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Neurology Exam II > Parkinson's Disease > Flashcards

Parkinson's Disease Flashcards

0
Q

What are the cardial signs of Parkinson’s disease?

A

Resting tremor (a slow rhythmic tremor in hands or extremities that subsides during movement), rigidity (often with cogwheeling), bradykinesia (slowness of movement), gait disturbances and postural instability

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1
Q

What is a progressive neurological disorder characterized by the progressive loss of dopaminergic neurons within the substantia nigra of the midbrain?

A

Parkinson’s

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2
Q

What is the mean age of onset for Parkinson’s disease?

A

55 years (incidence increases dramatically with age)

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3
Q

Is Parkinson’s considered to be a genetic or sporadic disorder?

A

Sporadic (95% forms of unknown etiology)

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4
Q

It has been hypothesized that sporadic Parkinson’s disease is due to what?

A

Exposure to environmental toxins in genetically susceptible individuals

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5
Q

Familial (inherited) forms of Parkinson’s disease is due to what?

A

AD or AR mutations in various genes, many of which are involved in proteosome functions

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6
Q

Pharmacological treatment of Parkinson’s disease is effective during what stage of the disease?

A

Early stages

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7
Q

Is there a cure for Parkinson’s disease?

A

No

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8
Q

What are the pathological hallmarks of Parkinson’s disease?

A

Loss of nigral dopaminergic neurons within the midbrain and cytoplasmic inclusions termed “Lewy Bodies”

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9
Q

The cytoplasmic inclusions “Lewy Bodies” in Parkinson’s disease contain what proteins?

A

Alpha-synuclein and ubiquitin (role unknown)

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10
Q

Is Parkinson’s a hypo or hyperkinetic disorder?

A

Hypokinetic

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11
Q

Parkinson’s disease is often contrasted to what hyperkinetic disorder that also affects basal ganglia function?

A

Huntington’s disease

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12
Q

What disease is exclusively a hereditary AD neurodegenerative disease characterized by the progressive degeneration of striatal GABAergic neurons?

A

Huntington’s

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13
Q

What disease is caused by an expanded Trinucleotide CAG repeat in the gene encoding the Huntington protein (unknown function) which causes neuronal inclusions that are comprised of aggregates of mutated Huntington protein?

A

Huntington’s

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14
Q

How does dopamine regulate basal ganglia function?

A

Suppresses indirect pathway (D2 receptor function)

Enhances direct pathway (D1 receptor function)

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15
Q

Over reactivity of the subthalamic nucleus and impaired motor function due to enhanced tonic inhibition of the thalamocortical neurons describes what?

A

Reduced inhibition of the indirect pathway

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16
Q

What pathway direct or indirect functions to facilitate movement in a healthy individual?

A

Direct

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17
Q

What is the net result of dopamine loss?

A

Tipping of the balance toward indirect pathway activity leading to impaired ability to initiate and terminate voluntary movements.

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18
Q

What Parkinson’s drug is a metabolic intermediary in the synthesis of Catecholamines?

A

Levodopa

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19
Q

What enzyme converts levodopa to dopamine in the CNS and the periphery?

A

AADC aka DDC (dopamine decarboxylase)

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20
Q

What percentage of levodopa is decarboxylated by DDC peripherally?

A

95%

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21
Q

Levodopa is administered with what other drug in order to reach therapeutic levels in the CNS?

A

Carbidopa

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22
Q

The trade name drug for the combination of levodopa and carbidopa is what?

A

Sinemet

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23
Q

What allows levodopa to cross the blood brain barrier?

A

Large Neutral Amino Acid transporter ( LNAA)

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24
Q

What takes up levodopa as it crosses the BBB?

A

Dopaminergic nerve terminals within the striatum

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25
Q

Involuntary movements (dyskinesias and dystonias) and psychiatric disturbances are side effects of long term use of what Parkinson’s drug?

A

Levodopa

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26
Q

What percentage of patients will suffer from some combination of insomnia, unpleasant dreams, anxiety, depression, mania, paranoia, or hallucinations?

A

15%

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27
Q

Psychiatric side effects of levodopa are usually related to what?

A

Dose

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28
Q

The administration of levodopa can produce what kind of clinically significant cardial effects by the conversion of peripheral dopamine to norepinephrine?

A

Sympathomimetic

29
Q

The cardiac side effects of levodopa administration can be controlled with what drug?

A

Propranolol

30
Q

What side effect of levodopa is common early in treatment?

A

Orthostatic hypotension

31
Q

What gastrointestinal side effects to levodopa are observed early in treatment and are thought to be due to stimulation of dopamine receptors in the emetic centers of the brain such as the area postrema where the BBB is not intact?

A

Nausea, vomiting, anorexia

32
Q

Concurrent use of levodopa with what other type of drug can lead to hypertensive crisis?

A

Non-selective monoamine oxidase inhibitors (phenylzine)

33
Q

What type of drugs can decrease the effectiveness of levodopa by a direct antagonistic action on dopamine receptors? ( treatment with dopamine receptor antagonists can lead to drug induced Parkinsonian symptoms)

A

Antipsychotic medications (haloperidol)

34
Q

What can decrease levodopa’s effectiveness by competing for the amino acid transport systems in the gut and brain?

A

Dietary amino acids (large doses)

35
Q

Patients develop tolerance to cardiovascular and gastrointestinal side effects of levodopa usage however patients never develop tolerance to what other side effects?

A

Psychiatric and involuntary movement side effects

36
Q

What Parkinson’s drug markedly reduces the symptoms of bradykinesia and rigidity and requires extreme precaution when administering to patients with a history of cardiac or psychiatric disease?

A

Levodopa

37
Q

What drug is a peripheral decarboxylase inhibitor (inhibits L-aromatic acid decarboxylase), in the ionized form and doesn’t cross the BBB, must be given with levodopa allowing a greater portion of levodopa to reach the CNS?

A

Carbidopa

38
Q

What are the advantages of using sinemet instead of levodopa therapy alone?

A
  • 1/4 dose of levodopa is needed compared to treatment without levodopa
  • levodopa/carbidopa combo nearly abolishes CV and GI side effects
  • effective therapeutic dose is achieved sooner
39
Q

Sinemet will not abolish what type of side effects?

A

CNS side effects (involuntary movements and psychiatric disturbances)

40
Q

Levodopa/carbidopa is administered in what ratios?

A

10:1 and 4:1 (levodopa:carbidopa)

41
Q

What are 2 examples of dopamine agonists?

A

Pramipexole and ropinerole

42
Q

What 2 dopamine agonists bind selectively to dopamine D2 receptors, are potent dopamine D3 receptor agonists, and are used as adjuncts to sinemet by reducing “off” times and improving motor function and by permitting a decrease in sinemet dosage?

A

Pramipexole and ropinerole

43
Q

What are some side effects of dopamine receptor agonists?

A

Orthostatic hypotension, nausia, hallucinations, somnelence and dyskinesia

44
Q

What is an antiviral drug that is used in Parkinson’s for the effect of release of dopamine from the functionally intact dopaminergic terminals of Parkinson’s patients?

A

Amantadine

45
Q

When is amantadine treatment most effective?

A

When administered with levodopa in patients who cannot attain a full therapeutic response with levodopa alone

46
Q

What are the 2 isozyme forms of monoamine oxidases?

A

MAOa and MAOb

47
Q

What monoamine oxidase metabolizes dopamine to a greater extent than serotonin and norepinephrine?

A

MAOb

48
Q

What monoamine oxidase metabolizes serotonin and norepinephrine?

A

MAOa

49
Q

What Parkinson’s drug is a relatively selective MAOb inhibitor and is used to conserve dopamine levels in the brain without causing a marked elevation in norepinephrine and serotonin levels?

A

Selegiline

50
Q

What Parkinson’s drug has been shown to block or reduce the destruction of substantia nigral neurons by the neurotoxin MPTP in laboratory animals, postpones the need for treatment with levodopa 6-9 months, reduces the required dose needed for levodopa, increases the duration of levodopa effect while minimizing the side effects and has reduced incidence of psychiatric side effects compared to dopamine agonists?

A

Selegiline

51
Q

What are 2 examples of reversible COMT inhibitors that are used as adjuncts to l-dopa therapy, decrease the clearance rate of l-dopa making more l-dopa available to the brain and prolonging the duration of action of l-dopa 20-30%?

A

Tolcapone and entacopone

52
Q

What percentage of l-dopa is O-methylated by COMT?

A

10%

53
Q

Where can COMT be found in the body?

A

Periphery ( liver and kidney) and CNS

54
Q

What COMT inhibitor used in Parkinson’s inhibits COMT peripherally and does not cross the BBB?

A

Entacopone

55
Q

What COMT inhibitor used in Parkinson’s inhibits COMT both peripherally and centrally?

A

Tolcapone

56
Q

Increased dyskinesias (which can be managed by decreasing the dose of l-dopa), nausea, mild somnelence, and rarely orthostatic hypertension are side effects of what drugs?

A

COMT inhibitors ( Entacopone, tolcapone)

57
Q

What muscarinic cholinergic antagonist help restore the DA/ACh balance by blunting the muscarinic cholinergic influence and has side effects similar to atropine in the blockade of the PNS?

A

Benztropine

58
Q

Anticholinergics (benztropine) are useful in what situations?

A
  • early in treatment when symptoms are minimal

- as an adjunct to l-dopa (sinemet) to enhance levodopa’s effectiveness

59
Q

In contrast to l-dopa Muscarinic cholinergic antagonist reduce tremor more effectively than they reduce what other two symptoms?

A

Rigidity and bradykinesia

60
Q

Levodopa is only maximally effective for what duration of time?

A

3-6 years

61
Q

What is the “wearing off” effect?

A

Nigrastriatal dopinergic neurons undergoing progressive degeneration, patients experience a shorter duration of drug action requiring a higher frequency of dosing and elevation of dose

62
Q

What percentage of Parkinson’s patients experience an on-off phase characterized by symptomatic relief being unpredictable following a given dose of sinemet?

A

50%

63
Q

Debilitating rigidity and immobility is characterized as what phase?

A

Off phase

64
Q

Debilitating dyskinesia or painful dystonia is characterized by what phase?

A

On phase

65
Q

If levodopa is discontinued how many days should it take to be tapered off?

A

3-4 days

66
Q

A state of fever, rigidity, and confusion resembling a neuroleptic malignant syndrome in addition to causing Classic Parkinson’s symptoms is characteristic of what?

A

Sudden discontinuation of levodopa

67
Q

What percentage of patients respond favorable to taking selegiline upon diagnoses of Parkinson’s and then taking the lowest effective dose of sinemet?

A

75%

68
Q

When low doses of sinemet are no longer effective, instead of increasing the dose of sinemet the addition of what drug has the effect of lowering the overall incidence of both “wearing off” effects and dyskinesias?

A

Dopamine receptor agonists (ropinirole)

69
Q

What type of drugs are used sparingly as an adjunct only when tremors are a prevalent symptom?

A

Muscarinic cholinergic antagonists

Neurology Exam II (3 decks)

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