Sleep medication for insomnia

• In general, a sedative-hypnotic drug for the

management of insomnia should be
prescribed only as a short-term aid during an
illness or some unusual circumstance, i.e., for
acute insomnia.
• For patients who have difficulty falling asleep,
a quick-acting, fairly rapidly metabolized
hypnotic is useful
 Perbedaan sedative & hypnotic drug

• Sedative (anxiolytic)  reduce anxiety and

exert a calming effect
• Hypnotics  produce drowsiness and
encourage the onset and maintenance of a
state of sleep
 Sedative-hypnotics drug
• Benzodazepine (BZD)
• barbiturates
• other hypnotics
 benzodiazepine
• Widely use sedative-hypnotics
• Replace barbiturates meprobamate in the
treatment of anxiety and insomnia, because
benzodiazepines are generally considered to
be safer and more effective
• Composed : benzene ring & diazepine ring

• Classification :
– Long acting (1-3 hari) diazepam, flurazepam,
clonazepam, chlordiazepoxide
– Intermediate acting (10-20 jam) alprazolam,
estazolam, temazepam, lorazepam, nitrazepam
– Short acting (3-8 jam) triazolam, oxazepam,
midazolam
 MoA
• Bind to specific GABAa receptor subunits at
central nervous system (CNS) neuronal
synapses facilitating frequency of GABA-
mediated chloride ion channel opening—
enhance membrane hyperpolarization
 effects
• Reduce anxiety  inhibiting neuronal circuits
in limbic system brain
• Sedative & hypnotic
• Anterograde amnesia  temporary
impairment of memory
• Anticonvulsant
• Muscle relactant  increasing presynaptic
inhibition in spinal cord
 indikasi
• Anxiety disorder (panic disorder, generalized
anxiety disorder (GAD), social anxiety disorder,
performance anxiety, posttraumatic stress
disorder, obsessive–compulsive disorder, and
extreme anxiety associated with phobias, such
as fear of flying.)
• Sleep disorder benzodiazepine decrease
latency to sleep onset & increase NREM 2
• kejang
 contraindikasi
• Gangguan hati
• Miastenia gravis
• Depresi pernapasan
• Hipersensitivitas terhadap benzodiazepine
• Trimester pertama kehamilan
• Acute angle-closure glukoma
 Efek samping
• Mengantuk
• Kelemahan otot
• Ataksia
• Amnesia
• Ketergantungan (down regulation of GABA
receptor)
• Gangguan mental
• bingung
 Drug interaction
• Additive CNS depression with ethanol & other
CNS depressant
• Enzyme inhibitor (ketoconazole)  enhance
BZD receptor
• Smoking & aminophyline  antagonises BZD
receptor
 barbiturates
• formerly the mainstay of treatment to sedate
patients or to induce and maintain sleep
• replaced by the benzodiazepines, primarily
because barbiturates induce tolerance and
physical dependence and are associated with
very severe withdrawal symptoms
 moa
• Bind to specific GABAA receptor subunits at
CNS neuronal synapses increasing duration of
GABAmediated chloride ion channel opening •
enhance membrane hyperpolarization
 effect
• Depression on CNS : sedation, hypnosis,
anesthesia
• Respiratory depression : suppress hypoxic &
chemoreceptor to co2
 PK
• High lipid solubility cross BBB & result in short
onset
• Distribution to other tissue
• Metabolizes in liver
• Inactive metabolite excreted in urine
 indikasi
• Anesthesia  thiopental
• Anticonvulsant  phenobarbital
• Sedative/hypnotic  insomnia, relieve anxiety
 classification
• Long acting (1-2 hari) :
phenobarbital
• Short acting (3-8 jam) :
pentobarbital, secobarbital,
amobarbital
• Ultra short acting (20 menit) :
thiopental
 Efek samping
• Addiction
• Drowsiness
• Nausea
• Vertigo
• Tremor
• Enzyme induction CYP450
(diminished action drug that
metabolize in CYP450)
 contraindikasi
• Insomnia yang disebabkan oleh nyeri
• Hamil
• Menyusui
• Gangguan hati
• Hipoksia
• Hipersensitivitas terhadap barbiturate
 Other hypnotic
• Zolpidem
• Zaleplon Non Benzodiazepine Hypnotics
• Eszopiclon (newer hypnotic)
• Ramelteon
• Antihistamin
• Antidepressant
 Non benzodiazepine
• not benzodiazepines per se, but they act on
the same benzodiazepine and gamma
aminobutyric acid-a receptors
• have more selective hypnotic effects.
• MoA : BZD receptor – alpha 1 subunit
• Effect : antianxiety, sedative, don’t altered
REM sleep patern, minimal day time
sleepiness, risk tolerance much less than BZD
 ramelteon
• Melatonin receptor agonist
• Moa : Activates MT1 and MT2 receptors in
suprachiasmatic nuclei in the CNS
– MT1  promotes onset of sleep
– MT2  shift timing circadian sistem
• Indication : transient & chronic insomnia
• Dosage : 8 mg tablet taken 30 minutes before
bedtime
• Efek samping : dizziness, somnolence, fatigue,
and endocrine changes as well as decreases in
testosterone and increases in prolactin.
 antihistamin
• Some antihistamines with sedating properties,
such as diphenhydramine (benadryl),
hydroxyzine (atarax), and doxylamine, are
effective in treating mild types of situational
insomnia.
• MoA : competitive antagonis histamin H1
receptor within CNS
• Efek samping : dry mouth, urine retention,
blurred vision, impotensi
 antidepressan
• Depresi  defisiensi aminergic
neurotransmitter (serotonin, norepinephrine,
dopamin)
• Moa : inhibit re-uptake neurotransmitter &
inhibit degeneration of neurotransmitter by
monoamine oxidase
• Obat : trazodone, tricyclic, SSRI (selective
serotonin reuptake inhibitor)
• Trazodone : sedating, improve sleep continuity, increase slow-
wave sleep
• Tricyclics (amitriptyline & doxepin) : improve sleep continuity,
reduction REM sleep
• Newer generation  selective serotonin reuptake inhibitor
(SSRI) such as fluoxetine & sertraline, may produced insomnia
• Small doses  treating insomnia than depression
• Can be very helpful in sleep disturbances with depressed
patient
• Very few studies have examined the efficacy and safety of
those agents when used as hypnotics with non-depressed
insomniacs. Therefore, antidepressants are not
recommended as the first line of treatment for primary
insomnia.