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Clinical Pharmacology > Parkinson's Disease > Flashcards

Parkinson's Disease Flashcards

1
Q

Clinical signs of PD (TRAP pneumonic)

A
  • Tremor at rest
  • Rigidity
  • Akinesia or bradykinesia
  • Postural/gait instability
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2
Q

Neurotransmitters involved in PD

A
  • Dopamine*** (deficiency)
  • NE
  • ACh
  • Glutamate
  • Seratonin
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3
Q

“1st Line PD drugs”

A
  • Levodopa plus carbidopa +/- entacopone

- Dopamine agonists

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4
Q

“2nd Line PD drugs”

A
  • Anticholinergics
  • Selective MOA B inhibitors
  • NMDA antagonists
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5
Q

Levodopa Products

A
  • Carbidopa/Levodopa

- Carbidopa/Levodopa/Entacapone

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6
Q

Levodopa MOA

A

Travels to BBB where it gets decarboxylated to dopamine

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7
Q

Carbidopa MOA

A
  • blocks conversion of levo to dopamine before BBB

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

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8
Q

Entacapone

A

-Prolong action of levo by inhibiting O-methylation

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9
Q

Anticholinergics

A

Trihexyphenidyl and Benztropine

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10
Q

Anticholinergics MOA

A

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

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11
Q

Clinical indications of anticholinergics

A

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

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12
Q

Anticholinergics pearl

A

Both can be used to treat drug-induced EPS

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13
Q

NMDA Antagonists

A

Amantadine

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14
Q

NMDA MOA

A

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

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15
Q

Clinical indications of NMDA Antagonists

A

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

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16
Q

NMDA Antag Interactions

A

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

17
Q

NMDA Antag ADRs

A

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

18
Q

Adenosine A2A Rec Antag

A

Istradefylline

19
Q

Clinical indications of Adenosine A2A Rec Antag

A

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

20
Q

Adenosine A2A Rec Antag pearls

A

Pts who smoke over 20 ciggies/day need higher dose

Do NOT use in pts with major psychotic disorder

21
Q

Most common ADR of Adenosine A2A Rec Antag

A

Dyskinesia

22
Q

Levodopa Pearls

A
  • 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
23
Q

Carbidopa Pearls

A

No activity on its own

24
Q

Entacapone Pearls

A
  • No activity on its own
  • When added, levo dose needs to be decreased
  • May cause orange urine
25
Q

Levo dosing/admin

A
  • ER cap–> swallow whole or sprinkle on applesauce
  • ER used once IR tolerated
  • No response >1000 mg/day, probs not PD
26
Q

Levodopa Product Pk

A
  • Absorption issues: high protein, iron foods

- Block metabolism: MOAI (HTN crisis)

27
Q

Levodopa Product Pd

A
  • Block levo effects–> anti-HTN meds

- Old antipsychotics/old nausea meds–> dopamine receptor blockade

28
Q

Levodopa Products ADRs

A
  • 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)**
29
Q

Levodopa “special” ADRs

A
  • “On-off” fluctuations- >5 yr therapy
  • Wearing off syndrome- end of dose effect <4hr following dose
  • Neurotox?
  • Inhalation levo- cough, URI, sputum discoloration
30
Q

Dopamine Receptor Agonists (ergot derivates)

A
  • Bromocriptine

- **Minimal use d/t ADRs

31
Q

Dopamine Receptor Agonists (non-ergot derivates)

A
  • Ropinirole
  • Pramipexole
  • Rotigotine
  • Apomorphine
  • **must do 4 week taper
32
Q

Dopamine Receptor Agonist MOA

A

Stimulate dopamine activity in striatum and substantia nigra

33
Q

Dopamine Receptor Agonist indications (oral/transdermal)

A
  • Alt 1st line or add on to levo

- **Pramipexole, ropinirole, rotigotine FDA approved for RLS

34
Q

Dopamine Receptor Agonist Indications (SQ/SL)

A
  • Tx of “off” episodes
  • Take with trimethobenzamide** for N/V
  • **Seratonin receptor antagonist (ondansetron) CI b/c hypotension with LOC
35
Q

Dopamine Receptor Agonist ADRs (pramipexole, ropirinole, rotigotine)

A
  • Nausea
  • Somnolence–> falling asleep when driving
  • Impulse control
36
Q

MAOI-B

A
  • Irreversible–> selegiline, rasagiline

- Reversible–> safinamide

37
Q

MAOI-B MOA

A

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

38
Q

MAOI-B indications

A
  • Early dz–> initial therapy to improve sx but **moderately effective (rasagiline)
  • Late sz–> **adjunctive mgmt when levo efficacy deteriorating
39
Q

MAOI-B ADRs

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

Clinical Pharmacology (54 decks)

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