OBAT HIPNOTIKSEDATIF

Fathiyah Safithri
Laboratorium Farmakologi FK-UMM

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Abnormalities of sleep

Insomnia
Causes - noise, worries, stress, drugs, pain,

uncomfortable temperature, disease, etc.

Types
onset insomnia - trouble falling asleep
maintenance insomnia - awaken frequently during the
night
termination insomnia - wake up too early and cannot
get back to sleep

Hipnotic agents

Hypnotic
Agents That Act by Enhancing

GABA
Hypnotic Agents That Act by Blocking
Wake-Promoting Neurotransmitter
Systems

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Benzodiazepin

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BARBITURAT

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A Crucial Difference
barbiturate

benzodiazepine

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Benzodiazepin

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Mechanism:
Increase the frequency of opening
of the GABAreceptor, thereby
increasing the effect of GABAmediated hyperpolarization. Also
increase GABAbinding.

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Benzodiazepine effects
Therapeutic:

Adverse:

Anxiolytic (diazepam,
alprazolam)

Cognitive impairment, decreased motor

skills, daytime sedation

Hypnotic (triazolam)

Additive CNS depression (ethanol,

antihistamines, opioids)

Muscle relaxant
(diazepam, lorazepam)

Dependence

Anticonvulsant
(diazepam, lorazepam,
clonazepam)
Sedation (midazolam)

Behavioral disinhibition (paradoxical)

Anterograde amnesia
Abrupt withdrawal panic attack,
rebound anxiety

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Anxiolytic and Hypnotic Drugs

1. Sedasi: arousal, behaviour, alertness, response

to stimuli
2. Hypnotic:
- Semua sedative/hypnotics pada dosis besar
menyebabkan tidur.
- Normal sleep terdiri dari beberapa stage (berdasarkan
3 ukuran :electroencephalogram, electromyogram,
electronystagmogram.
- Ada 2 phases yang terjadi secara siklik tiap 90 min:
1) Non-rapid eye movement (NREM). 70-75% dari total
sleep.
Ada 4 stages. Hampir semua tidur stage 2.
2) Rapid eye movement (REM). Fase mimpi (dreams).

Hypnotic
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 terjadinya
somnambulismdan nightmares occur)
Efek tolerance terjadi setelah 1-2 minggu (BARBITURAT),
4-6 MINGGU (Benzodiazepin
Benzodiazepin)
Penghentianmendadak meningkatkan fase REM sleep
(reboundeffects)
REM sleep ( (55-HT dan NE activity di RAS

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Perubahan fase tidur setelah

pemberian obat hipnotic

3. Anesthesia:
Dosis besar menghilangkan kesadaran, amnesia
(anterogade amnesia), dan hilangnya reflex
Beberapa BARBs (Thiopental) dan BZDs (Midazolam)
menyebabkan anestesia
4. Antieplepsi:
Efek antiepilepsi sebaiknya dibawwah efek sedasi
Phenobarbital,Diazepam,Lorazepam dipakai pada
status epilepticus
5.Relaksasi otot bergaris (Muscle Relaxant):
Semua sedative-Hypnotic dosis besar relaksasi
otot bergaris
Diazepam dosis sedasi muscle relaxant
6.Medullary Depressant:
Dosis besar menekan neuron di medulla repiratory
arrest, hypotensi,cardiovascular collapsfatal

7. Tolerance dan Drug Dependence:

Menyebabkan terjadinya :
tolerance, psychological dependence, physical
dependence
Penghentian mendadak menyebabkan
abstinencia syndrome (anxiety, hyperreflexia, seizure)
Sering pada golongan short-acting (Pentobarbital,
Secobarbital)
Buspirone tidak menyebabkan ketergantungan obat

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Mechanism:
Prolongs the open time of the
GABAreceptor (a chloride
channel), thereby increasing the
effect of GABA-mediated
hyperpolarization.

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Barbiturat effects
Therapeutic:
Anticonvulsant (phenobarbital)
Anesthesia (thiopental)
Sedative-hypnotic (pentobarbital)

Adverse (narrow margin of safety):

Respiratory depression
Abuse potential and dependence
P-450 enzyme induction drug interactions
Interferes with REM sleep

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Obat-obat lain

Antidepressan(antiH1,

Antagonis5HT2)
Zolpidem
Chloralhydrate
Hydroxyzine
Meprobamate(miripBARBS)

Zolpidem

Merupakan turunan Imidazopyridine (bukan BZDs)).

Pengobatan untuk insomnia profil mirip Triazolam
Efek : muscle relaxant dan anticonvulsant sangat lemah, hang over
(-), addiksi (-), rebound insomnia (-)
Metabolisme di liverinactive metabolites (t :3-5 j)j)..
Onset cepat, waktu paruh pendek
Dosis harus dikurangi pada penderita dgn hepatic dysfunction,,usia
lanjut, dan penderita yang menggunakan cimetidine.

Kombinasi dengan TCA,Antipsychotic,Antihistaminedepresi SSP

meningkat
Agonist selektif thd BZ1 receptors.
Mekanisme
kerja : Facilitates GABA--mediated neuronal inhibition.
Menyebabkan
Efek diantagonist oleh Flumazenil

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Anxiolitics

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Buspirone (buspar)
Golongan anxiolytic yang relatif baru
Mengurangi symptom anxiety (2-4 minggu)
Mekanisme

kerja:

partial agonist pada presynaptic 5-HT1Areceptor

(dorsal raphe nuclei, cerebral cortex, amygdala)

Metabolite-nya:1-PP mempunyai blokade 2 -AR.
Derivat baru : Gepirone, Ipsapirone,Tandospirone

Buspirone

Mengurangianxiety
Indikasi : kecemasan yang disertai depresi
Efek : sedasi (-), gangguan motor (-), antiepilepsi (-) dan
muscle relaxant (-), addiksi (-), toleransi (-), rebound
anxiety (-)/withdrawl(-)
Mula kerja 1 4 minggu
Kombinasi dengan MAO tekanan darah naik
Tidak mengadakan potentiasi thd CNS depressants.
Margin of safety sangat lebar
ESbingung
: ringan, mual, muntah, sakit kepala, pening, gelisah,

Farmakokinetik buspirone
Pemberian p.o absorpsi cepat
Mengalami metabolisme di hepar (hydroxylation dan

dealkylation) beberapa active metabolites (e.g. 1(2-pyrimidyl-piperazine, 1-PP)

Dapat ditolerir pada usia lanjut, ttp mempunyai kliren
lambat

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