Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

'B33CNS - Pharmacology & Therapeutics > Motor symptoms; Parkinson's Disease > Flashcards

Motor symptoms; Parkinson's Disease Flashcards

1
Q

What is Parkinson’s Disease? 22:12

A

Neurodegenerative; death/depletion of DA-containing cells of the substantia nigra.

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

What is the substantia nigra?

A
  • Origin of dopaminergic afferents (neurones) implicated in Parkinson’s
  • DA neurones stretch from the substantia nigra to the higher centres of the brain; but information is compromised a result in Parkinson’s
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the pathophysiology of Parkinson’s?

A
  • DA neuron loss in the substantia nigra (primarily)

- But also loss of NA (locus coeruleus) and serotonergic (5-HT) neurons (Raphe nuclei)

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

What is a Lewy body, and its significance?

A
  • Accumulation of protein deposits (abnormal) in substantia nigra, locus coeruleus and other brain regions
  • Disrupt brain’s normal functioning; deplete DA
    = Parkinson’s (and Lewy-Dementia)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the genetic influence of Parkinson’s aetiology?

A
  • The earlier the age of onset, the greater the familial occurrence
  • About 15-25% of people w/Parkinson’s disease have a relative w/the disease
    »> Odds greatly increased if relative is parent or sibling.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the aetiology of Parkinson’s in regards to specific genes?

A
  • α-Synuclein; autosomal dominant
  • LRRK2 - autosomal dominant
  • Parkn - autosomal recessive
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is α-Synuclein, and its significance in Parkinson’s?

A

Key in aetiology of of Parkinson’s (genes):

  • Autosomal dominant
  • Major constituent of Lewy bodies (contains the protein α-5ynuclein)
  • Too much or abnormal α-Synuclein produced in familial Parkinson’s
  • Inhibits NT release (DA)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is LRRK2, and its significance in Parkinson’s?

A

Key in aetiology of of Parkinson’s (genes):

  • Autosomal dominant
  • leucine-rich repeat kinase 2
  • High prevalence in North African Arabs and Ashkenazi Jews (Central/Eastern Europe)
  • Responsible for 2% of PD in Western populations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is Parkin, and its significance in Parkinson’s?

A

Key in aetiology of of Parkinson’s (genes):
- Autosomal recessive
- Also known as Juvenile Parkinsonism; onset age < 30 years
- Acts as a ubiquitin-protein ligase; labels neurones for degradation (normally dead/damaged); mopped up by microglia afterwards
»> Wrongly labelled neurons w/mutation
- Portrayal of a protective role

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

What is meant by an autosomal dominant gene vs. an autosomal recessive one?

A
  • Autosomal dominant; only need contribution from one parent for Parkinson’s mutation
  • Autosomal recessive; need copies from both genes to result in mutated gene (Parkin)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the aetiology of Parkinson’s WRT the environment?

A
  • Rural living
  • MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
  • Ageing
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How is rural living implicated in the aetiology of Parkinson’s? Evidence?

A

Some pesticides known to be potent mitochondrial inhibitors:
- Mitochondrial complex 1
• Extracts energy from NADH
• Complex is deficient in patients who have died from Parkinson’s; pesticides inhibit mitochondrial complex 1, hence deficiency.

Additional evidence:
- Infusion of insecticide ROTENONE in rats caused dopaminergic cell death, Lewy body formation and motor deficit
»> Direct link w/pesticides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How is MPTP implicated in the aetiology of Parkinson’s?

A
  • Student tried to manufacture synthetic heroin, MPPP
  • However manufacture MPTP instead
  • Developed symptoms of PD, but responsive to treatment
  • Autopsy following death revealed:
    • Destruction in substantia nigra (hence Parkinson’s symptoms)
    • But lacking in Lewy bodies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How is ageing implicated in the aetiology of Parkinson’s?

A
  • Increased prevalence of PD at older ages
    »> Loss of striatal DA and DA cells (neurones) in the substantia nigra
    (Though precise role in pathogenesis still unclear)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the characteristic motor symptoms associated w/PD?

A
  • Bradykinesia; slowness of movement, ‘shuffling’, stooped posture
  • Resting tremor; shaking that disappears during active use of the affected body part (basal ganglia normally filter unwanted movement)
  • Rigidity; increased resistance to passive movement
  • Postural instability; instability when standing, or impaired balance and coordination
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What other symptoms are characteristic of PD?

A
  • Drooling
  • Fatigue
  • Loss of facial expression (effect on motor cortex)
  • Speech problems (talking = lots of muscles)
  • Dysphagia; problems swalling
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the characteristic non-motor (autonomic) symptoms of PD?

A
  • GI dysfunction
  • Genitourinary dysfunction
  • CV dysfunction
  • Cognitive dysfunction
  • Sleep disorders
  • Mood disorders
  • Pain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Describe GI dysfunction as a symptom of PD.

A
  • Autonomic, non-motor symptom:
    • Constipation (most common)
    • Incomplete bowel evacuation/bowel incontinence
    (Parasympathetic NS)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Describe the Genitourinary dysfunction that may arise as a result of PD.

A
  • Autonomic, non-motor symptom:
    • Urinary urgency/frequency/incontinence (M3 receptors)
    • Sexual dysfunction (ED in men)
20
Q

Describe CV dysfunction as a symptom of PD.

A
  • Autonomic, non-motor symptom:
    • Cardiac sympathetic denervation; responsible for orthostatic (postural) light-headedness and hypotension (SUSCEPTIBLE to falling; blood doesn’t recalibrate)
    • Though postural hypotension is more often related to dopaminergic medication
21
Q

Describe the degree of Cognitive dysfunction that may present in PD.

A
  • Autonomic, non-motor symptom:

• Slowness of thought and executive dysfunction; Parkinson’s Disease Dementia

22
Q

Describe the sleep disorders that may present in PD.

A
  • Autonomic, non-motor symptom:
    • Rapid eye movement disorder (act out their dreams)
    • Restless leg syndrome
    • Periodic limb movement of sleep (flexing limbs every 20-30 seconds)
    • Insomnia
    • Excessive daytime sleepiness
23
Q

Describe how mood disorders may present in PD.

A
  • Autonomic, non-motor symptom:
    • Depression
    • Psychosis
    • Anxiety; GAD, agoraphobia, panic disorder, social phobia (as a result of motor symptoms)
24
Q

Describe how Pain may present as a symptom of PD?

A
  • Autonomic, non-motor symptom:
    • Musculoskeletal (not utilising all muscles); cramping, aching, skeletal deformities (from stooping) etc.
    • Radicular neuropathic pain; radiates into the lower extremity directly along the course of a spinal nerve root
    • Dystonic pain; in the neck muscles; due to effects from medication
    • Central/primary pain; stabbing, burning, scalding pain
25
Q

What is the pharmacological management strategy of PD?

A
  • Treat symptoms; replenish DA

- Prevent, delay or reverse neurogeneration

26
Q

What are the recommended pharmacological agents to treat PD?

A
  • Levodopa (first line)
  • DA agonists
  • MAO type-B inhibitors
  • COMT inhibitors
  • Other; anticholinergics, Glu antagonists
27
Q

Describe Levodopa’s use in PD. What is it effective against? Mechanism?

A
  • First line therapy
  • Effective against bradykinesia (slowness of movement) and rigidity
  • Mechanism; levodopa (L-DOPA) is natural precursor to DA; converted to DA via DOPA-decarboxylase
28
Q

How is Levodopa prescribed for PD?

A
  • Prescribed with dopa-decarboxylase inhibitor; Carbidopa (Sinamet) or Benserazide (Madopar)
  • Reduces peripheral S/Es; N&V, CV (prophylactic measure)
  • Mainstay
    »> NOT used for younger patients; chronic use presents with complications later on.
29
Q

Why is Levodopa prescribed with a dopa-decarboxylase inhibtor (as Carbidopa/Benserazide)?

A
  • L-DOPA given in general instead of DA as peripherally administered DA cannot penetrate BBB; L-DOPA can, and is converted to DA by dopa-decarboxylase in the brain
  • PO administration of Levodopa alone results in rapid peripheral conversion of L-DOPA to DA = GIT S/Es (N&V), decreases therapeutic effect
    »> Thus, as Carbidopa (w/DOPA-decarboxylase inhibitor), peripherally circling L-DOPA is not converted into DA (inhibits peripheral DOPA-decarboxylase), minising S/Es, improving therapeutics
30
Q

When are DA agonists used for PD treatment? Give examples. Mechanism?

A

E.g. ropinirole, pramipexole, rotigotine

  • First line in younger patients (< 30); reduced motor complications
  • Combination therapy w/levodopa v. effective; give lower dose of levodopa in this instance
  • Mechanism; DA agonists selective for D2 and D3 postsynaptic receptors
31
Q

What are the S/Es associated with DA agonist therapy?

A
  • Nausea
  • Sleepiness
  • Dizziness
  • Hallucinations
  • Psychiatric disorders
    »> Due to elevated DA throughout body
32
Q

What is the mechanism for MAO inhibitors? Give examples. S/Es?

A

Mechanism:
Prevents degradation (metabolism) of DA; by inhibiting MAO.
- Selegiline; S/Es = excitement, anxiety, insomnia (central)
- Rasagaline (S/Es specific to Selegiline)
»> Generally well tolerated; option for younger patients.

33
Q

What is the mechanism for COMT inhibitors? Give an example. Advantages?

A

Catechol-O-methyltransferase inhibitors
E.g. entacapone
- Mechanism; prevents DA degradation
- Increased ‘on time’ in patients w/advanced PD
»> On time = patient experience good response to medication

34
Q

What is a potential method of improving compliance in PD treatment?

A

Using combination therapy of levodopa + carbidopa + entacapone
»> Stalevo (3 in 1)

35
Q

What are the other options for the pharmacological management of PD? Mechanisms? S/Es?

A
  • Amantadine
    • Initially an anti-viral
    • Mild anti-Parkinsonian effect ( short term use)
    • Mechanism; unclear; mixed dopaminergic and glutamatergic actions
    • S/Es: confusion, insomnia
  • Antimuscarinics e.g. benzhexol
    • Inhibits DA suppression
    • Compensatory mechanism for decreasing DA
36
Q

How are the non-motor symptoms of PD approached pharmacologically?

A

GI dysfunction
- Constipation; Macrogol (osmotic laxative)

Cognitive dysfunction
- Dementia; rivastigmine (AcetylCoE inhibitor; hallucinations&raquo_space; amnesia)

Mood disorders
- Depression; DA agonist 
• Pramipexole (w/efficacy against depression too)
• TCA (nortriptyline)
• SSRI

Psychosis
- Atypical neuroleptics (e.g. risperidone)

37
Q

What is the requirement criteria for surgical management of PD?

A
  • Excellent response to levodopa
  • Younger age
  • No/mild cognitive impairment
  • Absent/well controlled psychiatric disease (e.g. depression)
38
Q

What does surgical management of PD entail?

A
  • Permanent implantation of leads into the subthalamic nucleus or globus pallidus (both part of basal ganglia)
  • Leads deliver high frequency electrical impulses controlled by stimulator
  • Alleviates motor symptoms
  • Presents opportunity to decrease levodopa dose (preventing chronic use, or even stopping L-DOPA)
39
Q

What are the non-pharmacological management options for PD?

A
  • Cell replacement therapy
  • Exercise/physiotherapy
  • Vitamin D
40
Q

What does Cell replacement therapy propose for PD management? Advantages?

A

Non-pharmacological management:
- No therapies currently availible
- Current research; embryonic, mesenchymal, neural, pluripotent stem cells
+ Long stability of the grafted cells (no rejection)
+ Long-lasting function recovery
+ Effective restoration of DA release in vivo

41
Q

How does exercise/physiotherapy aid PD therapy? Evidence?

A
  • Dance/martial arts: considered useful as an adjunct to pharmacological therapy
    • Evidence; rat model of PD demonstrated decreased DA degeneration when ‘forced’ to use affected limb;&raquo_space;> exercise protective in PD???
42
Q

What does Vitamin D have to do with PD?

A
  • Low in PD patients
  • Related to bone health in PD
  • Related to severity of PD symptoms
    »> NEUROPROTECTIVE role in animal studies
  • Most exciting, but also challenging translating to humans
43
Q

What complications (and their resulting modifications) arise in treating PD with Levodopa?

A

> Consider decreasing dose w/adjuncts; DA agonist, MAO and COMT inhibitors

Example S/Es
Dyskinesia:
- Involuntary writhing which develops in most patients
- Amantadine or clozapine effective

Fluctuations in clinical state

  • Hypokinesia (decreased body movement) and rigidity worsening for a few minutes/hours, then improving
  • Levodopa-SR or levodopa + COMT inhibitor (maintaining steady state to avoid troughs)

Nausea:
- Administer w/food; combination w/carbidopa/benserazide; domperidone (peripheral DA antagonist)

44
Q

What complications (and their resulting modifications) arise in treating PD with DA agonists?

A

Impulsive compulsive behaviour:
- Exacerbated in a patient w/history of OCD, impulsive personality, addictive behaviour

Action:
• Reduce/discontinue DA agonists
• Anticonvulsant zonisamide; reduces impulsive behaviour

45
Q

What complications (and their resulting modifications) arise in treating PD-induced psychosis with Clozapine?

A

Requires blood monitoring (weekly) due to agranulocytosis risk (neutropenia risk etc.)

46
Q

What commodities are associated w/PD, and their treatments?

A

Depression
- Widespread in early-onset PD
- Challenging diagnosis due to symptom overlap; e.g. weight loss and insomnia
- Pathophysiology; abnormalities of serotonergic, noradrenergic and dopaminergic function
»> Current recommended treatment (SSRIs)

Cognitive impairment
- Cholinergic dysfunction observed in patients over time
»> Treatment (clinical trials); acetylcholinesterase inhibitor (rivastigmine, donepezil)
- 2 year treatment required (not 100% efficacious)

Orthostatic (postural) hypotension (common; due to meds)
- Due to autonomic dysfunction OR ADR of dopaminergic medication
»> Treatment (clinical trials);
• Fludrocortisone (corticosteroid, increases blood volume, thus BP)
• Pyridostigmine (cholinesterase inhibitor)
• Indomethacin (NSAID)
• Domperidone
• Increase salt and fluid consumption BUT monitor for hypertension!!!

'B33CNS - Pharmacology & Therapeutics (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions