Cns Pharmacology 2014

INTRODUCTION CNS PHARMACOLOGY

ELLY NURUS SAKINAHCentral Nervous System PHARMACOLOGYNEUROTRANSMITTERNeurotransmitterKelebihanKekurangan AsetilkolinDelirium, psikosisPenyakit alzeimerDopaminePsikosis, sindrom Tourette, choreaParkinson, depresiGABADepresi CNS, SedasiKejang, gangguan gerakGlutamatKejangn degenerasi neuronSkizofren, depresi, gangguan kognitifNorepinefrinAnsietas, panic, anoreksia, insomniaDepresi SerotoninTidur, halusinasi, penurunan nafsu makan, ansietasDepresi, sensitive nyeri,ansietasTARGET MOLEKULAR FARMAKOLOGI SISTEM SARAF PUSAT

ELLY NURUS SAKINAHSEDATIF HIPNOTIKPENGERTIANAnxiolytic (sedative) adalah obat yang mengurangi gejala cemas, memberikan efek menenangkan dengan sedikit atau tanpa efek terhadap status mental atau motorik. Sedangkan hipnotik (sleep-inducing) adalah obat yang menghasilkan efek induksi tidur, mempengaruhi onset tidur dan mempertahankan fase tidur.Graded dose-dependent depression of central nervous system function

Barbiturat dan alkoholBenzodia zepin6Teori neurobiologi terjadinya gangguan anxietasKelebihan serotonin (5-HT) dan kekurangan NT noradrenergicKekurangan GABAKelebihan GlutamatPenurunan BDNF (Brain-derived neurotropic factor)

OBAT SEDATIF-HIPNOTIKBENZODIAZEPINE (BZD)BARBITURATZ DRUGRAMELTEONBUSPIRONBENZODIAZEPINEFARMAKOKINETIKRates of oral absorption : lipophilicity major role drug enters the CNSTriazolam, barbiturat, newer hypnotics more rapidClorazepate prodrug, active desmethyldiazepam (nordiazepam)Cross the placental barrier depression of neonatusAlso detectable in breast milk depressant effect of nursing infantBiotransformationPhase 1 (CYP3A4), phase II (eventually excreted as glucuronide conjugates in the urine)

Understanding of the importance of drug half life in determining appropriate drug therapy and minimizing adverse effectsObat penenang ideal:Menenangkan, day time sedation -, ketergantungan fisik/psikis -, TI lebar Obat tidur yg ideal:Onset of sleep cepat, mempertahankan kualitas dan lamanya tidur, hang over -, ketergantungan fisik/psikis -11Drug Tmax(hr)T1/2 (hr)Comments Alprazolam 1-212-15Rapid oral absorptionChloediazepoxide2-415-40Active metaboliteClorazepate1-2 (nordiazepam)50-100Prodrug, hydrolized to active form in stomachDiazepam1-220-80Active metabolicEszoplicone16Minor active metabolitesFlurazepam1-240-100Active metabolite with long half liveLorazepam1-610-20No active metabolitesOxazepam2-410-20No active metabolitesTemazepam2-310-40Slow oral absorptionTriazolam12-3Rapid onset, short DOA, is affected by inhibitor and inducer CYP3A4Zaleplon