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Updated: Sep 3 2022

Parkinson Disease Drugs

Images disease drugs - moises dominguez - updated.jpg
  • Overview
  • Snapshot
    • A 73-year-old man presents with fatigue. He reports having difficulty with activities of daily living. He states that his wife notes he is not swinging his arms as much as he used to when walking. On physical examination, a tremor is noted at rest, that improves with purposeful movement. He also walks with a stooped posture during gait testing. He is eventually started on levodopa and carbidopa.
  • Introduction
    • L-DOPA
      • catecholamine precursor
      • medications
        • levodopa/carbidopa
          • carbidopa prevents peripheral conversion of L-DOPA into dopamine by inhibiting aromatic L-amino acid (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
              • nausea/vomiting
              • dizziness
              • headache
            • chronic use can result in
              • dyskinesia (post-administration)
              • akinesia (intra-dose)
    • Dopamine receptor agonists
      • bromocriptine (ergot alkaloid)
      • pramipexole and ropinirole (non-ergot)
        • used in the treatment of restless leg syndrome
    • 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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