Download - Parkinson
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PARKINSON & GG PERGERAKAN LAINNYA
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PARKINSON
gg pergerakan krn disfungsi pada basal ganglia & bag otak yg berkaitan
Gejala :. rigiditas otot skeletal. akinesia (bradikinesia). flat facies. tremor pada waktu istirahat
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Parkinson alamiah
Parkinson karena obat
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Parkinson alamiah
frekwensi : usia 50-60 tahunan
patofisiologi : . kadar dopamin striatal . degenerasi neuron dopaminergik
- dopamin & acetylcholine tak seimbang
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Parkinson k/ Obat
Reversibel Antipsikotik
– butyrophenone & phenothiazine blok res dopamin otak
Reserpine – dosis >> pengosongan dopamin
otak MPTP
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M P T P
analog meperidine sering disalahgunakan parkinson irreversible destruksi neuron dopaminergik
nigrostriatal tx neurotoksisitas : MAOI tipe B
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Terapi Parkinson
Tujuan tx :
aktifitas dopamin atau
aktifitas kolinergik
muskarinik
di otak
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Levodopa
Dopamin :– bioavailabilitas jelek & – tak dp menembus BBB– precursornya : l-dopa (levodopa)
Carbidopa. t’ menembus BBB . hambat DOPA decarboxylase di
perifer
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Efek Farmakologi Levodopa :
gej parkinson, tu bradikinesia
angka mortalitas
tidak menyembuhkan parkinson
on-off phenomena
– k/ perub kadar levodopa dl plasma
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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
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Bromocriptine & Agonis Dopamine
Bromocriptine & Pergolide : alkaloid ergot agonis parsial res dopamin D2 aktifitas fungsional pada jaras
neurotransmitor dopamine
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Penggunaan klinis Bromocriptine & Pergolide
digunakan sendiri-sendiri
dikombinasi dengan levodopa
& antikolinergik
u/ px refrakter levodopa
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Toksisitas
GIT : anoreksia, nausea & vomiting
Kardiovaskuler : hipotensi postural & aritmia jantung
Diskinesia Tingkah laku : confusion,
halusinasi & delusi
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Kontra indikasi :
Levodopa, bromocriptin & pergolide
: px psikosis
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Efek ergot lain:
krn bromocriptine
infiltrasi pulmonary &
erythromelalgia
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Pramipexole & Ropinirole agonis reseptor dopamin
bukan derivat ergot
efektif = bromocriptine
ES ergot
ES : diskinesia, hipotensi postural, lassitude, sleepiness & fatigue
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Amantadine
neurotransmisi dopaminergik
sintesa atau rilis dopamin atau
menghambat reuptake dopamin
blok muskarinik
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Efek farmakologis
bradikinesia, rigiditas dan
tremor
efektif hanya dalam beberapa
minggu
efek antiviral (+)
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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
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Selegiline
inhibitor selektif MAO tipe B
kadar dopamin otak
sebagai tambahan levodopa
selegilin metabolisme hepatik
amphetamine
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Toksisitas
ES : insomnia, perubahan mood,
diskinesia, gg GIT & hipotensi
Meperidine + selegiline
agitasi, delirium & kematian
Selegiline ‘sindroma
serotonin’
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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
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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
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Toksisitas
SSP : mengantuk, tak dp memusatkan perhatian, bingung, delusi & halusinasi
Perifer = atropine-like drug
Eksaserbasi tardive dyskinesia
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Tx GG PERGERAKAN LAIN
Tremor
beta-bloker (propranolol)
hati-hati pd
– Gagal jantung kongestif
– Asma
– Diabetes
– Hipoglikemia
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Huntington’s Disease
penyakit yang diturunkan
karena ketidakseimbangan : fungsi GABA dan fungsi dopaminergik
defisit kolinergik : krn choline acetyltransferase pada basal ganglia
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Terapi
amine-depleting (mis, reserpine, tetrabenazine)
antipsikotik (haloperidol) blok res dopamin
tak dp dg GABA otak dan aktifitas acetylcholine
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Gilles de la Tourettee’s Syndrome
Penyebab : ?
Tx : . haloperidol . bloker res dopamine D2 : pimozide
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Diskinesia karena obat
parkinson krn antipsikotik reversibel bila dosis obat di
Tx : bloker muskarinik Levodopa & bromocriptine :
tidak dapat digunakan Tardive dyskinesia karena
neuroleptik
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Wilson’s Disease
peny herediter resesif metab cooper
deposisi garam cooper pd liver & jar
lain
kerusakan hepatik dan neurologis
parah & fatal
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Tx : senyawa chelating penicillamine (dimethylcysteine) kelebihan cooper
Efek toksik penicilamine : gg GIT, miastenia, neuropati optik & diskrasia darah
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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
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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