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Psychiatric Pharmacotherapy > Parkinson's Disease > Flashcards

Parkinson's Disease Flashcards

1
Q

*The 3 cardinal signs of PD are: __, __, __.

A

Akinesia/Bradykinesia
Rigidity
Tremors

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2
Q

*Subjective sense of weakness, loss of dexterity, difficulty using kitchen tools, loss of facial expression, reduced blinking, difficulty getting out of bed/chair, difficulty turning while walking.

These are a sign of __.

A

Akinesia/Bradykinesia (Cardinal sign of PD)

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3
Q

*A patient describes “ratchet”-like stiffness (cogwheel rigidity); also leadpipe rigidity.

These are a sign of __.

A

Rigidity (Cardinal sign of PD)

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4
Q

*Resting tremors that disappears with movement), but increases with stress. A pill rolling movement around 4-8hz may be observed.

These are a sign of __.

A

Tremors (Cardinal sign of PD)

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5
Q 
A patient presenting with idiopathic PD will usually have:
\_\_ features
Positive response to \_\_/\_\_
\_\_ progression of PD
No presence of \_\_ or \_\_
A
  1. Asymmetric
  2. levodopa/apomorphine
  3. Slow
  4. postural instability i.e. falls or autonomic dysfunction
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6
Q

*PD pts are unable to perform these Activities for daily living (ADLs). They include:

A 
–Mobility (walking, using stairs)
–Feeding self
–Grooming, personal hygiene
–Toileting
–Showering/bathing
–Continence (bowel and bladder)
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7
Q

*PD pts experience interference to their ADLs in the form of:

A

•Choking
•Pneumonia
•Falls
(CPF)

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8
Q

Rapid PD disease progression is defined as __.

A

H and Y stage 3 after 3 years

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9
Q

As the H and Y scale progresses from 1 to 5, there is increasing disability and dependence. H and Y stage 3 refers to __.

A

Impaired postural reflexes

Physically independent

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10
Q

The ‘ON’ state for PD patients refers to __.

A

when pt is responding to levodopa

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11
Q

The ‘OFF’ state for PD patients refers to __.

A

when pt is not responding to levodopa

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12
Q

The H and Y scale assess __. Patients on treatment should be assessed in their __ and __.

A
  1. mobility

2. ON and OFF states

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13
Q 
Non-motor symptoms of PD may lead to:
\_\_ impairment
\_\_ symptoms
\_\_ disorders
\_\_ dysfunction
Fatigue
Non-motor symptoms are monitored by the UPDRS scale.
A
  1. Cognitive
  2. Psychiatric
  3. Sleep
  4. Autonomic
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14
Q

Young-onset PD pts generally have __ disease progression, __ decline and __ motor complications (with treatment).

A

slower
less cognitive
earlier

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15
Q

__ is a more common initial presentation for young-onset PD vs __ and __ in late-onset

A

Dystonia

falls and freezing

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16
Q

The use of __ treatment is preferred to levodopa in young-onset PD in order to __

A

Dopamine agonist

delay onset of levodopa induced motor complications

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17
Q

*The goal of PD management is to __, __ and __. It is not curative and no PD treatment has been shown to be neuroprotective.

A

Manage symptoms, maintain function/autonomy

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18
Q

*The focus of pharmacological treatment in PD is to increase central dopamine, dopaminergic transmission. There are 4 classes which include:

A
  1. Levodopa + DCI
  2. Dopamine agonists
  3. COMT inhibitors
  4. MAO-B inhibitors
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19
Q

Non-pharmacological options for PD patients include:

  1. __ (Stretching, transfers, posture, walking)
  2. __ (Mobility aids, home and workplace safety)
  3. Speech and __
  4. Surgery
A
  1. Physiotherapy
  2. Occupational therapy
  3. Swallowing
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20
Q

Correcting imbalances in pathways are a viable pharmacological treatment option, but are not very good in __.

A

relieving cardinal symptoms of PD

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21
Q

*Levodopa is the most effective drug for treatment of symptoms, especially bradykinesia and rigidity. It is less effective for __, __ and __.

A

speech, postural reflex and gait disturbances

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22
Q

*Peripheral conversion of levodopa can cause __ and __. Therefore, it makes sense that levodopa has a DDI with alpha blockers as it __, increasing fall risk.

A

N/V and hypotension

increases postural hypotension

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23
Q

*Levodopa has drug-food interactions, which is __ and __. As a result, the 2 should be spaced 2-4h apart.

A

lowered absorption with high fat/protein meals and iron

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24
Q

__ of DCI is required to saturate Dopa decarboxylase daily. It does not cross the BBB.

A

75-100mg

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25
Q

What is the formulation and strength ratio for Sinemet?

A

25mg Carbidopa : 100mg levodopa (1:4)

25mg Carbidopa : 250mg levodopa (1:10) - SR/CR

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26
Q

What is the formulation and strength ratio for Madopar?

A

25mg Benserazide : 100mg levodopa (1:4)

25mg Benserazide : 250mg levodopa (1:10)

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27
Q

*Levodopa induced dyskinesias have a usual onset of __.

A

within 3-5years of initiating treatment

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28
Q
  • Levodopa has CNS side effects which include:
  • __, sudden sleep onset
  • hallucinations and __
A

drowsiness

psychosis

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29
Q

Since antipsychotics work by decreasing dopaminergic transmission, it makes sense that levodopa (dopamine agonist) can cause __ effects.

A

psychosis

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30
Q

The unpredictable ‘On’-‘Off’ phenomenon may be more common with __. It is difficult to __ and has been described as “throwing a light switch”.

A

younger neurologic patients

control with medications

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31
Q

*The ‘wearing off’ effect of levodopa refers to __ (aka decreased ‘ON’ duration). It is associated with __.

A
  1. reduced effect before end of dosing interval

2. disease progression

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32
Q
  • How can we manage the ‘wearing off’ effect of levodopa?
    1. Modify __
    2. Replace __
A

Modify times of administration, and/or

Replace with modified-release preparations at the appropriate time

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33
Q
  • How can we manage levodopa induced dyskinesias?
    1. add __ or __
    2. replace __
A
  1. add amantadine or dopamine agonists

2. replace specific doses with modified-release levodopa (at times of day where dyskinesia is more troublesome)

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34
Q

Levodopa dyskinesias are most common at __. They involve Involuntary, uncontrollable twitching, jerking and __ (painful muscle contractions).

A

Peak doses

Dystonias

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35
Q

*With progression of PD, the response threshold is __ while the dyskinesia threshold is __. This leads to the increase in SEs.

A
  1. increased

2. lowered

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36
Q

*Dose adjustments may be needed when switching between immediate-release (IR) and controlled-release (CR) forms because __.
–IR to CR : generally __ doses (~25%-50%)
–CR to IR : generally __doses
Dose adjustments may be limited by __.

A
  1. CR dosage forms have lower bioavailability
  2. increase
  3. decrease
  4. available dosage forms
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37
Q

*Controlled-release (CR) levodopa formulations are designed to release levodopa/DCI over a longer period of time, around __. They are more useful for __.

A

4-6h

stiffness on waking

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38
Q

Some administration precautions to note for Sinemet SR?

A

Do not crush

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39
Q

Some administration precautions to note for Sinemet CR?

A

Do not cut

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40
Q

Some administration precautions to note for Madopar HBS?

A

Do not open capsule

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41
Q

Pyridoxine is a co-factor for dopa decarboxylase. Will interactions be expected between levodopa and pyridoxine use in TB patients?

A

No, as only low doses are used

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42
Q

Pyridoxine is a co-factor for dopa decarboxylase. Will interactions be expected between levodopa and pyridoxine use in hematological patients?

A

Yes, as high potency doses are used

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43
Q

*Common anti-emetics such as Metoclopramide and prochlorperazine are __ and will reduce effectiveness of levodopa. The anti-emetic of choice in PD is __.

A
  1. anti-dopaminergic drugs (crosses BBB more)

2. domperidone (crosses BBB less)

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44
Q

*Antipsychotics i.e. Risperidone have opposite MOA compared to Levodopa and may cause __ or even __.

A

EPSEs or even inhibit levodopa action

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45
Q

For foreign travelers, we should note the interaction between levodopa and __ (drug class not stocked in SG) due to its anti-dopaminergic effects.

A

Non-selective MAO-I

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46
Q

*What are some ergot derivatives of dopamine agonists available in SG?

A 
Pergolide 
(ergot)
Cabergoline
Bromocriptine
(PECB)
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47
Q 
*What are some non-ergot derivatives of dopamine agonists available in SG?
– \_\_
– \_\_
– \_\_ (transdermal)
– \_\_ (SQ)
A 
(non-ergot)
–Pramipexole
–Ropinirole
–Rotigotine (transdermal)
–Apomorphine (SQ)
(NEPRRA)
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48
Q

*What are the 3 key clinically important differences between ergot and non-ergot derivatives?

A
  1. Lower F for ergot derived due to extensive 1st pass
  2. Higher fibrosis risk for ergot derived
  3. Higher Valvular heart disease risk for ergot derived
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49
Q

*Compared to Levodopa, Dopamine agonists have a __ and cause less __.

A

longer half life/duration of action

less motor complications

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50
Q

*Ropinirole is mainly metabolized via __. Dose adjustments should be made for __.

A

Hepatic route

hepatic impairment

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51
Q

*Pramipexole is mainly excreted via __. Dose adjustments should be made for __.

A 
Renal route (excreted unchanged)
renal impairment
52
Q

*Dopamine agonists cause similar peripheral dopaminergic side effects as levodopa. They include: __/__ and __. Similar CNS dopaminergic side effects include: __.

A
  1. N/V and Orthostatic hypotension

2. Somnolence, day-time sleepiness

53
Q

*Dopamine agonists cause more __ compared to levodopa.

A

CNS dopaminergic side effects

54
Q

*Dopamine agonists may cause __ as part of its CNS dopaminergic side effects. They are likely to be __.

A

Hallucinations

Visual rather than auditory

55
Q

*Dopamine agonists may cause __ as part of its CNS dopaminergic side effects. They may manifest as Gambling, shopping, eating, hypersexuality

A

compulsive behaviours

56
Q

*Compared to levodopa, __ is a peripheral dopaminergic SE more common for dopamine agonists.

57
Q

Among the dopamine agonists, __ has the lowest incidence of postural hypotension.

A

Ropinirole

58
Q
  • Dopamine agonists may cause the following NON-dopaminergic adverse effects, both of which have lower incidence in non-ergot agents.
    1. __ (partially reversible on withdrawal)
    2. __
A
  1. Fibrosis (Pulmonary, pericardiac, retro-peritoneal)

2. Valvular Heart disease

59
Q

*Dopamine agonists may be used as monotherapy in __ and as an adjunct to __ in moderate/severe PD.

A

young-onset PD

levodopa

60
Q

Dopamine agonists are less preferred in __ compared to levodopa due to the possibility CNS side effects exacerbating existing CNS insults.

A

elderly patients

61
Q

*__ and __ are non-ergot derivative dopamine agonists available in sustained release formulations.

A

Pramipexole and Ropinirole

62
Q

Dostinex contains 0.5mg of __ (the only brand registered in SG) which is commonly used for hyperprolactinemia. Due to the low dose, use in PD is difficult as it would be expensive (many pills required).

A

Cabergoline

63
Q

*The MAOB-i used for PD treatment in Singapore are __ and __. They are both irreversible inhibitors.

A

Selegiline and rasagiline

64
Q

In the context of PD, MAOB-I are effective as __ in the early stages of PD because they can __ unlike COMT inhibitors.

A

monotherapy

cross BBB

65
Q

*MAOB-i have a short half life but __ which allows for OD/BD dosing.

A

long duration of action (irreversible inhibitors)

66
Q

*The common dosing for Selegiline is __.

67
Q

*The common dosing for Rasagiline is __. There is no need to dose Rasagiline in the afternoon unlike Selegiline because __.

A

0.5-2mg OD

Rasagiline is not metabolized to amphetamines

68
Q

Due to __ metabolism to stimulatory amphetamines, the second dose of Selegiline should be taken __ due to avoid insomnia .

A

hepatic

in the afternoon

69
Q

*A key Drug-Drug interaction of MAOB-I are that they may cause __ with SSRIs/SNRIs/TCAs. A __ is recommended to avoid this interaction.

A

serotonin syndrome

wash-out period

70
Q

*A key Drug-Food interaction of MAOB-I is __ with __. Patients should be advised to avoid these foods.

A

Cheese reaction with tyramine rich foods

71
Q

*The improvement in UPRDS scores for MAOB-I is __ compared to dopamine agonist/levodopa.

A

not as good

72
Q

MAOB-i is commonly used as monotherapy in __ and may be used as an adjunct in __.

A

early stages of young onset PD

later stages of PD

73
Q

The antipsychotic of choice in PD patients is __ (avoid self harm/harming others).

A

Quetiapine

74
Q

Comparing Levodopa vs Dopamine agonists vs MAOB-I, Which of these have the best effect on motor symptoms?

75
Q

Comparing Levodopa vs Dopamine agonists vs MAOB-I, Which of these have the best improvement in ADLs?

76
Q

Comparing Levodopa vs Dopamine agonists vs MAOB-I, Which of these have the most motor complications?

77
Q

Comparing Levodopa vs Dopamine agonists vs MAOB-I, Which of these have the most adverse events?

A

Dopamine agonists

78
Q

*The only selective and reversible COMT inhibitor available in SG is __. __ is not available in SG and is more for travelers.

A

Entacapone

Tolcapone

79
Q

*COMT inhibitors are not effective without __. They should be taken at the same time.

A

concurrent Levodopa

80
Q

*COMT inhibitors work by __.

A

increasing the ‘ON’ time (levodopa duration of action)

81
Q

*Entacapone may cause __ and __ (important to assure patients that it is harmless).

A

diarrhea and urine discoloration

82
Q

*Due to chelation reactions with __ and __, entacapone should be __.

A

Iron and calcium

spaced out 2-4h apart

83
Q

*Entacapone has an interaction with warfarin as it __.

A

enhances the anti-coagulation effect.

84
Q

*For patients on Entacapone, they should avoid __ and __. Caution should be taken with __.

A

Non-selective MAOIs
Any catecholamine drugs
Selective MAOA-Is

85
Q

*Can Entacapone be used with these MAO inhibitors?
Non-selective MAO inhibitors?
MAO-A inhibitors?
MAO-B inhibitors?

A

Non-selective MAO inhibitors: Avoid
MAO-A inhibitors: caution
MAO-B inhibitors: safe

86
Q

*If a PD patient with hepatic impairment is planning to start Entacapone, we should __. LFT monitoring is __.

A

use with caution

not required

87
Q

*Entacapone may potentiate __ and cause __ upon initiation. A __ may be required to avoid this.

A
  1. other peripheral dopaminergic SEs (N/V, orthostatic hypotension)
  2. dyskinesias
  3. levodopa dose reduction (depending on available dosage forms)
88
Q

What is stalevo?

A

entacapone 200mg + levodopa:carbidopa in 1:4 ratio

89
Q

What is comtan?

A

entacapone 200mg

90
Q

Compared to entacapone, tolcapone is more __ with a __ duration of action. LFTs are indicated every __ for after initiation of tolcapone.

A

potent with a longer duration of action

2-4wk x 6months

91
Q

*Anticholinergics have limited use in PD because __. In practice, they are primarily used to __.

A

they usually worsen PD symptoms

control tremors

92
Q

*The side effects of anticholinergics are:

A 
Dry mouth, constipation, urinary retention (Dry as a bone)
Blurred vision (blind as a bat)
Confusion (mad as a hatter)
93
Q

Benztropine is rarely used in PD. It has a total PO daily dose of __ and is dosed __ times daily.

A

2-16mg/day

at most 2

94
Q

Benzhexol or trihexyphenidyl has a total PO daily dose of __ and is dosed __ times daily.

A

5-15mg/day

3-4

95
Q

Glutamate is associated with __. Glutaminergic activity (activated NMDA receptors) contribute to development and maintenance of __. Therefore, an __ like amantadine can help manage levodopa-induced dyskinesias.

A
  1. neurotoxicity
  2. levodopa-induced dyskinesias
  3. NMDA antagonist
96
Q

*NMDA antagonists are excreted __ with dose reductions required for patients with __.

A

renally

renal impairment

97
Q

*NMDA antagonists are __ and the 2nd dose (if required) should be given in the afternoon and not the evening.

A

stimulatory

98
Q

*Concurrent use of 2 NMDA antagonists i.e. memantine and amantadine is not recommended as it may lead to__.

A

over-stimulation and psychosis

99
Q

A patient on amantadine shows you spider web pattern on their skin and is worried. What should you do as a pharmacist?

A

Inform the patient that the pattern is purely cosmetic and they should not worry
Alternatively, may raise to doctor for assessment.

100
Q

*What is the use of amantadine in PD?

A

As an adjunct in management of levodopa induced dyskinesias.

101
Q

*What are some adverse effects that amantadine may cause?

A 
Nausea
Light headedness
Insomnia
Confusion
Hallucinations 
Livedo reticularis 
(NLICHL)
102
Q

What is the use of apomorphine in PD?

A

For treatment of motor fluctuations

103
Q

What is the difference between parkinsonism and Parkinson’s disease?

A

Parkinson’s disease refers to idiopathic PD (caused by degeneration of dopaminergic neurons) while parkinsonism may be due to a variety of causes.

104
Q

In PD, patients usually present with unilateral symptoms. Compared to PD, vascular parkinsonism (VP) patients __.

A

usually present with bilateral symptoms

105
Q

In PD, resting tremor is a cardinal symptom. Compared to PD, VP patients __.

A

usually do not have resting tremor

106
Q

Idiopathic PD has gradual progression, not worsened by any particular event. On the other hand, VP has __.

A

stepwise progression (i.e. worsened with more CNS insults)

107
Q

In VP, __ are usually present. __ is a risk factor for VP as well.

A

vascular risk factors (i.e. 3 highs)

Age

108
Q

In PD, dopaminergic neuronal death in the substantia nigra occurs. However, most cases of VP are __. Therefore, __ is not very effective in management of symptoms in VP.

A

not caused by infarcts/lesions in the basal ganglia.

levodopa

109
Q

For drug induced parkinsonism (DIP), __ and __ are risk factors.

A

increasing age and being female

110
Q

In PD, patients usually present with unilateral symptoms. Compared to PD, DIP patients __.

A

usually present with bilateral symptoms (symmetrical)

111
Q

Idiopathic PD has gradual progression, not worsened by any particular event. On the other hand, DIP may have __ onset.

A

acute or subacute

112
Q

PD remains progressive despite treatment. On the other hand, __ may be potentially reversible on treatment.

113
Q

__ patients usually respond poorly to levodopa.

114
Q

Other than PD-like symptoms, what are some other symptoms a DIP patient may present with?

A

Orofacial dyskineisa and akathisia

115
Q

Of the cardinal symptoms for PD, __ is uncommon while __ is usually manifested in DIP.

A

resting tremor

bradykinesia/akinesia

116
Q

*PD is caused by insufficient dopaminergic transmission. Therefore, drugs that __ or __ have a risk of DIP.

A

reduce dopaminergic transmission or cause dopamine block

117
Q

Some common suspects of DIP include __, __ and __.

A

Antipsychotics
Cinnarizine
Antiemetics/gastric motility agents (prochlorperazine, metoclopramide)

118
Q

Patients repeating short term courses of __ or __ should be advised to check with their doctors as they may induce DIP.

A

Cinnarizine

Antiemetics/gastric motility agents (prochlorperazine, metoclopramide)

119
Q

DIP may unmask existing PD. The course of DIP is variable but onset may occur __ within exposure to offending agent.

120
Q

*__ and __ may be used to reduce the severity of DIP.

A

Amantadine and anticholinergics

121
Q

Parkinson Hyperpyrexia Syndrome (PHS) is a rare but fatal condition. It may be caused by:
– changes in __
– provoked by trauma, surgery, and infections;
– may have no apparent trigger.

A

dopaminergic treatment

122
Q

In severe cases of PHS, there is no response to __ and symptoms deteriorate rapidly, patient becomes progressively more immobile and rigid.

A

dopaminergic rescue medications

123
Q

*If the cause of PHS is a reduction in dopaminergic medications, we should __ and gradually increase __.

A

Reinstate previous treatment

dose of levodopa

124
Q

As PHS patients may be rigid and unable to swallow, non-PO options such as __ patch or __ injection may be used if available. __ and __ are also options that are likely available at most institutions.

A

Rotigotine
Amantadine
Dantrolene
Bromocriptine

125
Q

Madopar Dispersible is similar to effervescent tablets and is more commonly used for morning doses. (meant to relieve __) It is administered by dropping the tablet in a glass of water to drink. (faster __ = faster __)

A

morning stiffness on waking
absorption
onset of action

126
Q

*Common DDIs in the context of PD patients will include:
__ and __ (due to risk of EPSEs)
Common __

A

SSRIs and Dopamine antagonists (due to risk of EPSEs)

Common anti-emetics

127
Q

What are some problems PD patients may face when it comes to physically using the medications?

  1. Hard to __
  2. Hard to __
  3. __ pills
A
  1. Hard to unscrew caps
  2. Hard to pop blister packs
  3. Dropping pills

Psychiatric Pharmacotherapy (5 decks)

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