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PHRM 845: Therapeutics III > Parkinson's Disease > Flashcards

Parkinson's Disease Flashcards

1
Q

What is Parkinson’s Disease?

A
  • A chronic, progessive, IRREVERSIBLE, disease that forms a neurological deficit of the extrapyramidal system [In basal ganglia]
  • Issues with noncortical voluntary motor control
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2
Q

What are some of the symptoms of Parkinson’s Disease?

A
  • Resting Tremor [pill rolling motion], Rigidity, Slow Movement [Akinesia] Impaired balence, Speech issues…
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3
Q

What is the neuropathological underpinnings of Parkinsons Disease?

A
  • A loss of dopamine releasing neurons in the Substantia Nigra Pars Compacta [darkly pigmented areas]
  • Presence of Lewy Bodies in the brain; clump of a-synuclein on nerve cells resulting in the symptoms
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4
Q

What are the Braak Stages?

A
  • Stage 1: Lower Brainstem [Start]
  • Stage 2: Raphe
  • Stage 3: Substatia Nigra [necessary for PD] [Midbrain]
  • Stage 4: Mesocortex/Thalamus
  • Stage 5: Neocortex/Prefrontal Cortex
  • Stage 6: Entire Cortex
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5
Q

What is the Braak Stages based on?

A
  • Based on the distribution and density of the Lewy Bodies [a-Synuclein] within the brain
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6
Q

What are the two dopamine signaling pathways in neurons?

A
  • DIRECT: D1 receptors [SNpc - Striatum - Gpi/SNpr - Thalamus - cortex]
  • INDIRECT: D2 receptors [SNpc - Stiatum - Gpe - STN- Gpi/SNpr -Thalamus - cortex]
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7
Q

What happens then Thalamocortical signaling is interrupted?

A
  • Since both D1 and D2 receptors faver this signaling; it will DECREASE dopamine leading to DECREASED movement [main problem in parkinsons]
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8
Q

What is the way that Anticholinergics are used in Parkinsons Disease?

A
  • Add on therapy for tremors [Caused by an imbalance between Dopamine and cholinergic]
  • The decrease in dopamine will increase the cholinergic pathway = tremors
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9
Q

What is L-DOPA?

A
  • A precursor of dopamine and the “GOLD STANDARD” in parkinsons treatment
  • Able to enter the CNS [Brain] because of no charge
  • SE: Nausea, Vomiting, Hypertension, Psychosis
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10
Q

Why is L-DOPA given with Carbidopa?

A
  • Inhibits DCC from breakdown L-DOPA in the periphery; allowing it to get into the CNS [Brain
  • Decrease the side effects
  • Dopamine really can’t cross the BBB since its got a net positive charge
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11
Q

What are some of the challeneges associated with L-DOPA therapy?

A
  • On/Off Oscillations: After some times of using L-DOPA the drug effect may begin to fall off unpredictably [give continuos L-DOPA to fix]
  • Dyskinesias: Uncontrolled, Involuntary movement with long term use of L-DOPA
  • Since L-DOPA needs converted; the body may become unresponsive
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12
Q

What are the dopamine agonsts?

A
  • Apomorphine, Ergolines [Bromocriptine], Non-Eroglines [Ropinirole, Pramipexole, Rotigotine]
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13
Q

What is the function of Apomorphine in parkinsons disease?

A
  • Mixed D1/D2 Agonist [D2 deals with movement] that increases dopamine to the brain
  • Used in late stage Parkinsons for rapid relief of the off state
  • Non Ergot
  • SE: N/V, Hallucinations, ICD, $$$$
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14
Q

What is the funcation of the ergolines [Bromocriptine] in parkinsons disease?

A
  • D2 agonist with some effects in PD
  • Helps minimize LD motor fluctuations
  • Add on to L-DOPA
  • Pergolide and Cabergoline [Strong D2 Agonist] arent used because of Heart Valve Damage
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15
Q

What is the function of the Non-Ergolines [Ropinirole, Pramipexole, Rotigotine] in parkinsons disease?

A
  • D2/D3 agonist with fewer side effects than the ergolines and are used as monotherapies in early-stage PD
  • Rotigotine is a transdermal patch
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16
Q

What are the MAO-B inhibitors that are used in parksinsons disease?

A
  • Selegiline, Rasagiline, Safinamide
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17
Q

What is the function of Selegiline and Rasagiline in parkinsons disease?

A
  • both are propargylamines causing the irreversible inhibition of MAO-B [MAO-B will break down dopamine], so these will inhibit MAO-B from breaking down dopamine = INCREASING it
  • Mainly monotherapies but can be added on
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18
Q

What is the function of Safinamide in Parkinsons disease?

A
  • reversible inhibition of the MAO-B
  • Add on therapy to L-DOPA/Carbidopa
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19
Q

What are the COMT inhibitors used in parkinsons disease?

A
  • Entacapone, Tolcapone, Opicapone
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20
Q

What is the function of the COMT inhibitors?

A
  • They inhibit the methylation of the 3-OH group of DA or L-DOPA by COMT
  • Entacapone & Opicapone: decrease metabolism of L-DOPA in PERIPHERY
  • Tolcapone: keeps dopamine levels high in the CNS
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21
Q

What are the motors symptoms of Parkinsons disease?

A
  • Tremor, Bradykinesia [slow movement], Rigidity, Parkinsons Gait
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22
Q

What are the non-motor symptoms of Parkinsons disease?

A
  • Anxiety, depression, constipation, insomnia, psychosis, sexual dysfunction
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23
Q

What is the type of assessment used in diagnosing parkinsons disease?

A
  • Unified Parkinson’s Disease Rating Scale [UPDRS]
  • Looks as signs/symptoms of parkinsons disease
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24
Q

What are the goals of therapy for Parkinsons disease?

A
  • Manage motor and non-motor symptoms
  • Increase QOL
  • Preserve daily activities
  • Manage adverse drug reactions
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25
Q

What are some of the non-pharmacological treatments used in Parkinsons Disease?

A
  • EXERCISE [always started before actual treatment], Nutritional Counseling, Occupational therapy, Psychotherapy, Speech Therapy
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26
Q

What is the initial treatment for Parkinsons Disease?

A
  • 1st Line: Rule out drug-induced PD [anti-psychotics?]; DOPAMINE PRECURSOR [Gold Standard], Dopamine Agonist, MAO-B inhibitors
  • 2nd Line: COMT Inhibitors, Amantadine
27
Q

What should be the first medication used in the treatment of Parkinsons Disease?

A
  • Levodopa/Carbidopa
  • Maybe a Dopamine Agonist
28
Q

When may a Dopamine Agonist be used as initial treatment?

A
  • if the patient is <60 and is at high risk of dyskinesia [involuntary and uncontrolled movements]
29
Q

When should you avoid Dopamine Agonist as initial treatment?

A
  • if the patient is >70, history of ICD, cognitive impairment, daytime sleepiness, hallucinations
30
Q

When would be the best time to start a patient on Levodopa/Carbidopa for Parkinsons Disease?

A
  • when symptoms start affecting their daily life
  • Levodopa/Carbidopa > DA > MAOB-I
31
Q

What is the Dopamine Precursor used in Parkinsons Disease?

A
  • Levodopa/Carbidopa
  • First line for PD and the “GOLD STANDARD”
  • Add on with Dopamine Agonist or other meds
32
Q

What are the side effects for Levodopa/Carbidopa in Parkinsons?

A
  • Nausea, Vomiting, LD motor fluctuations, Hallucinations [high dopamine level]
33
Q

What are some of the clinical pearls for Levodopa/Carbidopa in Parkinsons Disease?

A
  • Increase absorption with empty stomach but food Decrease nausea
  • STARTING DOSE: 25/100 LD/CD PO BID-TID
34
Q

What are some of the long term conplications of using Levodopa/Carbidopa in Parkinsons Disease?

A
  • Levodopa will slowly overtime become more unresponsive and not work as well
35
Q

What are the Dopamine Agonist used in the treatment of Parkinsons Disease?

A
  • Nonergot and Ergot
36
Q

What are the Non-Ergot drugs used in Parkinsons Disease?

A
  • Pramipexole, Ropinirole, Rotigotine, Apomorphine
37
Q

What are the Ergot drugs used in Parkinsons Disease?

A
  • Bromocriptine, Cabergoline
38
Q

What are the side effects of the Dopamine Agonist [Non-Ergots and Ergots]?

A
  • Nausea. Vomiting, Sudden Sleep, Hallucinations, Impulse Control Disorder, Edema, $$$$
39
Q

What are the clinical pearls for the Dopamine Agonist?

A

STARTING DOSES:
- Pramipexole IR 0.125mg PO TID; ER 0.375 mg PO daily
- Ropinirole IR 0.25 mg PO TID; ER 2 mg PO daily
- Rotigotine 2 mg PATCH Q24H
- Apomorphine 2 mg SubQ injection

40
Q

What are the MAO-B Inhibitors used in Parkinsons Disease?

A
  • Rasagiline, Selegiline, Safinamide
41
Q

What is the MOA of MAO-B Inhibitors in Parkinsons Disease?

A
  • It will prevent the break down of dopamine; increased dopamine will decrease any motor issues
42
Q

What are the side effects of the MAO-B Inhibitors in parkinsons disease?

A
  • Nausea, Vomiting, Headache, Insomnia [selegiline], Hypo- and Hypertension
43
Q

What are some of the clinical pearls for the MAO-B Inhibitors in parkinsons disease?

A

STARTING DOSES:
- Rasagiline 0.5 mg PO Daily
- Selegiline 5 mg PO Daily
- Safinamide 50 mg PO Daily

  • Risk of serotonin syndrome
44
Q

What are the COMT Inhibitors used in Parkinsons disease?

A
  • Entacapone, Opicapone, tolcapone
45
Q

What is the MOA for the COMT inhibitors for Parkinsons Disease?

A
  • stops the breakdown of dopamine within the brain, increasing the levels of it in and minimizing the affects of Parkinsons
46
Q

What are the side effects for the COMT inhibitors in parkinsons disease?

A
  • Nausea, Vomiting, Brown/Orang urine color [entacapone], hepatotoxicity [tolcapone]
47
Q

What are the clinical pearls for the COMT inhibitors in parkinsons disease?

A
  • NOT used in early PD patients with LD/CD
    STARTING DOSE
  • Entacapone 200 mg PO
  • Tolcapone 100 mg PO TID
  • Opicapone 50 PO QHS
48
Q

What is the function of Amantadine in parkinsons disease?

A
  • MOA: increase the release and block the reuptake of dopamine within the brain
  • RARELY used in monotherapy
49
Q

What are some of the side effects of Amantadine in parkinsons disases?

A
  • Insomnia, Confusion, Halluciantion, Livedo Reticularis
50
Q

What are some of the clinical pearls for Amantadine in parkinsons disease?

A
  • reserved for LD/CD peak dose dyskinesias
  • STARTING DOSE: 100 mg PO BID
51
Q

What is the function of the Anticholinergics in Parkinsons disease?

A
  • MOA: blocks the overreactive cholinergic neurons in the brain; this reduces the dopamine/cholinergic imbalance
52
Q

What are the Anticholinergics in parkinsons disease?

A
  • Benztropine, Trihexyphenidyl
53
Q

What are some of the side effects for the anticholinergics in parkinsons disease?

A
  • Blurry vision, Urinary retention, Dry mouth, Constipation, Confusion/dementia
54
Q

What are some clinical pearls for anticholinergics in parkinsons diseases?

A

STARTING DOSE:
- Benzotropine 05mg PO QHS
- Trihexphenidyl 1 mg PO daily

  • Avoid if > 65 yo because of the Anti-muscarinic SE
55
Q

What medications do you really not want to use in a patient that has parkinsons disease?

A
  • Antipsychotics
56
Q

What are the pros of using Levodopa/Carbidopa in parkinsons disease?

A
  • GOLD STANDARD
  • Cheapo
  • bunch of dosages forms
57
Q

What are some cons of using Levodopa/Carbidopa in parkinsons disease?

A
  • Motor Fluctuations
  • Multiple time a day
58
Q

What are some pros for Dopamine agonists in parkinsons disease?

A
  • Once daily
  • Better in young patients
  • Limited motor fluctuations
59
Q

What are some cons for Dopamine Agonists in parkinsons disease?

A
  • $$$
  • Less benefit than LD/CD
  • MANY adverse effects
60
Q

Who should take dopamine agonist for Parkinsons disease?

A
  • Age < 60 & high risk of dyskinesias
  • AVOID if: >70yo, history of ICD, Cognitive impairment, sleepiness, hallucinations
61
Q

What are some pro for MAO-B inhibitors in parkinsons disease?

A
  • Well tolerated
  • delays motor fluctuations
62
Q

What ares some cons for MAO-B inhibitors in parkinsons disease?

A
  • Least effective against motor symptoms
  • serotonin syndrome?
63
Q

Who should get MAO-B inhibitors in parkinsons disease?

A
  • Have minor symptoms
  • Have higher risk of motor fluctuations

PHRM 845: Therapeutics III (25 decks)

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