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PHARMACOLOGIC TX FOR IDIOPATHIC PARKINSONSStrategy Class / Drug MOA Side Effects USE

AgonizeDopamineReceptors

ERGOT:BromocriptinePergolide

NON-ERGOTPramipexoleRopiniroleRotigotine (patch)

DA that can be taken up at synapsewithout need for enzymaticconversions

Bind DA striatal teceptors TargetingD1 and D2 (D2 mainly) in striatum.

Rotigotine: has broad action on allDA-R types but does not causefibrosis!

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. L-

dopa), antidepressants, neuro-protective

Non-ergots are preferred Good in early stages of disease as

initialmonoTx or adjunct w/ low

dose L-DOPA in early/late PD

BENEFIT: preventing dyskinesias byreplacing early L-DOPA Tx in youngerpatients or L-dopa dose

IncreaseDopamine

ANTI-VIRAL AGENTAmantidine

Works against influenza virus also.? Glu-R antagonistDA release and inhibits reuptake

Ataxia Livedo Reticularis Alleviates Tremor & LDID(L-dopa induced dyskinesia)

Alleviates fatigueL-dopa + carbidopaSinemet

L-dopa (prodrug) crosses BBB andDA in brain.

Carbidopa (peripheraldecarboxylase inhibitor) bioavail.of L-dopa & limits the peripheralASEs

Therapeutic Window w/ PD progression Long-term useDyskinesiafollowing admin,

Akinesiab/w doses.on/off effectsdue to fluctuation of DA

* Gold Standard* Improved PD Sx

Prevent

Dopaminebreakdown

MAO-B-Is

SelegilineRasagiline

Selectively inhibits MAO-B (which

preferentially metabolizes DA over NEand 5-HT), thereby bioavailabilityof DA.

Malignant HTN (but only at very high dosesb/c that is when it may have effects on blockingMAO-A, leading to the tyramine interactions andHTN crisis).

Insomnia (b/c metabolized to an amphetamine) $$$$ Expensive

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 delayedstart did not catch up to Tx group]

COMT InhibitorTolcaponeEntacapone

Inhibits COMT, which normally degradescatecholamines thus circulating L-dopa that can go to BBB and beconverted to DA in the brain.

Tolcapone = more potent, cross BBB,hepatic death (LFTs)

Entacapone = short acting, works peripherallyNo LFT monitoring necessary

Adjunct to L-dopaSTALEVO = combination Tx of

Entacapone + Sinemet (L-DOPA + C-DOPA)

CurbExcessCholinergic

Activity

ACH-INHIBITORSBenztropineTrihexyphidyl

Block muscarinic receptors Dry mouth Cognitive SE in elderly Used primarily in YOUNG PD patients **Not good in older PD pts b/c cognitive

SE due to age relatedAch

Improves tremor and dystonia

> TREMOR RIGIDITY AKINESIA/BRADYKINESIA Dystonia [foot turning inward not everyone gets this) Constipation (common) REMSleep Behavior D/O may be the very 1st symptom Depression

o SSRIs anxietyo TCAs insomnia/tremor

> POSTURAL INSTABILITY falling backwards, etc. Freezing Speech Abnormalities (low volume voice) Autonomic Dysfunction Eye Movement problems Anosmia DEMENTIA

o Cholinesterase inhibitors (Aricept) dementia +hallucinationso Anti-psychotics (Seroquel) hallucinations +/- dementia

BALSA

BromocriptineAmantadineLevodopa (+carbidopa)Selegiline (& COMT-I)Antimuscarinics

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