This document discusses sedative-hypnotic drugs, focusing on barbiturates and benzodiazepines. It describes how barbiturates produce a dose-dependent sedative and hypnotic effect by potentiating GABAergic neurotransmission through direct activation of GABA receptors. Barbiturates are well absorbed orally but demonstrate variability in protein binding and passage through biological barriers. Common uses include anesthesia and seizure treatment, but they can cause idiosyncratic reactions and dependence. Benzodiazepines also potentiate GABA receptors to reduce anxiety, induce sedation/hypnosis, cause amnesia, and have anticonvulsant effects in a subtype-specific manner. Their

1. Sedative- Hypnotics
SHAMI IQBAL
ASSISTANT PROFESSOR
GIPS

2. Introduction
Sedative- A drug that subdues excitement and calms the subject without
inducing sleep, though
drowsiness may be produced.
Hypnotic A drug that induces and/or maintains sleep, similar to normal
arousable sleep

3. The sedatives and hypnotics are more or less global CNS depressants with
somewhat differing time-action and dose-action relationships
Those with quicker onset, shorter duration and steeper dose-response curves
are preferred as hypnotics
while more slowly acting drugs with flatter dose-response curves are employed
as sedatives
Thus, sedation—hypnosis—general anaesthesia may be regarded as increasing
grades of CNS depression

5. Barbiturates
Pharmacological Action
1- CNS- Barbiturates produce dose-dependent effects:
sedation → sleep → anaesthesia → coma
2- CVS- Hypnotic doses of barbiturates produce a slight decrease in
BP and heart rate.
3- Skeletal muscles- Hypnotic doses have little effect but anaesthetic
doses reduce muscle contraction by action on neuromuscular
junction.

6. Mechanism of Action
Barbiturates appear to act primarily at the GABA : BZD receptor–Cl¯ channel
complex and potentiate GABAergic inhibition by increasing the lifetime of Cl¯
channel opening induced by GABA.
They do not bind to the BZD receptor, but bind to another site on the same
macromolecular complex to exert the GABA facilitatory action.
At high concentrations, barbiturates directly increase Cl¯ conductance (GABA-
mimetic action; contrast BZDs which have only GABA-facilitatory action) and inhibit
Ca2+ dependent release of neurotransmitters.

7. Pharmacokinetics
Barbiturates are well absorbed from the g.i. tract.
They are widely distributed in the body. The rate of entry into CNS is dependent
on lipid solubility. Highly-lipid soluble thiopentone has practically instantaneous
entry, while less lipid-soluble ones (pentobarbitone) take longer;
phenobarbitone enters very slowly.
Plasma protein binding varies with the compound, e.g. thiopentone 75%,
phenobarbitone 20%. Barbiturates cross placenta and are secreted in milk; can
produce effects on the foetus and suckling infant

8. USES & Adverse Effects
Anesthesia
Anticonvulsant
Sedative/hypnotic
ADR
Idiosyncrasy
Hypersensitivity
Tolerance and dependence

9. Benzodiazepines
MOA
The targets for benzodiazepine actions are the γ-aminobutyric acid (GABAA) receptors. The
GABAA receptors are composed of a combination of five α, β, and γ subunits that span the
postsynaptic membrane. For each subunit, many subtypes exist (for example, there are six
subtypes of the α subunit). Binding of GABA to its receptor triggers an opening of the central ion
channel, allowing chloride through the pore. The influx of chloride ions causes hyperpolarization
of the neuron and decreases neurotransmission by inhibiting the formation of action potentials.

11. Actions
1- Reduction of anxiety: At low doses, the benzodiazepines are anxiolytic. They
are thought to reduce anxiety by selectively enhancing GABAergic transmission
in neurons having the α2 subunit in their GABAA receptors, thereby inhibiting
neuronal circuits in the limbic system of the brain.
2- Sedative/hypnotic: All benzodiazepines have sedative and calming
properties, and some can produce hypnosis (artificially produced sleep) at
higher doses. The hypnotic effects are mediated by the α1-GABAA receptors
3- Anterograde amnesia: Temporary impairment of memory with use of the
benzodiazepines is also mediated by the α1-GABAA receptors.

12. 4- Anticonvulsant: Several benzodiazepines have anticonvulsant activity. This
effect is partially, although not completely, mediated by α1-GABAA receptors.
5. Muscle relaxant: At high doses, the benzodiazepines relax the spasticity of
skeletal muscle, probably by increasing presynaptic inhibition in the spinal cord,
where the α2-GABAA receptors are largely located. Baclofen [BAK-loe-fen] is a
muscle relaxant that is believed to affect GABA receptors at the level of the
spinal cord.

13. References
Tripathi, K. D. Essentials of Medical Pharmacology. 8th ed., Jaypee Brothers Medical, 2018.
Whalen, Karen. Lippincott Illustrated Reviews: Pharmacology. 7th ed., Lippincott Williams and
Wilkins, 2018.