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PARKINSON & GG PERGERAKAN LAINNYA

PARKINSON

gg pergerakan krn disfungsi pada basal ganglia & bag otak yg berkaitan
Gejala : . rigiditas otot skeletal . akinesia (bradikinesia) . flat facies . tremor pada waktu istirahat

Parkinson alamiah
Parkinson karena obat

Parkinson alamiah

frekwensi : usia 50-60 tahunan


patofisiologi : . kadar dopamin striatal . degenerasi neuron dopaminergik

- dopamin & acetylcholine tak seimbang

Parkinson k/ Obat

Reversibel Antipsikotik
butyrophenone & phenothiazine blok res dopamin otak

Reserpine
dosis >> pengosongan dopamin otak

MPTP

MPTP

analog meperidine
sering disalahgunakan

parkinson irreversible
destruksi neuron dopaminergik nigrostriatal tx neurotoksisitas : MAOI tipe B

Terapi Parkinson
Tujuan tx :

aktifitas dopamin atau

aktifitas kolinergik muskarinik

di otak

Levodopa

Dopamin :
bioavailabilitas jelek & tak dp menembus BBB precursornya : l-dopa (levodopa)

Carbidopa . t menembus BBB . hambat DOPA decarboxylase di perifer

Efek Farmakologi Levodopa :

gej parkinson, tu bradikinesia


angka mortalitas

tidak menyembuhkan parkinson


on-off phenomena
k/ perub kadar levodopa dl plasma

Toksisitas

dose-dependent GIT : anoreksia, nausea & emesis Kardiovaskuler : hipotensi postural, takikardi, asistole & aritmia Diskinesia : choreoathetosis, chorea, ballismus, myoclonus , tics & tremor Tingkah Laku : ansietas, agitasi, confusion, delusi, halusinasi & depresi

Bromocriptine & Agonis Dopamine


Bromocriptine & Pergolide :

alkaloid ergot

agonis parsial res dopamin D2


aktifitas fungsional pada jaras neurotransmitor dopamine

Penggunaan klinis Bromocriptine & Pergolide

digunakan sendiri-sendiri
dikombinasi dengan levodopa &

antikolinergik

u/ px refrakter levodopa

Toksisitas

GIT : anoreksia, nausea & vomiting Kardiovaskuler : hipotensi postural & aritmia jantung Diskinesia Tingkah laku : confusion, halusinasi & delusi

Kontra indikasi :

Levodopa, bromocriptin & pergolide


: px psikosis

Efek ergot lain:

krn bromocriptine
infiltrasi pulmonary &

erythromelalgia

Pramipexole & Ropinirole

agonis reseptor dopamin


bukan derivat ergot

efektif = bromocriptine
ES ergot ES : diskinesia, hipotensi postural, lassitude, sleepiness & fatigue

Amantadine

neurotransmisi dopaminergik
sintesa atau rilis dopamin atau

menghambat reuptake dopamin

blok muskarinik

Efek farmakologis

bradikinesia, rigiditas dan tremor


efektif hanya dalam beberapa

minggu

efek antiviral (+)

Toksisitas

Efek tingkah laku : reslessness, agitasi, insomnia, confusion, halusinasi & psikosis toksik akut Reaksi dermatologis : livedo reticularis Efek lain : gg GIT, retensi urin & hipotensi postural edema perifer tx diuretik

Selegiline

inhibitor selektif MAO tipe B


kadar dopamin otak

sebagai tambahan levodopa


selegilin metabolisme hepatik

amphetamine

Toksisitas

ES : insomnia, perubahan mood,


diskinesia, gg GIT & hipotensi

Meperidine + selegiline agitasi,


delirium & kematian Selegiline sindroma serotonin

Entacapone dan Tolkapone

inhibitor COMT u/ tambahan levodopa-carbidopa memperbaiki respons & memperpanjang on-time. ES krn kadar levodopa : diskinesia, gg GIT & hipotensi postural Tolcapone : gg hepar akut

Acetylcholine-bloker (antimuskarinik)

efek eksitatori neuron kolinergik pada sel di striatum blok reseptor muskarinik Benztropine a/ trihexyphenidyl tremor & rigiditas efek bradikinesia << u/ gej ekstrapiramidal k/antipsikotik

Toksisitas

SSP : mengantuk, tak dp memusatkan perhatian, bingung, delusi & halusinasi


Perifer = atropine-like drug Eksaserbasi tardive dyskinesia

Tx GG PERGERAKAN LAIN
Tremor

beta-bloker (propranolol)

hati-hati pd
Gagal jantung kongestif Asma Diabetes Hipoglikemia

Huntingtons Disease

penyakit yang diturunkan


karena ketidakseimbangan : fungsi GABA dan fungsi dopaminergik defisit kolinergik : krn choline acetyltransferase pada basal ganglia

Terapi

amine-depleting (mis, reserpine, tetrabenazine)


antipsikotik (haloperidol) blok res dopamin tak dp dg GABA otak dan aktifitas acetylcholine

Gilles de la Tourettees Syndrome

Penyebab : ?
Tx : . haloperidol . bloker res dopamine D2 : pimozide

Diskinesia karena obat

parkinson krn antipsikotik reversibel bila dosis obat di Tx : bloker muskarinik Levodopa & bromocriptine : tidak dapat digunakan Tardive dyskinesia karena neuroleptik

Wilsons Disease

peny herediter resesif metab cooper


deposisi garam cooper pd liver & jar

lain

kerusakan hepatik dan neurologis

parah & fatal

Tx : senyawa chelating penicillamine (dimethylcysteine) kelebihan cooper


Efek toksik penicilamine : gg GIT, miastenia, neuropati optik & diskrasia darah

Bradykinesia has made drug treatment necessary in a 60-year-old male patient with Parkinson's disease. You decide to initiate therapy with levodopa. 1. As the physician, you could tell the patient (and close family members) all of the following things about levodopa EXCEPT
A. Taking the drug in divided doses will decrease nausea and vomiting B. He should be careful when he stands up because he may get dizzy C. Uncontrollable muscle jerks may occur D. A netlike reddish to blue discoloration of the skin is a likely side effect of the medication E. The drug will probably improve his symptoms for a period of time but not indefinitely

2. As the physician who is prescribing levodopa, you will note that the drug
A. Causes less severe behavioral side effects if given with carbidopa B. Fluctuates in its effectiveness with increasing frequency as treatment continues C. Prevents extrapyramidal adverse effects of antipsychotic drugs D. Protects against cancer in patients with melanoma E. Has toxic effects that include pulmonary infiltrates