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Therapeutics III > Parkinson's - Block 1 > Flashcards

Parkinson's - Block 1 Flashcards

1
Q

What is the problem with PD?

A

Low dopamine from low producing neurons

-> less instructions to the brain -> motor symptoms

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2
Q

What is the mechanism of dopamine?

A
  1. Produced by neurons in the substantia nigra
  2. Activation of DR signals the motor cortex
  3. Smooth, coordinated function of body muscles and movement

*Dopamine gives the brain instructions to move

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3
Q

What are the sx of PD?

A

Tremor
Rigidity
Akinesia/Bradykinesia
Postural instability

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4
Q

What is the most common sx of PD? Most common type?

A

Tremor; pill rolling

Occurs at rest

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5
Q

How occurs during rigidity?

A

Stiffness and pain with alterations of motion

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6
Q

What is Akinesia/Bradykinesia?

A

Absence or slowness of movement and difficulty to move
* Decreased dexteritity

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7
Q

What is postural instability?

A
  1. Shuffling walk
  2. Stooped posture
  3. Unable to recover balance
  4. Risk of falling
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8
Q

Other motor sx of PD?

A

Falls
Freezing
Dysphagia
Micrographia
Slurred speech
Drooling
Reduced voice volume
Dystonia
Difficulty rising from a seated position

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9
Q

Non motor sx of PD?

A

Hypotension
Bladder dysfunction
Sexual dysfunction
Sleep disturbances
Depression
Anxiety
Psychosis/hallucinations
Cognitive impairment
Decreased sense of smell

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10
Q

How do we diagnose PD?

A
  1. Presence of bradykinesia and at least 1 other TRAP symptom
  2. Other conditions have been ruled out
  3. Presence of 3 supportive findings:
    * Asymmetry of motor features
    * Unilateral onset
    * Resting tremor
    * Progressive disorder
    * Responsive to dopaminergic therapy
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11
Q

What does it feel like for a PD patient?

A

Put yourself in the patient’s shoes.

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12
Q

What can we do about PD?

A

Replace dopamine

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13
Q

How do we replace dopamine? Tx for PD

A

Give dopamine (precursor): Sinemet
Give something to preserve dopamine: COMT Inhibitors, MAO-B Inhibitors
Give something that acts like dopamine: Dopamine Agonists
Give drugs to treat specific symptoms: Anticholinergics, Amantadine, Adenosine A2A Antagonists

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14
Q

What are the first line agents for PD?

A
  1. MAO-B Inhibitors
  2. Dopamine Agonists
  3. Sinemet
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15
Q

Sinemet

Generic, Indication, ADR, CI, Counseling

A

Carbidopa-Levodopa
Indication: Bradykinesia and rigidity are predominant, patient is elderly or has cognitive impairment
* prevents peripheral conversion of levodopa

ADR: GI, orthostasis, dz, psych, dark body fluids, dyskinesias, wearing off phenomenon
CI: MAOI use within 14 days, narrow angle glaucoma
Counseling: Do not DC abruptly
* Best absorbed on an empty stomach (avoid iron and high protein foods)
* Don’t crush or chew
* Dry powder levodopa inhaler may be used for breakthrough symptoms

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16
Q

What is the on/off phenomenon?

A

Fluctuations in movement sx:
* On: good movement
* Off: poor movement

Wearing off is the worsening sx prior to the next dose of med
* Short half-life of levodopa and decline in the ability of the brain to store dopamine

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17
Q

What are the tx for wearing off sx?

A
  • Give Sinemet more frequently (reduce dosing interval)
  • Give IR formulation on empty stomach (consistent absorption)
  • Add COMT inhibitor, MAO-B inhibitor, or DA to extend action of Sinemet
  • Add ER formulation
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18
Q

What is peak dose dyskinesias?

A
  1. Involuntary movements that occur in patients taking levodopa
  2. Associated with peak dose of dopamine
  3. Tardive dyskinesia
19
Q

What is the tx for peal dose dyskinesias?

A

Lowering levodopa dose -> suboptimal control of PD

20
Q

What are your dopamine agonsits?

A

Ropinirole (Requip)
Pramipexole (Mirapex)
Rotigotine (Neupro)
Apomorphine (Apokyn)
Bromocriptine (Parlodel)

21
Q

Dopamine Agonists

Indication, ADR, CI, COunseling

A

Indication: initial, add on therapy
* Younger patients
* May be added to Sinemet to help with wearing off
* RLS
* Pramipexole may also improve depression
* Less risk of motor complications compared to Sinemet

ADR: GI, psych, orthostasis, drowsiness, obsessive behaviors
CI: Bromocriptine – avoid if allergic to ergots
* Neupro – avoid if sensitive to sulfites
* Apomorphine: Do not use with SHT3 antagonists (ondansetron, etc.) due to severe hypotension, Do not use if patient develops orthostatic hypotension with test dose

Couseling: Don’t stop abruptly
* Titrate slowly (weekly) due to side effects
* Patch: QD, do not use application site for 14 days, remove before MRI

21
Q

What are you COMT inhibitors?

A

Entacapone (Comtan)
Tolcapone (Tasmar)

22
Q

COMT Inhibitors

Indication, ADR, Counseling

A

Indication: Preserve levodopa (adjuct only, may need to reduce Sinemet)
ADR: dyskinesias, discolor urine, delayed onset diarrhea (entacapone), hepatotoxicity (tolcapone)
Counseling Do NOT stop abruptly

23
Q

Types of Selective MAO-B Inhibitors?

A

Selegiline (Eldepryl, Zelapar)

Rasagiline (Azilect)

Safinamide (Xadago)

24
Q

Selective MAO-B Inhibitors

Indications, ADR, CI

A

Indication: Block the breakdown of dopamine, mild motor sx
ADR: Gi, psych, HA, DZ, HTN, Drowsiness, Insomnia (selegiline)
CI: Do NOT use with other MAOIs
* Tyramine interaction potential -> hypertensive crisis (loss of selectivity at higher doses)
* Serotonin syndrome potential: Avoid other serotonergic drugs

25
Q

What are the anticholinerigcs for PD?

A

Benztropine (Cogentin)

Trihexyphenidyl (Artane)

26
Q

Anticholinergics

Indications, ADR, CI, Counseling

A

Indication: Tremors, improve dystonia, taper to avoid rebound PD sx
ADR: dry mouth, constipation, urinary retention, blurred vision, somnolence, confusion/CNS changes
CI: elderly, BPH, closed angle glaucoma, dementia, tardive dyskinesia, amantadne may cause additive effects
Counseling: Taper to avoid rebound PD symptoms

27
Q

Amantadine

Brand, Indication, Caution, ADR

A

Symmetrel
Indication: treating Sinemet-induced EPS (dyskinesias)
Caution: elderly and hx of seizures
ADR: Anticholinergic effects, Reversible skin reaction (Livedo reticularis – reddish purple mottling of the skin)

28
Q

Types of Adenosine A2A Antagonists?

A

Istradefylline (Nourianz)

29
Q

Adenosine A2A Antagonists

Indication, ADR, Caution,

A

Indication: adjunct treatment with Sinemet to reduce “off” episodes
ADR: GI, hallucinations, psychosis, insomnia, dyskinesias
Caution: dose adjustment for smokers and CYP3A4 inhibitors
* dyskinesias or psychotic disorders

30
Q

What are the drugs that induce PD?

A

Metoclopramide: Used to treat gastroparesis, nausea/vomiting
Antipsychotics: First generation – most likely to cause EPS (Haloperidol, prochlorperazine)
* Some second generation – risperidone, paliperidone
* Quetiapine, clozapine – least likely

31
Q

What are frequent comorbidities of PD? Drugs that induce them?

A
  1. Depression (Choose treatment based on side effects and drug interactions)
  2. Psychosis (Pimavanserin, quetiapine, clozapine)
  3. Dementia (Rivastigmine)
32
Q

What is an essential tremor?

A

A neurological disorder characterized by rhythmic, involuntary shaking mainly in the upper extremities
* bilateral and symmetric

33
Q

What are the sx associated with ET?

A
  1. head, voice, tongue, face/jaw, or lower limbs movement
  2. worsened by stress, fatigue, caffeine, or extreme temperatures
  3. Can interfere with daily tasks
    4.>70 YO
34
Q

Compare PD vs ET?

35
Q

How is ET diagnosed?

A
  1. Bilateral postural and/or kinetic tremor, involving the hands and arms, that is visible and persistent
  2. Duration >5 years
  3. Rule out other causes
  4. ET does NOT respond to levodopa treatment.
36
Q

What are the tx for ET?

A

Beta blockers: Propranolol, atenolol, nadolol
Anticonvulsants: Primidone, gabapentin, topiramate, pregabalin
Benzodiazepines: Alprazolam, clonazepam
Botulinum Toxin Type A (Botox)
Surgery

37
Q

What is the first line for ET?

A
  1. Propranolol
  2. Primidone
38
Q

What is RLS?

A

Paresthesia felt deep in the calf muscle (or arms/thighs) resulting in the urge to keep limps in motion

39
Q

What are the RF of RLS?

A
  1. CKD
  2. Iron def
  3. Pregnancy
  4. Caffeine
  5. Stress
  6. Alcohol
  7. Fatigue
41
Q

How do you diagnose RLS?

A
  1. Urge to move limbs usually associated with discomfort
  2. Symptoms begin/worsen during rest or inactivity
  3. Symptoms exclusively present or worse in the evening or at night
  4. Symptoms are temporarily relieved by movement
  5. Symptoms are not accounted for by other medical conditions
  6. Discomfort returns when the person tries to sleep -> insomnia
42
Q

What are the tx for RLS?

A

DA: monitor for compulsive behaviors
Sinemet: monitor for more symptoms
Gabapentin/Pregabalin: monitor for dizziness/falls
Opiods: monitor for tolerance, RLS symptoms and response to therapy
Sedative hypnotics: monitor for sedation
Iron: if def, but montior for constipation

Therapeutics III (40 decks)

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