Week 10

Question 1

What are the characteristic features of Parkinson Disease?

Answer 1

tremor
rigidity
bradykinesia
postural instability

Question 2

What occurs from complications in Parkinson’s?

Answer 2

death

Question 3

What is the pathophysiology of Parkinson’s disease?

Answer 3

loss of dopaminergic neurons in the extrapyramidal system, mainly substantia nigra

Question 4

What percentage of patients on levodopa greater than 5 years will develop motor complications or Parkinson’s?

Answer 4

50-90%

Question 5

What are the two most common motor complications of Parkinson’s?

Answer 5

wearing off

on-off effect

Question 6

How is “wearing off” treated in Parkinson’s?

Answer 6

initially treat by dosing more often (shorten dose interval)

later on, add a dopamine agonist

Question 7

How is “on-off” effect treated in Parkinson’s?

Answer 7

treat with rescue apomorphine, or adjust dose/frequency of levodopa

Question 8

IN Parkinson’s the physical disability is ____ and ____.

Answer 8

progressive; unavoidable

Question 9

initiation of therapy and dosing is _____ ____.

Answer 9

highly individualized

Question 10

What is the mainstay of treatment since 1960s and most effective agent for Parkinson’s?

Answer 10

Levodopa (L-dopa)

Question 11

Does dopamine cross the BBB?

Answer 11

NO

Question 12

Does L-dopa cross the BBB?

Answer 12

Yes

Question 13

What are the significant peripheral adverse effects of Parkinson’s?

Answer 13

dyskinesias
N&V, anorexia
Postural Hypotension
Mental disturbances
Cardiac arrhythmia

Question 14

What should levodopa (Ldopa) always be administered with?

Answer 14

peripheral DDC inhibitor (Carbidopa)

Question 15

How can GI upset be minimized and help absorption of Levodopa in Parkinson’s?

Answer 15

LOW protein meals

Competes for absorption with other amino acids

Question 16

What is the peripheral dopa decarboxylase (DDC) inhibitor?

Answer 16

Carbidopa (Lodosyn)

Question 17

What are the COMT- Inhibitors? (2)

Answer 17

Entacapone (Comtan)

Tolcapone (Tasmar)

Question 18

What are the MAO-B Inhibitors? (2)

Answer 18

Selegiline (Eldepryl, Zelapar)

Rasagiline (Azilect)

Question 19

What are the 2 ways Carbidopa (Lodosyn) is available?

Answer 19

alone-Lodosyn

combo with Levodopa (Sinemet)

Question 20

What is the dose of carbidopa needed to inhibit peripheral DDC?

Answer 20

75-100mg Carbidopa/ daily

Question 21

How do you usually start treatment with Carbidopa?

Answer 21

IR product of 25/100mg (carbidopa/levodopa-Sinemet) TID

Question 22

What dosage of Levodopa do most patients respond to?

Answer 22

750-1,000mg

Question 23

When can you switch to 25/250mg tab TID of sinemet?

Answer 23

After 8 tabs daily of 25/100mg

Question 24

What is the benefit of Carbidopa (Lodosyn) alone for Parkinson’s?

Answer 24

allows greater individualization for patients with advanced Parkinson’s

Question 25

COMT inhibits are widely distributed.....

Answer 25

peripheral and central

Question 26

What are the COMT Inhibitors that precent conversion of Levodopa to 3-O-methyl dopa?

Answer 26

Entacapone (Comtan) | Tolcapine (Tasmar)

Question 27

How is Entacapone available?

Answer 27

200mg tablet OR Combo with Sinemet (Stalevo)

Question 28

What COMT Inhibitor is dosed as a single drug TID and associated with fatal cases of acute liver failure

Answer 28

Talcapone (Tasmar)

Question 29

What COMT inhibitor has limited clinical use?

Answer 29

Talcapone (Tasmar)

Question 30

What is the MOA of MAO-B Inhibitors?

Answer 30

selective MAO-B inhibition prolongs dopamine effects by inhibiting dopamine metabolism in the brain

Question 31

When are MAO-B Inhibitors used?

Answer 31

usually as adjunctive(add-on) therapy in advanced cases of Parkinson's

Question 32

What is important to remember when using MAO-B Inhibitors?

Answer 32

minimize tyramine intake | avoid concomitant use of SSRIs (potential for serotonin syndrome)

Question 33

What medication may delay levodopa therapy by 9 months?

Answer 33

early of Selegiline (Eldepryl, Zelapar)

Question 34

Selegiline (Eldepryl, Zelapar) is effective in improving ______ effect by 50-70% but is less effective in improving ______ effects.

Answer 34

"wearing off" | "on-off"

Question 35

What medication is more potent inhibition of MAO-B than selegiline?

Answer 35

Rasagiline (Azilect)

Question 36

What medication is used as adjunctive to sinemet and useful for treatment of "off" episodes?

Answer 36

Safinamide (Xadago)

Question 37

What are the adverse effects of Safinamide (Xadago)?

Answer 37

severe htn (at greater than >100mg once daily, greater than recommended dosage) Hypersexual behavior Retinal degeneration

Question 38

What medications cross the BBB and stimulate the dopamine (D2) receptor?

Answer 38

Dopamine agonists

Question 39

How are dopamine agonists used?

Answer 39

``` mono therapy (early) adjunctive (late therapy) ```

Question 40

What is the improvement of ADLs with dopamine agonists vs levodopa?

Answer 40

improve 30% on dopamine agonists vs 40-50% on levodopa

Question 41

When is mono therapy with dopamine agonists more effective?

Answer 41

in younger patients (<65 years) | early use may postpone use of levodopa

Question 42

What is the dopamine agonist that is an Ergot derivative?

Answer 42

Bromocriptine (Parlodel)

Question 43

What are the dopamine agonist that are a non-ergot derivative?

Answer 43

Pramipexole (Mirapex) Ropinirole (Requip) Apomorphine (Apokyn) Rotigotine (Neupro) transdermal

Question 44

What are the increased risk major adverse effects of Bromocriptine (Parlodel)?

Answer 44

pericardial fibrosis cardiac valve fibrosis rarely used now

Question 45

Pts on pramipexole (Mirapex) AND levodopa showed what outcomes? (3)

Answer 45

fewer dyskinesias fewer "wearing off" effects fewer motor complications

Question 46

What is the only renally eliminated dopamine agonist?

Answer 46

pramipexole (Mirapex) adjust for CrCl <50

Question 47

Is there a recommended taper for pramipexole (Mirapex)?

Answer 47

No

Question 48

How is Ropinirole (Requip) metabolized?

Answer 48

hepatically metabolized therefore no dose adjustment for renal dysfunction

Question 49

How is Ropinirole (Requip) discontinued?

Answer 49

taper over 7 days

Question 50

What is an injectable dopamine agonist?

Answer 50

Apomorphine (Apokyn)

Question 51

What is Apomorphine (Apokyn) FDA approved for?

Answer 51

rescue therapy for hypomobility and "off" episodes

Question 52

What is a side effect of Apomorphine (Apokyn)?

Answer 52

may cause severe emesis; take with antiemetic

Question 53

What is contraindicated with Apomorphine (Apokyn) and why?

Answer 53

Serotonin RAs (ondansetron-Zofran), together can cause severe hypotension & syncope

Question 54

What is the dosage of Apomorphine (Apokyn)?

Answer 54

2-6mg SUBCUTANEOUS 3-5x daily PRN NOT IV!!!

Question 55

What is the only dopamine agonist transdermal patch?

Answer 55

Rotigotine (Neupro) $$$$

Question 56

What was the mainstay treatment for Parkinson's until the late 1960s?

Answer 56

Anticholinergics

Question 57

What are anticholinergics used for Parkinson's?

Answer 57

reserved for resting tremor in early disease, especially if less than 65 years old

Question 58

What are the side effects of anticholinergics?

Answer 58

``` consitpation dry mouth blurred vision confusion urinary retention ```

Question 59

What are the anticholinergics used for Parkinson's?

Answer 59

Benztropin (Cogentin) | Triphenidyl (Artane)

Question 60

What medication is primarily an antiviral agent, found to have anti Parkinson's activity?

Answer 60

Amantadine (Symmetrel)

Question 61

What medication was previously used as early mono therapy but now used as an on add for levodopa induced dyskinesias?

Answer 61

Amantadine (Symmetrel)