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PHARM EXAM 2 > Parkinson's > Flashcards

Parkinson's Flashcards

1
Q

Parkinson’s Pathophys

A

Neurodegenerative disorder of the extrapyramidal system associated with disruption of neurotransmission in the striatum

Imbalance in the balance of acetylcholine and dopamine results in degeneration of neurons that supply dopamine to the striatum
> without adequate dopamine, acetylcholine causes excessive stimulation of neurons that release gamma-aminobutyric acid

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2
Q

Therapeutic Goals of Parkinson’s

A
  • Improve ADLS

- Ideally treatment would reverse but this does not exist

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3
Q

Drug Selection for Parkinson’s: Initial Treatment

A

Mild Symptoms: MAO-B inhibitors (selegiline, rasagiline)

More Severe Symptoms: Levodopa (combined with carbidopa) as dopamine replacement or dopamine agonist

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4
Q

Parkinson’s: Management of Fluctuations

- Drug-Induced Dyskinesias

A

Involuntary Movements: often involves hyperkinetic movement including chorea, dystonia and athetosis

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5
Q

Parkinson’s Treatment: “Off Times”

A
  • Can be reduced with dopamine agonists, COMT inhibitors, and MAO-B inhibitors

Improve Motor Function: LEVODOPA
Improve drug induced dyskinesia: DOPAMINE AGONIST

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6
Q

Parkinson’s Treatment

  • ON OFF
    > Freezing
  • WEARING OFF
A
  • ON OFF: switch between mobility and immobility
    > Freezing: gait episodes: often when subtherapeutic
  • WEARING OFF: worsening in motor function and unpredictable motor function
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7
Q

Levodopa

  • Combo with?
  • How long for effectiveness takes place?
  • How long after taking before not effective?

Food implications

A
  • Only given in combo with carbidopa
  • HIGHLY effective
  • SEVERAL MONTHS OF TREATMENT NEEDED FOR FULL THERAPEUTIC EFFECT
  • SX WELL CONTROLLED FOR FIRST 2 YEARS
  • RETURN TO PRETREATMENT STATE AT END OF 5 YEARS
  • Orally administered; rapidly absorbed in the small intestine
    > food delays absorption
    > neutral amino acids compete with levodopa for intestinal absorption
    > high protein foods reduce therapeutic effects
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8
Q

Gradual Loss/Wearing Off of Levodopa

3 THINGS TO MINIMIZE WEARING OFF

A
  • Develops near the end of dosing interval and indicates that drug levels have declined past subtherapeutic value

Three ways to be minimized:
1. Shortening dosing interval (give more frequently)
2. Giving a drug that prolongs levodopa’s half-life (ie entacapone)
» WHAT CLASS OF DRUG IS THIS? (COMT)
» Inhibits metabolism of Levodopa in periphery
3. Giving direct-acting dopamine agonist
» pramipexole and ropinirole and rotigimine

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9
Q

Adverse Effect of Levodopa

A

N/V
- Activation of dopamine receptors trigger medulla
- Treatment:
> low initial doses and with food (by lowering absorption)
> Giving carbidopa (without levodopa) can reduce n/v

Postural Hypotension 
- Treatment 
> Increase intake of salt and water 
> use the lowest dose necessary 
> limit alpha antagonist (-osins)

CNS Effects:
- Psychosis, hallucinations, vivid dreams, nightmares, paranoia, impulse control problems, behavioral changes (alcohol abuse, binge eating, gambling, hypersexual)
- Caused by activation of dopamine receptors
- Treatment:
> lower the dose

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10
Q

Dyskinesia’s from Levodopa

A
  • Develop just before or after optimal dosage is achieved
  • Managed in three ways
    1. Reduce levodopa
    2. Amantadine or dopamine agonist
    » why would these help??? bc they block the dopamine?
  1. Surgery or electrical stimulation
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11
Q

Levodopa Adverse Effects

A
  • Darkens sweat and urine

- Activates malignant melanoma: Important to perform careful skin inspections

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12
Q

Dopamine Agonists

A 
- Compared to Levodopa: 
> less effective
> not dependent on enzyme conversion to be active 
> does not compete with dietary proteins
> lower incidence of response failure 
> less likely to cause dyskinesias

Two Types:

  1. Derivatives of ergot
  2. Nonergot derivatives
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13
Q

Nonergot Derivative Dopamine Agonist

A

Pramipexole & Ropinirole (and also rotigotine)

  • Can be used alone in early therapy or as adjunct to levodopa in worsening disease
  • Can be used as first line in younger pts ( <50yo )
  • Can be added to levodopa for reduced off time and improve dyskinesia caused by levodopa
  • Also used in restless leg syndrome

> Max benefits take several weeks
Not as effective as levodopa

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14
Q

Pramipexole Adverse Effects

A

Nonergot Derivative Dopamine Agonist

Monotherapy:
- nausea, dizziness, daytime somnolence, insomnia, constipation, weakness, hallucinations

Combined:
- orthostatic hypotension, dyskinesia, increased hallucinations

  • Rarely: sleep attacks, gambling, self-rewarding behaviors
    » WHAT OTHER DRUG HAS THIS SAME EFFECT?
  • levodopa?? and ropinirole
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15
Q

Rotigotine

A

Nonergot Dopamine Agonist

  • Transdermal
  • Management of PD from early to advanced stages
  • Management of mod-sev primary restless leg syndrome
  • Most common adverse effects: CNS
  • Other side effects: orthostatic hypotension, peripheral edema, n/a, skin reaction at transdermal site, hyperhidrosis
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16
Q

COMT inhibitors

A
  • Inhibit metabolism of Levodopa in periphery
  • NOT FOR MONOTHERAPY: no direct effects of their own
  • Added to levodopa to reduce off time
  • Increases Levodopa/Carbidopa AE: May need to decrease levodopa

TWO COMT INHIBITORS AVAILABLE:
1. entacapone: safer and more effective, reduces pill burden
> causes orange urine + GI side effects
2. tolcapone: liver function tests required
> causes GI side effects

17
Q

MAO-B Inhibitors

A

Selegiline + Rasagiline

  • Monotherapy or used with levodopa
  • Modest improve in motor function
  • CAUSES SELECTIVE and irreversible inhibition of MAO-B
  • Can suppress the destruction of dopamine derived from levodopa and prolong effects of levodopa -
  • Benefits decline dramatically within 12-24mo
  • USED AS FIRST-LINE THERAPY for patients who have mild impairment and bradykinesia as the main symptoms
    » MILD IMPAIRMENT AND BRADYKINESIA (SLOW MOVEMENTS)
  • ALSO USED as first-line for postural instability and/or gait improvement
18
Q

Amantadine

A
  • Developed first as antiviral drug
  • Effects much less profound than levodopa or the dopamine agonist
  • Responses may diminish with 3-6mo
  • NOT considered first line treatment
  • MAY be helpful for dyskinesia caused by levodopa
  • A/E: livedo reticularis
    > skin condition characterized by mottled discoloration of the skin
19
Q

Benztropine

A

Centrally Acting Anticholinergic

  • Reduces tremor and possible rigidity
  • Most appropriate for younger patients with mild symptoms
  • Less effective than levodopa or dopamine agonist but better tolerated
  • Avoided in the elderly due to CNS effects
  • Has anticholinergic effects: dry mouth, urinary retention, constipation
    > Could be used to prevent symptoms of drooling
20
Q

Why do you give carbidopa with levodopa?

A

In addition to helping prevent nausea, carbidopa prevents levodopa from being converted into dopamine prematurely in the bloodstream, allowing more of it to get to the brain.

carbidopa is an inhibitor of aromatic amino acid decarboxylation, thereby slowing the conversion of levodopa to dopamine in the extracerebral tissues, making more levodopa available for transport to the brain. Carbidopa does not cross the blood brain barrier

21
Q

Ropinirole Most Common Side Effects

A

NAUSEA DIZZINESS SOMNOLENCE AND HALLUCINATIONS
- What would you do

VOMITING FATIGUE NAUSEA Monotherapy

PHARM EXAM 2 (19 decks)

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