Sedatives and Hypnotics
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Content
• Introduction
• Classification of Drugs
• Mechanism of Action
• Barbiturates
• Benzodiazepines
• Newer Nonbenzodiazepines hypnotics
• References
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Introduction
SEDATIVE
• 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
• Site of action is on the limbic system which regulates thought and mental
function.
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HYPNOTICS
• A Drug which produces sleep resembling natural sleep.
• They are used for initiation or maintenance of sleep.
• Hypnotics in higher doses produce General Anaesthesia.
• Site of action is on the midbrain and ascending RAS which maintain
wakefulness.
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Stages of Sleep
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Classification
Sedative – Hypnotics Drugs
Barbiturates Benzodiazepines Newer nonbenzodiazepines
hypnotics
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Dose Response Curve
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Mechanism Of Action
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Barbiturates
Pharmacokinetics
• They are well absorbed from the G.I. Tract.
• They are widely distributed in the body.
• Distribution and Duration of Action determined by Lipid Solubility
– More lipid soluble = fast onset & short duration of action.
• All barbiturates redistribute from the brain to the splanchnic areas, to
skeletal muscle and finally to adipose tissue.
• Metabolised in the liver , and inactive metabolites are excreted in urine.
• Readily cross the placenta and can depress the fetus.
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ACTIONS
CNS
Kidney CVS
Actions
Skeletal Respira
Muscles tion
Smooth
Muscles
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Uses
Anaesthesia • Ultra short acting e.g Thiopentol used I.V to
induced anaesthesia.
• Phenobarbital is used in long term management
of tonic- clonic seizures.
Anticonvulsant
• Also used for the treatment of refractory status
epilepticus.
Sedative/Hypnotics • Used as mild sedatives to relieve anxiety, nervous
tension.
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Adverse Effects
• Due to the long duration of action , hangover is common.
• Learning and memory impairment can occur.
• Idiosyncratic reaction resulting in excitement can occur in some patients.
• These are absolutely contraindicated in acute intermittent porphyria.
• At high doses , acute poisoning may occur.
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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
• The longer acting agents from active metabolites with long half lives.
• All benzodiazepines are metabolized in liver.
• Cross the placental barrier during pregnancy and are excreted in milk
( Fetal and neonatal depression)
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Actions
Reduction
of Anxiety
Muscle
Actions Sedative/
Relaxant Hypnotics
Anticon
vulsant
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Uses
Sleep
disorders
Muscular Uses Amnesia
disorders
Seizures
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Adverse Effects
• Drowsiness and confusion.
• Ataxia occurs at high doses.
• Cognitive impairment can occur.
• Flurazepam results in paradoxical stimulation and increase in nightmares
in some patients.
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Newer nonbenzodiazepine hypnotics
A> Zopiclone:
-It stimulates the GABA A receptors by binding to a site different
than benzodiazepines.
– It prolongs stage 3 & 4 sleep and does nor effect REM sleep.
– Chances of rebound insomnia and hangover are less.
– It is used in the treatment of the insomnia.
– Side effects,
metallic or bitter after taste,
psychological disturbances,
dry mouth.
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B>Zolpidem:
-It binds selectively to subtype of benzodiazepine receptor
and increases GABA mediated neuronal inhibition.
-It possesses pronounced hypnotic and amnesic effect.
-Abuse potential is very low.
C>Zaleplon:
-It is rapidly absorbed.
-It decreases sleep latency without affecting total sleep
time.
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References
1] Essentials of medical pharmacology by K. D. Tripathi, Sixth
edition ,Page No;388- 400
2] Review of Pharmacology by Gobind Rai Garg and Sparsh
Gupta, Ninth edition, Page No;313- 315
3] Pharmacology by H.P. Rang and M.M. Dale, Sixth edition
Page No; 536- 544
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