Pharmo

• Medications for Parkinson's Disease

  • Levodopa
  • Levodopa/Carbidopa (Sinemet)
  • Pramipexole (Mirapex)
  • Selegiline (Deprenyl)
  • Anticholinergics
• Levodopa Mechanism of Action


  Levodopa enters the brain (crosses the BBB) and converts to dopamine, thus restoring a balance between acetylcholine and dopamine
• Levodopa does not cure PD or delay disease progression
• Levodopa


  • Administered orally, therapeutic response can take several months
  • Most effective drug for PD
• Effectiveness of Levodopa decreases over time (symptoms are usually well controlled in first 2 years of treatment and effectiveness declines)
• Carbidopa


  Has no therapeutic effects on its own, delays the process of peripheral drug metabolism, allowing for more levodopa to enter the brain
• Patients on sinemet should avoid high protein meals BECAUSE they compete for absorption in gut
• On/Off Phenomenon


  1. Abrupt/acute return of PD symptoms

  2. On Phenomenon = therapeutic effect & reduction of symptoms

  3. Off Phenomenon = sudden return of PD symptoms (lasting minutes – hours) / Increased intensity & frequency with time
• Wearing off phenomenon


  1. Gradual return of PD symptoms

  2. Related to gradual loss of effect of Levodopa; return of symptoms are generally seen at the end of a dose interval when drug levels are low
• Pramipexole (Mirapex)


  Non-ergot dopamine receptor agonist, stimulates dopamine receptors in the striatum
• Medications for Parkinson's Disease

  • Levodopa
  • Levodopa/Carbidopa (Sinemet)
  • Pramipexole (Mirapex)
  • Selegiline (Deprenyl)
  • Anticholinergics
• Pramipexole (Mirapex) does not cure PD or delay progression of disease
• Levodopa Mechanism of Action


  Levodopa enters the brain (crosses the BBB) and converts to dopamine, thus restoring a balance between acetylcholine and dopamine
• Indication for levodopa


  Parkinson's Disease
• Pramipexole (Mirapex)


  • Stimulates parts of the brain that need dopamine
  • Less likely to cause disabling dyskinesias
  • Improves motor symptoms
  • Not dependent on enzymatic conversion, not converting to toxic metabolites, does not compete with dietary proteins for uptake in the intestine, or transport across the BBB
• Therapeutic Effect for levodopa

  Reduction in symptom severity, improvement in carrying out ADL's
• Levodopa does not cure PD or delay disease progression
• Levodopa


  • Administered orally, therapeutic response can take several months
  • Most effective drug for PD
  • Effectiveness decreases over time (symptoms are usually well controlled in first 2 years of treatment and effectiveness declines)
• Selegiline (Deprenyl)


  MAO-B Inhibitor, suppresses the destruction of dopamine derived from Levodopa which prolongs the effects of Levodopa and decreases consequential fluctuations in motor control – thereby reducing on-off & wearing off effect
• A small fraction of medication reaches the brain when levodopa is given alone, and for this reason, Levodopa is given in combination
• Carbidopa


  Has no therapeutic effects on its own
• Carbidopa


  Delays the process of peripheral drug metabolism, allowing for more levodopa to enter the brain
• Anticholinergics


  Block action of acetylcholine, often used in combination with other antiparkinsonian medications
• Adverse Effects of Sinemet (Levodopa/Carbidopa)


  • Nausea and Vomiting
  • Dyskinesias (tics, head bobbing, grimacing, rapid involuntary jerking, writhing movements, etc)
  • Postural hypotension
  • Psychosis (visual hallucinations, vivid dreams, paranoia)
  • Anxiety, agitation, memory loss, cognitive impairment, issues with impulse control
  • Can darken sweat and urine
• Patients on sinemet should avoid high protein meals because they compete for absorption in gut
• In Parkinson's there is an imbalance between dopamine and acetylcholine
• On/Off Phenomenon


  1. Abrupt/acute return of PD symptoms

  2. On Phenomenon = therapeutic effect & reduction of symptoms

  3. Off Phenomenon = sudden return of PD symptoms (lasting minutes – hours) / Increased intensity & frequency with time
• Methylprednisolone (Solu-Medrol)


  Mimics cortisol (a hormone produced by our adrenal glands) + potent anti-inflammatory and immunosuppressant. Works rapidly and is often only used for a short period of time
• Wearing off phenomenon


  1. Gradual return of PD symptoms

  2. Related to gradual loss of effect of Levodopa; return of symptoms are generally seen at the end of a dose interval when drug levels are low
• Brain cells become sensitive to use of levodopa
• Pramipexole (Mirapex)


  Non-ergot dopamine receptor agonist
• Anticholinergics


  Indication: Parkinson's, asthma, COPD, incontinence, dizziness, diarrhea
• Pramipexole (Mirapex) Mechanism of Action

  Stimulates dopamine receptors in the striatum
• Anticholinergics


  • Studies show it can greatly improve tremors, does not improve bradykinesia + used in younger patients with mild symptoms
• Pramipexole (Mirapex) Indication


  Parkinson's Disease
• Pramipexole (Mirapex) Therapeutic Effect


  Improve ability to carry out ADL's + improvement in motor symptoms by reducing fluctuations in motor control (i.e., "off" times)
• Anticholinergics


  Common side effects include blurred vision, dry mouth, constipation, and urinary retention + In the elderly, there is increased risk of cognitive decline developing dementia and confusion not prescribed to patients above the age of 70. DO NOT GIVE OVER THE AGE OF 70!
• Pramipexole (Mirapex) does not cure PD or delay progression of disease
• Pramipexole (Mirapex)


  • Stimulates parts of the brain that need dopamine
  • Doesn't have the nursing considerations of levodopa
  • Less likely to cause disabling dyskinesias
  • Improves motor symptoms
• Pramipexole (Mirapex)


  BETTER BECAUSE: not dependent on enzymatic conversion, not converting to toxic metabolites, does not compete with dietary proteins for uptake in the intestine, or transport across the BBB