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D1 Spring > Pharmacology - Drug Tx of Parkinson's (Exam 3) > Flashcards

Pharmacology - Drug Tx of Parkinson's (Exam 3) Flashcards

1
Q

Tremor at rest, postural instability, dysphagia, drooling, bradykinesia, may progress to akinesia

A

Dyskinesias

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1
Q

Chronic, idiopathic neurodegeneration of extrapyramidal system causing loss of control of movement

A

Parkinson’s Disease

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2
Q

Dementia, depression, impaired memory

A

Psychological disturbances of PD

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3
Q

Parkinson’s like symptoms:

Drug side effects
Component of other disorders (Shy-Drager syndrome)
Less responsive to drug therapy used for PD

A

Parkinsonism

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4
Q

Idiopathic loss of nigrostriatal dopaminergic neurons

A

Parkinson’s Disease

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5
Q

Drug therapy increases _________ in striatum

A

dopamine

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6
Q

Levels of what neurotransmitter are reduced in PD?

A

Striatal dopamine

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7
Q

What are potential side effects, complications, and interactions of PD?

A

Facial movements
Hypotension
Nausea
Opioid interactions
Catecholamine interactions

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8
Q

Describe the neuropathophysiology of PD (4 things)

A
  1. Loss of cell bodies in substantia nigra
  2. Genetic risk factors
  3. Antipsychotic drugs/environmental agents can cause parkinson-like syndrome
  4. MPTP (dopamine neurotoxin) causes parkinson-like syndrome
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9
Q

What is involved in the extrapyramidal system? (4 things)

A
  1. Nigrostriatal dopaminergic pathway
  2. Striatal cholinergic neurons
  3. GABAergic neurons
  4. Balance between dopaminergic and cholinergic activity (controls voluntary movement)
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10
Q

Inhibitory neurons innervating striatum

A

Nigrostriatal dopaminergic pathway

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11
Q

What is the goal of drug therapy for PD?

A

Raise dopamine levels

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12
Q

What is the goal of drug therapy for parkinsonism?

A

Lower ACh levels

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13
Q

Disease where there is a defect in GABAergic neurons

A

Huntington’s Disease

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14
Q

Genetic disease caused by triplet nucleotide repeat

A

Huntington’s Disease

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15
Q

Mechanism of Levodopa (L-dopa)

A

Converted to dopamine in striatum

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16
Q

T/F dopamine crosses the blood brain barrier

A

FALSE

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17
Q

T/F DOPA crosses the blood brain barrier

A

True

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18
Q

Which enzyme converts Tyrosine to Dihydroxyphenylalanine (DOPA)?

A

Tyrosine hydroxylase

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19
Q

Which enzyme converts Dihydroxyphenylalanine (DOPA) to dopamine?

A

Aromatic L-amino acid decarboxylase

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20
Q

What are the symptoms of peripheral toxicity of Levodopa?

A

GI: nausea, vomiting
Heart: postural hypotension, arrhythmia

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21
Q

What are the symptoms of CNS toxicity of Levodopa?

A

Neurological: dyskinesias (abnormal mouth movements, tongue thrusting, chewing motions)

Behavioral: insomnia, anxiety, delirium, depression

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22
Q

Sympathomimetic drug (B agonist) + Levodopa

A

Cardiac stimulation

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23
Q

Pyridoxine (vitamin B6) + Levodopa

A

Decreased efficacy of Levodopa

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24
Q

Antipsychotic drugs + Levodopa

A

Decreased efficacy of Levodopa

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25
Q

Monoamine oxidase inhibitors (MAOIs) + Levodopa

A

Hypertensive crisis

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26
Q

What are the 2 fluctuations in therapeutic response of Levodopa?

A
  1. “Wearing off” phenomenon
  2. “On-off” phenomenon
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27
Q

What are the components of the “wearing off” phenomenon of Levodopa?

A

Related to timing
Nigrostriatal tract degeneration

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28
Q

What are the components of the “on-off” phenomenon of Levodopa?

A

Alterations in drug availability NOT related to timing

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29
Q

What is Sinemet a mix of?

A

Levodopa + Carbidopa

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30
Q

Advantages of Carbidopa

A
  1. Increased half-life of Levodopa
  2. Decreased peripheral side effects
  3. Diminished CNS (dopamine) fluctuations
31
Q

Disadvantages of Carbidopa

A

Increased CNS side effects

32
Q

T/F Carbidopa does NOT cross the blood brain barrier

33
Q

What is the mechanism of Carbidopa?

A

Inhibits dopa-decarboxylase

34
Q

What is the mechanism of Amantadine?

A

Increases synaptic dopamine concentration

35
Q

What is Amantadine frequently administered with?

36
Q

T/F Amantadine is less efficacious and less toxic than Levodopa

37
Q

Which drugs are the dopamine receptor agonists (also called ergot alkaloids)?

A

Bromocriptine
Pergolide

38
Q

What are the symptoms of toxicity of Bromocriptine and Pergolide?

A

Arrhythmia
Nausea
Dyskinesias
Delusions
Hallucinations
Hypotension

39
Q

What are Bromocriptine and Pergolide used for?

A

Additive therapeutic effects with Levodopa

40
Q

Which drug has been associated with valvular heart disease and is therefore no longer available?

41
Q

What drugs are the synthetic dopamine agonists? What receptors are they involved with?

A

Pramipexole (D3 agonist)
Ropinirole (D2 agonist)

42
Q

T/F Pramipexole and Ropinirole are used alone in the early stages of PD

43
Q

What effects do Pramipexole and Ropinirole have?

A

Effects similar to older agonists

44
Q

What is Ropinirole metabolized by?

45
Q

What can inhibit CYP1A2 and cause decreased metabolism/increased blood concentration of Ropinirole?

A

Ciprofloxacin

46
Q

What is the rare side effect of Pramipexole and Ropinirole?

A

Compulsive gambling

47
Q

What is the mechanism of Apomorphine?

A

Dopamine agonist

48
Q

What is Apomorphine used for?

A

Rescue of akinesia in “off” periods

49
Q

How is Apomorphine administered?

A

Injected subcutaneously (fast action)

50
Q

What are the side effects of Apomorphine?

51
Q

What can you use as a pretreatment to prevent nausea associated with Apomorphine?

A

Trimethobenzamide

52
Q

What drugs are monoamine oxidase B inhibitors?

A

Selegiline
Rasagiline

53
Q

What does Selegiline decrease?

A

“On-off” fluctuations

54
Q

What does Selegiline prolong?

A

The usefulness of Levodopa

55
Q

What is a side effect of high doses of Selegiline when given with Levodopa?

A

Dyskinesias

56
Q

T/F Rasagiline is a less potent MAO-B inhibitor

A

FALSE, it is more potent

57
Q

T/F Rasagiline is NOT metabolized to amphetamine/methamphetamine

58
Q

What drugs are the Catechol-O-Methyltransferase (COMT) inhibitors?

A

Tolcapone
Entacapone

59
Q

What is the mechanism of Tolcapone and Entacapone?

A

Inhibit metabolism of Levodopa to 3-O-methyldopa

60
Q

What do Tolcapone and Entacapone enhance?

A

Uptake of Levodopa

61
Q

Tolcapone has action in the __________ and the __________

A

periphery; CNS

62
Q

Entacapone has action in the __________ only

63
Q

Selegiline has action in the __________ only

64
Q

Which MAO receptor is in the periphery?

65
Q

Which MAO receptor is in the brain?

66
Q

What drugs are the anticholinergic drugs? What do they treat?

A

Benztropine
Trihexyphenidyl

They treat Parkinsonism

67
Q

What is the mechanism of Benztropine and Trihexyphenidyl?

A

Block muscarinic receptors to restore balance of neurotransmitters

68
Q

Benztropine and Trihexyphenidyl have ________ efficacy compared to Levodopa

69
Q

What are the symptoms of toxicity for Benztropine and Trihexyphenidyl?

A

Peripheral atropine-like effects
CNS toxicity (delirium, confusion)

70
Q

PD is a _________ disease

A

progressive

71
Q

T/F Levodopa does not lose its effectiveness

72
Q

What are the drug interactions for drugs used to treat PD?

A

MAO inhibitors
Catecholamines
Anti-muscarinics

73
Q

What are the important side effects of drugs used to treat PD? (3 things)

A
  1. Oral dyskinesias
    (causes dental problems: inflammation, tooth movement, difficulty wearing dentures)
  2. Orthostatic hypotension
  3. Sensitive to epinephrine induced arrhythmias
74
Q

What are some important things to consider for patients with PD?

A
  1. Drug induced xerostomia
  2. Nausea/vomiting effects on enamel
  3. Difficulty brushing/flossing
  4. Dysphagia
  5. Difficulty comprehending/remembering - be sure to write down instructions

D1 Spring (47 decks)

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