1. Sedative-Hypnotic Drugs

2. A sedative drug decreases activity, moderates excitement and calms the recipient
A hypnotic drug produces drowsiness and facilitates the onset and maintenance of a state of sleep

3. Sedative (Anxiolytic)
Exert a calming effect,
Reduce tension, nervousness,
fear, and apprehension,
little or no effect on motor or
mental function.

4. Hypnotics Produce state of drowsiness,
promote onset and maintenance of sleep,
Patient can be awakened readily.

5. Drug Classification
Barbiturates
Benzodiazepines
Miscellaneous agents

6. Barbiturates (duration of action)
Ultra Short action (8-10 h)
Thiopental
Short action (10-40 h)
Amobarbital, Secobarbital, pentobarbital
Intermediate action (35-50 h)
Butabarbital
Long action ( h)
Phenobarbital,

7. Benzodiazepines (duration of action)
Ultra Short action (4-6 h)
Triazolam, Midazolam
Short action (12-18 h)
Lorazepam, Oxazepam, Temazepam, Lormetazepam
Intermediate action (24h)
Alperazolam, Nitrazepam
Long action (24-48 h)
Diazepam, Chlordiazepoxide, Florazepam, Clonazepam

8. Pharmacodynamics Both enhance action of GABA by binding to
different site of GABAA receptor/chloride channel
Barbiturates are less specific than Benzodiazepines.
Barbiturates increase the duration but
Benzodiazepines increase the frequency of GABA-
mediated chloride ion channel opening.

9. Pharmacodynamics Barbiturates Block the excitatory transmitter
glutamic acid.
Barbiturates At high concentration block the
sodium channels.

10. GABAA receptors

11. Pharmacokinetics Absorption
Oral absorption of Benzodiazepines depend on lipophilicity
(Triazolam extremely rapid and Diazepam more rapid than others)
Barbiturates are usually absorbed very rapidly
Distribution
The more lipid solubility the more entrance the CNS
(Benzodiazepines: Diazepam & Teriazolam) (Barbiturates:
Thiopental)
Redistribution (Barbiturates: Thiopental)
Protein binding (Benzodiazepines: 60-95%)

12. Pharmacokinetics Biotransformation -Benzodiazepines: Next slide
-Barbiturates: Oxidation & Glucuronide conjugation
Excretion
- Both of them are excreted via the kidney,
% of Phenobarbital and trace amount of benzodiazepines
is excreted unchanged,
- Elimination of barbiturates can be increased by alkalinization of
urine

13. Pharmacokinetic of BZD

14. Pharmacokinetic of BZD

15. Pharmacokinetics Barbiturates: Potent inducer (cytochrome
p450), cause drug interactions & acute
porphyria

16. Pharmacological effects and uses
Sedation
Hypnosis
(decrease in REM duration)
Anesthesia
(Benzodiazepines: midazolam, Barbiturates: thiopental)
Anticonvulsant action
(Benzodiazepines: clonazepam, diazepam, Barbiturates: phenobarbital)

17. Pharmacological effects and uses
Muscle relaxation (Diazepam)
Tolerance & dependence
CNS depression
Hepatic metabolic uses (Phenobarbital in hyperbilirubinemia & kernicterus in neonates)

18. Tolerance to sleep facilitation
Barbiturates weeks
Benzodiazepines 4-6 weeks
Discontinuation
rebound REM Sleep, Psychological
Dependence

19. Benzodiazepines Replaced Barbiturates Benzodiazepine Advantages
-Safer- higher therapeutic index
-Tolerance- lower
-Addictive liability- lower
-Less drug interactions

20. Adverse Effects Unwanted daytime sedation (especially with triazolam)
(especially with Diazepam, flurazepam)
Daytime anxiety and amnesia
(especially with triazolam)
Respiratory and cardiovascular depression
(especially with Barbiturates overdosage)

21. Miscellaneous agents 5-HT1A partial agonists
(Buspirone, Ipsapirone, gepirone)
Alcohols
(Chloral hydrate, glutetimide)
Other BZ receptor agonists
(Zaleplon, Zolpidem)
Others

22. 5-HT1A partial agonists Atypical Anxiolytic
No hypnotic,anticonvulsant or muscle relaxant
Acts at 5-HT1A (partial agonist) and Dopamine
receptors
Does not produce tolerance and physical dependence
Side effect:
nausea, dizziness, headache, tachicardia,…

23. Alcohols Chloral Hydrate: Metabolized to trichloroethanol
Short duration
No enzyme induction
Tolerance/Dependence Withdrawal can
be severe

24. BZ receptor agonists Not a benzodiazepine but binds to BZ receptor
(Zolpidem…)
Not a benzodiazepine but binds to BZ receptor
Minimal muscle relaxing & anticonvulsant effect
Good hypnotic, with less effects on stages of sleep
Can suppress REM in higher doses
Low incidence of rebound insomnia, daytime
sedation

25. BZ receptor agonists Side effects: -Respiratory depression
-Tolerance less than Benzodiazepines

26. Others Meprobamate RARELY if ever used, Similar to Barbs.
Beta- Blockers
useful in alleviating performance anxiety.

27. Flumazenil Benzodiazepine competitive Antagonist,
no activity in its own right
It reverse CNS depressant effect of
Benzodiazepines, Zolpidem and Zaleplone
Ineffective for most other sedatives

28. Side effects of Flumazenil
Agitation
Confusion
Dizziness
Nausea
Seizure & cardiac arrhytmia (patient treated with TCA)
Transient improvement in mental status has been reported in patient with hepatic encephalopathy