442-Fin-Parki

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Author:
jgiantess
ID:
146720
Filename:
442-Fin-Parki
Updated:
2012-04-10 01:41:12
Tags:
pharmacology
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Description:
pharmacology
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  1. 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
  2. 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)
  3. Dopamine agonists - apomorphine, bromocriptine, lisuride, pergolide, cabergoline, pramipexole, ropinirole
    SE: NV, orthostatic hypotension, hallucinations, psychosis, fibrotic lesions (ergot), somnolence
  4. 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    • (tolcapone is peripheral and central COMT inhibitor, but withdrawn due to fatal hepatotoxicity)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
  5. 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
  6. rasagiline
    • MAO-B highly irreversible inhibitor
    • can improve symptoms, and MAY reduce progression of parki? no metabolized to amphetamine derivatives
  7. rotigotine
    • lipophilic DA agonist
    • transdermal use can provide more continuous DA effect

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