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