SEDATIVES AND HYPNOTICS

1. Sedatives and Hypnotics
Classification
PREPARED BY :
Ms. PRIYA PATEL,
4th SEM B.PHARM.
SVBIP.
GUIDED BY:
Ms. KHUSHBU B. PATEL,
ASSISTANT PROFESSOR,
P’CEUTICAL CHEMISTRY
DEPT.
SVBIP.

2. SEDATIVE & HYPNOTICS
Sedative :
● Sedative are the drugs that cause decrease in physical and
mental activities.
● Drugs that clam the patient and reduce anxiety without
inducing normal sleep
Hypnotics :
● Hypnotics are the used mainly to produce a sleep. Drug
that initiate and maintain the normal sleep.

3. Sedative and Hypnotics
Barbiturates Benzodiazepines (BZDs)
a : Long acting BZDs
b : Short acting BZDs
Non-benzodiazepine
agonists at BZD
receptors
Imides Alcohols Miscellaneous

4. CLASSIFICATION OF SEDATIVE HYPNOTICS
 Barbiturates have been popular hypnotics and sedatives
up to 1960s, but are not used nowadays to promote sleep
or calm patients. However, they are the prototype of CNS
depressants.
 Barbiturates are substituted derivatives of barbituric acid.
 Barbituric acid is chemically pyrimidine-2,4,6-trione,
synthesized from urea and malonic acid.
I. Barbiturates :

5. Urea
Malonic acid Barbituric acid

6.  The reticular activating system (Responsible for
wakefulness and sleep-awake transition) is most sensitive to
be depressed by barbiturates.
 Smaller dose of a long acting barbiturate given at daytime
produce sedation.
 Larger dose of a short acting barbiturate given at night-time
produce hypnosis.
 They disrupt the balance between REM : NREM sleep by
decreasing the duration of REM sleep. Hence on
withdrawal, there is a rebound increase in REM sleep
duration resulting into bad dreams and nightmares.
 Relatively higher doses cause respiratory and
cardiovascular depression.

7. Mechanism of action :
 Barbiturates bind to the barbiturate receptors, located
either on α or β subunit of GABA benzodiazepine
receptor-chloride channel complex and potentiaste the
GABA mediated opening of CГ channel (GABA
facilitatory effect).
 At higher concentrations, they directly open the CГ
channel (GABA mimetic effect.)
 Opening of CГ channel  Increased CГ influx  Hyper
polarization  Inhibition of initiation of action potential
 CNS inhibition.

9. II. Benzodiazepines (BZDs)
● Benzodiazepines are used as daytime anxiolytics,
hypnotics, anticonvulsants, anesthetics and muscle
relaxants.
● The advantages of BZDs over barbiturates as sedative
hypnotics are –
• BZDs have a high therapeutic index. Hypnotic doses do
not affect respiration or cardiovascular functions.
• BZDs cause mild suppression of REM sleep.
• They have lower abuse liability, tolerance, dependence
and withdrawal syndrome.
• A specific BZD antagonist Flumazenil is available which
can be used in case of BZD poisoning.

10. Mechanism of Action :
 BZDs bind to the BZD receptor, located between α an ϒ
subunit of GABAA benzodiazepine receptor-chloride
channel complex and potentiate the GABA mediated
opening of CГ channel (GABA facilitatory effect).
 Opening of CГ channel  increased CГ influx  Hyper
polarization inhibition of initiation of action potential
 CNS inhibition.

11. a ) : Long acting BZDs :
 These BZDs are slowly eliminated or are metabolized to
slowly eliminated active metabolites.
 As a result of their slow elimination, there is
accumulation of drug or its active metabolite (s) in blood
and brain on repeated use. This is responsible of the
residual effects in the daytime, which are hangover effects
or over sedation.

12. Diazepam
● Diazepam produces active metabolite by N-dealkylation
and then hydroxylation.

14. Synthesis of Diazepam

15. Flurazepam
●It is absorbed most rapidly.
●It is primarily metabolized by N-dealkylation and hydroxylation
to active metabolites.

16. Quazepam

17. ●Quazepam is metabolized by oxidative desulfurization
and N-dealkylation to give active metabolites.
●Both flurazepam nad quazepam form active metabolites
that are slowly eliminated and are associated with slow
development of tolerance to the hypnotic effects.
●Both these drugs exhibit good efficacy as hypnotics with
long-term use.

18. Nitrazepam
●Nitrazepam has elimination half-life of 30 hours. It does
not give active metabolites.

19. Clorazepate :

20. b) : Short acting BZDs :
 On development of the newer triazolo-benzodiazepines,
such as estazolam and triazolam, it was anticipated that
the problem of daytime sedation would be eliminated.
 These drugs have high receptor binding affinity and more
rapid elimination.
 These drugs do not give active metabolites.

21. ●Because of their short duration of action, they often
produce withdrawal symptoms on next day-rebound
anxiety, tenseness and early morning insomnia.
Estazolam Triazolam

22. ●The elimination half-life of triazolam is less than 4 hours.
Temazepam
Absorbed very slowly

23. III. Non-benzodiazepine agonists at
BZD receptors :
●This new class of sedative-hypnotics bind to the same BZD
receptors, where BZDs do bind.
●They have short duration of action. So they do not have
residual side effects (Day time sedation).
●In spite of short duration, they do not produce withdrawal
syndromes (Rebound anxiety, insomnia).

24. ●These agents are very lipophilic, facilitating their
rapid absorption.
●These agents are used for short term insomnia.

25. IV. Imides
Glutethimide
●It was discovered as a safe alternative to barbiturates to
treat insomnia. But, it causes addiction and withdrawal
symptoms as likely as barbiturates.

26. V. Alcohols :
Ethchlorvynol
● It has been largely replaced by other drugs.

27. VI. Miscellaneous
● It is used rarely for treating insomnia.
Triclofos Sodium

28. Paraldehyde
● It is cyclic trimer of acetaldehyde.