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AIM - The Brain > Pharm - Parkinson's > Flashcards

Pharm - Parkinson's Flashcards

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1
Q

goals of therapy for Parkinson’s drugs

A
  • manage symptoms

- nothing to slow/prevent disease

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2
Q

basic pathology of Parkinson’s

A
  • depletion of dopinergic neurons in the substantia nigra

- hard to stop/start movements

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3
Q

if there is no response to dopaminergic drugs, then __________

A

if there is no response to dopaminergic drugs, then RULE OUT Parkinson’s

-Parkinson’s should respond to dopamine

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4
Q

features of Parkinson’s

A

Classic signs:

  • akinesia/bradykinesia
  • rigidity
  • tremor
  • gait disturbances

Differentiating signs

  • asymmetry
  • resting tremor
  • good response to levodopa
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5
Q

co morbid problems of Parkinson’s

A
  • daytime sleepiness
  • hallucinations (side fx)
  • psychosis (side fx)
  • depression
  • fatigue
  • dementia
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6
Q

restorative/regenerative treatment for Parkinson’s

A
  • surgical procedures
  • electrical stimulation

reserved only for pts w ADVANCED DISEASE

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7
Q

symptomatic treatments for Parkinson’s

A
  • levodopa/extenders

- dopamine agonists

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8
Q

why not just use dopamine for Tx of Parkinson’s (instead of levodopa)?

A
  • cannot cross BBB

- low bioavailability (F)

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9
Q

benefits of using L-dopa

A
  • high bioavailability

- crosses BBB

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10
Q

purpose of carbidopa

A
  • peripheral carboxylase inhibitor
  • prevents premature conversion of L-dopa to dopamine
  • combined with levodopa
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11
Q

dosing schedule of levodopa/carbidopa

A
  • both dosed multiple times per day

- need higher dosage as disease progresses

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12
Q

side fx of levodopa

A
  • nausea/orthostasis (due to incr DA in periphery)

- agitation, confusion, hallucinations, delusions, dyskinesia (due to DA toxicity in CNS)

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13
Q

drug combinations to avoid with Parkinson’s drugs

A

-avoid combination with NON SELECTIVE MAO inhibitors

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14
Q

non selective MAO inhibitors

A
  • inhibits degradation of all substrates in dopamine pathway

- causes accumulation of NE (hypertension)

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15
Q

concerns with CHRONIC use of levodopa

A

-wearing off effect (need increased dose)
-toxicity (dyskinesia)
-
-must balance disease progression vs side effects

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16
Q

how is methyldopa formed? what do we want to do with it?

A

levodopa –> methyldopa

  • via COMT
  • another pathway depleting L-dopa
  • want to inhibit
  • Entacapone, Tolcapone inhibit COMT
17
Q

how do we inhibit formation of methyldopa?

A
  • Entacapone, Tolcapone
  • COMT inhibitors
  • allow more L-dopa to get to the brain
  • stress the liver
  • always used in adjunct with levidopa/carbidopa
18
Q

side effects on COMT inhibitors

A
  • nausea, dizziness, psychotic symptoms, dyskinesia
  • avoid use with non selective MAO inhibitors
  • diarrhea (explosive), discolored urine, increased LFTs
19
Q

selective MAO inhibitors

A

MAO-type B inhibitors

  • result in accumulation of dopamine
  • degradation of NE remains intact, so no weird side effects from that
20
Q

side effects of MAO-type B inhibitors

A
  • nausea, dizziness, psychotic symptoms, dyskinesia (too much dopamine)
  • insomnia (selegiline)
21
Q

net effect of dopamine receptor agonists

A
  • act directly on D2 receptors in the striatum
  • less fluctuations and dyskinesia
  • take longer to work
22
Q

types of dopamine agonists

A
  • ergot derived (not used for parkinsons)
  • non ergot derived
  • –less potent, less side fx, effective early on
23
Q

side fx of ergot-derived dopamine agonists

A
  • nausea
  • orthostasis and dizziness
  • dyskinesia
  • somnolence
  • reduced prolactin levels
  • FIBROTIC PULMONARY/SKIN REACTIONS (life threatening)
  • heart valve damage
24
Q

side fx of non-ergot derived dopamine agonists

A
  • COMPULSIVE behaviors
  • nausea
  • orthostasis, dizziness
  • dyskinesia
  • somnolence
  • reduced prolactin levels

NO heart valve, or fibrotic damage

25
Q

apomorphine (Apokyn)

A
  • used to rescue from “frozen” episodes

- subQ injection

26
Q

side effects of apomorphine

A
  • nausea/vomiting
  • orthostasis
  • hypersomnia
  • priapism
27
Q

use of anticholinergic agents for Parkinsons

A
  • corrects imbalance btwn ACh and DA
  • better for tremor (not really for rigidity or akinesia)
  • many side fx

-or use antihistimine

28
Q

side fx of blocking post-synaptic muscarinic receptors

A
  • dry mouth
  • blurred vision
  • urinary retention
  • constipation
  • tachycardia
  • memory/cognition issues
29
Q

amantadine

A
  • MOA for Parkinson’s unknown
  • improvement in rigidity and tremor
  • may improve drug-related dyskinesia
30
Q

side fx of amantadine

A
  • mostly CNS related

- some GI (nausea)

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