Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

PR3136 therapeutics > PD > Flashcards

PD Flashcards

1
Q

Describe how PD affects basic ADLs

A

Unable to perform basic ADLs (or to perform them safetly)

  • Mobility (walking, using stairs)
  • Feeding self
  • Grooming, personal hygiene
  • Toileting
  • Showering/bathing
  • Continence (bowel and bladder)

Dysphagia (→ pneumonia)

Falls (due to gait instability)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Explain the goal of managing PD

A

Not replace dopamine or cure

But to manage symptoms and maintain function & autonomy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is Parkinson’s disease?

A

Idiopathic, degenerative, CNS disorder with 4 characteristic features

  1. Slowness and poverty of movement
  2. Muscular rigidity
  3. Resting tremor
  4. Postural instability
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How is a diagnosis for PD made?

A

Based on clinical signs, physical examination, history.
2 of the 3 cardinal signs must be present:
- Tremor (resting tremor)
- Rigidity (“ratchet” like stiffness)
- Akinesia/bradykinesia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Features of idiopathic PD at initial presentation

A
  • Asymmetric
  • Positive response to levodopa or apomorphine
  • Postural instability (&falls) - not present
  • Less rapid progression (rapid = H&Y 3 in 3 years)
  • Autonomic dysfunction - not present
  • Neuroimaging - may not be able to see anything on neuroimaging
  • Impaired olfaction?
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Pathology of PD

A

Loss of dopaminergic neurons in the substantia nigra
about 80% loss → clinical symptoms

  • Age-related
  • Environmental toxin/insults
  • Genetics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is used to measure PD? What does it measure?

A

Hoen and Yahr staging of PD
1-5
(1 is mildest symptoms, 5 is most severe symptoms)
Assesses mobility (not nonmotor symptoms)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How many % of neurons need to be lost before seeing symptoms?

A

80%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which agents are used in early/young onset PD?

A

Dopamine agonists used in preference to levodopa due to longer elimination half life or duration of action, and prevent the development of dyskinesia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Features of early/young onset PD

A 
Slower disease progression 
Features 
- Less cognitive decline
- Earlier motor complications
- Dystonia is common initial presentation vs falls and freezing in late onset
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which agent can be used to prevent nerves from degenerating, i.e. neuroprotective agent?

A

No treatment for PD has ever been shown to be “neuroprotective”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Are non-pharmacologic treatments important in the management of PD? What are some examples?

A

Yes. helps patients cope with symptoms.

  • PT - stretching, transfers, posture walking
  • OT - mobility aids, home and workplace safety
  • Speech and swallowing
  • Surgery
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Pharmacological management of PD

A

Increase central dopamine, dopaminergic transmission

  • Levodopa + DCI
  • Dopamine agonists
  • MAO B inhibitors
  • COMT inhibitors

Correct imbalance in other pathways

  • Anticholinergics
  • NMDA antagonists
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

MOA of PD pharmacologicals

A

Increase central dopamine
Increase dopaminergic transmission
Correct imbalance in other pathways

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What symptoms are levodopa most effective and less effective in treating?

A

More effective in bradykinesia and rigidity

Less effective for speech, postural reflex and gait disturbancs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Why do we need to administer levodopa with DCI?

A

Dopamine cannot cross the BBB

Peripheral conversion of levodopa to dopamine is catalysed by DOPA decarboxylase, MAO, COMT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How to increase bioavailability of levodopa?

A

Add benserazide or carbidopa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How is absorption of levodopa affected by high fat or high protein meals? Implication?

A

Levodopa is absorbed by an active saturable carrier system for large neutral amino acids

If patients are required to be on high protein meals, need to seperate the administration of both by at least 2 hours.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the targets in reducing peripheral conversion of levodopa and dopamine? Examples of each?

A

Decarboxylase (carbidopa, benserazide)
COMT (entacapone)
MAO-B (selegiline)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Do DCIs cross the BBB?

A

No, they do not

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Adverse effects of levodopa

A
  • Nausea and Vomiting
  • Orthostatic hypotension
  • Drowsiness, sudden sleep onset
  • Hallucinations, psychosis
  • Dyskinesias (usual onset: 3-5 years of initiating treatment with levodopa)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Motor complications with levodopa

A

“on-off phenomenon”
“wearing off”
Dyskinesias

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the “on off phenomenon”?

A

ON = response to levodopa
OFF = no response to levodopa
Mechanism unclear

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the “wearing off” phenomenon?

A

Effect of levodopa wanes before the end of the dosing interval
Shortened “ON” time
Associated with disease progression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
How to manage "wearing off"
Modify times of administration | Replace with modified-release preparations at the appropriate time
26
What is dyskinesia? When does it occur and how to manage?
Involuntary, uncontrollable twitching and jerking Peak dose Management: add amantadine, replace specific doses with modified release levodopa
27
What are the changes in levodopa response associated with progression of PD?
In early PD: long duration of motor response, low incidence of dyskinesia Moderate PD: shorter duration of motor response, increased incidence of dyskinesia Advanced PD: short duration motor response, "ON"-time consistently associated with dyskinesia
28
What is the advantage of sustained release Levodopa?
Releases levodopa/DCI over a longer period which mitigates the wearing off effect
29
Why do dose adjustments have to be made with SR levodopa and how are they made?
Lower bioavailability with SR. IR to SR: generally increase dose needed SR to IR: generally decrease dose needed
30
Does dosing frequency change when SR formulations of levodopa are used?
No, frequency remains the same even in sustained release formulations
31
What is levodopa SR forms useful for?
Useful for reducing stiffness on waking
32
What should be avoided when taking sinemet SR and madopar HBS?
Sinemet SR → do not crush | Madopar HBS → do not open capsule
33
Drug interactions with levodopa
- Pyridoxine (B6) - Iron (space out administration) - Protein (space out administration) - Antidopaminergic drugs - antiemetics (metoclopramide, prochlorperazine), 1st generation antipsychotics, risperidone - Nonselective MAOis
34
What is the antiemetic of choice in PD?
Domperidone
35
What are ergot derivative dopamine agonists?
Bromocriptine Cabergoline Pergolide (not reg in singapore)
36
Non-ergot derivative dopamine agonists
Ropinirole Pramipexole Rotigotine (transdermal) Apomorphine (subcut)
37
Transdermal dopamine agonist
Rotigotine
38
MOA of dopamine agonists
Act on dopamine d2 receptors in the basal ganglia and mimic action of dopamine
39
Does ergot derived have higher or low F than non-ergot derived?
Lower, due to extensive first-pass metabolism
40
How does half life and duration of action of dopamine agonists compare with levodopa?
Longer half life and duration of action than levodopa
41
Which dopamine agonists require dose adjustments in hepatic or renal impairment?
Ropinirole: mainly metabolised by the liver, to inactive metabolites → dose adjust for hepatic impairment Pramipexole: excreted largely unchanged in the urine → dose adjust for renal impairment
42
Adverse effects of dopamine agonists
Dopaminergic - peripheral - Nausea, vomiting - Orthostatic hypotension - Leg edema Dopaminergic - central - Hallucinations - Somnolence, day-time sleepiness - Compulsive behaviors (gambling, shopping, eating, hypersexuality) Non-dopaminergic adverse effects - Fibrosis (higher with ergot) - Valvular heart disease (higher with ergot)
43
How does dopamine agonist compare with levodopa in terms of adverse effects?
Less motor complications than levodopa but | More hallucinations, sleep disturbances, leg edema, orthostatic hypotension
44
Dopamine agonists: place in the management of PD
- Monotherapy in young-onset PD - Adjunct to levodopa in moderate/severe PD - Management of motor complications caused by levodopa - Rotigotine patch - if patients not suitable for tube feeding and taking things orally - Neuroprotection, disease modification NOT proven
45
Which MAO is specific to PD
MAO-B (central, dopamine)
46
Rate of MAO regeneration
14-28 days
47
MAO-B inhibitors? | What kind of enzyme inhibitors are they?
Irreversible enzyme inhibitors - Selegiline - Rasagiline Short half life but long duration of action (takes 2-4 weeks to regenerate)
48
Are MAO-B inhibitors effective as monotherapy
Yes during early stages
49
Why might selegiline cause insomnia?
It is hepatically metabolised to amphetamines which are stimulating
50
Drug interactions of MAO-B inhibitors | - Not totally specific for MAO-B hence at higher doses may affect MAO-A which catalyses noradrenaline and 5HT.
SSRIs, SNRIs, TCAs - washout periods are recommended Pethidine, tramadol Linezolid Dextromethorphan Dopamine Sympathomimetics: nasal congestants eg pseudoephedrine, phenylephrine Another MAOi
51
Place of MAO-B inhibitors in the management of PD
- Improvement in UPDRS scores not as great as with dopamine agonists or levodopa - Monotherapy in early stages, or adjunct in later stages - More commonly used in early stages of young onset PD
52
How does levodopa compare with dopamine agonists and MAO-B inhibitors?
More improvements in motor symptoms More improvement in activities of daily living More motor complications Fewer specified adverse events
53
What are COM-T inhibitors? Examples?
COMT is major metaboliser of levodopa in the presence of a DCI - Entacapone - Tolcapone Decreases "off" time of levodopa Not effective without concurrent levodopa
54
What is entacapone? What are the dosing considerations?
Selective, reversible COMT inhibitor | must be taken at the same time as levodopa
55
Drug interactions and adverse effects of entacapone
Drug interactions: - Iron, calcium - avoid concurrent nonselective MAOi - any cathecholamine drug - enhance anticoagulant effect of warfarin AEs: diarrhea, urine discolouration
56
Which drugs may cause dyskinesia upon initiation?
Entacapone
57
How does tolcapone compare with entacapone?
More potent and longer duration of effect than entacapone - Less "off time: - May also need a greater reduction in levodopa dose - Need to monitor LFTs
58
What is the use of anticholinergics in PD?
Limited use, in practice, primarily used to control tremor
59
Side effects of anticholinergics
Constipation Blurred vision Urinary retention Confusion
60
Can ipratropium, hyoscine N-butylbromide, tolterodine be used to manage symptoms in PD?
No because it is a peripherally acting anticholinergic
61
What does glutamate do?
Glutamate activates NMDA receptor activity which activates processes that encourage cell death. Increased glutamatergic activity is linked to the development of, and maintenance of levodopa-induced dyskinesias
62
What is amantadine's MOA?
NMDA antagonist Anticholinergic Upregulates D2 receptors, increase sensitivity of D2 receptors Helps to manage dyskinesia
63
Amantadine dosing considerations?
- Renally excreted - reduce dose in renal impairment - Can be stimulating, 2nd dose should be in the afternoon not night - Avoid concurrent use with memantine
64
Adverse effects of NMDA antagonists?
Nausea, light-headedness, insomnia, confusion, hallucinations, livedo reticularis
65
Place in therapy of amantadine in the management of PD
Adjunctive | Managing levodopa-induced dyskinesias
66
how to distinguish Drug-induced parkinsonism from PD
Symptoms tend to occur bilaterally Withdrawal of the drug usually leads to improvement in symptoms in 80% of patients in 8 weeks Treatment should be withdrawal of offending drug
67
Age correlation with parkinson disease and parkinsonism
Incidence of disease increases with age
68
Which drugs have high risk of DIP?
Dopamine D2 receptor blockers - Typical antipsychotics (haloperidol) - Atypical antipsychotics (at higher doses) - risperidone, olanzapine, aripiprazole Antiemetics such as prochlorperazine, metoclopramide
69
Onset of drug-induced parkinsonism
~3 months within exposure to the offending agent
70
Is drug-induced parkinsonism reversible?
Not always. | Best "treatment" = prevention
71
What agents may be used for drug-induced parkinsonism?
Amantadine and anticholinergics
72
What is parkinson hyperpyrexia syndrome caused by?
Changes in dopaminergic treatment provoked by trauma, surgery and pulmonary, gastrointestinal and urinary tract infections May have no apparent trigger
73
What happens during severe cases of PHS?
No response to dopaminergic rescue medications, symptoms deteriorate rapidly, patient becomes progressively more immobile and rigid
74
Systemic complications of PHS
Reduced consciousness → aspiration pneumonia Rhabdomyolysis → ARF Immobility → DVT, PE DIVC
75
Management of PHS
If cause is reduction in dopaminergic meds, reinstate previous treatment and increase dose of levodopa gradually If PO route cannot be used, options are rotigotine patch, amantadine injection Dantrolene, bromocriptine
76
What drugs should be avoided when reviewing meds for PD patients?
Antidopaminergics and anticholinergics
77
Complications of PD
Aspiration pneumonia Dopamine agonist withdrawal Psychosis Dyskinesia

PR3136 therapeutics (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions