Parkinson's Flashcards

1
Q

Bradykinesia, Muscle Rigidity and Tremor are examples of what type of Symptom in Parkinson’s?

A

Motor

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2
Q

What are the examples of non-motor symptoms in Parkinson’s?

A

Depression/anxiety, Fatigue, Cognitive impairment/dementia, sleep disturbance, constipation, hyposmia, sialorrhoea, excessive sweating, urinary/bladder problems, pain, hypotension

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3
Q

In the Dopaminergic pathway, Motor control is what system?

A

Nigrostriatal

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4
Q

In the Dopaminergic pathways, Behavioural effects are controlled by what system?

A

Mesolimbic and Mesocortical systems

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5
Q

In the Dopaminergic pathways, Endocrine control is controlled by what system?

A

Tuberohypophyseal system

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5
Q

What is Bradykinesia?

A

‘Slowness of voluntary movement’

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5
Q

A Parkinson’s patient which is presenting with asymmetrical, mask-like face/limited expressions with limited blinking, a soft or monotone voice, small handwriting, difficulty performing fine motor actions and a shuffling gait is having what symptom of Parkinson’s?

A

Motor Symptoms - Bradykinesia

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5
Q

What Rigidity motor symptoms could be seen in a Parkinson’s patient?

A

-Increased muscle tension
-Stooping posture
-Rigidity affecting balance increasing the risk of falls *due to slower reactions = -Bradykinesia
-Muscle pain
-Affects elbow and knee

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6
Q

Do all Parkinson’s patients have a tremor?

A

No!

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7
Q

There are many drugs which can cause a Tremor, what ones can cause a Intention tremor?

A

Lithium, Salbutamol, Salmeterol, Ethanol, Epinephrine, Tacrolimus, Ciclosporin

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8
Q

What drugs can cause a Resting Tremor?

A

Co-trimoxazole, SSRI’s, Lithium, Valproic acid, Metoclopramide, Haloperidol, Cinnarizine,

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9
Q

What intrinsic causes of Parkinson’s are there?

A

Genetic
*lewy body *parkin gene *A-synuclein point mutations
Age

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10
Q

What groups of prescription drugs can cause Parkinson’s?

A

Antipsychotics & Antiemetics

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11
Q

What can cause lewy body formation?

A

A-Synuclein

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12
Q

What can a-Synuclein cause?

A

DNA damage / inherited, which is autosomal dominant = early onset

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13
Q

How does pre-synaptic protein a-Synuclein make Lewy bodies?

A

1) Brain plascity and misfolded proteins are made which aggregate in the neuron,
2) Damages cellular components
3) Lewy Bodies are formed causing neuronal misfunction which results in cell death.
4) Dementia

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14
Q

A genetic cause of Parkinson’s is ‘Parkin’ what is this?

A

A neuroprotective protein, made from a-synuclein and cellular damage. Loss of this causes cell damage and cell death.

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15
Q

What gene encodes for Parkin?

A

PARK2 Gene

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16
Q

What anti-emetics can cause Parkinson’s?

A

Metoclopramide, Prochlorperazine

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17
Q

What effect do recreational drugs have on inducing Parkinson’s?

A

MPTP which is found in synthetic Heroin,
-This metabolite kills dopaminergic neurons in substantia nigra Sudden,
=Irreversible Parkinsonism

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18
Q

Are Antipsychotics that cause Parkinson’s reversible?

A

Yes

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19
Q

What drugs deplete monoamines from pre-synaptic storage, reducing Dopamine release?

A

Reserpine, Tetrabenazine

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20
Q

What viral illness can cause Parkinson’s?

A

Encephalitis lethargica epidemic, patients end up in a state of permanent rigidity, = some short term relief from L-DOPA

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21
Q

What is first line therapy for motor symptoms of Parkinson’s disease when QoL is affected?

A

QoL affected - Levodopa

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22
Q

If quality of life isn’t affected in a patient with Parkinson’s what medications should be offered?

A

Dopamine agonist and Monoamine inhibitor

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23
Q

When is add on therapy given for motor symptoms of Parkinson’s disease?

A

1) First line is optimised
2) When dyskinesia or motor fluctuations develop

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24
Q

WHAT is add on therapy for Motor symptoms of Parkinson’s disease?

A

1) Dopamine agonists, monoamine oxidase B inhibitors or catechol-O-methyl transferase inhibitors as an adjunct to levodopa

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25
Q

If Dyskinesia is not adequately managed by modifying existing therapy what drug should be considered?

A

Amantadine

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26
Q

When is Levodopa started?

A

Individualised patient plan, different for all.
-80+ start ASAP
-Young onset start later on…

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27
Q

What are the THREE unwanted effects of Levodopa?

A

1) Dyskinesia
2) Fluctuations in clinical state
3) Acute side effects

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28
Q

What are incorporated with Levodopa?

A

Dopadecarboxylase Inhibitors

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29
Q

What are examples of Dopadecarboxylase inhibitors?

A

-Carbidopa
-Benserazide

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30
Q

Why is Levodopa a combined medication?

A

As levodopa is metabolised in the periphery and the brain therefore, these peripheral inhibitors prevent the majority of it being metabolised in the periphery and more can cross the BBB and more dopamine can be active in the brain.

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31
Q

What combination is Sinemet?

A

Carbidopa + Levodopa

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32
Q

What combination is Madopar?

A

Benserazide + Levodopa

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33
Q

What are COMT Inhibitors?

A

Entacapone and Tolcapone

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34
Q

Can COMT inhibitors be used with Levodopa products?

A

YES! ADD ON and in Combination

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35
Q

What COMT inhibitor can cause liver toxicity?

A

Tolcapone

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36
Q

What does a COMT inhibitor do?

A

Potentiate the effects of Levodopa - increases Levodopa effect

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37
Q

What are Brand examples of Co-careldopa + Entacapone

A

Stanek, Stalevo, Sastravi

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38
Q

What side effects should a patient be counselled on when taking Entacapone?

A

Red/Orange urine, Loose stool - which should settle over time.

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39
Q

What is the MAX dose of Levodopa?

A

800mg

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40
Q

What do small does of Levodopa at increased frequencies do?

A

Reduce peaks and troughs and dyskinesia

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41
Q

How and why should you wait before eating after taking Levodopa?

A

Proteins inhibit absorption, wait 30-60 mins- can have a low protein snack such as a cracker

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42
Q

Should Levodopa be prescribed by brand?

A

YES

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43
Q

How many hours does an iron supplement need to be taken if the patient is on Levodopa?

A

2-3 hour gap

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44
Q

Examples of Non-ergot Dopamine Receptor Agonists?

A

-Ropinirole
-Rotigotine
-Pramipexole

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45
Q

Examples of Ergot derived Dopamine Receptor Agonists?

A

Bromocriptine
Cabergoline
Lisuride
Pergolide

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46
Q

What type of Dopamine Receptor Agonists are best tolerated?

A

Non-ergot derived

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47
Q

What type of Dopamine Receptor Agonists can cause fibrotic lungs/heart valve?

A

Ergot derived

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48
Q

When are Ergot Derived Dopamine Receptor Agonists used?

A

If inadequate response to non-ergot derived

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49
Q

Dopamine Agonists can increase the risk of Impulse Control Disorders, Why is this?

A

Function of Dopamine is reward pathways, behaviour, attention and concentration.

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50
Q

What are examples of Monoamine Oxidase B inhibitors?

A

Selegeline and Rasagiline

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51
Q

What does Monoamine oxidase B inhibitors do?

A

Monoamine oxidase B metabolises dopamine therefore inhibiting this, increases Dopamine concentration

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52
Q

Do Monoamine oxidase B inhibitors interact with tyramine?

A

NO as they are selective for B type receptors

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53
Q

What are some common side effects to Monoamine oxidase B inhibitors?

A

Nausea, postural hypotension, dyskinesia, confusion in the elderly

54
Q

What does Amantadine do?

A

Increases dopamine levels

55
Q

What can possibly prolong effectiveness of Amantadine?

A

Slowly withdrawing and reintroducing the drug

56
Q

Can Amantadine cause, psychological effects, sleep disturbances, GI effects, Hypotension and palpitations?

A

YES

57
Q

Which drug shows no evidence in improving motor symptoms?

A

Amantadine

58
Q

What drug has no evidence of improving quality of life in Parkinson’s disease?

A

Amantadine

59
Q

Which drug for Parkinson’s disease has the fewest side effects?

A

MOA-B inhibitors

60
Q

What Parkinson’s drug has a lower risk of causing Hallucinations?

A

MOA-B inhibitors and COMT inhibitors

61
Q

What Parkinson’s drug has a higher risk of causing Hallucinations?

A

Dopamine Receptor Agonists

62
Q

What can happen if a patient with Parkinson’s misses a dose?

A

-Acute Akinesia (unable to initiate movement)
-More physically dependent on others
-Loss of ability to swallow increasing risk of aspiration
-Increased risk of falls
-Neuroleptic-like malignant syndrome (V.RARE)

63
Q

Symptoms of Neuroleptic-like malignant syndrome (V.RARE!!!)

A

Fever, marked rigidity, altered consciousness, leucocytosis, elevated creatine kinase.

64
Q

What causes Neuroleptic-like malignant syndrome?

A

Sudden, marked reduction in dopamine activity, either from withdrawal of dopaminergic agent or from blockage of dopamine receptors

65
Q

Who is more likely to get Neuroleptic-like malignant syndrome?

A

Severe PD symptoms on high doses of levodopa

66
Q

What can be given to a patient suffering from Depression in Parkinson’s disease?

A

Normal 1st line SSRI!

67
Q

What can be given to a patient suffering from Dementia in Parkinson’s disease?

A

Rivastigmine or off label use of Donepezil and Galantamine

68
Q

What can be given to a patient suffering from confusion and hallucinations in Parkinson’s disease?

A

1st line - Quetiapine
2nd line - Clozapine

69
Q

What can be given to a patient suffering from Impusle control and psychotic symptoms in Parkinson’s disease?

A

Optimise drug therapy

70
Q

What is the first line treatment for a Patient with Parkinson’s suffering from Constipation?

A

Stimulant + Softener

71
Q

What is the first line treatment for a Patient with Parkinson’s suffering from Postural hypotension?

A

1st line - Midodrine / fludrocortisone

72
Q

What is the first line treatment for a Patient with Parkinson’s suffering from Dysphagia?

A

Medicines optimisation

73
Q

What is the first line treatment for a Patient with Parkinson’s suffering from Salvation/drooling?

A

Glycopyrronium

74
Q

What is the first line treatment for a Patient with Parkinson’s suffering from Bladder Dysfunction?

A

Anti-muscarinic

75
Q

What is the first line treatment for a Patient with Parkinson’s suffering from Sexual Dysfunction?

A

PDE5 Inhibitors - Sildenafil

76
Q

What is the first line treatment for a Patient with Parkinson’s suffering from Nausea and Vomiting?

A

1st line - Domperidone
Consider Cyclizine or Ondansetron

77
Q

What is the first line treatment for a Patient with Parkinson’s suffering from Pain?

A

Follow pain ladder, Consider side effects, Physiotherapy

78
Q

What is the first line treatment for a Patient with Parkinson’s suffering from Sleep disturbances?

A

Sedatives BUT can increase falls risk, PRN only

79
Q

What drugs is Vigilance required?

A

Antihistamines, Antidepressants and Antipsychotics

80
Q

When should a Parkinson’s patient’s medications be reviewed?

A

Every 6-12 months Specialist only

81
Q

What should be on the labels of Parkinson patients medications?

A

Timings of when to take

82
Q

What OTC medications should be avoided in a patient in Parkinson’s?

A

-Sympathomimetics: Pseudoephedrine + MOA-B inhibitors
-Antihistamines

83
Q

Can Calcium Channel Blockers be used in patients with Parkinson’s disease?

A

YES! - Monitor as low BP is a common issue

84
Q

Parkinson patients have an increased risk of Osteoporosis, therefore what should they be recommended?

A

Cholecalciferol

85
Q

What type of D-like receptor acts via Gas to increase cAMP. PKA phosphorylates DARPP-32 which inhibits protein phosphatase-1?

A

D1-Like

86
Q

What type of D-like receptor acts via Gai/o to decrease cAMP. The By subunits open K channels and inhibit voltage-gated Ca2+ channels?

A

D2-like

87
Q

What D channel is inhibitory?

A

D2

88
Q

What D channel is Excitatory?

A

D1

89
Q

D1 and D5 are?

A

D1-like

90
Q

D2, D3 and D4 are?

A

D2-like

91
Q

What is the Dopamine function?

A

Acts on areas of the brain to give feelings of pleasure, satisfaction and motivation; memory, mood, sleep, learning, concentration and movement

92
Q

What when binds to Dopamine can agonise a response? ‘Agonists’

A

Dopamine, Bromocriptine, Apomorphine, Cabergoline, Pergolide, Pramipexole, Ropinirole, Ariprazole

93
Q

What when binds to Dopamine can STOP a response? ‘Antagonists’

A

Haloperidol, Sulpiride, Domperidone, Metoclopramide

94
Q

What pathway accounts for 75% of DA in the brain, cell bodies in the substantia nigra protein the striatum, Controls movement and is of significance to Parkinson’s disease?

A

Nigrostriatal

95
Q

What pathway?
VTA to limbic areas, notably the nucleus accumben’s, hippocampus and amygdala
-Plays a part in the behavioural and reward pathways, is of significance to Schizophrenia (+ve symptoms)?

A

Mesolimbic

96
Q

What pathway? VTA to frontal cortex, cognition and thought, and plays a part in the negative symptoms and Schizophrenia?

A

Mesocortical

97
Q

What pathway? Hypothalamus to the pituitary, controls hormone secretion and DA inhibits the prolactin secretion = S/E of drugs @ dopamine receptors.

A

Tuberohypophyseal

98
Q

What type of receptors are most abundant and expressed at high density in the nigrostriatal, mesolimbic and mesocortical pathways?

A

D1 receptors

99
Q

What receptor is most expressed in the CNS

A

D1

99
Q

What type of receptors are at there highest density in the nigrostriatal, mesolimbic and tuberohypophyseal pathways, and also are in the CTZ medulla?

A

D2 receptors

99
Q

What receptor is only really expressed in the limbic system?

A

D5

100
Q

What receptor is widely expressed, and expressed in the tuberohypophyseal?

A

D2

101
Q

What receptor is restricted / has week expression?

A

D3

102
Q

What receptor is expressed in various places and has lower expression?

A

D4

103
Q

Where is vomiting triggered?

A

Chemoreceptor trigger zone (CTZ)

104
Q

Loss of dopaminergic neurons in the nigrostriatal pathway, is known of what disease?

A

Parkinson’s

105
Q

What does the direct pathway do in the Nigrostriatal pathway?

A

Enables movement

106
Q

What does the indirect pathway do in the Nigrostriatal pathway?

A

Inhibits movement

107
Q

Where are Cholinergic interneurons abundant?

A

Striatum

108
Q

What does Dopamine inhibit in the striatum?

A

Inhibits ACh release

109
Q

A lack of dopamine in parkinson’s leaves ACh unopposed causing what?

A

Hyperactivity of cholinergic synapses

110
Q

What does the release of ACh do?

A

Initiate movement

111
Q

A decrease in dopamine means an increase in ACh, what does this cause?

A

Hyperactivity of cholinergic synapse = Tremor

112
Q

What are intracellular aggregations of a-synucein found in neuronal cells known as?

A

Lewy bodies

113
Q

What is A-synuclein involved in?

A

Exocytosis of synaptic vesicles and vesicle recycling

114
Q

What causes plaque formation?

A

Misfolding

115
Q

Plaque formation is usually removed via proteasomal pathways, this is decreased in PD’s, what does this cause?

A

Accumulation = Lewy bodies

116
Q

What does a mutation of a-synuclein cause?

A

Early onset PD

117
Q

As dopaminergic neurons require a lot of energy for their function what does that mean they require a lot of within their cell’s?

A

Mitochondria

118
Q

Chemicals that induce PD cause stress and dysfunction to what, which is thought to play a role in causing PD?

A

Mitochondrial

119
Q

What genes when mutated can cause PD?

A

Parkin and PINK1

120
Q

What can lead to the death of dopaminergic neurons?

A

Mitochondrial damage

121
Q

What will try to help with neuroinflammation?

A

Microglia

122
Q

What neurotransitter is most associated with the pathophysiology of parkinson’s disease?

A

Dopamine

123
Q

VMAT takes dopamine into synaptic vesicles in exchange for what ion?

A

H+

124
Q

What pathways are dopamine pathways?

A

Mesocortical, Mesolimbic, Nigrostriatal, Tuberohypophyseal

125
Q

What is the pharmacological target of carbidopa?

A

DOPA decarboxylase

126
Q

What of the following is the pharmacological target of pramipexole?

A

D2-like receptors

127
Q

What drug is used for daytime sleepiness and sudden onset of sleep in Parkinson’s?

A

Modafinil

128
Q

What drug is used for Nocturnal Akinesia in parkinsons?

A

1st - Levodopa or Dopamine agonists
2nd - Rotigotine

129
Q

What drug is used for Postural Hypotension in parkinsons?

A

1st) Are any drugs they are taking causing it
2) Midodrine hydrochloride or Fludrocortisone

130
Q

What drug is used for rapid eye movement, sleep behaviour in parkinsons?

A

Clonazepam and Melatonin

131
Q

If a patient with parkinsons is experiencing hallucinations or delusions, and has no cognitive impairment what should be offered?

A

1) Quetiapine
2) Clozapine

132
Q

What can be given for a patient who has excessive drooling in parkinsons?

A

1) Glycopyrronium bromide
2) Botulinmum toxin type A

133
Q

If a patient with parkinsons gets dementia what should be given?

A

Mild-mod = AChEi