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
togetherdepressant 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