Parkinson's Disease

Question 1

Clinical signs of PD (TRAP pneumonic)

Answer 1

• Tremor at rest
• Rigidity
• Akinesia or bradykinesia
• Postural/gait instability

Question 2

Neurotransmitters involved in PD

Answer 2

• Dopamine*** (deficiency)
• NE
• ACh
• Glutamate
• Seratonin

Question 3

“1st Line PD drugs”

Answer 3

• Levodopa plus carbidopa +/- entacopone

- Dopamine agonists

Question 4

“2nd Line PD drugs”

Answer 4

• Anticholinergics
• Selective MOA B inhibitors
• NMDA antagonists

Question 5

Levodopa Products

Answer 5

• Carbidopa/Levodopa

- Carbidopa/Levodopa/Entacapone

Question 6

Levodopa MOA

Answer 6

Travels to BBB where it gets decarboxylated to dopamine

Question 7

Carbidopa MOA

Answer 7

• blocks conversion of levo to dopamine before BBB

- *Minimize N/V, orthostatic hypoTN ass with levo

Question 8

Entacapone

Answer 8

-Prolong action of levo by inhibiting O-methylation

Question 9

Anticholinergics

Answer 9

Trihexyphenidyl and Benztropine

Question 10

Anticholinergics MOA

Answer 10

Dopamine depletion in PD = state of cholinergic sensitivity, cholinergic drugs excite and anticholinergic drugs improve parkinsonian symptoms

Question 11

Clinical indications of anticholinergics

Answer 11

Early: mild tremor
Later: enhance the effects of levodopa, may help with drooling but ADRs frequently limit widespread application

Question 12

Anticholinergics pearl

Answer 12

Both can be used to treat drug-induced EPS

Question 13

NMDA Antagonists

Answer 13

Amantadine

Question 14

NMDA MOA

Answer 14

Increase dopamine release, decrease dopamine reuptake, stimulate dopamine receptors; interferes with excessive glutamate neurotransmission

Question 15

Clinical indications of NMDA Antagonists

Answer 15

Early: limited data
Later: *adjunct tx, usually in pts with levodopa-induced dyskinesia)
Less effective after 1 year of use

Question 16

NMDA Antag Interactions

Answer 16

Amantadine + anticholinergics/ETOH –> additive adverse effects on mental function

Question 17

NMDA Antag ADRs

Answer 17

Low-dose: well tolerated
High-dose: sedation/confusion, anticholinergic ADRs, LIVEDO RETICULARIS, sudden withdrawal may cause exacerbation of parkinsonian symptoms or NMS

Question 18

Adenosine A2A Rec Antag

Answer 18

Istradefylline

Question 19

Clinical indications of Adenosine A2A Rec Antag

Answer 19

Adjunct to carbidopa/levodopa in adults with PD who experience “off” episodes

Question 20

Adenosine A2A Rec Antag pearls

Answer 20

Pts who smoke over 20 ciggies/day need higher dose

Do NOT use in pts with major psychotic disorder

Question 21

Most common ADR of Adenosine A2A Rec Antag

Answer 21

Dyskinesia

Question 22

Levodopa Pearls

Answer 22

• Most effective drug for sx tx (akinetic sx > tremor/rigidity&raquo_space; postural instability)
• “on” time 5-6 hrs, 5-6 doses needed/day
• new pts- take with snack
• advanced pts: take on empty stomach

Question 23

Carbidopa Pearls

Answer 23

No activity on its own

Question 24

Entacapone Pearls

Answer 24

• No activity on its own
• When added, levo dose needs to be decreased
• May cause orange urine

Question 25

Levo dosing/admin

Answer 25

- ER cap--> swallow whole or sprinkle on applesauce - ER used once IR tolerated - No response >1000 mg/day, probs not PD

Question 26

Levodopa Product Pk

Answer 26

- Absorption issues: high protein, iron foods | - Block metabolism: MOAI (HTN crisis)

Question 27

Levodopa Product Pd

Answer 27

- Block levo effects--> anti-HTN meds | - Old antipsychotics/old nausea meds--> dopamine receptor blockade

Question 28

Levodopa Products ADRs

Answer 28

- N/V, anorexia - **Orthostatics--> common w initiation and increasing dose; no alpha-antagonists (BPH meds, cavedilol) - CNS--> vivid dreams, hallucinations, delusion, confusion (with chronic therapy or dose escalation)**

Question 29

Levodopa "special" ADRs

Answer 29

- "On-off" fluctuations- >5 yr therapy - Wearing off syndrome- end of dose effect <4hr following dose - Neurotox? - Inhalation levo- cough, URI, sputum discoloration

Question 30

Dopamine Receptor Agonists (ergot derivates)

Answer 30

- Bromocriptine | - **Minimal use d/t ADRs

Question 31

Dopamine Receptor Agonists (non-ergot derivates)

Answer 31

- Ropinirole - Pramipexole - Rotigotine - Apomorphine - **must do 4 week taper

Question 32

Dopamine Receptor Agonist MOA

Answer 32

Stimulate dopamine activity in striatum and substantia nigra

Question 33

Dopamine Receptor Agonist indications (oral/transdermal)

Answer 33

- Alt 1st line or add on to levo | - **Pramipexole, ropinirole, rotigotine FDA approved for RLS

Question 34

Dopamine Receptor Agonist Indications (SQ/SL)

Answer 34

- Tx of "off" episodes - Take with trimethobenzamide** for N/V - **Seratonin receptor antagonist (ondansetron) CI b/c hypotension with LOC

Question 35

Dopamine Receptor Agonist ADRs (pramipexole, ropirinole, rotigotine)

Answer 35

- Nausea - Somnolence--> falling asleep when driving - Impulse control

Question 36

MAOI-B

Answer 36

- Irreversible--> selegiline, rasagiline | - Reversible--> safinamide

Question 37

MAOI-B MOA

Answer 37

-MAOI-B breaks down dopamine--> drug blocks this in striatum

Question 38

MAOI-B indications

Answer 38

- Early dz--> initial therapy to improve sx but **moderately effective (rasagiline) - Late sz--> **adjunctive mgmt when levo efficacy deteriorating

Question 39

MAOI-B ADRs

Answer 39

- Nausea/HA - Orthostatics - Confusion (elderly) - **HTN crisis + tyramine rich foods or levo--> very low risk at usual doses