PsychopharmacologyKELOMPOK 5SAKINAHAIN NABILLA ZRANANTA SAPUTRA S

PEMBIMBINGDr. Dharmawan, 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

PrinPrinssipip mekanisme kerja obat mekanisme kerja obat psikofarmakapsikofarmaka

Mekanisme agonis-antagonis

Antipsikotik (Neuroleptik)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

• Obat Acuan : Chlorpromazine (CPZ)

NEUROLEPTICS

MAJOR TRANQULIZE

RS

Anti Psikotik

Teori Dopamine-Pathways

Anti Psikotik

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

Overview of Antipsychotics

Conventional AntipsychoticsConventional Antipsychotics(TYPICAL)(TYPICAL)Chem. GroupChem. Group Generic NameGeneric Name Trade MarkTrade Mark Dose (mg)Dose (mg)

PhenothiazinPhenothiazineses

chlorpromazinechlorpromazine CHLORPROMAZIN, CHLORPROMAZIN, LARGACTIL, LARGACTIL, PLEGOMAZIN, PLEGOMAZIN, MEGAPHEN, MEGAPHEN, THORAZINTHORAZIN

200-800200-800

levomepromazinlevomepromazinee

TISERCIN, NOZINAN TISERCIN, NOZINAN 50-40050-400

thioridazinethioridazine THIORIDAZIN, THIORIDAZIN, MELLERILMELLERIL

100-600100-600

periciazinepericiazine NEULEPTIL NEULEPTIL 10-4010-40

ThioxanthesThioxanthes

chlorprothixenechlorprothixene CHLORPROTHIXEN, CHLORPROTHIXEN, TRUXALTRUXAL

100-600100-600

clopenthixolclopenthixol CISORDINOL, CISORDINOL, CLOPIXOLCLOPIXOL

20-10020-100

Overview of AntipsychoticsConventional AntipsychoticsConventional Antipsychotics

Chem. GroupChem. Group Generic NameGeneric Name Trade MarkTrade Mark Dose (mg)Dose (mg)

PhenothiazinePhenothiaziness

perfenazineperfenazine PERFENAZIN, PERFENAZIN, TRILAFON, PERATSINTRILAFON, PERATSIN

16-2416-24

prochlorperaziprochlorperazinene

PROCHLORPERAZIN, PROCHLORPERAZIN, STEMETILSTEMETIL

20-8020-80

flufenazineflufenazine MODITENMODITEN 2-162-16

trifluoperazinetrifluoperazine STELAZINSTELAZIN 10-5010-50

ThioxanthenesThioxanthenes flupenthixolflupenthixol FLUANXOLFLUANXOL 6-186-18

ButyrophenonButyrophenoneses

haloperidolhaloperidol HALOPERIDOL, HALOPERIDOL, HALDOL, APO-HALDOL, APO-HALOPERIDOLHALOPERIDOL

2,5-102,5-10

melperonemelperone BURONILBURONIL 50-30050-300

DiphenylbutylDiphenylbutylpiperidinespiperidines

pimozidepimozide ORAPORAP 2-102-10

fluspirilenfluspirilen IMAPIMAP 2-102-10

penfluridolpenfluridol SEMAPSEMAP 2-602-60

PerathiepinesPerathiepines oxyprothepinoxyprothepin MECLOPINMECLOPIN 5-205-20

Antipsychotics of the 2nd Generation (atypical)

Generic NameGeneric Name Trade MarkTrade Mark Dose (mg)Dose (mg)

D2, D3 selective antagonistsD2, D3 selective antagonists

sulpiridesulpiride DOGMATIL, PROSULPINDOGMATIL, PROSULPIN 50-120050-1200

amisulprideamisulpride SOLIAN, DENIBANSOLIAN, DENIBAN 50-120050-1200

SDASDA

risperidonerisperidone RISPERDAL, RISPENRISPERDAL, RISPEN, , RISPERDAL QUICKLETRISPERDAL QUICKLET

4-84-8

AripripazolAripripazol ABILIFYABILIFY 15-3015-30

ziprasidoneziprasidone ZELDOXZELDOX 40-16040-160

sertindolesertindole SERDOLECTSERDOLECT 12-2012-20

MARTAMARTA

clozapineclozapine LEPONEXLEPONEX 200-600200-600

olanzapineolanzapine ZYPREXAZYPREXA i.m. inj. 10 mg i.m. inj. 10 mg 5-205-20

quetiapinequetiapine SEROQUELSEROQUEL 300-600300-600

Depot Antipsychotics

Generic NameGeneric Name Trade MarkTrade Mark Mean Dose Mean Dose (mg)(mg)

IntervalInterval

flufenazinflufenazin MODITEN DEPOTMODITEN DEPOT 2525

14-28 14-28 daysdays

oxyprothepinoxyprothepin MECLOPINMECLOPIN 2525

haloperidolhaloperidol HALDOL DEPOTHALDOL DEPOT 100100

flupenthixolflupenthixol FLUANXOL DEPOTFLUANXOL DEPOT 4040

zuclopenthixolzuclopenthixol CISORDINOL CISORDINOL DEPOTDEPOT

200200

fluspirilenfluspirilen IMAPIMAP 66 7 days !!7 days !!

risperidonerisperidone RISPERDAL RISPERDAL CONSTACONSTA

20-3020-30 14 days14 days

Comparison of Some Antipsychotic AgentsComparison of Some Antipsychotic AgentsDrugDrug Relative Relative

Antipsychotic Antipsychotic PotencyPotency

SedationSedation Extra-Extra-pyramidalpyramidal

Anti-Anti-cholinergiccholinergic

HypotensionHypotension

chlorpromazine(Thorazine)

+ +++ +++ + +++

thioridazine(Mellaril)

+ +++ + +++ +++

fluphenazine(Prolixin)

+++ + +++ + ++

haloperidol(Haldol)

+++ + +++ +/- +

loxapine(Loxitane)

++ + ++ +/- +

molindone(Moban)

++ ++ + + +

clozapine(Clozaril)

++ +++ +/- +++ +++

risperidone(Risperdal)

+++ + + + ++

Some Adverse Effects of Second Generation AntipsychoticsSome Adverse Effects of Second Generation Antipsychotics

DrugDrug DiabetesDiabetes ExtrapyramidExtrapyramidal Symptomsal Symptoms

Elevated Elevated ProlactinProlactin

QTc QTc ProlongationProlongation

Weight Weight GainGain

Aripiprazole +/- + +/- +/- +/-

Clozapine* ++++ +/- +/- + ++++

Olanzapine ++++ + +/- + ++++

Quetiapine ++ +/- +/- +/- +++

Risperidone ++ +++ +++ + ++

Ziprasidone +/- + + ++ +/-

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

Guideline for Schizophrenia

No response

No response

No response

No response

AntidepresanAntidepresan

OBAT ACUAN AMITRIPTYLINE

Penggolongan

AntidepressanAntidepressan

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)1st Generation of Antidepressants (TCA, TeCA)

Generic NameGeneric Name Trade MarkTrade Mark Doses (mg)Doses (mg) Mechanism of Mechanism of EfficacyEfficacy

amitriptyline amitriptyline AMITRIPTYLINAMITRIPTYLIN 75-20075-200Inhibition of Inhibition of Serotonin Serotonin and/or and/or Norepinephrine Norepinephrine Reuptake Reuptake Followed by Followed by Increase of Increase of their their Concentrations Concentrations in Synaptic in Synaptic CleftCleft

nortriptylinenortriptyline NORTRILENNORTRILEN 50-15050-150

imipramineimipramine MELIPRAMINMELIPRAMIN 75-25075-250

clomipramineclomipramine ANAFRANIL, ANAFRANIL, HYDIPHENHYDIPHEN

75-22575-225

dosulepindosulepin PROTHIADENPROTHIADEN 100-300100-300

dibenzepinedibenzepine NOVERILNOVERIL 240-720240-720

maprotilinemaprotiline LUDIOMIL, LUDIOMIL, MAPROTILINEMAPROTILINE

75-15075-150

3rd Generation of AntidepressantsGeneric NameGeneric Name Trade MarkTrade Mark Mean Doses Mean Doses

(mg)(mg)MechanismMechanism

SSRISSRI

fluvoxaminefluvoxamine FEVARIN FEVARIN 100-300100-300

Selective Selective Serotonin Serotonin Reuptake Reuptake InhibitionInhibition

fluoxetinefluoxetine DEPREX, DEPRENON, DEPREX, DEPRENON, PROZAC, PORTAL, PROZAC, PORTAL, FLOXET, FLUXONIL, FLOXET, FLUXONIL, MAGRILANMAGRILAN

20-6020-60

citalopramcitalopram SEROPRAM, CITALECSEROPRAM, CITALEC, , CEROTER, PRAMCEROTER, PRAM

20-6020-60

escitalopramescitalopram CIPRALEX CIPRALEX 10-2010-20

paroxetineparoxetine SEROXAT, PAROLEXSEROXAT, PAROLEX, , APO-PAROX, REMODAPO-PAROX, REMOD

20-6020-60

sertralinesertraline ZOLOFT, SERLIFT, ZOLOFT, SERLIFT, ASENTRAASENTRA, STIMULOTON, STIMULOTON

50-20050-200

SSRI-Common Side EffectsSSRI-Common Side Effects

SSRI: Other IndicationsSSRI: Other Indications

• Anxiety/PanicAnxiety/Panic• Bulimia NervosaBulimia Nervosa• PMDDPMDD• OCD-SpectrumOCD-Spectrum• Impulse ControlImpulse Control

3rd Generation of Antidepressants

Generic NameGeneric Name Trade MarkTrade Mark Mean Doses Mean Doses (mg)(mg)

MechanismMechanism

SARISARIAntidepressants with Doubled Serotonergic EfficacyAntidepressants with Doubled Serotonergic Efficacy

trazodonetrazodone TRITTICO AC TRITTICO AC 4-84-8Double Serotonergic Double Serotonergic EfficacyEfficacynefazodonnefazodon

eeSERZONE, SERZONE, DUTONIN DUTONIN

100-300100-300

NARINARI

reboxetinereboxetine EDRONAXEDRONAX 4-84-8 Norepinephrine Norepinephrine Reuptake InhibitionReuptake Inhibition

tianeptinetianeptine COAXILCOAXIL 7575 Increasing of Serotonin Increasing of Serotonin ReuptakeReuptake

MAO Inhibitors

Non Selective and Irreversible: (IMAO A, IMAO B)Non Selective and Irreversible: (IMAO A, IMAO B)

phenelzinephenelzine NARDILNARDIL

isocarboxazidisocarboxazid MARPLANMARPLAN

nialamidenialamide NIAMID, NUREDALNIAMID, NUREDAL

tranylcyprominetranylcypromine PARNATEPARNATE

Selective and ReversibleSelective and Reversible

MAO AMAO A

moclobemidemoclobemide AURORIXAURORIX

brofarominebrofaromine CONSONARCONSONAR

toloxatonetoloxatoneHUMORYLHUMORYL

MAO BMAO B selegiline (L-deprenyl)selegiline (L-deprenyl) SEPATREM, JUMEXSEPATREM, JUMEX

Other Psychotropics with Antidepressant Effect

ThymoprophylacticsThymoprophylactics

lithiumlithium LITHIUM CARBONICUM, CONTEMNOLLITHIUM CARBONICUM, CONTEMNOL

Antiepileptics Antiepileptics of 2nd of 2nd GenerationGeneration

carbamazepinecarbamazepine BISTON, TEGRETOL, FINLEPSIN, BISTON, TEGRETOL, FINLEPSIN, TIMONILTIMONIL

salts of valproic salts of valproic acidacid

EVERIDEN, CONVULEX, ORFIRIL, EVERIDEN, CONVULEX, ORFIRIL, DEPAMIDDEPAMID

Antiepileptics Antiepileptics of 3rd of 3rd GenerationGeneration

lamotriginelamotrigine LAMICTALLAMICTAL

gabapentinegabapentine GABAPENTIN, NEURONTINGABAPENTIN, NEURONTIN

topiramatetopiramate TOPAMAXTOPAMAX

Atypical Antipsychotics - SDAAtypical Antipsychotics - SDA

clozapineclozapine LEPONEX, CLOZARIL, ALEMOXANLEPONEX, CLOZARIL, ALEMOXAN

olanzapineolanzapine ZYPREXAZYPREXA

quetiapinequetiapine SEROQUELSEROQUEL

Depresi ringan dan sedang

3 bulan

Mood StabilizerMood Stabilizer

Digunakan utk mengendalikan mood pad Digunakan utk mengendalikan mood pad “Bipolar” atau “Manik-Depresif” to“Bipolar” atau “Manik-Depresif” to

• Lithium carbonateLithium carbonate –mood stabilizer –mood stabilizer klasik klasik. . monitor kdr lithium dlm darah monitor kdr lithium dlm darah ((bts tbts terapeutierapeutikk: 0.8 – 1.2 : 0.8 – 1.2 mEq/L) mEq/L) hati-hati gjl toksisitas hati-hati gjl toksisitas ((mual,muntahmual,muntah, , diare, diare, ataxiaataxia))

• Valproic Acid (Depakene) & Divalproex Sodium Valproic Acid (Depakene) & Divalproex Sodium (Depakote®) – (Depakote®) – menyebabkan iritasi lambungmenyebabkan iritasi lambung. . Monitor Monitor fx hepar dan PDLfx hepar dan PDL

• Carbamazepine (Tegretol®) – Carbamazepine (Tegretol®) – menurunkan hitung sel menurunkan hitung sel

darah putihdarah putih. . Perlu monitor kdr obat dlm darah dan Perlu monitor kdr obat dlm darah dan monitor tanda dan gjl monitor tanda dan gjl ssiindromStevens-Johnson. ndromStevens-Johnson.

• Lamotrigine (Lamictal®) – Lamotrigine (Lamictal®) – Efektif utk Bipolar episode Efektif utk Bipolar episode depresi.depresi.

• Oxcarbazepine (TOxcarbazepine (Trileptal®) – rileptal®) – belum diakui FDA belum diakui FDA utk Bipolarutk Bipolar. .

Mood StabilizerMood Stabilizer

Pengobatan:Pengobatan:APA Practice Guidelines 2002APA Practice Guidelines 2002

• Manik gjl akut/tipe campuran:Manik gjl akut/tipe campuran:– 11stst line: lithium line: lithium oror valproate valproate oror antipsychotic* antipsychotic*– 11stst line severe: lithium line severe: lithium oror valproate + valproate +

antipsychotic*antipsychotic*• Depresi akut:Depresi akut:

– 11stst line: lithium line: lithium oror lamotrigine lamotrigine– 11stst line severe: lithium + antidepressant line severe: lithium + antidepressant

• MaintenanceMaintenance– lithium lithium oror valproate: valproate:– Alternatif: lamotrigine, carbamazepine, Alternatif: lamotrigine, carbamazepine,

oxycarbazepineoxycarbazepine– Atipikal antipsikotik dapt diberikanAtipikal antipsikotik dapt diberikan

Penggunaan antipsikotik pada gangguan Penggunaan antipsikotik pada gangguan bipolarbipolar

• Berefek pd serangan manik akut dan Berefek pd serangan manik akut dan melambatkan serangan pd episode melambatkan serangan pd episode manikmanik

• Hanya berefek baik pada gangguan Hanya berefek baik pada gangguan bipolar Ibipolar I

Mood Stabilizers:Mood Stabilizers:LithiumLithium• kelebihan:kelebihan:

– ((FDA-approved 1970)FDA-approved 1970)– Efektif pd manik dan hipomanikEfektif pd manik dan hipomanik– Tidak mahalTidak mahal– Menurunkan kdr bunuh diriMenurunkan kdr bunuh diri

• kekurangan:kekurangan:– Onset lmbat ~14 hariOnset lmbat ~14 hari– Indeks terapeutik redahIndeks terapeutik redah– Tdk berespon pd > 50% (pd subtipe Tdk berespon pd > 50% (pd subtipe

bipolar)bipolar)– ES (polyuria, tremor, GI s) and non-ES (polyuria, tremor, GI s) and non-

compliancecompliance– Kejadian Relaps meningkat krn berhenti Kejadian Relaps meningkat krn berhenti

minum obatminum obat

Mood Stabilizers:Mood Stabilizers:DivalproexDivalproex

• Kelebihan: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:Mood Stabilizer:DivalproexDivalproex

• Kekurangan: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:Mood Stabilizers:LamictalLamictal

• FDA-approved utk terapi rumatan FDA-approved utk terapi rumatan Gangg Bipolar IGangg Bipolar I

• Hati –hati dgn efek timbulnya kelainan Hati –hati dgn efek timbulnya kelainan kulit spt ruam (itermasuk Stevens-kulit spt ruam (itermasuk Stevens-Johnson Syndrome dan Toxic epidermal Johnson Syndrome dan Toxic epidermal necrolysis)necrolysis)

• Interaksi obat dgn AED(tu valproic acid Interaksi obat dgn AED(tu valproic acid and carbamazepine) and carbamazepine)

ANXIOLYTICS/ANXIOLYTICS/ANTI CEMAS/ANTI CEMAS/

ANTI ANSIETASANTI ANSIETAS

sekelompok psikofarmaka yang sekelompok psikofarmaka yang mengurangi atau menghilangkan mengurangi atau menghilangkan gejala cemas gejala cemas

Penggolongan anti ansietas

BenzodiazepinesBenzodiazepines

Non-benzodiazepinesNon-benzodiazepines• 5-HT5-HT1A1Areceptoragonists: receptoragonists:

Azaspirodecanedion- BuspironeAzaspirodecanedion- Buspirone• Barbiturat : fenobarbital,teopentalBarbiturat : fenobarbital,teopental• ß-Blockers : Propranololß-Blockers : Propranolol• ßß2-AR partial agonist : Clonidine2-AR partial agonist : Clonidine• Antidepressants : TCAs, SSRIsAntidepressants : TCAs, SSRIs• Antihistaminicdrugs : Antihistaminicdrugs :

DDiiphenhydraminephenhydramine

• 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

PharmacoPharmacodynamdynamics of Benzodiazepinesics 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 benzodiazepinEfek toksik /overdosis benzodiazepin

• Diberi flumazenil (antagonist reseptor Diberi flumazenil (antagonist reseptor BDZ,masa ½ pendek).BDZ,masa ½ pendek).

• Kejang dan aritmia ---apbl BDZ +TCA’sKejang dan aritmia ---apbl BDZ +TCA’s• Flumazenil tidak efektif utk overFlumazenil tidak efektif utk over.dosis

barbiturat

BARBITURAT• Efek samping

– Depresi SSP dan pernafasan

• Kegunaan klinis– Anestesia,antikonvulsan– Anxietas telah digantikan dg benzodiazepin

• Obat antiansietas agonis parsial pd Obat antiansietas agonis parsial pd reseptor 5-HTreseptor 5-HT1A 1A receptor menghambat receptor menghambat pelepasan serotonin dan mempunyai pelepasan serotonin dan mempunyai afinitas pd reseptor D2 dopamine pd otak afinitas pd reseptor D2 dopamine pd otak yg dpt bertindak sbg antagonist dan yg dpt bertindak sbg antagonist dan agonist. agonist.

• Pengobatan simptomatik kerja cepat pd Pengobatan simptomatik kerja cepat pd pasien gangg cemas menyeluruhpasien gangg cemas menyeluruh

BUSPIRONEBUSPIRONE

BUSPIRONEBUSPIRONE• Tidak ada efek sedatif dan tidak menekan

SSP• margin of safety tinggi • tdk menimbulkan ketergantungan.

Efek samping:Efek samping:• Dpt menimbulkan takikardia, palpitasi,

cemas, gangg GI dan parestesia.• Menyebabkan konstriksi pupil-trgntung

dosis

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