psychopharmacology (1)
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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
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
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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