and blood pressure
what is considered a first-line treatment for PD?
MAO-B inhibitors - selegiline (Eldepryl) and rasagiline (Azilect)
what else should be known about MAO-B inhibitors?
- modest improvement in motor function
- combination with levodopa can reduce the wearing-off effect
what is an example of a dopamine releaser?
amantadine
what is the action of a dopamine releaser?
stimulates dopamine release
what are the side effects of dopamine releasers?
can cause atropine-like effects
- chest pain
- cough
- dryness
- eye dilation
what are dopamine releasers used for?
- originally used for the flu
- can be used to combat dyskinesia of levodopa
- more for mild PD
what anticholinergic drugs are used for PD?
benztropine (Cogentin)
what drugs are used for mild symptoms of PD?
MAO-B inhibitors: selegiline or rasagiline
what drugs are used for more severe symptoms of PD?
dopamine replacement (levodopa) or dopamine agonist (pramipexole)
true or false: the longer you are on levodopa the more movement issues there are
true
how many patients develop nonmotor symptoms with PD?
90% - autonomic disturbances, depression, dementia, and psychosis
what drug is effective in treating depression with PD?
amitriptyline
what are other adverse effects of PD?
- falls
- stress and anxiety
- dementia
- sleep
what are other nontraditional drug treatments for PD?
- speech therapy
- PT and OT
- deep brain stimulation
- stem cell
what is the pathophysiology for Alzheimer’s?
- loss of acetylcholine
- plaques of beta-amyloid
- neurofibrillary tangles
- loss of neural connections
with Alzheimer’s is acetylcholine levels high or low?
low
what is the action of cholinesterase inhibitors?
prevents the breakdown of acetylcholine
what are examples of cholinesterase inhibitors?
- donepezil (aricept)
- galantamine (razadyne)
- rivastigmine (exelon)
- tacrine (cognex)
what cholinesterase inhibitor can be used for all stages of Alzheimer’s?
donepezil (Aricept)
what cholinesterase inhibitors can be used for mild to moderate s/s of Alzheimer’s?
- galantamine (razadyne)
- rivastigmine (exelon)
- tacrine (cognex)
when should cholinesterase inhibitors be taken?
at night
what is the use of cholinesterase inhibitors?
doesn’t stop the progression of Alzheimer’s but delays it for 55 weeks
what are drug interactions with cholinesterase inhibitors?
- TCA’s
- antipsychotics
- antihistamines
what are the side effects of cholinesterase inhibitors?
- bronchoconstriction
- diarrhea
- decreased appetite
- bradycardia
what is the antidote for donepezil (Aricept)?
atropine (helps battle acetylcholine)
what are the side effects of donepezil (Aricept) overdose?
- N/V
- decreased HR
- drooling
- sweating
- fatigue
what is an example of an NMDA inhibitor?
memantine (Namenda)
what is NMDA inhibitor used for?
moderate to severe Alzheimer’s
what is the action of NMDA inhibitors?
- reduces glutamate at NMDA receptors
- slows neural toxicity to prevent over the action of glutamate receptors
- slows down activity in the brain to improve memory
what are drug interactions with NMDA inhibitors?
NMDA antagonists: such as amantadine or ketamine
what are the side effects of NMDA inhibitors?
- headache
- constipation
- confusion
- dizziness
what percentage of Alzheimer’s patients experience neuropsychiatric symptoms? what are the symptoms?
80%
- depression
- aggression
- impulsiveness
- hallucinations
- apathy
what are two examples of atypical antipsychotic drugs used for Alzheimer’s?
- risperidone
- olanzapine
what are other possible treatments to delay the onset of AD?
- statins
- folic acid
- Mediterranean diet
- light to moderate alcohol intake
