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MOA
DA that can be taken up at synapse without need for enzymatic conversions Bind DA striatal teceptors Targeting D1 and D2 (D2 mainly) in striatum. Rotigotine: has broad action on all DA-R types but does not cause
Side Effects
Nausea/Sedation Hallucinations Fibrosis due to 5HT2b-R activation (Ergolines), lungs/heart valves Therapeutic window s with: disease progression, causing chorea Newer DA Agonists: Dyskinesia (vs. Ldopa), antidepressants, neuro-protective Ataxia Livedo Reticularis Therapeutic Window w/ PD progression Long-term use Dyskinesia following admin, Akinesia b/w doses. on/off effects due to fluctuation of DA Malignant HTN (but only at very high doses b/c that is when it may have effects on blocking MAO-A, leading to the tyramine interactions and HTN crisis). Insomnia (b/c metabolized to an amphetamine) $$$$ Expensive Tolcapone = more potent, cross BBB, hepatic death (LFTs) Entacapone = short acting, works peripherally No LFT monitoring necessary Dry mouth Cognitive SE in elderly
USE
Non-ergots are preferred Good in early stages of disease as initial monoTx or adjunct w/ low dose L-DOPA in early/late PD BENEFIT: preventing dyskinesias by replacing early L-DOPA Tx in younger patients or L-dopa dose Alleviates Tremor & LDID Alleviates fatigue Improved PD Sx
Increase Dopamine
fibrosis!
Works against influenza virus also. ? Glu-R antagonist DA release and inhibits reuptake L-dopa (prodrug) crosses BBB and DA in brain. Carbidopa (peripheral decarboxylase inhibitor) bioavail. of L-dopa & limits the peripheral ASEs Selectively inhibits MAO-B (which preferentially metabolizes DA over NE and 5-HT), thereby bioavailability of DA. Inhibits COMT, which normally degrades catecholamines thus circulating Ldopa that can go to BBB and be converted to DA in the brain. Block muscarinic receptors
* Gold Standard*
Key in preventing progression of PD Effectively time needed to initiate L-DOPA Tx Shown to have disease modifying effect + Therapeutic effect [i.e. placebo delayed start did not catch up to Tx group] Adjunct to L-dopa STALEVO = combination Tx of Entacapone + Sinemet (L-DOPA + CDOPA) Used primarily in YOUNG PD patients **Not good in older PD pts b/c cognitive SE due to age related Ach Improves tremor and dystonia
<< TREATABLE SYMPTOMS >> TREMOR RIGIDITY AKINESIA/BRADYKINESIA Dystonia [foot turning inward not everyone gets this) Constipation (common) REM Sleep Behavior D/O may be the very 1st symptom Depression o SSRIs anxiety o TCAs insomnia/tremor
<< SYMPTOMS LESS RESPONSIVE TO TX >> POSTURAL INSTABILITY falling backwards, etc. Freezing Speech Abnormalities (low volume voice) Autonomic Dysfunction Eye Movement problems Anosmia DEMENTIA o Cholinesterase inhibitors (Aricept) dementia + hallucinations o Anti-psychotics (Seroquel) hallucinations +/- dementia