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PHRM 845 Module #1 > Lecture 43 - Pharmacotherapy of Parkinson's Disease > Flashcards

Lecture 43 - Pharmacotherapy of Parkinson's Disease Flashcards

1
Q

Disease Progression

A

Slow developing and progressive disease
- Develops over 5-10 years with an increase in motor symptoms
- Cognitive symptoms may present after several years of PD
- Life expectancy after diagnosis (~15 years) can be similar to general population
must have bradykinesia (cardinal sign) for diagnosis

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2
Q

Clinical Presentation: motor symptoms

A

Motor Symptoms
- Tremor
- Bradykinesia
- Rigidity
- Parkinsonian gait

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3
Q

Clinical Presentation: non-motor symptoms

A
  • Anxiety, depression
  • Constipation
  • Dementia
  • Insomnia
  • Orthostatic hypotension
  • Psychosis/delirium
  • Sexual dysfunction
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4
Q

Assessment of Disease

A

Unified Parkinson’s Disease Rating Scale (UPDRS)
- Standardized rating scale to assess signs/symptoms of PD - Scale scores from 0-4 to assess 42 domains for PD severity
- Higher UPDRS score = worse PD symptoms
Clinical assessment
- Observation of motor symptoms
- Impact of disease on quality of life (QOL)

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5
Q

Goals of Therapy

A
  1. Minimize/manage motor and non-motor symptoms
  2. Maintain highest quality of life (QOL) possible
  3. Preserve activities of daily living (ADLs)
  4. Minimize/manage adverse drug reactions
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6
Q

Non-pharmacologic Therapy

A
  • Exercise/physical therapy
  • Nutritional counseling
  • Occupational therapy
  • Psychotherapy/support groups
  • Speech therapy
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7
Q

Pharmacologic Therapy – Initial Treatment

A

1st line: rule out drug induced PD, (drugs that block dopamine: antipsychotics, promethazine, anti-emetics), dopamine precursor (introduce potential risks, can progress disease/cause more dyskinesias), dopamine agonists, MAO-B inhibitor
2nd line: COMT inhibitors, amantadine

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8
Q

Treatment initiation

A
  • For most, initiate with Levodopa (Dopamine Precursor) - generally start with IR
  • Dopamine agonist may be used as initial treatment if age <60 years and higher risk for dyskinesia
  • Avoid dopamine agonists as initial treatment if:
  • age >70 years, or
  • those with history of ICD, or
  • cognitive impairment, or
  • excessive daytime sleepiness, or
  • hallucinations
    In general, initiate with IR > CR
  • In general, initiate with lowest effective dose to delay adverse effects or dyskinesias
  • Efficacy with Motor Symptoms: Levodopa/Carbidopa > DA > MAOB-I
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9
Q

Dopamine Precursor

A

levodopa (carbidopa/levodopa)
1st line for initial PD therapy and throughout course, most effective monotherapy for motor sx (gold standard), adjunctive therapy with dopamine agonists and other agents

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10
Q

Dopamine precusor SE

A

N/V
LD motor fluctuations/dyskinesias
hallucinations

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11
Q

Dopamine precursor

A

↑ absorption with empty stomach, but food ↓ nausea
Starting dose: 25/100 mg CD/LD PO BID-TID with meals
Maintenance: Frequency can increase as needed (5-6x/day) or switch to CR/XR forms
Titrate dose to balance efficacy and side effects
- Limit nausea/vomiting and motor fluctuations

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12
Q

LD motor fluctuations

A

wearing off: before next dosing interval, signs of motor symptoms
freezing: inability to move sue to insufficicnet or fluctuating DA levels
delayed onset: therapeutic benefits delayed
peak-dose dyskinesias: involuntary body movement caused by high DA levels

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13
Q

Management of LD motor fluctuations

A

wearing off: increase CD/LD dose or frequency; add DA agonist, MAOI, or COMTI; XR CD/LD
freezing: increase CD/LD dose or frequency; add DA agonist, (apomorphine); add ODT CD/LD
delayed onset: take CD/LD on empty stomach; ODT CD/LD; avoid CR/XR CD/LD
peak-dose dyskinesias: add amantadine; decrease dose of DA or CD/LD
deep brain stimulation

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14
Q

Dopamine agonists

A

Non-ergot
-Pramipexole (Mirapex®)
-Ropinirole (Requip®)
-Rotigotine (Neupro®)
-Apomorphine (Apokyn® injection and SL film)
Ergot
-Bromocriptine (Parlodel®)
-Cabergoline (Dostinex®)

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15
Q

Dopamine agonists place in therapy

A

Non-ergot DA agonists first-line for initial PD therapy
Minimize LD motor fluctuations
Ergots used rarely due to toxicity
Treatment: off (Apomorphine)

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16
Q

Dopamine agonsits SE

A

Nausea/ vomiting
Sudden onset sleep/EDS
Hallucinations
Impulse control disorder (ICD)
Edema
Orthostatic hypotension
$$$$

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17
Q

Dopamine agonists clinical pearls

A

Starting doses:
- pramipexole IR 0.125 mg PO
TID; ER 0.375 mg PO daily
- ropinirole IR 0.25 mg PO
TID; ER 2 mg PO daily
- rotigotine 2 mg patch
applied to the skin Q24H
-apomorphine 2 mg SC
injection prn up to 5 x daily or 10 mg SL Film up to 5 x daily
Advantages
- Fewer motor fluctuations
- Long-acting formulations

18
Q

MAO-B inhibitors

A

Rasagiline (Azilect®)
Selegiline (Eldepryl®)
Safinamide (Xadago®)

19
Q

MAO-B inhibitors place in therapy

A

First line for mild symptoms
Second-line for adjunctive therapy
Manage LD motor fluctuations
Adjunctive for PD depression

20
Q

MAO-B inhibitors SE

A

Nausea/ vomiting
Headache
Insomnia (selegiline)
Hypotension/ Hypertension

21
Q

MAO-B inhibitors clinical pearls

A

Starting doses:
- rasagiline 0.5 mg PO daily
- selegiline 5 mg PO BID
- safinamide 50 mg PO daily
Dietary restrictions (tyramine-rich foods)
Risk of serotonin syndrome with drug-drug interactions
serotonergic antidepressants
 dextromethorphan serotonergic opioids

22
Q

COMT inhibitors

A

Entacapone (Comtan®)
(also co- formulated with CD/LD as Stalevo®)
Opicapone (Ongentys®)
Tolcapone (Tasmar®)

23
Q

COMT inhibitors place in therapy

A

In combination to manage symptom fluctuation (wearing off)

24
Q

COMT inhibitors SE

A

Nausea/vomiting
Brown/orange urine discoloration (entacapone)
Hepatotoxicity (tolcapone use limiting side effect)

25
Q

COMT inhibitors clinical pearls

A

In early PD, no benefit of COMT inhibitors with CD/LD compared to CD/LD alone
Starting dose:
- entacapone 200 mg PO with
each CD/LD dose
- tolcapone 100 mg PO TID
- opicapone 50 mg po QHS

26
Q

Amantadine place in therapy

A

Management of LD motor fluctuations
Modest Effect in controlling motor symptoms, but rarely used monotherapy (tremor)

27
Q

Amantadine SE

A

Insomnia
Confusion/ Hallucinations
Livedo Reticularis

28
Q

Amantadine clinical pearls

A

Utility limited due to cognitive side effects
Usually reserved CD/LD peak dose dyskinesias
Starting dose:
- amantadine 100 mg PO BID

29
Q

Anticholinergics

A

Benztropine (Cogentin®)
Trihexyphenidyl (Artane®)

30
Q

Anticholinergies place in therapy

A

Management of tremor-dominant symptom in patients < 65 years old

31
Q

Anticholinergics SE

A

Confusion/ dementia
Blurry vision
Urinary retention
Dry mouth
Constipation

32
Q

Anticholinergic clinical pearls

A

Starting doses:
- benztropine 0.5 mg PO QHS - trihexyphenidyl 1 mg PO
daily
Use limited by confusion and anti-muscarinic side effects
- Avoid if > 65 years old

33
Q

Monitoring

A
  • Evaluate motor symptoms
  • Assess for side effects related to pharmacotherapy
  • Identify medications which can worsen PD: dopamine antagonists, antipsychotics
34
Q

Patient Education

A
  • Stress importance of adherence and timing of medication administration to patient/caregiver
    ◦ Make rescue plan
    ◦ Multiple formulations/schedule options to personalize care
  • Pros/Cons of taking medications with food
  • Report side effects and symptoms to healthcare provider
  • Support group and education referral
35
Q

Deep Brain Stimulation

A

Elective surgical procedure offered after maximizing pharmacotherapy
May allow for reduction of treatments and reduction in adverse events
Risks: infection, device malfunction, headache, tingling of face or limbs (during stimulation), cost

36
Q

Treatment of Non-motor Symptoms: constipation

A

Evaluate for meds causing constipation
Increase fluid intake, physical activity
Stool softeners/laxatives or probiotics may be effective

37
Q

Treatment of Non-motor Symptoms: insomnia

A

Non-pharmacologic counseling
Melatonin
avoid: benzodiazepines (diazepam, lorazepam, oxazepam)

38
Q

Treatment of Non-motor Symptoms: orthostatic hypotension

A

Non-pharmacologic counseling
Midodrine, Droxidopa
Medical equipment to stabilize patients

39
Q

Treatment of Non-motor Symptoms: anxiety, depression

A

Cognitive behavioral therapy (or other non-pharmacologic approach)
Selective serotonin reuptake inhibitor (SSRI)
Serotonin-norepinephrine reuptake inhibitor (SNRI)
AVOID: benzodiazepines
CAUTION: tricyclic antidepressant (TCA)

40
Q

Treatment of Non-motor Symptoms: dementia

A

Cholinesterase inhibitor (donepezil, rivastigmine)
AVOID: anticholinergics, benzodiazepines, antihistamines, sedatives

41
Q

Treatment of Non-motor Symptoms: psychosis/delirium

A

Reduce PD medication doses (if appropriate)
Pimavanserin: new(ish) antipsychotic for PD psychosis
Atypical antipsychotics (clozapine, quetiapine)
AVOID: haloperidol, olanzapine, paliperidone, risperidone

PHRM 845 Module #1 (50 decks)

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