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

M P T P

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

Huntington’s 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 Tourettee’s 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

Wilson’s 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 EXCEPTA. Taking the drug in divided doses will decrease

nausea and vomitingB. He should be careful when he stands up because he

may get dizzyC. Uncontrollable muscle jerks may occurD. 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