SEDATIVES AND HYPNOTICS

Dr. Heethal Jaiprakash

Pharmacology and therapeutics
Email:heethaljaiprakash@imu.edu.my
(Extension-1223)
Lesson Outcomes
On completing this lecture, you should be able to:
Classify sedative-hypnotic drugs and state prototype drug for each drug
class.

Explain the general mechanism of action of sedative-hypnotic drugs.

Describe pharmacokinetics and pharmacodynamics of barbiturates

(phenobarbital) and the common/major adverse effects.
Describe the important pharmacokinetic features and pharmacodynamics of
benzodiazepines (diazepam, midazolam, lorazepam) and list their
common/major adverse effects.
Explain why benzodiazepines are preferred over barbiturates for the
treatment of insomnia.
Lesson Outcomes
On completing this lecture, you should be able to:

Describe the important pharmacokinetic features and pharmacodynamics of new

hypnotic drugs (zolpidem) and list their common/major adverse effects.

Classify anxiolytics according to their mechanism of action.

Discuss the pharmacokinetics and pharmacodynamics of buspirone and its

common/major adverse reactions.
What is happening
in these pictures?
Sedative :
Reduces
excitement
Calms down
No sleep but
drowsiness

Hypnotic :
Induces or
maintains sleep
like normal
arousable sleep
Classification :
1. Barbiturates :
Phenobarbitone(long acting), thiopentone(Ultra short acting)
2. Benzodiazepines :
Diazepam(long acting), Lorazepam(Intermediate acting),
Midazolam(short acting)
3. Newer nonbenzodiazepine hypnotics(Z drugs):
zolpidem
4. Atypical anxiolytics:
Buspirone
5. Beta adrenoceptor antagonists(non-sedative anxiolytics):
Propranolol
Anxiolytics :
• Sedative-hypnotics: BZD: diazepam, lorazepam, oxazepam

• Non-sedating Anxiolytic: 5HT1A –agonist: buspirone

• Anti-depressants: SSRIs (Fluoxetine), SNRI,(venlafaxine)-

WILL BE COVERED IN ANTIDEPRESSANTS

• Beta blockers: propranolol

Mechanism of action of benzodiazepines

GABA facilitatory effect

Mechanism of action of barbiturates

GABA mimmetic effect

Difference in the mechanism of action of BZD and
Barbiturates
Benzodiazepines Barbiturates
• They prolong the
• Increase frequency of
duration of chloride
chloride channel opening
channel opening
• GABA facilitatory effect
• GABA mimetic effect
• Block the excitatory
glutamate receptors

Both act on GABA : BZD receptor –CL- complex

Both act on GABA A receptors
 Pharmacological actions of barbiturates and benzodiazepines
Barbiturates Benzodiazepines
• Disrupt the Balance between •Less distortion of sleep architecture. Hasten
REM:NON-REM onset of sleep.

• CVS: effect on CVS function •No effect CVS or respiratory functions

•Has high therapeutic index

• Respiration: risk of respiratory
depression •No enzyme induction

• Enzyme inducer •Low abuse liability

•Specific antidote-Flumazenil

•Anterograde amnesia(automatism)
A patient with insomnia was prescribed diazepam. Which
one of the following mechanisms is responsible for its
use in insomnia?

A. Prolongation of the duration of chloride channel

opening
B. GABA mimetic effect
C. Blocking of glutamate receptors
D. Increase frequency of chloride channel opening
 Adverse effects of barbiturates and benzodiazepines
Barbiturates Benzodiazepines

Hangover
Drowsiness

Tolerance and dependence
Impairment of psychomotor functions

Abuse liability
Tremors , delirium

Withdrawal symptoms
Flunitrazepam(date rape drug)-

Respiratory depression
sedative amnestic effect

Amnesia
Drug interaction: Potentiates the

Drug interaction: Reduce
effects of other CNS depressants
effectiveness of oral contraceptives,
anticoagulants
 Uses of barbiturates and
benzodiazepines
Barbiturates Benzodiazepines
Anesthesia
Anxiety
Anticonvulsant
Insomnia

Preanesthetic medication and

induction of anesthesia
Skeletal muscle relaxant

Anticonvulsant
 Treatment of barbiturate and
benzodiazepine overdose
Barbiturates Benzodiazepines
Gastric lavage Gastric lavage
Supportive measures Supportive measures
Forced alkaline diuresis- Specific antidote-Flumazenil
mannitol, sodium bicarbonate
 BZD has
high
therapeutic
index
Has
Less
specific
distortion of
antidote
for Advantages of sleep
benzodiazepines architecture
poisoning
over
barbiturates

No
Low
enzyme
abuse
induction
liability
property
Which of the following drugs is contraindicated in
a patient with acute porphyria?

A. Phenobarbitone
B. Midazolam
C. Propofol
D. Diazepam
 Zolpidem

Agonist at GABA receptor


Short term treatment of insomnia

Its advantages are:


No effect on stages of sleep-Minimal day time sedation


No / little rebound insomnia on stoppage


Rarely causes tolerance or physical dependence- Low abuse potential


Short half life-less hangover
 Buspirone
They act through non-GABAergic systems

They act as partial agonist at brain 5HT 1A receptors

IT IS AN ANXIOLYTIC AND NOT A HYPNOTIC DRUG

Used in anxiety

Less abuse liability, impairment of psychomotor skills

No withdrawal reactions

Propranolol :

It decreases the symptoms of sympathetic over activity due to

anxiety

JUST REDUCES SYMPTOMS NOT ANOXIOLYTIC OR HYPNOTIC

Flumazenil :
It is a benzodiazepine antagonist

Action starts in a second and lasts for 1-2 hrs

Use to reverse the action of BZD employed for IV anaesthesia

Antidote for BZD poisoning

This hypnotic drug facilitates the inhibitory actions
of GABA but has no anticonvulsant or muscle
relaxation property and has minimal effect on
sleep architecture

A. Diazepam
B. Buspirone
C. Zolpidem
D. Phenobarbitone
 Summary

Benzodiazepines Barbiturates Other drugs

• Increase frequency of • They prolong the • Zolpidem less hangover
chloride channel duration of chloride • Buspirone is an anxiolytic
opening channel opening
• Propranolol only reduces
• GABA facilitatory • GABA mimetic effect symptoms of anxiety
• Anterograde amnesia • Distorts sleep
• Antidote- Flumazenil architecture
• Enzyme inducer
 Knowledge check-True or false
Flumazenil is the antidote for barbiturate poisoning:

Phenobarbitone has GABA mimetic effect:

Diazepam is an enzyme inducer:

Phenobarbitone causes anterograde amnesia:

Zolpidem has high potential to cause hangover:

SUMMARISE
Q&A
 References
Prescribed textbook

• Brunton L.L., & Hilal-Dandan R, & Knollmann B.C.(Eds.), (2017). Goodman &
Gilman's: The Pharmacological Basis of Therapeutics, 13e. McGraw-Hill.
https://accessmedicine-mhmedical-com.ezp2.imu.edu.my/content.aspx?bookid=2
189&sectionid=165936846

Recommended textbook

• Katzung B.G.(Ed.), (2017). Basic & Clinical Pharmacology, 14e. McGraw-Hill.

https://accessmedicine-mhmedical-com.ezp2.imu.edu.my/content.aspx?bookid=2
249&sectionid=175215162

• Ritter, J., Flower, R., Hendersen, G., Loke, Y., MacEwan, D., & Rang, H. (2020). Rang
& Dale’s Pharmacology, 9e. Elsevier.
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