Sedatives & Hypnotics Sedatives ➢ It is a drug that reduces excitement and calms the person ➢ A drug that reduces excitement, calms the patient (without inducing sleep) ➢ Sedatives in therapeutic doses are anxiolytic agents ➢ Most sedatives in larger doses produce hypnosis (trans like state in which subject becomes passive and highly suggestible)

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ASSIGNMENT 02: Sedatives & Hypnotics
Name: Shivam Dubey
Pharmacology - I
Instructor Name: Prof. Mr.Anurag Agrawal
Date: 24/04/2020

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Sedatives & Hypnotics
Sedatives
➢ It is a drug that reduces excitement and calms the person
➢ A drug that reduces excitement, calms the patient (without inducing sleep)
➢ Sedatives in therapeutic doses are anxiolytic agents
➢ Most sedatives in larger doses produce hypnosis (trans like state in which
subject becomes passive and highly suggestible)
➢ Site of action is on the limbic system which regulates thought and mental
function.
Hypnotics
➢ It is the drug that produces sleep resembling the normal sleep
➢ A drug which produces sleep resembling natural sleep
➢ They are used for initiation and / or maintenance of sleep.
➢ Hypnotics in higher doses produce General anaesthesia.
➢ Site of action is on the midbrain and ascending RAS which maintain
wakefulness.
The sedatives and hypnotics are more or less general CNS depressants with some
what differing time- action and dose-action relationships. Those with quicker
onset, shorter duration and steeper dose response curve are preferred as
hypnotics while more slowly acting drugs with flatter dose response curves are
employed as sedatives.
Anxiolytic
➢ Anxiety is an unpleasant state of tension, apprehension, or uneasiness that
arises from either a known or an unknown source
➢ Anxiolytic is an agent which decreases worriness manifested as the psychic
awareness of anxiety which is accompanied with increased vigilance, motor
tension, and autonomic hyperreactivity.
Other Anxiolytic Agents
➢ Buspirone

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➢ Acts as a partial agonist at the 5-HT1A receptor presynaptically inhibiting
serotonin release.
➢ The metabolite 1-PP (1-(2-pyrimidyl-piperazine) has 2 receptor blocking
action – Indicated for generalized anxiety disorders but takes 1 to 2 weeks
to exert anxiolytic effects – no anticonvulsant or muscle relaxant properties
Advantages:
➢ Does not have sedative effects and does not potentiate CNS depressants
Few Side Effects
➢ Relatively high margin of safety,
➢ Not associated with drug dependence
➢ No rebound anxiety or signs of withdrawal when discontinued
Classifications
1. Barbiturates
Long acting
➢ Phenobarbitone
➢ Pentobarbitone
Short acting
➢ Butobarbitone
➢ Methohexitone
Ultra short acting
➢ Thiopentone
Benzodiazepines
⬧ Hypnotic
➢ Diazepam
➢ Flurazepam
➢ Nitrazepam
➢ Alprazolam

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➢ Temazepam
➢ Triazolam
⬧ Antianxiety
➢ Diazepam
➢ Chlordiazepoxide
➢ Oxazepam
➢ Lorazepam
➢ Alprazolam
⬧ Anticonvulsant
➢ Diazepam
➢ Lorazepam
➢ Clonazepam
➢ Clobazam
➢ Alprazolam
Newer Non-benzodiazepine Hypnotics
➢ Zopiclone
➢ Zolpidem
➢ Zaleplon
Barbiturates
MECHANISM OF ACTION
Facilitation of GABA action on the brain: Barbiturates bind at the β sub unit of
GABA-A receptor and increase the duration of the GABA gated channel opening
but in large dose, they can directly activating chloride channels.
SUB-ANAESTHETIC DOSES:
➢ Depress excitatory neurotransmitter actions
ANAESTHETIC DOSES:

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➢ Interfere with Na+ & K+ transport across cell membranes (reticular
activating system inhibition).
PHARMACOKINETICS
➢ All barbiturates are weak acids
➢ Lipid soluble
➢ Absorbed orally.
➢ Distribute throughout the body
➢ Thiopentone is highly lipid soluble (high rate of entry into CNS- quick onset
of action).
➢ Redistribute in the body from the brain to skeletal muscles- adipose tissues.
➢ Metabolized in the liver to inactive metabolites
➢ Excreted in the urine.
➢ Alkalinization increases excretion (NaHCO3)
➢ Cross the placenta ( pregnancy).
PHARMACOLOGICAL ACTIONS
CENTRAL NERVOUS SYSTEM:
➢ In a dose-dependent fashion.
➢ Sedative
➢ Hypnotic
➢ Anesthesia in large dose
➢ Anticonvulsant action
➢ Coma and death.
RESPIRATORY SYSTEM:
➢ Suppress hypoxic and chemoreceptor response to CO2
➢ Large doses leads to respiratory depression & death
PHARMACOLOGICAL ACTIONS
CVS:
➢ Healthy patient: at low doses, they have insignificant effects.
➢ Hypovolemicstates, CHF: normal doses may cause cardiovascular collapse.
➢ Large dose → circulatory collapse due to medullary vasomotor depression.

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SKELETAL MUSCLE:
➢ Anesthetic dose reduce muscle contraction by depressing excitability of
neuromuscular junction
Barbiturates Poisoning
➢ Maintain ABC
➢ Maintain electrolyte balance
➢ Gastric lavage- after stomach wash, administered activated charchoal it may
enhance the elimination of phenobarbitone. Endotracheal intubation is
performed before gastric lavage to protect the airway in uncouncious
patient.
Figure 1 Sedatives & Hypnotics
Alkaline Diuresis:
➢ NaHCO3
➢ Haemodialysis is employed in severe cases.

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➢ Drug interactions: Barbiturates are potent microsomnal enzymes and
reduces the effectiveness of oral drugs ( e.g. OCP, oral anticoagulants, oral
hypoglycemics etc.)
Therapeutic Uses
➢ Sedation and Hypnosis : barbiturates were used in the treatment of
insomnia. At present barbiturates are not recommended.
➢ General anesthesia (GA) ultra short acting barbiturates ( thiopentone and
methohexitone ) are used in induction of GA.
➢ Anticonvulsant: Phenobarbitone has anticonvulsant effect and used in
treatment of status epilepticus and generalized tonic- clonic seizures ( GTCS
, grand mal epilepsy )
➢ Neonatal jaundice and non-haemolytic type: phenobarbitone may be used
to reduce serum bilurubin levels. It induces glucuronyl transferase enzyme
and hastens the metabolism of bilurubin.
➢ Diagnostic aid and Psychiatry: i.v. thiopentone in subanesthetic dose
produces a state of deep sedation. The patient becomes more communative,
which helps in diagnostic of psychiatric disorders like histeria
ADVERSE EFFECTS
➢ Common side effects are drowsiness, confusion, headache, ataxia,
hypotension and respiratory depression
➢ Hangover: residual sedation after awakening.
➢ Tolerance
➢ Withdrawal symptoms
➢ Precipitation of acute attack of porphyria.
➢ Allergic reaction: urticaria and skin rash. Toxicity: drowsiness, Restlessness,
hallucinations, hypotension Respiratory depression, convulsion,
Cardiovascular collapse, coma and death.
MECHANISM OF ACTION
➢ Benzodiazepines act very selectively on GABAA-receptors, which mediate
the fast inhibitory synaptic response produced by activity in GABA-ergic
neurons.
➢ The effect of benzodiazepines is to enhance the response to GABA, by
facilitating the opening of GABA-activated chloride channels (an increase in

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the frequency of channel opening, but no change in the conductance or
mean open time).
Other Hypnotic Agents
Antihistamines –
➢ Some antihistamines with sedating properties, such as diphenhydramine,
hydroxyzine, and doxylamine, are effective in treating mild types of
situational insomnia.
➢ However, they have undesirable side effects (such as anticholinergic effects)
that make them less useful than the benzodiazepines and the
nonbenzodiazepines.
Antidepressants –
➢ Doxepin an older tricyclic agent with SNRI mechanisms of antidepressant
and anxiolytic action, was recently approved at low doses for the
management of insomnia. – Other antidepressants, such as trazodone,
mirtazapine and other older tricyclic antidepressants with strong
antihistamine properties are used off-label for the treatment of insomnia
Benzodiazepines
Pharmacokinetics
➢ Lipophilic
➢ Rapidly and completely absorbed after oral administration
➢ Distribute throughout the body and penetrate into the CNS
➢ Redistribution occurs from CNS to skeletal muscles& adipose tissue
(termination of action)
➢ The longer-acting agents form active metabolites with long half-lives.
Metabolism
➢ All Benzodiazepines are metabolized in the liver – Phase I: ( liver
microsomal system) – Phase II: glucouronide conjugation and excreted in
the urine.
➢ Many of Phase I metabolites are active: Increase elimination half life of the
parent compound , cumulative effect with multiple doses.

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➢ EXCEPTION: No active metabolites are formed for (LEO) Lorazepam,
Estazolam, Oxazepam. • Cross placental barrier during pregnancy and are
excreted in milk (Fetal & neonatal depression)
Actions
➢ Reduction of anxiety – At low doses, the benzodiazepines are anxiolytic –
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 – The antianxiety effects
of the benzodiazepines are less subject to tolerance than the sedative and
hypnotic effects.
➢ Sedative/hypnotic – All benzodiazepines have sedative and calming
properties – some can produce hypnosis (artificially produced sleep) at
higher doses – The hypnotic effects are mediated by the α1- GABAA
receptors.
➢ Anterograde amnesia – Temporary impairment of memory with use of the
benzodiazepines – mediated by the α1-GABAA receptors. – The ability to
learn and form new memories is also impaired.
➢ Anticonvulsant – Several benzodiazepines have anticonvulsant activity. –
This effect is partially, although not completely, mediated by α1-GABAA
receptors.
➢ Muscle relaxant – At high doses, the benzodiazepines relax the spasticity of
skeletal muscle – by increasing presynaptic inhibition in the spinal cord,
where the α2-GABAA receptors are largely located.
Dependence
➢ Psychological and physical dependence can develop if high doses are given
for a prolonged period.
➢ Abrupt discontinuation results in withdrawal symptoms – confusion, anxiety,
agitation, restlessness, insomnia, tension, and (rarely) seizures.
➢ Benzodiazepines with a short elimination half-life, such as triazolam, induce
more abrupt and severe withdrawal reactions than those seen with drugs
that are slowly eliminated such as flurazepam
Adverse Effects
➢ Drowsiness and confusion: Most common AE

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➢ Ataxia occurs at high doses
➢ Cognitive impairment (decreased long-term recall and retention of new
knowledge) can occur with use of benzodiazepines.
➢ Benzodiazepines should be used cautiously in patients with liver disease.
➢ Alcohol and other CNS depressants enhance the sedative–hypnotic effects of
the benzodiazepines.
➢ Administration in third trimester can result in “floppy-infant syndrome”
References
o https://www.slideshare.net/madansigdel5/sedatives-and-hypnotics-
52415614
o http://lms.itmuniversity.ac.in/pluginfile.php/72843/mod_resource/cont
ent/1/Sedative%20%20Hypnotics.pdf
o https://www.google.com/url?sa=i&url=https%3A%2F%2Fcanadiem.or
g%2Fcrackcast-e165-sedative-hypnotics%2F&psig=AOvVaw0Qz25-
FmsT93wVJrpK5Rsj&ust=1587830812306000&source=images&cd=vfe
&ved=0CAIQjRxqFwoTCPi78-64gekCFQAAAAAdAAAAABAD
o https://www.slideshare.net/drashutoshtiwari/sedative-hypnotic-
45187755
o https://www.health.harvard.edu/a_to_z/sedative-hypnotic-or-
anxiolytic-drug-use-disorder-a-to-z