az/pd

Question 1

primary patho of Parkinson’s disease

Answer 1

disease of dopamine depletion, primarily affecting the substantia nigra

Question 2

when do cardinal symptoms of Parkinson’s disease typically appear

Answer 2

symptoms appear when 70-80% of substantia nigra neurons are depleted

Question 3

what does the TRAP acronym stand for (cardinal symptoms of Parkinson’s)

Answer 3

*tremor
*rigidity (cog wheeling or hypomimia)
*akinesia/bradykinesia
*postural instability

Question 4

which two classes of meds are commonly associated w/ drug-induced parkinsonism

Answer 4

dopamine antagonists (antipsychotics (except clozapine and antiemetics))

Question 5

why is peripheral administered dopamine ineffective for treating parkinsons

Answer 5

dopamine is hydrophilic and cannot cross BBB

Question 6

an immediate precursor of dopamine that can cross the BBB and can be converted to dopamine in the brain

Answer 6

levodopa

Question 7

what is the purpose of combining carbidopa and levodopa

Answer 7

carbidopa inhibits peripheral decarboxylation of L-dopa, allowing more of it to reach the brain and reducing peripheral side effects (i.e. nausea)

Question 8

in which pt population is levodopa/carbidopa the preferred initial therapy for parkinson’s disease

Answer 8

preferred in older adults 65+ d/t its safer side effect profile compared to other agents

Question 9

what is a major limitation of levodopa tx

Answer 9

it is only effective for a finite period of time

Question 10

what is a key pt counseling point regarding carbidopa/levodopa admin and diet

Answer 10

levodopa competes w/ protein for absorption, so it should not be taken w/ a high protein meal

Question 11

adverse effects of levodopa

Answer 11

• n/v
• postural hypotension
• dyskinesias
• psychiatric disturbances

Question 12

what is the general therapeutic strategy for dopamine agonists in PD, particularly in younger pts

Answer 12

they may be used as early monotherapy in initial L-DOPA sparing strategy

Question 13

adverse effects of ropinerol and pramipexole

Answer 13

• sudden, irresistable episodes of sleep, often referred to as sleep attacks

caution while driving

Question 14

what unique adverse effects are associated w/ dopamine agonists such as ropinerole and pramipexole

Answer 14

hallucinations and impulse control disorders, such as compulsive gambling or shopping

Question 15

which dopamine agonist is available as a daily transdermal patch, making it useful for pts w/ swallowing difficulties

Answer 15

rotigotine (neupro)

Question 16

in PD tx, the motor complication known as “wearing off” effect refers to what phenomenon

Answer 16

occurs when an adequate dose of L-DOPA does not last until the next scheduled dose, causing sx to return

Question 17

dyskinesias in PD are characterized by rapid, irregular, nonpurposeful movements known as ______; and more disabling sustained contractions called _________

Answer 17

chorea; dystonia

Question 18

selectively and reversibly inhibit the COMT enzyme, which inhibits the degradation of dopamine and extends the life of L-DOPA

Answer 18

COMT inhibitors (entacapone)

Question 19

true or false:

COMT inhibitors can be used as monotherapy for PD

Answer 19

false; they are ineffective when given as monotherapy and must be administered simultaneously w/ levodopa

Question 20

what is a unique, harmless side effect of the COMT inhibitor entacapone

Answer 20

urine discoloration

Question 21

selectively and irreversibly inhibit monoamine oxidase-B (MAO-B) in the brain, interferring w/ the degradation of dopamine

Answer 21

MAO-B inhibitors (rasagiline and selegiline)

Question 22

MAO-B inhibitors are contraindicated w/ which two major classes of drugs d/t risk of serotonin syndrome or hypertensive crisis

Answer 22

opioids and serotonergic drugs (SSRIs, SNRIs)

Question 23

role of apomorphine (apokyn) in PD tx

Answer 23

dopamine agonist used as a rescue tx for intermittent L-DOPA “off” episodes, particularly freezing

Question 24

why must a test dose of apomorphine be administered under medical supervision

Answer 24

risk of severe hypotension

Question 25

in PD, an imbalance where acetylcholine activity is relatively higher than dopamine activity primarily contributes to which sx?

Answer 25

tremor

Question 26

in which pt population are anticholinergics such as benztropine used as a monotherapy in PD

Answer 26

in pts younger than 65 whose only sx is tremor

Question 27

classic adverse effects of anticholinergic meds that limit their use, especially in older adults

Answer 27

* dry mouth * blurred vision * retention * constipation * confusion * sedation

Question 28

used as an adjunct tx to decrease the intensity of L-DOPA induced dyskinesia

Answer 28

primary role of amantadine in modern PD therapy

Question 29

four major pathophysiological alterations found in AD

Answer 29

* extracellular B- amyloid plaques * intracellular neurofibrillary tangles * degeneration of cholinergic neurons * cortical atrophy

Question 30

destruction of acetylcholine-synthesizing neurons in the ___________ and ___________ is a key feature of AZ

Answer 30

hippocampus; cortex

Question 31

3 most common reversible causes of cognitive impairment

Answer 31

* drugs * depression * metabolic disturbances

Question 32

primary pharmacologic goal of AZ tx

Answer 32

* improve pt and family's QoL by managing sx * maximizing independent function (not a cure)

Question 33

inhibit acetylcholinesterase, preventing hydrolysis of acetylcholine and thus increasing its concentration in synaptic cleft

Answer 33

cholinesterase inhibitors

Question 34

for which stages of AZ is donezipil (aricept) FDA-approved

Answer 34

mild, moderate, and severe AZ

Question 35

what is a key advantage of donezipil (aricept) compared to other cholinesterase inhibitors

Answer 35

allows once-daily dosing and generally has fewer SEs

Question 36

what are the most common dose-related adverse effects of donezipil

Answer 36

GI effects (nausea, diarrhea) and CNS effects (insomnia)

Question 37

besides AZ, rivastigmine (exelon) is also indicated for mild-moderate dementia associated w/ what other neurodegenerative disease

Answer 37

parkinson's disease

Question 37

what is a major disadvantage of the oral formulation of rivastigmine (exelon)

Answer 37

BID dosing and longer titration period

Question 38

what is a critical counseling pt for rivastigmine (exelon) transdermal to prevent med errors

Answer 38

* apply 1 patch daily to a new location, avoiding reapplication to the same spot for 14 days * never cut patch

Question 39

for which stages of AD is galantamine (razadyne) indicated

Answer 39

mild to moderate alzheimers

Question 40

what may happen if cholinesterase inhibitors are abruptly d/c'ed in a pt w/ alzheimer's disease

Answer 40

cognition may abruply decline to placebo

Question 41

in AZ patho, abnormall activity of the neurotransmitter _______ leads to sustained action of NMDA receptors, causing neuronal damage

Answer 41

glutamate

Question 42

NMDA receptor antagonist that blocks the receptor only under conditions of excessive stimulation, preventing further excitotoxic damage

Answer 42

memantine (namenda)

Question 43

for which stages of AZ is memantine (namenda) FDA-approved

Answer 43

moderate to severe AZ

Question 44

a clinically significant drug-drug interaction w/ memantine involves _____________, which can increase its serum concentration and risk of myoclonus

Answer 44

trimethoprim

Question 45

what is the therapeutic goal of disease-modifying therapies like lecanemab and donanemab in early AD

Answer 45

slow disease progression by clearing beta-amyloid plaque from the brain

Question 46

amyloid-related imaging abnormalities

Answer 46

ARIA

Question 47

what are two types of ARIA associated w/ anti-amyloid monoclonal antibodies

Answer 47

ARIA-E (edema/brain swelling) ARIA-H (hemorrhage/microbleeds)

Question 48

what is a common rxn that can occur w/ the admin of anti-amyloid antibodies such as lecanemab

Answer 48

infusion-related rxns (ie flu-like sx, flushing, rash, BP changes)

Question 49

what must be confirmed prior to initiating therapy w/ an anti-amyloid antibody like lecanemab

Answer 49

presence of amyloid-beta pathology, typically via PET scan or lumbar puncture

Question 50

what neurological assessment tool is used not to dx AZ, but to track the severity and progression of cognitive decline over time

Answer 50

mini-mental status exam (MMSE)

Question 51

common symptom of dementia that involves an exacerbation of symptomatology in the evening

Answer 51

sundowning