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Levodopa/Carbidopa
- L-dopa: pro-drug, larger doses worked but lots of N&V because cleaved to DA in periphery (act at CTZ)
- Carbidopa: does not cross BBB, no DA activity, bt at 75-150mg/day, inhibits peripheral ALAA so that more L-dopa can enter CNS...then, dopamine can act on D1 and D2 receptors to reduce PD sx
- SE: NV, orthostatic hypotension, hallucinations, confusion, urine discoloration, dyskinesias, motor fluctuations
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Amantadine
- antiviral, used to reduce risk of influenza A infection or treat an active infection
- improve symptoms of PD by increasing DA release from nerve terminals, and inhibiting re-uptake or as NMDA antag
- tolerance over several months?
- SE: NV, dizziness, insomnia, antichol, exacerbate CHF, epilepsy
- withdrawal cause neuroleptic malignant syndrome
- chronic use cause reversible livedo reticularis (reddish-purple discoloration)
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Dopamine agonists - apomorphine, bromocriptine, lisuride, pergolide, cabergoline, pramipexole, ropinirole
SE: NV, orthostatic hypotension, hallucinations, psychosis, fibrotic lesions (ergot), somnolence
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Entacapone
- peripheral COMT inhibitor
- reduces L-dopa clearance and increases plasma concentrations
- peripheral changes help smooth effects of L-dopa later in therapy
- (tolcapone is peripheral and central COMT inhibitor, but withdrawn due to fatal hepatotoxicity)
- SE: dyskinesia, nausea, sleep disturbance, anorexia, diarrhea, hallucinations
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Selegiline
- MAO-B selective irreversible inhiitor
- reduces degradation of intracellular DA at terminal end of dopaminergic neurons
- blocks neuronal tyramine uptake and NA release
- may reduce oxidative damage to DA neurons caused by reactive free radical metabolites of DA
- inhibit MPP metab to MPP, and prevent MPTP induced Parki
- but did not appear to have effect on progression...probably not increase mortality
- can be used early to delay need for L-Dopa, or later in therapy to manage motor complications of L-Dopa
- metabolized to amphetamine derivatives
- SE: dyskinesia, insomnia, confusion, autonomic dysfunction
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rasagiline
- MAO-B highly irreversible inhibitor
- can improve symptoms, and MAY reduce progression of parki? no metabolized to amphetamine derivatives
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rotigotine
- lipophilic DA agonist
- transdermal use can provide more continuous DA effect
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