Lec 36 Drugs for Movement Disorders Flashcards

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1
Q

What is the pathophysiology of parkinsons?

A
  • substantia nigra degenerates –> striatum deprived of dopamine input
  • causes less excitation of direct path and less inhibition of indirect path
  • this leads to greater activity of GPi –> more inhibition of thalamus sending info to corte
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2
Q

What are the direct and indirect paths via which dopamine from substantia nigra effects globus pallidus interna [GPi] inhibition of thalamus

A

direct:
substantia nigra DA –> activate striatum GABA –> inhibit GPi

indirect:
substantia nigra DA –> inhibits striatum GABA –> which is inhibiting GPe –> which is inhibiting STN –> activates GPi

thus if you increase direct path you get inhibition of GPi

if you increase indirect path you get excitation of GPi

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3
Q

What are roles of ACh vs DA in the path from striatum to thalamus? the balance in parkinsons?

A

more ACh = more inhibition of thalamus
more DA = less inhibition of thalamus

–> in parkinsons more ACh than DA = imbalance –> more inhibition of thalamus

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4
Q

Why administer L-dopa instead of dopamine itself?

A
  • dopamine has poor access to brain from periphery, not good at crossing BBB
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5
Q

What are the two enzymes that act on L-Dopa in the periphery?

A

COMT –> product is inactive

DOPA decarboxylase –> product is dopamine

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6
Q

What is side effect of dopamine?

A

arrhythmias

after long term us: dyskinesia after dose + akinesia between doses

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7
Q

What is reason for giving carbidopa with Ldopa?

A

decrease systemic conversion of L-dopa to dopamine –> increase bioavailability of L-dopa in brain

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8
Q

What is MAO-B? where is it found?

A
  • metabolizes DA but not NE or 5HT
  • predominant isoform in striatum

vs MAO-A metabolizes DA, NE, and 5HT

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9
Q

What is effect of COMT inhibitors?

A
  • give as adjunct to LDOPA to decrease response fluctuations

- inhibits COMT in periphery and CNS

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10
Q

Which drugs can induce parkinsonism?

A
  • antipsychotics [paticularly older tones that strongly block D2]
  • MPTP poisoning = contaminant of designer opioid MPPP
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11
Q

What is the first aid mneumonic for parkinsons treatment?

A

BALSA

  • bromocriptine [DA agonist]
  • amantadine [increase DA]
  • levodopa
  • selegiline [and COMT inhibitors]
  • Antimuscarinics [benzotropine = park your benz]
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12
Q

WHat is action of cholinergic interneurons of striatum in PD?

A
  • provide excitatory tone to indirect pathway via muscarinic receptors –> reduced thalamic drive, opposite to inhibitory effect of DA on D2 receptors
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13
Q

What treatments for the non-motor symptoms of PD?

A
  • central acting anticholinesterases for dementia
  • antidepressants
  • anxiolytics
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14
Q

What is pathophysiology of huntingtons?

A
  • degeneration of striatum
  • cholinergic interneurons die off
  • indirect path to thalamuc more affected than direct
  • excessive excitatory to cortex
  • -> chorea
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15
Q

What is spasticity?

A

excessive resting tone of skeletal muscle

  • exaggerated stretch reflex response
  • due to abnormal function spinal cord or higher CNS center
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