questions 2

Parkinson's Disease Drugs

Topic updated on 09/11/17 3:38pm

Overview
 
Snapshot
  • A 58-year-old man is brought by his wife due to worsening weakness and fatigue. She describes his movements as "sluggish." The patient reports difficulting with typing on his keyboard and buttoning up his pants. On physical exam, there is a "pill-rolling" tremor at rest that improves with purposeful movement. There is also increased resistance to passive movement at the wrist and elbow. He is started on levodopa and carbidopa.
Introduction
  • L-DOPA
    • catecholamine precursor
    • medications
      • levodopa/carbidopa
        • carbidopa prevents peripheral conversion of L-DOPA into dopamine via DOPA decarboxylase
          • L-DOPA delivery into the CNS
          • ↓ side effect from peripheral excess dopamine from DOPA decarboxylation of L-DOPA (e.g., nausea and vomiting)
        • L-DOPA can cross the blood-brain barrier
        • toxicity
          • excess catecholamine production in the periphery results in arrhythmias
          • immediate side effects include
            • hallucinations
            • dizziness
            • headache
          • chronic use can result in
            • dyskinesia (post-administration)
            • akinesia (intra-dose)
  • Dopamine receptor agonists
    • bromocriptine (ergot alkaloid) 
    • pramipexole and ropinirole (non-ergot)
  • Dopamine availability
    • amantadine
      • an antiviral medication that can improve parkinsonism
        • mechanism of action is unknown and possible mechanism may be
          • ↑ dopamine release from presynaptic neurons
          • ↓ dopmaine re-uptake into presynpatic neurons
      • toxicity
        • ataxia
        • livedo reticularis
  • Preventing dopamine metabolism 
    • monoamine oxidase type B inhibitors
      • prevents the degradation of dopamine into 3,4-dihydroxyphenylacetic acid (DOPAC)
      • medications
        • selegiline
        • rasagiline
    • catechol-O-methyltransferase (COMT) inhibitors
      • prevents the degradation of dopamine into 3-O-methyldopa (3-OMD)
      • medications
        • tolcapone (peripheral and central)
        • entacapone (peripheral)
  • Anticholinergics
    • under normal conditions, dopamine and acetylcholine are in electrochemical balance in the basal ganglia
      • ↓ dopamine in Parkinson's disease (PD) leads to ↑ cholinergic sensitivity
        • therefore, cholinergic medications worsen PD symptoms, and anticholinergics improve PD symptoms
    • medications
      • benztropine
      • trihexyphenidyl


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