Neuro part 2

Question 1

Long-term affects of dopamine replacement

Answer 1

Dyskinesia
Wearing-off phenomenon
On-off medication state

Question 2

3 ways to treat Parkinson’s disease

Answer 2

Dopamine replacement therapy

• Dopamine agonist therapy
• Anticholinergic therapy

Question 3

1st line for Parkinsons drug treatment

Answer 3

Levodopa-carbidopa (Sinemet)

Question 4

Levodopa-carbidopa (Sinemet) MOA

Answer 4

Levodopa (l-dopa) MOA: precursor to dopamine that can cross BBB and be converted to have CNS action
Carbidopa MOA: stops breakdown of l-dopa to dopamine in periphery so more l-dopa crosses BBB

Question 5

Levodopa-carbidopa (Sinemet) AE:

Answer 5

Problematic AE: motor disturbances
End of dose “wearing off” – stiffness and rigidity return
Due to short t½ of l-dopa and/or med nonadherence

“Delayed on” or “no on” – med is not having effect
Due to absorption issues

Freezing – sudden inhibition of lower-extremity function, “feel stuck to the floor”
Exacerbated by anxiety

“On” period dyskinesia- Usually due to peak drug levels causing increased dopamine response

don’t take with food/high protein food → decrease absorption

Question 6

MAO-B Inhibitors MOA, AE

Answer 6

MOA: inhibit monoamine oxidase B (MAO B) which typically breaks down dopamine thus increasing dopamine levels in CNS
Risk of serotonin syndrome when combined with serotonergic meds

Question 7

COMT Inhibitor MOA, AE

Answer 7

MOA: inhibits COMT which in turn decreases breakdown of l-dopa
AE >10%: involuntary movements, nausea

Question 8

Amantadine

Answer 8

MOA: unknown; possible increases dopamine release or may have direct effect on dopamine neurons (different sources classify as dopamine replacement or dopamine therapy)
AE: anticholinergic AE, CNS effects (confusion, hallucinations, dizziness)

Usually in early disease management

Question 9

ropinirole (Requip) MOA, AE

Answer 9

MOA: binds to and agonizes dopamine receptors

AE: nausea, drowsiness, dizziness, syncope
Monitor for light-headedness and postural hypotension (especially when start and ↑ dose)-especially with older patient, hallucinations, lower-extremity edema
Less common: impulsive behavior, sleep attacks

Question 10

Parkinson’s Disease Drug Concerns

Answer 10

Timing of PT session with delivery of medications
Improved motor function seen within 1-1.5 hr of taking dopamine replacement medication
PT during “on-cycle” can enable improved patient participation/performance
Still important to treat patients during “off-cycle” – to see how much impaired their mobility is during that off cycle

Long-term medication use and disease progression
Levadopa dosage less effective over time
More “off” cycles as disease state progresses

Question 11

symptoms of MS

Answer 11

weakness, fatigue, sensory loss, UMN signs,visual disturbance, autonomic dysfunction. All of these issues results in gait and balance deficits, memory problems, and disability

Question 12

most common MS

Answer 12

Relapsing-Remitting type most common

Question 13

Drugs to treat progression of MS

Answer 13

Interferon β
Glatiramer acetate
Sphingosine 1-Phosphate Receptor Modulator
Dimethyl fumarate
Monoclonal antibodies: natalizumab, ocrelizumab

Question 14

Interferon β

Answer 14

MOA: has an impact on immune function

AE >50%: flu-like symptoms, injection site reaction

Monitor for: neuropsychiatric changes, drug-induced hypothyroidism, worsening cardiac function in HF

Question 15

Glatiramer acetate

Answer 15

MOA: reduce autoimmune response to myelin by reducing T-cell response against myelin

Most common AE: injection site reaction (mass, pain, erythema, itching, lipoatrophy if not rotating site

Question 16

Fingolimod (Gilenya)

Answer 16

blocks release of lymphocytes into CNS = ↓ inflammation
AE >15%: headache, ↑ LFTs (liver function test
Monitor: bradycardia (especially within 24 hours of first dose; usually return to baseline HR after 1 month therapy

Question 17

Dimethyl fumarate

Answer 17

MOA: may have anti-inflammatory properties
AE: GI (N/V/D, abdominal pain in 12-18%) and flushing (up to 40%) usually improve with time

Question 18

Monoclonal Antibodies

Answer 18

Overall MOA: ↓ inflammation in CNS

Monitor for infection (respiratory, skin, herpes-related) due to increased risk

Question 19

What is PML?

Answer 19

serious risk associated natalizumab, ocrelizumab, dimethyl fumarate,
and SP1 Receptor modulators

Demyelinating CNS disorder

Refer if any suspicion of PML*
S/Sx: altered mental status (AMS), aphasia, ataxia, hemiparesis, hemiplegia, visual disturbance (double vision, partial blindness), seizure

Question 20

MS drug concerns

Answer 20

FATIGUE: most common and disabling MS symptom
Patient may take additional medications to address fatigue

Disease-modifying drugs can have substantial adverse effects including flu-like symptoms to immunosuppression

Question 21

AZD treatment

Answer 21

Blocking acetylcholinesterase

Medications targeting NMDA pathway

Question 22

General Treatment Approach AZD

Answer 22

Mild:
Cholinesterase inhibitor
Moderate:
Cholinesterase inhibitor + memantine more likely to delay progression

Question 23

Donepezil (Aricept)

Answer 23

Cholinesterase Inhibitors
MOA: inhibits acetylcholinesterase

Only modest improvements in cognition and activities of daily living
Weigh AE risk and cost vs. limited benefit
Duration of benefit: 3 to 24 months

AE: anticholinergic effects (DUMBELLS)

Taper if discontinuing, monitor for worsened cognitive function

Question 24

Memantine (Namenda)

Answer 24

antagonizes NMDA receptor = stops excessive receptor activation by glutamate = decreases excitation and neuronal death
AE: monitor for falls, dizness

Question 25

Who should not be taking with additonal AZD drugs?

Answer 25

Anticholinergic drugs
Some OTC antihistamines like diphenhydramine (Benadryl)
Inhaled anticholinergic drugs like tiotropium (Spiriva) for respiratory disorders
Some meds for overactive bladder like oxybutynin
Anticholinergic drugs for Parkinson Disease
Tricyclic antidepressants which are also used for neuropathic pain

Question 26

AZD drugs PT concerns

Answer 26

Be aware of potential AE with meds
Cholinergic meds: GI issues (NVD) most common-
Memantine may cause dizziness, watch for falls

Communicate behavioral issues to healthcare providers

Timing of ph ysical therapy
Provide structure to reduce behavioral issues
Reduce behavioral issues related to sundowning
Utilize time of day when patient most alert