SEDATIVE-

HYPNOTICS
 01
Introduction
SEDATIVE -HYPNOTICS
 SEDATIVE –HYPNOTICS
DRUGS
Sedative-hypnotics are a class of drugs that are primarily used
to promote relaxation, induce sleep, and alleviate anxiety.
These medications have the ability to depress the central
nervous system (CNS), resulting in sedation and, at higher
doses, inducing sleep.
 DEFINITION OF TERMS

SEDATIVES DRUGS: The drug which causes

calmness and, relaxation, reduction of anxiety.

HYPNOTICS DRUGS: A hypnotic drug produces

drowsiness and facilitates the onset and maintenance
of a state of sleep that resembles natural sleep.
 WHAT IS GABA?
• GABA (gamma-aminobutyric acid) is a
neurotransmitter in the brain.
• It is the major inhibitory neurotransmitter in
the central nervous system (CNS).
• Pentameric in form because it has 5 subunits.
• 2 alpha sub-unit
• 2 beta sub-unit
• 1 gamma sub-unit
WHAT IS GABA?
2 types of GABA receptors
1. GABA A- IONOTROPIC meaning they directly control the
flow of ions across the neuronal membrane.
2. GABA B-METABOTRPOPIC meaning they indirectly
influence the neuronal activity through intracellular
signaling pathways.
WHAT IS GABA?
1. GABA A- IONOTROPIC meaning they directly control the
flow of ions across the neuronal membrane.
• Binding GABA in the GABA A receptor (ligand gated)
stimulates the opening of cl- channels promoting Cl-influx
• Entry of cl-ions results to hyperpolarization of the post-
synaptic neuron to generate a post-synaptic potential
producing inhibitory effects.
Dose-response curves for two hypothetical
sedative-hypnotics.
 02
CLASSIFICATION
SEDATIVE -HYPNOTICS
CLASSIFICATIONS

1. BARBITURATES
2. BENZODIAZEPINES
3. NON-BENZODIAZEPINES
4. Others
BENZODIAZEPINES “-zepam; -zolam”
Mode of action
- Act on a receptor located between alpha and gamma subunits
- Stimulates binding of GABA on GABAA receptors
- Increase the frequency of opening the Cl- channels
 BENZODIAZEPINES
SHORT ACTING INTERMEDIATE ACTING LONG ACTING

Midazolam Lorazepam Diazepam

Triazolam Temazepam Clorazepate
Oxazepam Chlordiazepoxide
Alprazolam
Flunitrazepam
Clonazepam
 BENZODIAZEPINES
DRUGS WITH ACTIVE DRUGS WITHOUT
METABOLITES ACTIVE METABOLITES
Clonazepam
Nordiazepam Oxazepam
Oxazepam Lorazepam
Nordiazepam is the primary active metabolite of diazepam, Alprazolam
which is commonly known by the brand name Valium. When
diazepam is ingested, it undergoes metabolism in the liver,
where it is converted into nordiazepam. Nordiazepam, in
turn, can be further metabolized into other active
metabolites like oxazepam
 Benzodiazepines
Effects of BZDs on sleep pattern

 Stage 1: the latency of sleep onset is

decreased (time to fall asleep)
 Stage 2: the duration of stage 2 NREM
(nonrapid eye movement) sleep is increase
 The duration of REM sleep is decreased
 The duration of stage 4 NREM slow-wave
sleep is decreased
 Benzodiazepines antagonist
Flumazenil is a medication that functions as a selective antagonist at the
benzodiazepine binding site of the GABA-A receptor complex. It is
primarily used as an antidote to reverse the effects of benzodiazepines
and related sedative medications in cases of overdose or when the rapid
reversal of sedation is necessary.
 BARBITURATES
MODE OF ACTION
• Act on a receptor located between alpha and beta subunits
• Stimulates binding GABA on GABA-A receptors
• Increase the duration of opening the Cl-channels
• can bind directly on the receptors
• more potent
• higher toxicity
• narrow TI
• more pronounced central depressant effect
 BARBITURATES
ULTRA-SHORT ACTING
• Thiopental
• Thiamylal
• Methohexital
- Rapid onset: acts within seconds
- Short DOA: 30 mins
- Use: induction of anesthesia
- Very high lipophilicity
- Plasma binding: high (>70%)
 BARBITURATES
SHORT-ACTING
• pentobarbital
• Hexobarbital
• Secobarbital
- Use: Sedatives for insomnia
- Relatively rapid onset: 10-15 mins
- Relatively short DOA: 3-4 hours
- High lipophilicity
- Plasma binding: high (70%)
 BARBITURATES
INTERMEDIATE-ACTING
• Amobarbital
• Butobarbital
- Use: Hypnotics
- Relatively slow onset: 45-60 mins
- Intermediate DOA:6-8 hours
- Intermediate lipophilicity
- Plasma binding: intermediate (50%)
 BARBITURATES
LONG-ACTING
• phenobarbital
• Metharbital
• Mephobarbital
- Relative slow onset: 30-60 mins
- Relatively long DOA: 10-16 hours
- Use: Pain/ Migraine relief
- Relatively low lipophilicity
- Plasma binding: low (<40%)
 NON-BENZODIAZEPINES
also known as “Z-drugs”
Most Z-drugs, like Zolpidem, Zaleplon and Eszopiclone , are
approved and prescribed for insomnia or sleep disorders. For this
reason, they have very short half-lives ranging from 2-6 hours (in the
non-elderly).
 NON-BENZODIAZEPINES
1.Interaction with GABA receptors: Non-benzodiazepines primarily act on a
specific subset of GABA-A receptors that contain the alpha-1 subunit. These
receptors are involved in mediating the sedative and hypnotic effects of the
drugs.

2.Selective binding: Non-benzodiazepines bind to a specific site on the

alpha-1 subunit-containing GABA-A receptors, distinct from the
benzodiazepine binding site. This binding enhances the inhibitory effects of
GABA neurotransmitter at these receptors.
 OTHER HYPNOTICS
 RAMELTEON
- novel hypnotic drug; no direct effects on GABA
- activates melatonin receptors
- decreases latency of sleep onset with minimal rebound
insomnia or withdrawal symptoms
- less likely to be abused; not a controlled substance
 OTHER HYPNOTICS
 BUSPIRONE
- partial agonist of 5-HT1A receptors
- sedative anxiolytic with minimal CNS depressants effects
- No significant interaction with other sedative hypnotics
- no muscle relaxation
- no analgesia
- no dependence
- no euphoria
- no potential for abuse
CLINICAL EFFECTS
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