SEDATIVE-HYPNOTIC DRUGS

Sedative Hypnotic Drugs

The sedative-hypnotic produce dose dependent
CNS depressant effect
Sedation : Reduction of anxiety
Hypnosis : Induction of sleep
Subgroup :
- Benzodiazepine (Chlordiazepoxide, diazepam,
temazepam)
- Barbiturat (Phenobarbital, pentobarbital,
thiopental)
- Others (buspirone, zolpidem, chloralhydrate,
zaleplon)
Sedative Hypnotic Drugs
Benzodiazepine :
- short acting (triazolam)
- intermediate acting (estazolam,
temazepam)
- long acting (flurazepam, quazepam)

Sedative Hypnotic Drugs
Barbiturates :
- Ultra short acting
- Short acting
- Long acting
Sedative Hypnotic Drugs
(Pharmacokkinetics)

All sedative hypnotic are lipid soluble
and absorbed well from GI tract
Good distribution to the brain in oral
administration
Sedative Hypnotic Drugs
(Metabolism and Excretion)

Metabolized mainly by hepatic enzymes
Many benzodiazepine are converted to
active metabolites
Accumulation of active metabolites can
lead to excessive sedation
The barbiturates are extensively
metabolized,except phenobarbital
Sedative Hypnotic Drugs
(Mechanisms of Action)
BENZODIAZEPINES
Receptors for benzodiazepines (BZ receptors)
are present in the thalamus,limbic
structures,and the cerbralcortex.
Binding of Benzodiazepines facilitates the
inhibitory actions of GABA,which are exerted
through increased chloride ion conductance.
GABA is the major inhibitoric neurotransmitter
in the CNS
Sedative Hypnotic Drugs
(Mechanisms of Action)
Barbiturates
Barbiturates depress neuronalactivity in the
midbrain reticular formation, facilitating and
prolonging the inhibitory effects of GABA
Other drugs
Mechanism of anxiolytic effect of buspirone is
unknown, but buspirone interact with the 5-
HT as partial agonist
Zolpidem & zaleplon interact with BZ1 bind
selectively with GABAA receptor
Sedative Hypnotic Drugs
(Pharmacodynamics)
The CNS effect depend on dose
Effects : sedation & relief of anxiety, through
hypnosis (facilitation of sleep) to anesthesia
and coma
When 2 or more drugs are given
togetherdepressant effect +++
Sedation : sedative action with relief of
anxiety
Hypnosis : promote sleep onset and
duration of the sleep state
Sedative Hypnotic Drugs
(Pharmacodynamics)
Anesthesia : conscious with amnesia &
supressions of reflexes (at highdose). Can
produce by most barbiturates (eg,thiopental)
& certain benzodiazepines (eg,midazolam)
Anticonvulsant actions : supression of seizure
activity (high dose),usually accompany by
sedation effect.
Selective anticonvulsant (supression of
convulsion at dose that do not cause severe
sedation is Phenobarbital, clonazepam
Sedative Hypnotic Drugs
(Pharmacodynamics)
Muscle relaxation : relaxation of skeletal
muscle (at high dose)
Diazepam at sedative dose effective for
spasticity states
Selective muscle relaxant : Meprobomate
Medullary depression :
High dose can cause depression of medullarry
neurons,leading to respiratory arrest,
hypotension & CV collapse death
Sedative Hypnotic Drugs
(Pharmacodynamics)
Tolerance& dependence :
tolerance a decrease in responsiveness, occurs
when used chronically or in high dose

physiologic dependence an altered state that
leads to an abstinence syndrome (withdrawal
state) when the drug is discontinued
Sign : anxiety, tremors,hyperreflexia, seizure
Sedative Hypnotic Drugs
(Clinical Uses)
Anxiety states (alprazolam, clonazepam,
buspirone)
The anxiolityc effect of buspirone occur
without sedation or cognitive impairment
Sleep disorder (estazolam,flurazepam,
triazolam)
Induction of anesthesia (thiopental,
diazepam, midazolam)
Management of seizure disorders
(clonazepam,phenobarbital)
Sedative Hypnotic Drugs
(Clinical Uses)
Management of withdrawal states in
persons physiologically dependent on
ethanol & sedative hypnotics
(chlordiazepoxide, diazepam)
Sedative Hypnotic Drugs
(Toxicity)
Cognitive impairment
Decreased psychomotor skills
Unwanted daytime sedation
Anterograde amnesia
Additive CNS depression
when used with other drugs in the class
(antihistamines,antipsychotic drugs, opioid
analgesics, tricyclic antidepressants)
Overdosage severe respiratory & CV depression
Flumazenil may reverse CNS depressant effect of
benzodiazepines, zolpidem & zaleplon