Pembagian obat-obat yang bekerja

pada reseptor GABA

US (T1/2 < 2 hrs) Short ( < 6 hrs) IM ( 6-24 hrs) LA ( > 24)
Midazolam Triazolam Alprazolam Diazepam
Tiopental Zolpidem Lorazepam Quazepam
Estazolam Chlordiazepoksid
Temazepam
oxazepam
 Benzodiazepin untowards effect
• lightheadedness,
• lassitude,
• increased reaction time,
• motor incoordination,
• impairment of mental and motor functions,
confusion,
• anterograde amnesia.
• Cognition appears to be affected less than motor
performance
Benzodiazepin Psychological effect
• risk for development of dependence and
abuse
• Mild dependence may develop in many
patients who have taken therapeutic doses of
benzodiazepines on a regular basis for
prolonged periods.
• anxiety, irritability, tachycardia, and sweating.
Amnesia, euphoria, restlessness,
hallucinations, and hypomanic behavior
Gol. Agonis Melatonin

• The SCN express high levels of MT1 and MT2

receptors
• MT1 and MT2 receptors are believed to be
involved in maintenance of the sleep-wake
cycle
– Activation of MT1 receptors inhibits neuronal
firing
– Activation of MT2 receptors helps entrain the
circadian clock via phase synchronisation

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 Targeting MT1/MT2 Receptors
• Agents with high affinity and selectivity for
MT1
and MT2 receptors could provide novel
treatments for sleep and circadian rhythm
disorders
– With a favourable side effect profile
• Ramelteon is a highly selective and potent
agonist of MT1/MT2 receptors
5
 Chloral hydrate
• barbiturate-like effects on GABAA-receptor
channels in vitro
• for the production of sedation in children
undergoing diagnostic, dental, or other
potentially uncomfortable procedures.
hepatic damage; parenchymatous renal injury
• Produce less beta wave in EEG sedation
procedure in children
 First line drugs  GABA (select/non select)

Drug Chemical Class Recommendended T1/2 (hr) Receptor

dose (mg) in adults; Binding
in Older Adults

Estazolam Cyclopyrrolone 2; 1 8-24 Nonselective

Eszopiclone Benzodiazepine NDA, under FDA 5-7 Nonselective
review
Flurazepam Pyrazolopyrimidine 30; 15 48-120* Nonselective
Indiplon Benzodiazepine Under development 1.0-1.5 GABAA alpha 1
Quazepam Benzodiazepine 7.5 – 15; same 48-120* Nonselective
Temazepam Benzodiazepine 30; 15 8-20 Nonselective
Traizolam Pyrazolopyrimidine 0.25; 0.125 2-4 Nonselective
Zaleplon Imidazopyridine 10; 5 -1.0 GABAA alpha
1, gamma 3
Zolpidem 10;5 1.5-2.4 GabaA alpha 1

The benzodiazepine receptor agonists listed have an FDA indication for treatment of insomnia, or they are currently in phase
3 clinical trials.
*Refers to elimination half-life of active metabolite, desalkyflurazepam
FDA, US, food and Drug Administration GABAA, gamma-aminobutyric acid, type A receptors, NDA, new drug application. 7
 Tatalaksana
Insomnia
• Identifikasi
penyebab
insomnia
• Non farmakologis
– Sleep higiene
– Hindari kafein
• Farmakologis
 Penyebab Insomnia

Difficulty in initiating Difficulty in Early morning waking

sleep maintaining sleep
Poor sleep hygiene Pain, discomfort. Old age
Poor sleep envirenment Poor sleep environment Poor sleep environment
Drugs Drugs Drugs
Anxiety Medical problem, e.g. Depression
asthma, nocturia
Psychophysiological PLMS Mania
insomnia OSA, CSA, CSR ASPS
PLMS Dementia
DSPS Psychophysiological
insomnia

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 Sleep Hygiene
• Optimalkan suasana terkait tidur
– ruang tidur yang nyaman dan agak redup
– kamar tidur hanya untuk tidur dan seks
– tidak terlalu kenyang atau lapar saat tidur
– relaksasi dan hindarkan stress

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 Pemilihan obat Sedatif-Hipnotik
• Secara umum benzodiazepin intermediate acting,
zolpidem lebih terpilih untuk gangguan tidur karena
profil keamanannya, beberapa pertimbangan lain.
• Gangguan irama sirkardian
– Ramelteon, melatonin
• Ansietas
– Intermiediate – long acting benzodiazepin
• Depresi
– Antidepresan
• Non spesifik
– antihistamin