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HLSC 220 - Pharmacotherapeutics for Healthcare Professionals > Chapter 24 - Drugs for Parkinson's Disease > Flashcards

Chapter 24 - Drugs for Parkinson's Disease Flashcards

1
Q

What is Parkinson’s Disease?

A

a neurodegenerative disorder of the extrapyramidal system associated with the disruption of neurotransmission

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2
Q

PD is characterized by __________ and __________

A

dyskinesia and akinesia

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3
Q

PD causes an imbalance between ___________ and _____ due to the degeneration of neurons

A

dopamine and ACh

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4
Q

Why does inadequate dopamine affect neurons?

A

no dopamine means ACh causes excessive stimulation of neurons that release GABA

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5
Q

What causes motor symptoms of PD?

A

overactiivity of GABA neurons

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6
Q

What are symptoms dyskinesias?

A

-tremor at rest
-rigidity
-postural instability
-bradykinesia (slowed movement)

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7
Q

What are non-motor symptoms of PD?

A

-autonomic disturbances
-depression
-psychosis
-dementia

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8
Q

What is the therapeutic goal of PD?

A

improve patient’s ability to carry out ADLs

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9
Q

Is there a treatment that reverses neuronal degeneration?

A

no

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10
Q

What are the two drug categories for PD?

A

-dopaminergic agents
-anticholinergic agents

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11
Q

What are the most commonly used drugs for PD?

A

dopaminergic agents

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12
Q

What do dopaminergic agents do?

A

promote activation of dopamine receptors

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13
Q

What is the prototype dopaminergic agent?

A

levodopa

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14
Q

What do anticholinergic agents do?

A

prevent activation of cholinergic receptors

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15
Q

What is the prototype anticholinergic for PD?

A

Benztropine

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16
Q

What drug is used for mild symptoms of PD?

A

monoamine oxidase-B (MAO-B) inhibitor like SELEGILINE or RASAGILINE

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17
Q

What drugs are used for more severe PD symptoms?

A

Levodopa combined with carbidopa or benserazide

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18
Q

What is a long-term risk of Levodopa?

A

disabling dyskinesias

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19
Q

“OFF” times for motor fluctuations can be reduced with…

A

dopamine agonists, COMT inhibitors, MAO-B inhibitors

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20
Q

Are there drugs that provide neuroprotection for PD?

A

no

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21
Q

___________ is only given in combination with carbidopa or benserazide

A

Levodopa

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22
Q

How does Levodopa act?

A

-increases dopamine synthesis in the brain to restore the balance between dopamine and ACh

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23
Q

What is Levodopa?

A

the biological precursor of dopamine

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24
Q

What breaks levodopa down into dopamine?

A

enzyme dopa-decarboxylase (DDA)

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25
Q

How does levodopa enter the brain?

A

via an active transport system

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26
Q

What enhances the activity of decarboxylase?

A

pyridoxine (Vitamin B6)

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27
Q

Levodopa is useful for PD for ___ years before losing efficacy after 5 years

A

2

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28
Q

How is levodopa administered?

A

orally

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29
Q

What are food restrictions of Levodopa?

A

-food delays absorption

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30
Q

What kind of foods reduce therapeutic effects of levodopa?

A

high-protein foods

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31
Q

How can you minimize the wearing off effect of levodopa?

A

-shorten dosing interval
-give drug that prolongs half life
-give a direct-acting dopamine agonist

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32
Q

What are the adverse effects of Levodopa?

A

-N&V
-orthostatic hypotension
-palpitations
-agitation
-anxiety
-psychosis
-dyskinesias
-vivid dreams
-nightmares
-impulsivity
-memory impairment
-darkened sweat and urine
-activates malignant melanoma (SKIN ASSESSMENTS!!)

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33
Q

What does Levodopa interact with?

A

-1st gen. antipsychotics
-MAOIs (htn crisis)
-anticholinergics

34
Q

How do 1st gen antipsychotics interact with levodopa?

A

block DA receptors and decrease therapeutic effects

35
Q

How do MAOIs interact with levodopa?

A

htn crisis

36
Q

How do anticholinergic drugs interact with levodopa?

A

contribute to dyskinesias, cause enhanced response to levodopa

37
Q

Do carbidopa and benserazide have therapeutic effects of their own?

A

no

38
Q

What do carbidopa and benserazide do?

A

inhibit decarboxylation of levodopa in intestine (helps inhibit conversion of levodopa into DA allowing it to be available in the CNS), thus decreasing the needed dosage by 75%

39
Q

Carbidopa reduces what adverse effects of levodopa?

A

-CV
-N&V

40
Q

Dopamine agonists are _____-line drugs for PD

A

first

41
Q

How do dopamine agonists act?

A

directly activate dopamine receptors

42
Q

How do dopamine agonists compare to Levodopa?

A

-are less effective
-don’t depend on enzymatic conversion to be ACTIVE
-lower incidence of response failure
-less likely to cause dyskinesia

43
Q

What are the two types of dopamine agonists?

A

-derivatives of ergot
-non-ergot derivatives

44
Q

What kind of dopamine agonist is Pramipexole?

A

non-ergot

45
Q

How does pramipexole act?

A

D2 (some D3) receptor agonist

46
Q

When is pramipexole used?

A

-early PD
-with levodopa in advancing PD

47
Q

What are the adverse effects of pramipexole used alone?

A

-nausea
-dizziness
-somnolence
-insomnia
-constipation
-weakness
-hallucinations

48
Q

What are the adverse effects of pramipexole used in combo?

A

-orthostatic hypotension
-dyskinesias
-hallucinations

49
Q

What are rare adverse effects of pramipexole?

A

-impulse control disorders (gambling, shopping, eating)
-sleep attacks

50
Q

What kind of dopamine agonist is rotigotine?

A

non-ergot

51
Q

How does rotigotine act?

A

D2 and D3 receptor agonist, some action on other dopamine, alpha, and serotonin receptors

52
Q

When is rotigotine used?

A

-early in tmt
-with or without levodopa

53
Q

What are side effects of rotigotine?

A

-N&V
-dizziness
-somnolence
-site reactions

54
Q

How is rotigotine applied?

A

patch - do not cut to get lower dose

55
Q

What is a limitation of Bromocriptine?

A

poorly tolerated

56
Q

What kind of dopamine agonist is Bromocriptine?

A

ergot derivative

57
Q

How does Bromocriptine act?

A

direct dopamine agonist (activates dopamine receptors)

58
Q

How is Bromocriptine used?

A

-early PD
-in combo with levodopa for advance PD

59
Q

What are the adverse effects of Bromocriptine?

A

-nausea
-confusion
-nightmares
-hallucinations
-delusions
-retroperitoneal fibrosis
-pulmonary infiltrates
-Raynaud like phenomenon
-valvular heart disease

60
Q

How do COMT inhibitors act?

A

inhibit metabolism of levodopa in the periphery by inhibiting the COMT enzyme

61
Q

What are the direct therapeutic effects of COMTIs?

A

none. lol.

62
Q

What category is Entacapone?

A

COMT inhibitor

63
Q

Entacapone is combined with levodopa to:

A

-prolong the time levodopa is available in the brain
-inhibit levodopa metabolism in the intestine and periphery

64
Q

What are the adverse effects of Entacapone?

A

-dyskinesias
-orthostatic hypotension
-nausea
-hallucinations
-sleep disturbances
-impulse control disorders
-vomiting
-diarrhea
-constipation
-yellow-orange discolouration of urine

65
Q

What kind of drug is Selegiline?

A

a MAO-B inhibitor

66
Q

Selegiline causes…

A

modest improvement of motor function

67
Q

Benefits of Selegiline decline dramatically in ___ to ___ months

A

12-24 months

68
Q

When is selegiline used?

A

early in PD progression

69
Q

High doses of selegiline can interact with ___________

A

tyramine

70
Q

How does amantadine act?

A

-inhibits DA uptake and stimulates DA release
-blocks cholinergic receptors
-blocks glutamate receptors

71
Q

Is amantadine a first line agent?

A

no

72
Q

How long is the amantadine response?

A

starts in 2-3 days, diminishes in 3-6 months

73
Q

What is amantadine used for?

A

dyskinesias caused by levodopa

74
Q

What are the adverse effects of amantadine?

A

-confusion
-anxiety
-blurred vision
-urinary retention
-dry mouth
-constipation
-livedo reticularis

75
Q

Livedo reticularis

A

a condition characterized by mottle discolouration of the skin

76
Q

How do centrally acting anticholinergics act?

A

block muscarinic receptors in the striatum

77
Q

What are come centrally acting anticholinergic drugs?

A

-Benztropine
-Trihexyphenidyl
-Procyclidine

78
Q

How do centrally acting anticholinergic drugs compare to levodopa and dopamine agonists?

A

-less effective
-better tolerated

79
Q

Which drugs are used for younger patients with mild symptoms?

A

centrally acting anticholinergic drugs

80
Q

centrally acting anticholinergic drugs should be avoided in…

A

elderly patients

HLSC 220 - Pharmacotherapeutics for Healthcare Professionals (18 decks)

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