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Psychopharmacology

KELOMPOK 5
EZAFADDILA MAISARAH NURNABIHAH RIZQA RAZAQTANIA ROICHAN M. FIRDAUS

PEMBIMBING Dr. Prianto Djatmiko, spKJ

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.

Prinsip Titrasi Dosis


Pengaturan dosis dilakukan :
Dosis awal Dosis efektif dosis yg mulai berefek supresi gejala sasaran Dosis optimal dosis yg mampu mengendalikan gejala sasaran

Dosis pemeliharaan
dosis terkecil yg masih mampu mencegah kambuhnya gejala

Prinsip Titrasi DosiS(tailoring the dose of drugs)


Dosis dinaikkan secara

start low, go slow


bertahap,

Bila hasil terapinya berhasil, dosis diturunkan secara gradual sampai berhenti pemakaian obat.

Jenis Obat Gejala Sasaran Antipsychotics Psikosis Antidepressants Depresi Mood-Stabilizers Mania Anxiolytics Anxietas Hypnotics/anti-insomnia Insomnia Anti panik Panik

Prinsip mekanisme kerja obat psikofarmaka

Agonis

kerja obat menyerupai sifat neurotransmitter sasaran, berikatan dg reseptor dan memperkuat kerja neurotransmiter tsd di neuron suatu ligand yang bila berinteraksi dapat menghasilkan efek

Antagonis

kerja obat mem-blok reseptor neurotransmitter sasaran sehingga neurotransmitter tsb tdk

Mekanisme agonis-antagonis

Antipsikotik (Neuroleptik)
Golongan
Golongan Tipikal (FGA) Golongan Atipikal (SGA/SDA)

Indikasi
Gangguan Psikotik (Termasuk Psikosis organik) Skizofrenia Depresi berat disertai gejala psikotik Agitasi (Gaduh-gelisah) Delirium

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

Anti Psikotik

NEUROLEPTICS

MAJOR TRANQULIZERS

Obat Acuan : Chlorpromazine (CPZ)

Anti Psikotik

Mekanisme Kerja : Memblokade Dopamine pada reseptor pasca sinaps neuron di otak, khususnya di sistem limbik dan sistem ekstrapiramidal

Teori Dopamine-Pathways

Jalur dopaminergik saraf

1. Jalur nigrostriatal: dari substantianigrakebasal ganglia fungsi gerakan, EPS 2. jalur mesolimbik: dari tegmental area menujukesistemlimbik memori, sikap, kesadaran, prosesstimulus 3. jalur mesocortical : dari tegmental area menujukefrontal cortex kognisi, fungsi sosial, komunikasi, responsterhadapstress

Anti Psikotik
Efek Samping : - Sedasi dan Inhibisi Psikomotor - Gangguan Otonomik : hipotensi - Gangguan Ekstrapiramidal - Ggn Endokrin, metabolik, hematologik,

Overview of Antipsychotics
Conventional Antipsychotics(TYPICAL)
Chem. Group Generic Name Trade Mark Dose (mg)

chlorpromazine

Phenothiazin es

CHLORPROMAZIN, LARGACTIL, PLEGOMAZIN, MEGAPHEN, THORAZIN levomepromazine TISERCIN, NOZINAN

200-800

50-400 100-600

thioridazine

THIORIDAZIN, MELLERIL

periciazine
chlorprothixene Thioxanthes clopenthixol

NEULEPTIL
CHLORPROTHIXEN, TRUXAL CISORDINOL, CLOPIXOL

10-40
100-600 20-100

Overview of Antipsychotics
Conventional Antipsychotics
Chem. Group Generic Name Trade Mark
PERFENAZIN, TRILAFON, PERATSIN PROCHLORPERAZIN, STEMETIL
MODITEN STELAZIN FLUANXOL HALOPERIDOL, HALDOL, APOHALOPERIDOL BURONIL ORAP IMAP

Dose (mg)

perfenazine
Phenothiazine s prochlorperazi ne flufenazine trifluoperazine Thioxanthenes flupenthixol Butyrophenon es haloperidol melperone pimozide fluspirilen

16-24
20-80 2-16 10-50 6-18 2,5-10 50-300 2-10 2-10

Diphenylbutyl piperidines
Perathiepines

penfluridol
oxyprothepin

SEMAP
MECLOPIN

2-60
5-20

Antipsychotics of the 2nd Generation (atypical)


Generic Name Trade Mark Dose (mg)

D2, D3 selective antagonists sulpiride amisulpride risperidone Aripripazol ziprasidone sertindole clozapine olanzapine quetiapine DOGMATIL, PROSULPIN SOLIAN, DENIBAN SDA RISPERDAL, RISPEN, RISPERDAL QUICKLET ABILIFY ZELDOX SERDOLECT MARTA LEPONEX ZYPREXA i.m. inj. 10 mg SEROQUEL 200-600 5-20 300-600 4-8 15-30 40-160 12-20 50-1200 50-1200

Depot Antipsychotics
Generic Name Trade Mark Mean Dose (mg) Interval

flufenazin oxyprothepin haloperidol flupenthixol zuclopenthixol fluspirilen risperidone

MODITEN DEPOT MECLOPIN HALDOL DEPOT FLUANXOL DEPOT CISORDINOL DEPOT IMAP RISPERDAL CONSTA

25 25 100 40 200 6 20-30 7 days !! 14 days 14-28 days

Comparison of Some Antipsychotic Agents


Drug Relative Antipsychotic Potency
+ +

Sedation

Extrapyramidal
+++ +

Anticholinergic
+ +++

Hypotension

chlorpromazine (Thorazine) thioridazine (Mellaril)

+++ +++

+++ +++

fluphenazine (Prolixin)
haloperidol (Haldol)

+++
+++

+
+

+++
+++

+
+/-

++
+

loxapine (Loxitane)
molindone (Moban) clozapine (Clozaril) risperidone (Risperdal)

++
++ ++ +++

+
++ +++ +

++
+ +/+

+/+ +++ +

+
+ +++ ++

Some Adverse Effects of Second Generation Antipsychotics


Drug Diabetes Extrapyramid al Symptoms Elevated Prolactin QTc Weight Prolongation Gain

Aripiprazole Clozapine* Olanzapine Quetiapine Risperidone

+/++++ ++++ ++ ++

+ +/+ +/+++

+/+/+/+/+++

+/+ + +/+

+/++++ ++++ +++ ++

Ziprasidone

+/-

++

+/-

*Clozapine is also associated with myocarditis and agranulocytosis; the other secondgeneration antipsychotics are not.

Guideline for Schizophrenia


Second Generation Antipsychotic (SGA) #1, 4 -12 WEEKS No response SGA #2 4 -12 WEEKS

No response

Clozapine
No response

Conventional #1
4 12 WEEKS

3 - 9 MONTHS

No response

Two Antipsychotics (not 2 conventionals) ECT+/-Antipsychotic Different Antipsychotic (Atypical#3, Conventional#2)

Antidepresan

OBAT ACUAN AMITRIPTYLINE

SEROTONIN
The functions of serotonin are numerous and appear to Serotonin (5hydroxytryptamine, or 5- involve control of appetite, sleep, memory and learning, HT) is a monoamine temperature regulation, neurotransmitter synthesized in serotonergic mood, behavior (including sexual), cardiovascular neurons in the central function, muscle nervous system. contraction, endocrine regulation, and depression

Menghambat reuptake aminergic neurotransmitter


Menghambat penghancuran oleh ensim Monoamine Oxidase

jumlah aminergic neurotransmitterbpada celah sinaps

Aktivitas reseptor serotonin

Penggolongan
TRICYCLIC COMPOUND
Amitriptyline Imipramine Clomipramine

TETRACYCLIC COMPOUND
Maprotiline Mianserin

Mono-Amine Oxydase Inhibitor( MAOi)


Moclobemide

SSRI
Sertraline Fluoxetin Paroxetine

Antidepressan
Yang bersifat sedatif: Amitriptyline Imipramine Clomipramine Maproptiline Trazodone Mirtazapine Yang bersifat aktivasi/non-sedatif: Tianeptine Moclobemide SSRI (Fluoxetine,Sertraline, Citalopram,

Indication of Antidepressants
Depressive Disturbances Affective Disorders Obsessive-Compulsive Disorders Panic Disorders Eating Disorders Psychosomatic Disorders Posttraumatic Stress Disorder Alcohol and Drugs Withdrawal Symptoms Pain Syndromes Enuresis Narcolepsy

Antidepressants: Monoamine Reuptake Inhibitors


1st Generation of Antidepressants (TCA, TeCA)
Generic Name Trade Mark Doses (mg) Mechanism of Efficacy

amitriptyline
nortriptyline imipramine

AMITRIPTYLIN
NORTRILEN MELIPRAMIN

75-200
50-150 75-250 75-225 100-300 Inhibition of Serotonin and/or Norepinephrine Reuptake Followed by Increase of their Concentrations in Synaptic Cleft

clomipramine ANAFRANIL, HYDIPHEN dosulepin PROTHIADEN

dibenzepine
maprotiline

NOVERIL
LUDIOMIL, MAPROTILINE

240-720
75-150

3rd Generation of Antidepressants


Generic Name Trade Mark Mean Doses (mg) Mechanism

SSRI fluvoxamine fluoxetine


FEVARIN DEPREX, DEPRENON, PROZAC, PORTAL, FLOXET, FLUXONIL, MAGRILAN SEROPRAM, CITALEC, CEROTER, PRAM CIPRALEX SEROXAT, PAROLEX, APO-PAROX, REMOD ZOLOFT, SERLIFT, ASENTRA, STIMULOTON

100-300 20-60

citalopram escitalopram paroxetine sertraline

20-60 10-20 20-60 50-200

Selective Serotonin Reuptake Inhibition

Method of Action: They act within the brain to increase the amount of serotonin in the synaptic gap by inhibiting reuptake.

In contrast to other drugs, SSRIs are more potent inhibitors of serotonin reuptake, and they have less of an effect on 1, 2, histaminic, and muscarinic receptors

SSRI-Common Side Effects


Nausea, anorexia
Insomnia, headache
Diarrhea Constipation (Paxil)

Sexual dysfunction
Decreased libido Anorgasmia

Nervousness, tremor
Myoclonus Teeth-clenching

SSRI: Other Indications


Anxiety/Panic Bulimia Nervosa PMDD OCD-Spectrum Impulse Control

3rd Generation of Antidepressants


Generic Name Trade Mark Mean Doses (mg) Mechanism

SARI Antidepressants with Doubled Serotonergic Efficacy trazodone TRITTICO AC 4-8 100-300 NARI reboxetine EDRONAX 4-8 Norepinephrine Reuptake Inhibition Increasing of Serotonin Reuptake Double Serotonergic Efficacy

nefazodone SERZONE, DUTONIN

tianeptine

COAXIL

75

MAO Inhibitors
Non Selective and Irreversible: (IMAO A, IMAO B) phenelzine isocarboxazid nialamide tranylcypromine NARDIL MARPLAN NIAMID, NUREDAL PARNATE

Selective and Reversible moclobemide MAO A brofaromine toloxatone MAO B AURORIX CONSONAR HUMORYL

selegiline (L-deprenyl) SEPATREM, JUMEX

Other Psychotropics with Antidepressant Effect


Thymoprophylactics
lithium Antiepileptics carbamazepine of 2nd salts of valproic Generation acid Antiepileptics of 3rd gabapentine Generation topiramate lamotrigine
LITHIUM CARBONICUM, CONTEMNOL BISTON, TEGRETOL, FINLEPSIN, TIMONIL EVERIDEN, CONVULEX, ORFIRIL, DEPAMID LAMICTAL

GABAPENTIN, NEURONTIN
TOPAMAX

Atypical Antipsychotics - SDA


clozapine
LEPONEX, CLOZARIL, ALEMOXAN ZYPREXA SEROQUEL

olanzapine
quetiapine

Depresi ringan dan sedang


SSRI(Fluoxetine, sertraline)
3 bulan

Trisiklik (Amitriptiline)

Tetrasiklik(Maprotiline)

MAOI Reversible (Moclobemide)

Mood Stabilizer
Digunakan utk mengendalikan mood pad Bipolar atau Manik-Depresif to

Mood Stabilizer
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.

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

Penggunaan antipsikotik pada gangguan bipolar


Berefek pd serangan manik akut dan melambatkan serangan pd episode manik Hanya berefek baik pada gangguan bipolar I

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 noncompliance Kejadian Relaps meningkat krn berhenti minum obat

Mood Stabilizers: Lithium

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

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

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)

ANXIOLYTICS/ ANTI CEMAS/ ANTI ANSIETAS

sekelompok psikofarmaka yang mengurangi atau menghilangkan gejala cemas

Penggolongan anti ansietas


Benzodiazepines Non-benzodiazepines

5-HT1Areceptoragonists: Azaspirodecanedion- Buspirone Barbiturat : fenobarbital,teopental -Blockers : Propranolol 2-AR partial agonist : Clonidine Antidepressants : TCAs, SSRIs Antihistaminicdrugs : Diphenhydramine

Cemas dikarenakan GABA >>> reseptor khusus GABA terstimulasi CEMAS Obat-obatan benzodiazepin memiliki rumus kimia mirip GABA sehingga menduduki reseptor spesifik GABA TENANG

BENZODIAZEPIN
Cara kerja:
Me >>transmisi GABAergik

frekuensi pembukaan kanal GABAergik Benzodiazepin waktu pembukaaan kanal GABAergik Barbiturates afinitas reseptor GABA. BDZs and BARBS
Stimulasi reseptor 5-HT1A Inhibisi reseptor 5-HT2A, 5-HT2C, and 5-HT3

Benzodiazepin
Efek:
Menurunkan ansietas Hipnotik sedatif Anti konvulsif Pelemas otot

Pharmacodynamics of Benzodiazepines

Penggunaan dalam terapi


Gangguan anxietas Gangguan kekakuan otot Gangguan tidur Kejang

Benzodiazepin

Efek samping
Depresi nafas ,gangg SSP pusing,sedasi, mual ,muntah,konfusi dan gangg memori Toleransi obat

Efek toksik /overdosis benzodiazepin


Diberi flumazenil (antagonist reseptor BDZ,masa pendek). Kejang dan aritmia ---apbl BDZ +TCAs Flumazenil tidak efektif utk over.dosis barbiturat

BARBITURAT
Efek samping
Depresi SSP dan pernafasan

Kegunaan klinis
Anestesia,antikonvulsan Anxietas telah digantikan dg benzodiazepin

BUSPIRONE
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
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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