psikofarma latifah
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PSIKOFARMAKOLOGI
Oleh Latifah Agustina Lestari
(030.10.159)
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Definisi
Psikofarmaka = obat psikotropik = Psikotropika
Obat yang bekerja scr selektif pada susunan sarap pusat (SSP) dan mempunyai efek efek utama terhadap aktifitas mental dan perilaku, digunakan untuk terapi gangguan psikiatrik.
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Prinsip pengobatan
• Dosis dimulai dari dosis anjuran dinaikan perlahan secara bertahapndlm1-3 mgg sampai dicapai dosis optimal yg dpt mengendalikan gejala
Terapi inisial
• dosis optimal yg mampu mengendalikan gejala sasaran yang dipertahankan selama 8-10 mgg
Terapi pengawasan
• dosis terkecil yg masih mampu mencegah kambuhnya gejala.Kondisi akut smp 2 th. Kronis smp 5 th/ seumur hidup
Terapi pemeliharaan
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Prinsip Titrasi DosiS(tailoring the dose of drugs)
Dosis dinaikkan secara bertahap,
start low, go slow
Bila hasil terapinya berhasil, dosis diturunkan secara gradual sampai berhenti pemakaian obat.
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Berdasarkan efek klinis psikofarmaka dibagi :
Jenis Obat Gejala Sasaran
Antipsychotics Psikosis
Antidepressants Depresi
Mood-Stabilizers Mania
Anxiolytics Anxietas
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Prinsip mekanisme kerja obat psikofarmaka
• kerja obat menyerupai sifat neurotransmitter sasaran, berikatan dg reseptor dan memperkuat kerja neurotransmiter tsd di neuron
• suatu ligand yang bila berinteraksi dapat menghasilkan efek
Agonis
• kerja obat mem-blok reseptor neurotransmitter sasaran sehingga neurotransmitter tsb tdk
Antagonis
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Anti Psikotik
•Obat Acuan : Chlorpromazine (CPZ)
NEUROLEPTICS
MAJOR TRANQULIZE
RS
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Berdasarkan rumus kimia antipsikotik dibagi menjadi :•Golongan fenotiazine(low potency) :
cth :chlorpromazine
•Golongan non-fenotiazine (high potency): hanaya memerlukan dosis kecil untuk memperoleh efek yang setara dengan chlorpromazine 100 mg .
Cth :Haloperidol
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Antipsikotik berdasarkan cara kerjanya
Golongan• Golongan Tipikal (Dopamin
reseptor Antagonis)= Antipsikotik golongan I
• Golongan Atipikal (serotonin dopamine reseptor antagonis) = antipsikotik golongan II
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Antipsychotics
Used to treat
schizophrenia and
psychotic symptoms of other
disorders
Schizophrenia is a severe chronic disorder• Positive symptoms:
hallucinations, and delusions
• Negative symptoms: amotivation,
• poverty of speech, flat affect
• Disorganized symptoms: speech,
• thought, and behavior
Now being used to
treat Bipolar as
well
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Anti PsikotikMekanisme Kerja :sebagai
antagonis reseptor dopamine dan
serotonin di otak dengan target untuk menurunkan gejala
psikotok seperti halusinasi,waham,dll.
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Teori Dopamine-Pathways
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4. Sistem tuberoinfundibular•Yang mengurus system endokrin
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Anti Psikotik
1. Efek Samping neurologis :• Akatisia : kondisi yang secara subjektif
dirasakan berupa perasaan tidak nyaman, gelisah dan merasa selalu menggerakan tungkai
• Distonia akut : kekakuan dan kontraksi otot tiba-tiba biasanya mengenai otot leher,lidah,muka dan punggung
• Parkinsonism : kumpulan gejala bradykinesia,rigiditas,cog-wheel phenomena,tremor,muka topeng.
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Sindroma neuroleptic maligna
Reaksi idiosinkrasi yang sangat serius dengan gejala utama berupa rigiditas, hiperiretik ,gangguan system saraf otonom dan delirium
Efek samping antipsikotik kronis :
Tardive dislinesia
2. Efek non-neurologis :
Sistem kardiovaskular : hypotension ortostatic
Sistem gastrointestinal : efek antikolinergik perifer berupa rasa kering dimulut dan sering merasa haus
Fungsi endokrin : peningkatan prolakktin darah, disfungsi seksual
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Antipsychotics
Golongan NAMA OBAT DOSIS ANJURAN PER HARI
APG I HALOERIDOL 5-20 mg
KHLORPROMAZIN 100-400 mg
APG II RISPERIDON 2-8 mg mg
OLANZAPINE 10—20 mg
QUETIAPINE 200-800 mg
CLOZAPINE 150-450 mg
PALIPERODINE 6 mg
ARIPIPRAZOLE 10-30 mg
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Tatalaksana efek samping
•Bila terjadi efek smaping sindroma ektrapiramidall sepert dystonia akut, akatisisa atau parkinsonism biasanya terlebih dahulu dilakukan penuruna dosis dan bila tidak dapat ditanggulangi diberikan obat antikolinergik .bila tetap tidak berhasil disarankan mengganti ke golongan APG II
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Antikolinergik tidak diberikan secara rutin atau utk pencegahan efek samping karena munculnya efek samping bersifat individual dan baru perlu diberikan hanya bila terjadi efek samping
NAMA GENERIK NAMA DAGANG SEDIAAN DOSIS ORAL/HARI
BENZTROPINE COGENTIN 0.5 , 1,,2 mg tab1 mg/ml inj
2-3 x 0.5-2.0 mg
trihexyphenidyl artane 2, 5 mg tab2mg / 5 ml elixir
2- 4 x 2 mg
biperidine akineton 2 mg tab 2-4 x 2 mg
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Comparison of Some Antipsychotic AgentsDrug Relative
Antipsychotic Potency
Sedation Extra-pyramidal
Anti-cholinergic
Hypotension
chlorpromazine(Thorazine)
+ +++ +++ + +++
thioridazine(Mellaril)
+ +++ + +++ +++
fluphenazine(Prolixin)
+++ + +++ + ++
haloperidol(Haldol)
+++ + +++ +/- +
loxapine(Loxitane)
++ + ++ +/- +
molindone(Moban)
++ ++ + + +
clozapine(Clozaril)
++ +++ +/- +++ +++
risperidone(Risperdal)
+++ + + + ++
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Some Adverse Effects of Second Generation Antipsychotics
Drug Diabetes Extrapyramidal Symptoms
Elevated Prolactin
QTc Prolongation
Weight Gain
Aripiprazole +/- + +/- +/- +/-
Clozapine* ++++ +/- +/- + ++++
Olanzapine ++++ + +/- + ++++
Quetiapine ++ +/- +/- +/- +++
Risperidone ++ +++ +++ + ++
Ziprasidone +/- + + ++ +/-
*Clozapine is also associated with myocarditis and agranulocytosis; the other second-generation antipsychotics are not.
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Antidepresan
OBAT ACUAN AMITRIPTYLINE
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SEROTONINSerotonin (5-
hydroxytryptamine, or 5-HT) is a monoamine
neurotransmitter synthesized in
serotonergic neurons in the central
nervous system.
The functions of serotonin are numerous and
appear to involve control of appetite, sleep, memory and
learning, temperature
regulation, mood, behavior (including
sexual), cardiovascular
function, muscle contraction, endocrine
regulation, and depression
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Gol. Trisiklik dan tetrasiklik bersifat serotonergic Menghambat reuptake neurotransmitter yang dilepaskan dicelah sinap tetapi tidak selektif
Gol SSRI ; menghambat reuptake selektif hanya neurotransmitter serotonin(5HT2)Gol SNRI : menghambat reuptake serotonin dan norepinefrin
MAOI : bekerja di presinap menghambat enzim yang memmecah serotonin
↑ jumlah aminergic neurotransmitter pada celah sinaps
Aktivitas reseptor serotonin ↑ di post sinap
Mekanisme kerja anti-depresi
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PenggolonganTRICYCLIC COMPOUND• Amitriptyline(tofranil )• Imipramine( laroxyl)• Clomipramine
TETRACYCLIC COMPOUND• Maprotiline (ludiomil)• Mianserin(Tolvon)
Mono-Amine Oxydase Inhibitor( MAOi)• Moclobemide(Aurorix)
SSRI(selective serotonin Reuptake inhibitor)• Sertraline( Zoloft)• Fluoxetin(Prozac)• Paroxetine(seroxat)
SNRI(serotonin norepinefrin reuptake inhibitor) • Venlafaxine (Efexor XR)• Deslenlafaxine (pristiq)• Duloxetin(Cymbalta )
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Antidepressan
Yang bersifat sedatif:
• Amitriptyline• Imipramine• Clomipramine• Maproptiline• Trazodone• Mirtazapine
Yang bersifat aktivasi/non-sedatif:
• Tianeptine• Moclobemide• SSRI
(Fluoxetine,Sertraline,Citalopram,
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Indication of AntidepressantsDepressive
Disturbances
Affective Disorders
Obsessive-Compulsive Disorders
Panic Disorders
Eating Disorders
Psychosomatic Disorders
Posttraumatic Stress Disorder
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Antidepressants:Monoamine Reuptake Inhibitors
1st Generation of Antidepressants (TCA, TeCA)
Generic Name Trade Mark Doses (mg) Mechanism of Efficacy
amitriptyline AMITRIPTYLIN 75-200
Inhibition of Serotonin and/or Norepinephrine Reuptake Followed by Increase of their Concentrations in Synaptic Cleft
nortriptyline NORTRILEN 50-150
imipramine MELIPRAMIN 75-250
clomipramine ANAFRANIL, HYDIPHEN
75-225
dosulepin PROTHIADEN 100-300
dibenzepine NOVERIL 240-720
maprotiline LUDIOMIL, MAPROTILINE
75-150
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3rd Generation of AntidepressantsGeneric Name Trade Mark Mean Doses
(mg)Mechanism
SSRI
fluvoxamine FEVARIN 100-300
Selective Serotonin Reuptake Inhibition
fluoxetine DEPREX, DEPRENON, PROZAC, PORTAL, FLOXET, FLUXONIL, MAGRILAN
10-20
citalopram SEROPRAM, CITALEC, CEROTER, PRAM
20-60
escitalopram CIPRALEX 5-20
paroxetine SEROXAT, PAROLEX, APO-PAROX, REMOD
10-20
sertraline ZOLOFT, SERLIFT, ASENTRA, STIMULOTON
25-50
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SSRI-Common Side Effects
Insomnia, headache
Nausea, anorexia• Diarrhea • Constipation (Paxil)
Sexual dysfunction• Decreased libido• Anorgasmia
Nervousness, tremor• Myoclonus• Teeth-clenching
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Mood Stabilizer
Kelompok obat untuk mempertahankan stabilitas suasan perasaan, terutama mencegah munculnya kondisi manik pada gangguann afektif bipolar
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Klasifikasi umum
1. Garam lithium
Lithium carbonat – pradel
- Theralith
2. lain-lain
carbamazepine - tegretol
asam valproate -valproate acid
- depakene
Natrium Divalprpate -Depakote
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• Lithium carbonate –mood stabilizer klasik. monitor kdr lithium dlm darah (bts terapeutik: 0.8 – 1.2 mEq/L) hati-hati gjl toksisitas (mual,muntah, diare, ataxia)
• Valproic Acid (Depakene) & Divalproex Sodium (Depakote®) – menyebabkan iritasi lambung. Monitor fx hepar dan PDL
• Carbamazepine (Tegretol®) – menurunkan hitung sel
darah putih. Perlu monitor kdr obat dlm darah dan monitor tanda dan gjl sindromStevens-Johnson.
• Lamotrigine (Lamictal®) – Efektif utk Bipolar episode depresi.
• Oxcarbazepine (Trileptal®) – belum diakui FDA utk Bipolar.
Mood Stabilizer
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•Terapi dgn lithium dimulai dari dosis 2-3 kali 300 mg/hari sampai pasien stabil
•Dosis pemeliharaan dapat dicapai dengan pemeberian 900-1200 mg/hari
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Pengobatan:APA Practice Guidelines 2002
• Manik gjl akut/tipe campuran:– 1st line: lithium or valproate or antipsychotic*– 1st line severe: lithium or valproate +
antipsychotic*• Depresi akut:
– 1st line: lithium or lamotrigine– 1st line severe: lithium + antidepressant
• Maintenance– lithium or valproate:– Alternatif: lamotrigine, carbamazepine,
oxycarbazepine– Atipikal antipsikotik dapt diberikan
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Penggunaan antipsikotik pada gangguan bipolar
• Berefek pd serangan manik akut dan melambatkan serangan pd episode manik
• Hanya berefek baik pada gangguan bipolar I
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Mood Stabilizers:Lithium• kelebihan:
– (FDA-approved 1970)– Efektif pd manik dan hipomanik– Tidak mahal– Menurunkan kdr bunuh diri
• kekurangan:– Onset lmbat ~14 hari– Indeks terapeutik redah– Tdk berespon pd > 50% (pd subtipe
bipolar)– ES (polyuria, tremor, GI s) and non-
compliance– Kejadian Relaps meningkat krn berhenti
minum obat
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Mood Stabilizers:Divalproex
• Kelebihan:– (FDA-approved utk epilepsy 1983; utk
bipolar episode mania 1995)– Onset cepat (1-4 hari)– 77% menunjukkan respon– Efektif pada subtipe Bipolar– Efektif utk gejala psikotiktif– Efek samping Gangguan kognitif
kurang dari lithium
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Mood Stabilizer:Divalproex
• Kekurangan:– -Efek sedasi– -Rambut rontok– -Peningkatan BB– -tremor– -Gangguan GI– -thrombositopenia– -Hepatoksisitas ,pancreatitis (jarang)– -Polycystic Ovarian Syndrome– -Harus monitor kadar obat dlm plasma
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Mood Stabilizers:Lamictal
• FDA-approved utk terapi rumatan Gangg Bipolar I
• Hati –hati dgn efek timbulnya kelainan kulit spt ruam (itermasuk Stevens-Johnson Syndrome dan Toxic epidermal necrolysis)
• Interaksi obat dgn AED(tu valproic acid and carbamazepine)
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ANXIOLYTICS/ANTI CEMAS/
ANTI ANSIETAS
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sekelompok psikofarmaka yang mengurangi atau menghilangkan gejala cemas dan juga memiliki efek sedasi,relaksasi otot, amnestic dan antiepileptik
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Penggolongan anti ansietasBenzodiazepines• diazepam(valium)
• Lorazepam ( Ativan)
• Aprazolam (Xanax)
Non-benzodiazepines• 5-HT1Areceptoragonists:
Azaspirodecanedion- Buspirone• Barbiturat : fenobarbital,teopental• ß-Blockers : Propranolol• ß2-AR partial agonist : Clonidine• Antidepressants : TCAs, SSRIs• Antihistaminicdrugs :
Diphenhydramine
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BENZODIAZEPIN•Cara kerja:
•Pengikatan spesifik thd reseptor GABA•Secara selektif reseptor GABA (gamma aminobutyric acid A) membiarkan ion chlorid masuk kedalam sel sehingga terjadi hiperpolarisasi neuron dan menghambat pelepasan transimisi neuronal
• frekuensi pembukaan kanal GABAergik Benzodiazepin
• waktu pembukaaan kanal GABAergik Barbiturates
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Pharmacodynamics of Benzodiazepines
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Benzodiazepin
Penggunaan dalam terapi• Gangguan anxietas• Gangguan kekakuan otot• Gangguan tidur• Kejang
Efek samping • Depresi nafas ,gangg SSP• pusing,sedasi, mual ,muntah,konfusi dan
gangg memori• Toleransi obat
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Derivat benzodiazepin
nama generik Nama dagang sediaan Dosis per hari
diazepam valium 2,5,10 mg tab,10 mg inj
1 x2-40 mg
Clonazepam Klonopin 0.5, 1,2 mg tab 1x 0,5 -2 mg
aprazolam Xanax 0.25,0.5 , 1,2 mg tab
2-3 x 0.5-2 mg
Lorazepam Ativan 0.5, 1,2 mg tab 1-2 x 0.5 -2 mg
clobazam frisium 10 mg tab 2-3 x 5-10 mg
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BARBITURAT
Efek samping• Depresi SSP dan pernafasan
Kegunaan klinis• Anestesia,antikonvulsan• Anxietas telah digantikan dg
benzodiazepin
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• Obat antiansietas agonis parsial pd reseptor 5-HT1A receptor menghambat pelepasan serotonin dan mempunyai afinitas pd reseptor D2 dopamine pd otak yg dpt bertindak sbg antagonist dan agonist.
• Pengobatan simptomatik kerja cepat pd pasien gangg cemas menyeluruh
BUSPIRONE
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BUSPIRONE• Tidak ada efek sedatif dan tidak menekan
SSP• margin of safety tinggi • tdk menimbulkan ketergantungan.
Efek samping:• Dpt menimbulkan takikardia, palpitasi,
cemas, gangg GI dan parestesia.• Menyebabkan konstriksi pupil-trgntung
dosis
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TERIMA KASIH...