03 Neuropsychiatric System Farmakol Anti Parkinson Yanti
Transcript of 03 Neuropsychiatric System Farmakol Anti Parkinson Yanti
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ANTI PARKINSON
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Parkinson (paralisis
agitans) : st. sindrom dgn
gejala utama berupa trias
gangguan neuromuskular
tremor, rigiditas, akinesia
(hipokinesia) disertai
kelainan postur tubuh &
gaya berjalan.
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•Parkinsonisme pasca
ensefalitis.
•Parkinsonisme akibat
obat.
•Parkinsonisme idiopatik.
Berdasarkan etiologi
terdiri dari :
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Kerusakan pada traktus
nigrostriatum gangguan
keseimbangan kolinergik &
dopominergik.
PATOGENESIS
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I. Obat dopaminergik sentral :
a.Levodopa.
b.Bromokriptin.
c.Perangsang SSP : dextroamfetamin, metamfetamin, metilfenidat.
OBAT ANTI PARKINSON
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I. Obat antikolinergik
sentral :
a.Senyawa
parasimpatolitik :
triheksifenidil,
biperiden, sikrimin,
prosiklidin, karamifen,
benztropin mesilat.
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a.Senyawa antihistamin :
difenhidramin,
klorfenoksamin,
orfenadrin, fenindamin.
b.Derivat fenotiazin :
etopropazin, prometazin,
dietazin.
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I. Obat Dopamino - anti
kolinergik :
a.Amantadin.
b.Antidepresan trisiklik
: imipramin,
amitriptilin.
II.Penghambat MAO-B.
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•Absorbsi cepat,
tergantung kecepatan
pengosongan lambung.
•Cepat mengalami
pemecahan dlm
lambung.
•Dirusak oleh flora
usus.
LEVODOPA
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•Absorbsi lambat
dibagian distal
duodenum.
•Absorbsi dihambat oleh
makanan tinggi protein.
•22 – 30% dosis oral
mencapai sirkulasi.
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•60% mengalami
biotransformasi.
•80% diekskresi
sebagai DOPAC, HVA
50%, 1% levodopa.
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LEVODOPA
3-METOKSITIRAMIN
COMT
CDMELANIN3-D METILDOPA
DOPAMINDBH
MAOADNOREPINEPRIN
DOPAC(3-4 DIHIDROK-
SIFENIL ASETAT)HVA
(3-METOKSI-4 HIDROKSI-
FENIL ASETAT)
COMT MAOAD
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•Minggu I : 2 x 125 mg/hr.
•Minggu II : 4 x 125
mg/hr.
•Minggu III : 4 x 250
mg/hr.
•Minggu IV : 3 x 500
mg/hr.
Dosis levodopa untuk
penderita rawat jalan :
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•Minggu V : 4 x 500 mg/hr.
•Minggu VI : 5 x 500 mg/hr.
•Minggu VII : 3 x 1 gr/hr.
•Minggu VIII : 3 x 1 gr/hr +
500 mg malam hari.
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Berdasarkan pengisian
kembali kekurangan
DA di korpus striatum
Mekanisme Kerja
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75% penderita
parkinson gejala
berkurang 50%.
Efek Terapi
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•Saluran cerna : mual,
muntah, nafsu makan ↓.
•Diskinesia & gerakan
spontan abnormal.
•Psikis.
Efek Samping
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•Sistim kardiovask. :
hipotensi ortostatik,
takikardia, aritmia, pe↑ kontraktalitas jantung.
•Efek metabolik & endokrin.
•Ginjal : me↑ aliran plasma
ginjal, laju filtrasi
glomerulus & ekskresi Na+,
K1.
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1.Perpendekan masa
kerja levodopa (wearing-
off) gejala parkinson
timbul sebelum menelan
dosis berikut.
Gejala yang timbul setelah R/ jangka panjang (1 – 5
thn).
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1.Fenomena pasang surut
(on-off) fluktuasi efek
obat dalam waktu
singkat.
1.Pembekuan gerakan
(freezing).
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•Penghambat dekarboksilase menghambat bio-transformasi levodopa menjadi DA.
•Berguna untuk :
Me↑ jumlah levodopa di jaringan otak.
Interaksi Obat
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Dosis efektif lebih cepat tercapai.
ES berkurang.
Frekuensi dosis harian dapat dikurangi.
Perbaikan gejala me↑.Efek antagonisme
diridoksin dapat dihindari.
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•Sediaan :
Karbidopa.
Benzerazid.
•Perbandingan R/
kombinasi :
Karbidopa : levodopa
1:10 / 1:4.
Benzerazid : levodopa
1:4.
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•Merupakan prototip kel. Ergolin : alkaloid ergot yg bersifat dopaminergik.
•Mekanisme kerja : merangsang reseptor dopaminergik menyebabkan kadar HVA dlm CSS me↓.
BROMOKRIPTIN
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•30% bromokriptin
diabsorbsi.
•Kadar puncak plasma :
1,5 – 3 jam.
•Ekskresi sebagian besar
kedalam empedu.
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•Sebagai tambahan
levodopa.
•Sebagai pengganti
levodopa.
•R/
hiperprolaktinemia.
Indikasi
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•Dimulai dengan dosis 2 x
1,25 mg/hr.
Pe↑ dosis tiap 2 – 4 mgg
sebanyak 2,5 mg/hr.
•Hiperprolaktinemia :
1,25 – 2,5 mg, dosis
total 5 – 7,5 mg/hr.
Dosis
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•Mual, muntah.
•Hipotensi ortostatik,
kolaps KV.
•Halusinasi.
•Kemerahan, nyeri,
panas, udem tungkai
bawah.
Efek Samping
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•Memperlancar
transmisi DA.
•Umumnya dikombinasi
dengan antikolinergik.
PERANGSANG SSP
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•Dextroamfetamin : 2 x 5
mg/hr.
Metamfetamin : 2 x 2,5
mg/hr.
Metilfenidat : 2 x 5
mg/hr.
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Mekanisme kerja
•Me (-) aktifitas
kolinergik yang
berlebihan di ganglia
basal.
ANTIKOLINERGIK
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•Bermanfaat terhadap
parkinsonisme akibat
obat.
Triheksifenidil,
senyawa kongenerik,
benztropin
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•Triheksifenidil :
memperbaiki sialorrhoea
dan mood digunakan juga
untuk sindrom
atetokoriatik, tortikolis
spastik dan spasme facialis.
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•Kadar puncak tercapai
1 – 2 jam.
•Masa paruh : 10 dan
12 jam
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•Sentral : gangguan
neurologik :
Ataksia.
Disartia.
Hipertermia.
Gangguan mental.
Efek samping
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Pikiran kacau.
Amnesia.
Delusi.
Halusinasi.
Somnolen koma.
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•Perifer : serupa atropin.
•Triheksifenidil
kebutaan akibat
komplikasi glaukoma
sudut tertutup.
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Dosis
•Triheksifenidil : 2 – 3 x mg/hr.
•Biperidon : 2 – 4 x 0,5 – 2 mg/hr.
•Prosiklidin : 2 – 3 x 5 mg/hr.
•Benztropin : 0,5 – 1 mg/hr pada malam hari; oral untuk dewasa.
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AMANTADIN
•Me↑ aktifitas dopaminergik
serta menghambat
aktifitas kolinergik di
korpus striatum.
OBAT DOPAMINO-ANTIKOLINERGIK
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•Efektifitas anti
parkinson < levodopa
tetapi respon > cepat.
•Dosis awal : 100 mg/hr,
setelah 1 mgg 2 x 100
mg kemudian 3 x 100
mg/hr.
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Efek samping :
= Intoksikasi atropin.
•Disorientasi.
•Gelisah, insomnia,
pusing, gangguan
saluran cerna, mulut
kering, dermatitis.
•Halusinasi, ansictas.
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ANTIDEPRESI TRISIKLIK
•Kombinasi dengan anti
kolinergik.
•Dosis imipramin &
amitriptilin 4 x 10 – 25
mg/hr.
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SEGELIN
•Mekanisme kerja :
menghambat deaminasi
dopamin sehingga kadar
dopamin di ujung saraf
dopaminergik ↑.
PENGHAMBAT MAO-B
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•Sebagai terapi
tambahan dengan
levodopa untuk
fenomena wearing-off.
•Dosis : 10 mg/hr.
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