69. Parkinson Disease Flashcards

1
Q

Parkinson is a neurological disorder that occurs when neurons in the ____ (part of the brain) die or become impaired. These cells produce the NT ____ which allows smooth, coordination function and movement of body muscles.

A

substantia nigra
Dopamine (less dopamine&raquo_space; less instructions to the brain&raquo_space; movement problems (TRAP major symptoms)

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2
Q

What are the TRAP major symptoms of parkinson disease?

A

Tremor - when resting
Rigidity - in legs, arms, trunk, and face (mask-like face)
Akinesia/bradykinesia - lack of/slow start in movement
Postural instability - imbalance/falls

Other symptoms to know:
Small, cramped hand writing (micrographia)
Shuffling walk, stooped posture
muffled speech, drooling, dysphagia
Depression, anxiety (psychosis in advanced disease)
Constipation, incontinence

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3
Q

What tool can be used to measure involuntary movements (e..g tardive dyskinesias) from medications?

A

Abnormal involuntary movement scale (AIMS)

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4
Q

Dopamine blocking drugs that can worsen Parkinson Disease

A

Phenothiazines (e.g. prochlorperazine) used for psychosis, nausea, agitation
Butyrophenones (e.g. haloperidol, droperidol) used for psychosis and behavior disorders or nausea
First and second-generation antipsychotics (e.g. risperidone at higher doses, paliperidone); lowest risk with quetiapine
Metoclopramide, a renally-cleared drug that can accumulate in elderly pts

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5
Q

Even with high doses of Parkinson Disease drugs and various combinations, the disease will progress, including extended periods of “off time”. What does this mean?

A

When symptoms of the disease worsen before the next dose of med is due. An “off” episode, with muscle stiffness, slow movements and difficulty starting movement, is one of the most frustrating aspects of living with parkinson disease.

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6
Q

Patients with parkinson disease have a high incidence of depression. ___ are commonly used for treatment (concerns with may contribute tremor or increased risk of serotonin syndrome with other serotonergic drugs).
Other options include ___ (preferably secondary amines such as ____) and dopamine agonist pramipexole (reported to provide antidepressant effects).

A

SSRIs, SNRIs
TCAs - despiramine and nortriptyline

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7
Q

Psychosis can occur with advanced parkinson disease or can be d/t side effects of drug treatment. ____ is preferred d/t low risk of movement disorders but can cause _____ complications. ___ has low risk of movement disorders but high risk of seizures, agranulocytosis (requires frequent monitoring and reporting of WBC) and other serious complciations.

A

Quetiapine
metabolic complications (increased lipids and BG)

Clozapine

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8
Q

Rapid withdrawal of levodopa or dopamine agonists can lead to a condition similar to ___ which is a life-threatening condition sometimes seen with antipsychotics. Taper slowly when d/c.

A

neuroleptic malignant syndrome (NMS)

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9
Q

___ is the most effective drug treatment for Parkinson Disease

A

Levodopa (prodrug of Dopamine)

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10
Q

PD drug treatment: ___ is given with levodopa (in the combination product____ ) to prevent peripheral metabolism of levodopa which would destroy most of the drug before it crosses BBB

A

carbidopa
Sinemet

Note: important to provide right amt of carbidopa without causing excess side effects

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11
Q

Initial treatment with ____ is sometimes better tolerated in elderly pts with PD than the dopamine agonists

A

carbidopa/levodopa

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12
Q

___ are eventually used in most pts. As PD progresses, treatment will be directed at both reducing ___ and limiting ____. This will require multiple therapies such as _____ and ____.

A

Dopamine agonists
Reducing “off periods” and limiting dyskinesias
COMT inhibitors and MAO-B inhibitors

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13
Q

Tremor-predominant PD in younger pts can be treated with _____. Considerable side effects of these drugs make them difficult to use in elderly pts (Beers criteria says “avoid” use)

A

centrally-acting anticholintergic (e.g. benztropine)

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14
Q

PD treatment principles - primary treatment is to replace ____ by administering ____

A

dopamine
Precursor to dopamine that becomes dopamine in the brain (levodopa in Sinemet)
Dopamine agonist that acts like dopamine
Give other drugs for specific symptoms (e.g. benztropine for resting tremor)

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15
Q

How do carbidopa/levodopa in Sinemet work together for PD?

A

Levodopa is precursor of dopamine = replaces dopamine
Carbidopa inhibits dopa decarboxylase enzymes = prevents peripheral metabolism of levodopa

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16
Q

Starting dose of carbidopa/levodopa (Sinemet) IR

A

25/100mg PO TID

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17
Q

T/F: Sinemet ER tab cannot be cut in half

A

False - can be cut in half but do not crush or chew

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18
Q

T/F: carbidopa/levodopa (Rytary ER Capsule) can be opened and sprinkled on small amount of applesauce

A

True - take whole or sprinkle on applesauce

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19
Q

Contraindications of carbidopa/levodopa

A

Non-selective MAOi (e.g. phenelzine, isocarboxazid) within 14 days,
narrow angle glaucoma

20
Q

Side effects of carbidopa/levodopa

A

Nausea, dizziness, orthostasis, dyskinesias, hallucinations, psychosis, xerostoia (dry mouth), dystonias (occasional, painful), confusion

Can cause brown, black, or dark discoloring of urine, saliva or sweat (may discolor clothing
Positive Coombs test = d/c drug (hemolysis risk)
Usual sexual urges, priapism
Increased uric acid
Rytary: suicidal ideations and attempts

21
Q

___ mg/day of carbidopa required to inhibit dopa decarboxylase

22
Q

Long-term use of carbidopa/levodopa can lead to ___

A

fluctuations in response and dyskinesias

23
Q

T/F: Carbidopa/levodopa must be titrated up cautiously but can be d/c immediately

A

False - titrate up cautiously and taper off

24
Q

COMT inhibitor MOA

A

increase duration of action of levodopa; inhibit enzyme COMT to prevent peripheral conversion of levodopa - should ONLY be used with levodopa

25
Examples of COMT inhibitors
Entacapone (Comtan) Entacapone/carbidopa/levodopa (Stalevo) Opicapone (Ongentys) Olcapone (Tasmar)
26
Entacapone (Comtan) dose
200mg PO with each dose of carbidopa/levodopa Max = 1600 mg/day
27
Decrease in ____ dose of 10-30% is usually necessary when adding COMT inhibitor
levodopa
28
Why is COMT inhibitor tolcapone (Tasmar) rarely used?
hepatotoxicity risk
29
Examples of dopamine agonists used in parkinson disease
Pramipexole (Mirapex, Mirapex ER) Ropinirole (Requip XL) Others: Rotigotine (Neupro) - patch, also approved for RLS Apomorphine (Apokyn injection, Kynmobi SL film) - used as "rescue" movement drug for "off" periods
30
Warnings with dopamine agonists
Somnolence (including sudden daytime sleep attacks), orthostasis, hallucinations, dyskinesias, impulse control disorders Rotigotine (Neurpo) patch: application side reactions
31
Rotigotine (Neupro) patch administration notes
apply once daily at the same time each day to stomach, thigh, hip, side of body, shoulder, or upper arm Do not use same site for at least 14 days Remove patch before MRI Avoid if sensitivity/allergy to sulfites
32
Rotigotine (Neupro) patch should avoid if sensitivity/allergy to ___
sulfites
33
Pt is prescribed Apomorphine (Apokyn) injection. What must be done before starting?
Must be started with test dose in medical office
34
Contraindications with apomorphine
do not use with 5-HT-3 antagonists (e.g. ondansetron) d/t severe hypotension and loss of consciousness
35
Side effects with apomorphine
Severe N/V, hypotension, yawning, dyskinesias, somnolence, dizziness, QTprolongation SL film: dry mouth, tongue pain
36
Apomorphine can cause severe N/V. For emesis prevention what can be given?
Trimethobenzamide (Tigan) 300mg PO TID or a similar antiemetic, started 3 days prior to initial dose Do NOT give ondansetron (5HT-3 antagonist) d/t severe hypotension and loss of consciousness
37
_____ can decrease absorption of carbidopa/levodopa (Sinemet)
iron and protein-rich foods
38
Amantadine MOA
blocks dopamine reuptake into presynaptic neurons and increases dopamine release from presynaptic fibers Primarily used to treat dyskinesias a/w peak-dose of carbidopa/levodopa
39
Warnings with amantadine
Somnolence (including falling asleep without warning during ADLs) compulsive behaviors Psychosis (hallucinations, delusions, paranoia)
40
Side effects with amantadine
Dizziness, orthostatic hypotension, cutaneous reaction called livedo reticularis (reddish skin mottling = can require drug d/c) Others: syncope, insomnia, abnormal dreams, dry mouth, constipation
41
Examples of Selective MAO-B inhibitors used in PD
Selegiline Rasagiline (Azilect) Safinamide (Xadago)
42
MAO of Selective MAO-B inhibitors used in PD
block breakdown of dopamine which increases dopaminergic activity Primarily used as adj treatment to carbidopa/levodopa Rasagiline has indication for monotherapy
43
Contraindications of Selective MAO-B inhibitors used in PD (selegiline, rasagiline, safinamide)
Use in combo with other MAO inhibitors (including linezolid), opioids, SNRIs, TCAs, and others Safinamide (Xadago) - severe hepatic impairment
44
Warnings with Selective MAO-B inhibitors used in PD (selegiline, rasagiline, safinamide)
Serotonin syndrome, HTN Others: nausea, CNS depression, dyskinesias, impulse control disorders, caution in pts with psychotic disorders (may exacerbate), or ophthalmic disorders (Xadago) Rasagiline (monotherapy): HA, joint pain, indigestion
45
Centrally-acting anticholinergics used in PD
Benztropine (Cogentin) Others: trihexyphenidyl
46
Side effects of benztropine (Cogentin)
Dry mouth, constipation, urinary retention, blurred vision, mydriasis, somnolence, confusion, tachycardia