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Fathiyah SafthriLaboratorium Farmakologi FK-UMM
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OBAT HIPNOTIK-
SEDATIF
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Insomnia
Causes - noise, worries, stress, drugs, pain,uncomfortable temperature, disease, etc.
Types
& onset insomnia - trouble falling asleep
& maintenance insomnia - awaken frequently during thenight
& termination insomnia - wake up too early and cannotget back to sleep
Abnormalities of sleep
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Hypnotic Agents That Act by Enhancing
ABA Hypnotic Agents That Act by B!oc"ing#a"e-Promoting Ne$rotransmitterSystems
Hipnotic agents
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Benzodiazepin BARBITURAT
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A %r$cia! Di&erence
barbiturate
benzodiazepine
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Ben'o(ia'epin
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Mechanism:
Increase the frequency of opening
of the GABAreceptor, thereby
increasing the effect of GABA-
mediated hyperpolarization. Also
increase GABAbinding.
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Therapeutic!
'Anxiolytic diazepam,
alprazolam!
'"ypnotic triazolam!
'Muscle relaxant
diazepam, lorazepam!
'Anticon#ulsant
diazepam, lorazepam,
clonazepam!
'$edation midazolam!
Adverse:
'%ogniti#e impairment, decreased motor
s&ills, daytime sedation
'Additi#e %'$ depression ethanol,
antihistamines, opioids!
'(ependence
'Beha#ioral disinhibition paradoxical!
'Anterograde amnesia
'Abrupt )ithdra)al panic attac&,
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Benodiaepine e!ects
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Anxiolytic and Hypnotic Drugs
(# )e$asi! ↓ arousal* ↓ behaviour* ↓alertness* ↓ response
to stimuli
+# ,ypnotic!
- )emua se$ative"hypnotics pa$a $osis besar
menyebabkan ti$ur#
- ormal sleep ter$iri $ari beberapa stage ber$asarkan
. ukuran !electroencephalogram* electromyogram*
electronystagmogram#
- /$a + phases yang ter0a$i secara siklik tiap 12 min!(% on-rapi$ eye movement 34M%# 52-567 $ari total
sleep#
/$a 8 stages# ,ampir semua ti$ur stage +#
+% 3api$ eye movement 34M%# Fase mimpi $reams%#
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a! Menurunkan latency of sleep (waktu yang diperlukan untuk
mulai tidur).
b) Meningkatkan lama tidur stage 2 NREM
c) Memperpendek fase REM sleep
d) Memperpendek fase slow wave sleep (fase ter!adinya somnambulismdan nig"tmares occur)
Efek tolerance ter!adi setela" #2 minggu ($AR$%&'RA&)
($enodiaepin*+ M%N,,' $enodiaepin)
-eng"entianmendadak meningkatkan fase REM sleep(reboundeffects)
REM sleep ( (/& dan NE activity di RA0
,ypnotic
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"erubahan fase tidur setelahpemberian obat hipnotic
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3. Anesthesia:
Dosis besar enghilang!an !esadaran" anesia
#anterogade anesia$" dan hilangnya re%lex
Beberapa BARBs #Thiopental$ dan B&Ds #'idazola$
enyebab!an anestesia
(. Antieplepsi:
)%e! antiepilepsi sebai!nya diba**ah e%e! sedasi
+henobarbital"Diazepa",orazepa dipa!ai pada
status epilepticus
-.Rela!sasi otot bergaris #'uscle Relaxant$:
eua sedati/e0Hypnotic dosis besar rela!sasi
otot bergarisDiazepa dosis sedasi uscle relaxant
1.'edullary Depressant:
Dosis besar ene!an neuron di edulla repiratory
arrest" hypotensi"cardio/ascular collaps%atal
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2. Tolerance dan Drug Dependence:
'enyebab!an teradinya :tolerance" psychological dependence" physical
dependence +enghentian endada! enyebab!an
abstinencia syndroe #anxiety" hyperre%lexia" seizure$
ering pada golongan short0acting #+entobarbital"ecobarbital$Buspirone tida! enyebab!an !etergantungan obat
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Mec"anism:
-rolongs t"e open time of t"e
,A$Areceptor (a c"loride
c"annel) t"ereby increasing t"e
effect of ,A$Amediated
"yperpolariation.
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Therapeutic!
'Anticon#ulsant phenobarbital!
'Anesthesia thiopental!'$edati#e-hypnotic pentobarbital!
Adverse (narrow margin of safety):
'*espiratory depression
'Abuse potential and dependence
'-/ enzyme induction drug interactions
'Interferes )ith *0M sleep
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Barbiturat e!ects
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Antidepressan#antiH$,
Antagonis%HT&' (olpidem Chloralhydrate Hydro)yine
*eprobamate#miripBA+B'
bat-obat lain
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Zolpidem
!.1
1
1
1
1
1
Merupa&an turunan Imidazopyridine bu&an B2(s!engobatan untu& insomnia profil mirip 3riazolam
0fe& : muscle relaxant dan anticon#ulsant sangat lemah, hang o#er
-!, addi&si -!, rebound insomnia -!
Metabolisme di li#erinacti#e metabolites t 4 :5- 6!6!..
7nset cepat, )a&tu paruh pende&
(osis harus di&urangi pada penderita dgn hepatic dysfunction,,usia
lan6ut, dan penderita yang mengguna&an cimetidine.
8ombinasi dengan 3%A,Antipsychotic,Antihistaminedepresi $$
mening&at
Me&anisme &er6a :1 Agonist sele&tif thd B2+ receptors.
1 Menyebab&an 9acilitates GABA--mediated neuronal inhibition.
1
0fe& diantagonist oleh 9lumazenil
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An)iolitics
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,olongan an1iolytic yang relatif baru
Mengurangi symptom an1iety (2* minggu)
Mekanisme ker!a:partial agonist pada presynaptic /Areceptor
(dorsal rap"e nuclei cerebral corte1 amygdala)
Metabolitenya:#-- mempunyai blokade 2 AR.
erivat baru : ,epirone %psapirone&andospirone
Buspirone #buspar'
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1
1
1
1
1
1
1
1
Mengurangian1iety
%ndikasi : kecemasan yang disertai depresi
Efek : sedasi () gangguan motor () antiepilepsi () dan
muscle rela1ant () addiksi () toleransi () reboundan1iety ()3wit"drawl()
Mula ker!a # 4 * minggu
5ombinasi dengan MA6 tekanan dara" naik
&idak mengadakan potentiasi t"d 7N0 depressants.Margin of safety sangat lebar
E0 : ringan mual munta" sakit kepala pening gelisa"bingung
Buspirone
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1
1
emberian p.o absorpsi cepat
Mengalami metabolisme di hepar hydroxylation dan
deal&ylation! beberapa acti#e metabolites e.g. +-;-pyrimidyl-piperazine, +-!
1 (apat ditolerir pada usia lan6ut, ttp mempunyai &liren
lambat
armakokinetik buspirone
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