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levadopa (L-dopa)
- increase DA synthesis
- precursor of dopamine
- wearing off effect within 3-5 years
- oral, rapid small intestine absorption, 1-3% reaches the brain
- short half life - 1-2 hours
- peripheral side effects: nausea, vomiting, anorexia, arrhythmias, orthostatic hypotension
- CNS side effects: visual and auditory hallucinations, abnormal involuntary movements (dyskinesia), mood changes
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L-DOPA/carbidopa
- medication of choice for symptomatic treatment of Parkinson's
- carbidopa is an aromatic l-amino acid decarboxylase inhibitor, blocks metabolism of L-dopa into dopamine peripherally = 4-5 increase in L-DOPA in the brain
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entacapone
catechol-O-methyltransferase (COMT) inhibitor - blocks peripheral metabolism of L-DOPA into methyldopa = increase L-DOPA availability to brain
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selegiline
- inhibits MAO-B
- decreases production of byproduct hydrogen peroxide = limits formation of neurotoxic free radicals
- adjunctive treatment in Parkinson's
- orally active, half life 7-9 hrs, renal excretion
- metabolized to methamphetamine and amphetamine (insomnia)
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rasagiline
- selective inhibitor of MAO-B (more potent)
- not metabolized to amphetamine-like substance
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Bromocriptine
- D2 agonist and D1 partial agonist
- effective as monotherapy early in disease or as an adjunct later in disease
- adverse effects: cardiovascular effects (arrhythmias, postural hypotension), neurological effects (depression, confusion, hallucinations), GI problems, contraindicated in patients with heart or mental problems
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ropinirole and pramipexole
- D2 and D3 agonist
- effective as monotherapy early in disease or as an adjunct later in disease
- adverse effects: cardiovascular effects (arrhythmias, postural hypotension), neurological effects (depression, confusion, hallucinations), GI problems, contraindicated in patients with heart or mental problems
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apomorphine
- dopamine receptor agonist
- acute treatment of patients with advanced disease or for off periods (bradykinesia, immobility)
- SQ administration (NOT IV - may lead to thrombus formation and PE)
- adverse effects: nausea, vomiting, arrhythmias, postural hypotension, hallucinations, pronounced sleepiness
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benztropine and trihexyphenidyl
- muscarinic antagonists
- used to alleviate tremor and rigidity as monotherapy or with other drugs
- adverse effects: typical antimuscarinic effects - blurred vision, dry mouth, urinary retention, constipation, aggravation of glaucoma, may also produce delirium, psychosis, memory impairment
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amantadine
- used to alleviate bradykinesia and rigidity (not helpful for tremor) in patients with mild to moderate disease prior to L-DOPA initiation
- moderately increases DA release, blocks cholinergic muscarinic receptors and glutamatergic NMDA receptors
- adverse effects: hallucinations and confusion, nausea, dizziness, rash of low extremities; special caution in patients with congestive heart disease and with glaucoma
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donepezil, galantamine, ravastigmine, and tacrine
- AChE inhibitors
- blocks catabolism of ACh
- modest improvement in some alzheimers patients, benefits retained for several years
- good oral bioavailability
- variable pharmacokinetic and half-life time: donepezil - 70 hrs, galantamine - 7 hrs
- all metabolized by P450 except rivastigmine (plasma cholinesterase)
- adverse effects: Tacrine may produce hepatotoxicity; tremors, bradycardia, nausea and vomiting, diarrhea, anorexia
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memantine
- NMDA receptor antagonist (low affinity) - derivative of amantadine
- protects neurons from Calcium overload that leads to neuronal death
- improved ADL and cognitive fn
- benefits additive when given with donepezil
- adverse effects: dizziness, headache, confusion, agitation, constipation
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