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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 :

Prinsip Titrasi DosiS(tailoring the dose


of drugs)

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

Mekanisme agonisantagonis

Antipsikotik (Neuroleptik)

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

NEUROLEPT
ICS

MAJOR
TRANQULIZE
RS

Obat Acuan : Chlorpromazine (CPZ)

Anti Psikotik

Jalur dopaminergik saraf


Teori Dopamine-Pathways

1. Jalurnigrostriatal: dari substantianigrakebasal ganglia fungsi gerakan, EPS


2. jalurmesolimbik: dari tegmental areamenujukesistemlimbik memori, sikap,
kesadaran, prosesstimulus
3. jalurmesocortical : 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

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

chlorpromazine

Phenothiazin
es

Thioxanthes

thioridazine

THIORIDAZIN,
MELLERIL

periciazine

NEULEPTIL

chlorprothixene

CHLORPROTHIXEN,
TRUXAL

clopenthixol

CISORDINOL,
CLOPIXOL

Dose (mg)

200-800

50-400
100-600
10-40
100-600
20-100

Overview of Antipsychotics
Conventional Antipsychotics
Chem. Group

Phenothiazine
s

Generic Name

Trade Mark

Dose (mg)

perfenazine

PERFENAZIN,
TRILAFON, PERATSIN

16-24

prochlorperazi
ne
flufenazine

PROCHLORPERAZIN,
STEMETIL

20-80

MODITEN

2-16

trifluoperazine

STELAZIN

10-50

FLUANXOL

6-18

Thioxanthenes flupenthixol
Butyrophenon
es
Diphenylbutyl
piperidines
Perathiepines

haloperidol

HALOPERIDOL,
HALDOL, APOHALOPERIDOL

2,5-10

melperone

BURONIL

50-300

pimozide

ORAP

2-10

fluspirilen

IMAP

2-10

penfluridol

SEMAP

2-60

oxyprothepin

MECLOPIN

5-20

Antipsychotics of the 2nd Generation (atypical)


Generic Name

Trade Mark

Dose (mg)

D2, D3 selective antagonists


sulpiride

DOGMATIL, PROSULPIN

50-1200

amisulpride

SOLIAN, DENIBAN

50-1200

SDA
risperidone

4-8

Aripripazol

RISPERDAL, RISPEN,
RISPERDAL QUICKLET
ABILIFY

ziprasidone

ZELDOX

40-160

sertindole

SERDOLECT

12-20

15-30

MARTA
clozapine

LEPONEX

200-600

olanzapine

ZYPREXA i.m. inj. 10 mg

5-20

quetiapine

SEROQUEL

300-600

Depot Antipsychotics
Generic Name

Trade Mark

Mean Dose
(mg)

flufenazin

MODITEN DEPOT

25

oxyprothepin

MECLOPIN

25

haloperidol

HALDOL DEPOT

flupenthixol

FLUANXOL DEPOT

zuclopenthixol

CISORDINOL
DEPOT
IMAP

fluspirilen
risperidone

RISPERDAL
CONSTA

100

Interval

14-28
days

40
200
6

7 days !!

20-30

14 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


No response

No response

No response

No response

Antidepresan

OBAT ACUAN AMITRIPTYLINE

Penggolongan

Antidepressan

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)

amitriptyline

AMITRIPTYLIN

75-200

nortriptyline

NORTRILEN

50-150

imipramine

MELIPRAMIN

75-250

clomipramine ANAFRANIL,
HYDIPHEN
dosulepin
PROTHIADEN

75-225
100-300

dibenzepine

NOVERIL

240-720

maprotiline

LUDIOMIL,
MAPROTILINE

75-150

Mechanism of
Efficacy

Inhibition of
Serotonin
and/or
Norepinephrine
Reuptake
Followed by
Increase of
their
Concentrations
in Synaptic
Cleft

3rd Generation of Antidepressants


Generic Name

Trade Mark

Mean Doses
(mg)

Mechanism

SSRI
fluvoxamine

FEVARIN

fluoxetine

DEPREX, DEPRENON,
PROZAC, PORTAL,
FLOXET, FLUXONIL,
MAGRILAN
SEROPRAM, CITALEC,
CEROTER, PRAM

20-60

escitalopram

CIPRALEX

10-20

paroxetine

SEROXAT, PAROLEX,
APO-PAROX, REMOD

20-60

sertraline

ZOLOFT, SERLIFT,
ASENTRA, STIMULOTON

citalopram

100-300

20-60

50-200

Selective
Serotonin
Reuptake
Inhibition

SSRI-Common Side Effects

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
Double Serotonergic
nefazodon SERZONE,
100-300
Efficacy
e
DUTONIN
NARI
reboxetine

EDRONAX

4-8

Norepinephrine
Reuptake Inhibition

tianeptine

COAXIL

75

Increasing of Serotonin
Reuptake

MAO Inhibitors
Non Selective and Irreversible: (IMAO A, IMAO B)
phenelzine

NARDIL

isocarboxazid

MARPLAN

nialamide

NIAMID, NUREDAL

tranylcypromine

PARNATE

Selective and Reversible

MAO A

moclobemide

AURORIX

brofaromine

CONSONAR

toloxatone
MAO B

HUMORYL

selegiline (L-deprenyl) SEPATREM, JUMEX

Other Psychotropics with


Antidepressant Effect
Thymoprophylactics
lithium
Antiepileptics carbamazepine
of 2nd
salts of valproic
Generation
acid
lamotrigine

Antiepileptics
of 3rd
gabapentine
Generation
topiramate

LITHIUM CARBONICUM, CONTEMNOL


BISTON, TEGRETOL, FINLEPSIN,
TIMONIL
EVERIDEN, CONVULEX, ORFIRIL,
DEPAMID
LAMICTAL
GABAPENTIN, NEURONTIN
TOPAMAX

Atypical Antipsychotics - SDA


clozapine

LEPONEX, CLOZARIL, ALEMOXAN

olanzapine

ZYPREXA

quetiapine

SEROQUEL

Depresi ringan dan sedang

3 bulan

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

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

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 noncompliance
Kejadian Relaps meningkat krn berhenti

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 StevensJohnson 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

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

Efek toksik /overdosis benzodiazepin


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