Parkinson's Disease

  1. When does Parkinson's usually set in?
    45-70 years of age
  2. What are the causes of Parkinson's?
    • genetic link
    • toxins, oxidative stress
    • environmental factors (pesticides, rural living, well water)
    • medications (antipshychotics, antiemetics)
  3. What behaviors have an inverse relationship to PD?
    • caffeine
    • smoking
  4. Why doesn't glutathione protect against Parkinson's?
    We don't produce enough of it
  5. What are the effects of PD on the cortex?
    decreased direct pathway stimulation = decreased facilitation of movement

    increased indirect pathway stimulation = increased inhibition of movement
  6. When symptoms occur how much damage is already done to the DA neurons?
    70-80% loss of neurons
  7. 2 of what symptoms present in a patient are probable for Parkinson's diagnosis?
    • bradykinesia
    • resting tremor (usually unilateral)
    • rigidity
    • postural imbalance
  8. What are the motor symptoms of PD?
    • fenestrating gait
    • dysphagia
    • difficulty rising from sitting
    • hypophonia
    • diminished arm swing
    • hypomimia
    • micrographia
  9. What are the autonomic and sensory symptoms of PD?
    • sialorrhea
    • sexual dysfunction
    • constipation
    • incontinence
    • diaphoresis
    • olfactory disturbances
  10. What are the mental status changes of PD?
    • anxiety
    • apathy
    • slow thought process
    • depression
    • confusion
    • hallucinations
    • dementia
  11. What is not always present at PD diagnosis?
  12. What is often found on an autopsy of a person with PD?
    Lewy bodies
  13. What are the comorbidities of PD?
    • dementia ~ 40%
    • psychosis ~ 25%
    • mild psychotic symptoms ~ 50%
    • depression ~ 40%
  14. What are the goals of PD therapy?
    • improve QOL
    • minimize/improve symptoms
    • minimize side effects of medication
  15. What are the nonpharmacological treatments for PD?
    • exercise (tango is best)
    • deep brain stimulation (implanted stimulator)
    • implantation of DA secreting tissue in the brain
    • glial-derived neurotrophic factor (GDNF)
    • occupational therapy
    • speech therapy
    • support
    • diet
  16. What causes PD?
    decreased DA
  17. How do we treat PD?
    • Replace DA
    • L-Dopa
    • Mimic DA (stimulate the receptors)
    • pramipexole
    • ropinirole
    • bromocriptine
    • apomorphine
    • pergolide
    • Stop the breakdown of DA
    • selegiline (MAO-B in brain)
    • rasagiline (MAO-B in brain)
    • tolcapone (COMT in brain and periphery)
    • entacapone (stops breakdown of L-Dopa by COMT in periphery)
    • carbidopa (stops breakdown of L-Dopa by Dopa Decarboxylase in periphery)
  18. What causes depletion of DA?
    free radicals
  19. What factors increase risk of motor disturbances in PD?
    • age
    • duration of disease
    • dose of medication
    • severity of disease
  20. What drug is used in PD as a precursor to DA that can cross the BBB?
    levodopa (L-Dopa)
  21. What is used to increase the amount of L-Dopa that crosses the BBB?
    Carbidopa - inhibits the breakdown of L-Dopa in the periphery by Dopa Decarboxylase
  22. What is the half-life of L-Dopa?
    1-3 hrs (duration may exceed half-life during early treatment because the neurons can still absorb and use it)
  23. What are the advantages of L-Dopa?
    It works fast (peak in 1-2 hrs)
  24. What are the disadvantages of L-Dopa?
    • short half-life
    • waning effect results in "off" periods (motor fluctuations) = even shorter half-life
    • may be converted in periphery = increased SE and decreased levels in brain
    • dyskinesias
    • pharmacokinetic variability
    • NAUSEA if broken down in periphery
    • competes with proteins for absorption in the gut and for transport across BBB
    • absorption affected by GI conditions
  25. How can you combat the waning effect of L-Dopa?
    • increase dosing frequency
    • add entacapone
    • add risagiline
    • add a DA agonist (apomorphine - only helps for 100 min)
  26. What are the SE of L-Dopa?
    • nausea (tolerance develops; use antacids)
    • dyskinesias (as soon as 6 mo; reversible)
    • hallucinations
    • confusion
    • orthostatic hypotension
    • no use in pts with psychosis
  27. How do you combat delayed "on" or "no on" with L-Dopa?
    • use oral disintegrating tablets
    • separate from protein
    • give apomorphine
    • drug holiday
  28. How do you combat "freezing" with L-Dopa?
    • physical therapy
    • increase dose
    • add a DA agonist or MAO-B inhibitor
  29. How do you combat dyskinesias with L-Dopa?
    • decrease dose
    • give amantadine
  30. What DI does L-Dopa have?
    • MAO-A inhibitors
    • pyridoxine (vitamin B6)
  31. What are the CI of L-Dopa?
    • angle-closure glaucoma
    • psychosis
  32. Why not start L-Dopa in everyone right away?
    • motor complications
    • waning effects
    • other classes of drugs are effective
  33. What type of drug are selegiline and rasagiline?
    MAO-B inhibitors
  34. What is the MOA of selegiline and rasagiline?
    irreversible inhibition of MAO-B
  35. What are the advantages of selegiline and rasagiline?
    • May use as monotherapy in early PD (delays need for L-Dopa)
    • modest improvements in motor function
    • evidence that rasagiline delays functional decline
    • oral disintegrating tablet available
  36. What are the disadvantages of selegiline and rasagiline?
    • side effects from active metabolites....methamphetamine, amphetamine (selegiline only)
    • may augment motor and cognitive side effects of L-dopa therapy
    • interactions with tyramine containing foods (cheddar, tap beer, salami, wine, soy)
  37. What else can selegiline and rasagiline be used for besides PD?
    major depressive disorder
  38. What are the SE of selegiline and rasagiline?
    • anxiety
    • insomnia
    • hallucinations
    • worsens existing psychosis and dyskinesia SE of L-Dopa (selegiline)
    • orthostatic hypotension
  39. What are the DI of selegiline and rasagiline?
    • may increase risk of serotonin syndrome
    • pseudoephedrine and pheynylephrine cause HTN
  40. What are the CI of selegiline and rasagiline?
    • TCAs
    • meperidine
    • dextromethorphan, methadone, propoxyphene, tramadol - with the ODT
  41. Do selegiline and rasagiline modify the disease in PD?
    Yes, the slowed breakdown of DA may result in less free radicals
  42. When should selegiline and rasagiline be administered?
    • before meals
    • last dose should be early in day due to SE
  43. What are the COMT inhibitors used in PD?
    tolcapone and entacapone
  44. What is the MOA of tolcapone and entacapone?
    prevent peripheral conversion of L-Dopa by COMT
  45. What are the advantages of tolcapone and entacapone?
    • reduce off time
    • combination available with carbidopa/levodopa (entacapone)
    • extend duration of activity for L-Dopa
    • first line adjunct for motor fluctuations (entacapone)
  46. What are the disadvantages of tolcapone and entacapone?
    • cannot be used as monotherapy
    • administered up to 8 times daily (entacapone)
  47. What are the SE of tolcapone and entacapone?
    • hepatotoxicity (tolcapone)
    • delayed onset diarrhea (tolcapone)
    • brownish-orange colored urine (tolcapone)
    • nausea
    • orthostatic hypotension
    • dyskinesias
  48. How are tolcapone and entacapone administered for PD?
    • co-adminster with carbidopa/levodopa
    • do not stop abruptly
  49. What are the advantages to using DA agonists in PD?
    • fewer motor fluctuations; reduced risk
    • well tolerated in younger patients
    • longer DOA than L-Dopa
    • do not rely on neuronal functional capacity
    • monotherapy in mild disease
  50. What are the disadvantages of DA agonists in PD?
    • frequent dosing
    • worsening of L-Dopa induced dyskinesias
    • class SE (nausea, neurologic, postural hypotension, compulsive behaviors, hallucinations)
  51. What are the advantages of pramipexole and ropinirole in PD?
    • can titrate faster than ergot derivatives
    • safer than ergot derivatives
    • well tolerated in younger patients
    • duration of action longer than L-Dopa
    • potentially less generation of free radicals (d/t less catabolism of DA)
    • may be used as initial therapy (monotherapy in mild PD)
    • do not rely on neuronal function
    • may be taken with food to decrease nausea SE
  52. What are the disadvantages of pramipexole and ropinirole in PD?
    • tid administration
    • worsening of dyskinesias
  53. What are the SE of pramipexole and ropinirole?
    • somnolence
    • nausea
    • hallucinations
    • dyskinesias
    • orthostatic hypotension
    • constipation
  54. What are the DI of pramipexole and ropinirole?
  55. Do pramipexole and ropinirole modify the disease in PD?
    potentially (decreased free radicals)
  56. How are pramipexole and ropinirole administered for PD?
    with or without food (may help with nausea)
  57. What are the advantages of apomorphine in PD?
    rapidly triggers "on" response
  58. What are the disadvantages of apomorphine in PD?
    • adminstered SQ
    • severe nausea; premedicate with trimethobenzamide
  59. What are the SE of apomorphine?
    • nausea/vomiting
    • postural hypotension (test dose)
    • somnolence
  60. What are the CI for apomorphine?
    concomittant administration with 5-HT3 agents (ondansetron, dolasetron, granisetron, palonosetron)
  61. What is the duration of action of apomorphine?
    100 min
  62. Why are anticholinergics used in PD?
    because decreased levels of DA results in extra ACh (causes EPS - tremor, rigidity; drooling
  63. What are the disadvantages to anticholinergics?
    (trihexylphenidyl and benztropine)
    • minimal improvement of bradykinesia
    • elderly are more susceptible to SE of anticholinergics
    • no more effective than DA agents
  64. What are the side effects of anticholinergics?
    (tryhexyphenidyl and benztropine)
    • mad as a hatter
    • hot as a hen
    • red as a beet
    • dry as a bone
    • blind as a bat
  65. What is the MOA of trihexyphenidyl and benztropine in PD?
    inhibition of PNS
  66. What are the DI of trihexyphenidyl and benztropine?
    may increase levels and/or effect of potassium
  67. What are the CI of trihexyphenidyl and benztropine?
    • narrow angle glaucoma
    • use with caution in males with BPH
  68. What PD drugs are CI in glaucoma?
    • L-Dopa
    • trihexyphenidyl
    • benztropine
  69. Why is amantadine used in PD?
    it supresses L-Dopa induced dyskinesias
  70. What is the MOA of amantadine in PD?
  71. What are the disadvantages of amantadine?
    benefit is short lived
  72. What are the SE of amantadine?
    • confusion
    • dizziness
    • dry mouth
    • nausea
    • orthostatic hypotension
    • edema
    • livedo reticularis
  73. What are the DI of amantadine?
    may increase levels and/or effect of potassium
  74. What are the risks for PD psychosis?
    • disease duration and severity
    • medication use - dose and duration DO NOT MATTER
    • depression
    • cognitive impairment
    • age
  75. When removing PD agents to improve PD psychosis, in what order do you do so?
    • anticholinergics
    • MAO-B inhibitors
    • amantadine
    • DA agonists
    • COMT inhibitors
    • L-Dopa/carbidopa
  76. What drugs are used for PD psychosis?
    • clozapine
    • risperidone
    • olanzapine
    • quetiapine - DOC!!!!
    • ziprasidone
    • aripiprazole
  77. What should be the initial treatment for PD?
    • selegiline
    • L-Dopa
    • DA agonist
  78. What should you consider when choosing a PD agent?
    • delay initiation of L-Dopa if possible
    • MAO-B inhibitors for most patients
    • DA-agonists for younger patients
    • amantadine for dyskinesias
  79. What drugs should be used as adjuntive tx for "wearing off" in PD?
    • COMT inhibitors
    • MAOB inhibitors
    • DA agonists
Card Set
Parkinson's Disease
Parkinson's Disease