Sedative Hypnotics PCI Pattern
Sedative Hypnotics PCI Pattern
Sedative Hypnotics PCI Pattern
5. Other effects
lead to temporary amnesia
decrease the dosage of anesthetic;
depress respiratory and cardiovascular
fuction.
COMPARISON OF THE DURATIONS OF ACTION OF
THE BENZODIAZEPINES
Classifications
According to Duration of Action :
Chlorazepate Chlordiazepoxide
Diazepam Flurazepam.
Quazepam Prazepam
Nitrazepam
According to uses
Sedative (Anxiolytics)
Alprazolam Chlordiazepoxide
Diazepam Prazepam
Hypnotics
Triazolam
Lorazepam Estazolam Temazepam
Flurazepam Nitrazepam Quazepam
Preanesthetics
Diazepam - Midazolam
Chemical structures of benzodiazepines
MECHANISM OF ACTION
• Benzodiazepines act very selectively on
GABAA-receptors, which mediate the fast
inhibitory synaptic response produced by
activity in GABA-ergic neurons.
Rapid absorption
e.g. triazolam & Alprazolam
diazepam & chlorazepate
Slow absorption
e.g. lorazepam & oxazepam, temazepam
(LOT)
2. Chlorazepate is a prodrug converted by
acid hydrolysis in stomach to form
nordiazepam (desmethyldiazepam).
Reasons:
(1) have a narrow therapeutic-to-toxic dosage
range.
(2) suppress REM sleep.
(3) Tolerance develops relatively quickly.
(4) have a high potential for physical
dependence and abuse.
(5) potent inducers of hepatic drug-
metabolising enzymea.
Chemical structures of barbiturates and
other sedative-hypnotics
MECHANISM OF ACTION
(1) Barbiturates share with benzodiazepines
the ability to enhance the action of GABA,
but they bind a different site on the GABA-
receptor/chloride channel, and their action
seems to prolong the duration of the
opening of GABA-activated chloride
channels.
MECHANISM OF ACTION
(2) At high doses, barbiturates can inhibit the
release of the Ca2+-dependent
neurotransmitter.
Mechanism of Action
1. Facilitation of GABA action on the
brain. increase the duration of the
GABA gated channel opening but in
large dose, they can directly activating
chloride channels. (not through BZD
receptors).
2. depress excitatory neurotransmitter
actions
• Sedative-hypnotic agents
• Be used in the emergency treatment of
convulsions as in status epilepticus.
• Anesthetic (or be given before
anesthetic)
• Combination with antipyretic-analgesic
• Treatment of hyperbilirubinemia and
kernicterus in the neonate.
Adverse effects
• After effect: hangover---dizzy, drowsiness,
amnesia, impaired judgment, disorientation.
imidazopyridine derivative.
acts on benzodiazepine receptors (BZ
1) &
facilitate GABA mediated neuronal
inhibition.
Its action is antagonized by flumazenil.
rapidly absorbed from GIT and
metabolized to inactive metabolites via
liver CYT P450.
Short duration of action ( 2- 4 h).
Only hypnotic effect
Its efficacy is similar to
benzodiazepines.
Minor effect on sleep pattern, but high
doses suppress REM.
Respiratory depression occur at high
doses in combination with other CNS
depressant as ethanol.
has no muscle relaxant effect.
has no anticonvulsant effect.
Minimal psychomotor dysfunction
Minimal tolerance & dependence.
Minimal rebound insomnia.
Uses
a hypnotic drug for short term treatment
of insomnia
Drug interactions
Rifampicin (decreases half life)
Cimetidine (increases half life)
Zaleplon
Rapid absorption
rapid onset of action
Short duration of action (1 hr)
Metabolized by liver microsomal
enzymes
metabolism is inhibited by cimetidine.
Only hypnotic effect
decreases sleep latency
Little effect on sleep pattern
Potentiates action of other CNS
depressants (alcohol).
Dose reduction as before.
Used as hypnotic drug
Advantages
Less impairment of pyschomotor
performance than BZs or zolpidem.
Clinical uses of sedative-hypnotics