Sedatives, Hypnotics

1. Sedative Hypnotics

2. Sedative Hypnotics
• Sedatives are the drugs that decreases the activity,
moderates the excitement & calms the recipient. It
decreases the responsiveness of stimulation &
decreases motor activity.
• Hypnotics are the drugs that produce drowsiness &
facilitate the onset & maintenance of sleep that
resembles natural sleep.
• Sedative & Hypnotics are CNS depressants differing in
time & action.
• Hypnotics at low dose acts as Sedative.
• Hypnotics at high dose acts as General anaesthetic.
Increasing grades of CNS depression:
Sedation Hypnosis General Anaesthesia

3. Classification
1. Barbiturates
• Long acting: Phenobarbitone
• Short acting: Butobarbitone, Pentobarbitone
• Ultrashort acting: Thiopentone, Methohexitone
2. Benzodiazepines
• Hypnotics: Diazepam, Alprazolam, Nitrazepam
• Antianxiety: Diazepam, Chlordiazepoxide, Lorazepam
• Anticonvulsant: Diazepam, Clonazepam, Clobazam
3. Newer non-benzodiazepine hypnotics
• Zopiclone, Zolpidem, Zaleplon

4. Barbiturates
• Barbiturates are sedative & hypnotic drugs that
depresses CNS & excitable cells.
• Most popular upto 1960s (till benzodiazepines
were discovered)
• More lipid soluble are potent & short acting
Mechanism of action
• Barbiturates acts on GABA: Benzodiazepine
receptor Cl- channel complex & increases inhibition
by prolonging duration of Cl- channel opening.
• At high concentrations barbiturates depresses
voltage sensitive Na+ & K+ channels.

5. Pharmacological Actions:
CNS
• Dose dependent effects
Sedation Hypnosis General Anaesthesia Coma
• Decreases time to fall sleep & increases sleep duration
• REM-NREM cycle is disrupted
Respiration
• Depresses respiratory centre
CVS
• Decreases HR & BP
Skeletal Muscle
• Anaesthetic dose reduces muscle control
Smooth Muscle
• Decreases tone & motility of bowel

7. Kidney
• Decreases urine flow by decreasing BP & increasing ADH
release
Enzyme induction
• Barbiturates induces microsomal enzymes in liver.
Adverse Effects: Hangover, Dizziness, Precipitation of
Porphyria, Hypersensitivity, Tolerance & Dependence
Contraindications: Obstructive sleep apnoea, Liver &
kidney disease, Severe pulmonary insufficiency
Uses:
• Epilepsy (Phenobarbitone 30-60mg OD-TDS/100-200mg i.m./i.v.)
• Anaesthesia (Thiopentone sod. 1-2mg/kg i.v.)

8. Benzodiazepines
• Benzodiazepines are most widely used sedative
hypnotics that has replaced barbiturates.
• They are highly effective & safer having high
therapeutic index.
Mechanism of action
• Benzodiazepines act on GABA receptor &
increases the frequency of Cl- channel opening.
• The influx of chloride ions causes
hyperpolarization & inhibits the formation of
action potentials.

10. Benzodiazepines are preferred over Barbiturates:
1. High therapeutic index
2. Doesn’t affect respiration or cardiovascular
function
3. Doesn’t impair sleep architecture
4. No microsomal enzyme induction: Less drug
interaction
5. Low abuse liability: Low tolerance
6. Specific Antagonist/Antidote: Flumazenil
available

11. Pharmacological actions/Uses:
1. Sedative
2. Hypnotic
3. Anti-anxiety
4. Anti-convulsant
5. Muscle relaxant
Adverse Effects: Dizziness, Vertigo, Ataxia, Amnesia,
Weakness, Blurring of vision, Withdrawal
symptoms (FLUNITRAZEPAM: Date Rape Drug)
Contraindication: Pregnancy, Labour (Affects
neonates), Synergism with alcohol

12. Non Benzodiazepine Hypnotics
Zopiclone
• Acts similar to BZDs but not on BZD receptor
• It doesn’t alter REM sleep & prolong stage 3 & 4
• It doesn’t disturb sleep architecture, produce
hangover, withdrawal symptoms = SAFE
• Indicated for the treatment of Insomnia (7.5mg HS)
Zolpidem
• Has only hypnotic action
• Little suspension of REM, sleep duration is prolonged
• Indicated for the treatment of Insomnia (5-10mg HS)

13. Uses:
1. Hypnotic
2. Anxiolytic
3. Anticonvulsant
4. Centrally acting muscle relaxant
5. Preanaesthetic medication