This document discusses sedative and hypnotic drugs, focusing on barbiturates. It classifies barbiturates and describes their mechanism of action, pharmacological effects, kinetics, therapeutic uses, adverse effects, interactions, and compares them to benzodiazepines. It also discusses non-benzodiazepine hypnotics including zopiclone, zolpidem, zaleplon, buspirone, and chloral hydrate.

1. SEADTIVE HYPNOTIC DRUGS II
By
Dr. S. Amber Zaidi

2. CLASSIFICATION

3. BARBITURATES
Oldest among sedative and hypnotic class. Due to no. of
disadvantages not used as sedative.
• Low therapeutic index
• Cause dependence
• High abuse potential
• Repeated use leads to the development of tolerance
• Acute barbiturate withdrawal in drug abusers can cause a
fatal withdrawal syndrome
• Drug has been largely replaced by newer drugs

4. They are the CNS depressant used to sedate the patients or to
induce and maintain sleep. These drugs produce dose-
dependent effect.
Sedatives → Hypnotics → Anaesthesia → Coma.

5. CLASSIFICATION
Long Acting
(t1/2 > 8hrs)
Intermediate
Acting
(t1/2 4-8hrs)
Short Acting
(t1/2 < 4hrs)
Ultra short Acting
(t1/2 20 min)
Phenobartital Allobarbital Secobarbitone Thiopental sodium
Barbitone
Hexobarbitone Hexobarbitone Methohexital sodium
Barbital sodium
Pentohexital
sodium
Pentobarbitone
Mephobarbital Cyclobarbitone

6. MECHANISM OF ACTION
• Interact with GABA receptors at α/β subunit.
from that of the BZs.
• Potentiate GABA action on Cl-entry into the neuron by
increase the duration of opening.
• In addition, barbiturates can block excitatory glutamate
receptor (sub anesthetic dose).
• At high doses (anesthetics conc. of pentobarbital-reticular
activating system inhibition), also
– Open Cl-ion channels directly
– Block high frequency Na+channels.

7. GABA RECEPTOR

8. MECHANISM OF ACTION

9. PHARMACOLOGICAL EFFECTS
CNS:
– At low dose it produces sedation.
– At higher dose the drug causes hypnosis followed by
anaesthesia and finally coma and death.
– It can impair learning, short term memory loss and
judgment.
– Euphoria may be seen in addicts.
– They may have anti-convulsant property.

10. PHARMACOLOGICAL EFFECTS
Respiratory System: Barbiturates suppress hypoxic and
chemoreceptors response to Co2 and over dose is followed
by respiratory depression and death.
Skeletal muscles: Anaesthetic dose reduce muscle
contraction by depressing excitability of neuromuscular
junction.
Smooth muscle: Tone and motility of bowel is decreased.
CVS: Hypnotic dose produce slight decrease in BP and heart
rate. It decreases cardiac contractility

11. PHARMACOLOGICAL EFFECTS
Kidney:
• It reduces urine flow by decreasing BP and increasing
ADH release.
Enzyme induction:
• It induces cytochromeP450 microsomal enzymes in the
liver.
• Chronic administration reduces the action of drugs that are
dependent on P450 metabolism.

12. KINETICS
• 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
• Cross the placenta

13. THERAPEUTIC USES
• Now, they are not used as hypnotics and anxiolytics.
• Thiopental is used intravenously to induce anaesthesia.
• Phenobarbitone is used in epilepsy.
• They are used in long term management of tonic-clonic
seizure
• They are sometimes used as adjuvant in psychosomatic
disorder.

14. ADVERSE EFFECTS
• Drug hangover
– Nausea
– Dizziness
• CNS
– causes drowsiness
– impaired concentration
– mental and physical sluggishness.
• Tolerance
• Dependence (abuse liability)
• Withdrawal symptoms cause tremor, anxiety, weakness,
restlessness, nausea, vomiting and cardiac arrest.
• Neonatal flacidity & respiratory depression

15. ACUTE BARBITURATE POISONING
Mostly suicidal – excessive CNS depression – flabby and
comatose with shallow and failing respiration, CVS collapse,
renal shut down & pulmonary complications
Treatment:
• Supportive: patent airway, assisted respiration, oxygen, IV
fluid and vasopressors like Dopamine
• Gastric lavage (activated charcoal)
• Alkaline diuresis: Sodium bicarbonate 1 meq/kg IV with
or without mannitol for long acting drugs
• Haemodialysis: highly effective in long as well as short
acting drugs

16. DRUG INTERACTION
• Induce metabolism of many drugs – warfarin, steroids,
OCP, chloramphenicol, tolbutamide
• Alcohol, antihistamines, opioids – CNS depression
• Sodium valproate – increases plasma conc. of
Phenobarbitone
• Phenobarbitone – competitively induces phenytoin
metabolism

17. BENZODIAZEPINE Vs BARBITURATES
S.No BENZDIAZEPINES BARBITURATES
1
They do not produce anesthesia in
high doses & patient can be aroused
Produce loss of consciousness and have low
margin of safety
2 These are not enzyme inducers
Enzyme inducers. More drug interactions
3 Very low abuse liability. High abuse liability
4 Lesser distortion of normal hypnogram Marked suppression of REM sleep
5 No hyperalgesia. Hyperalgesic action
6
There is a specific antagonist-
Flumazenil
No specific antagonist

18. NON-BENZODIAZEPINES

19. ZOPICLONE
• Cyclopyrrolone derivative: active metabolite – N-
desmethylzopiclone
• MOA: Binds to α subunit of BZ receptor– hypnotic action
• No sleep architecture distortion or withdrawal phenomena
• Uses: to wean off insomniacs on BZ and short term
therapy for insomnia
• ADRs: Metallic taste, impairment of judgment and
alertness, psychological disturbance – addictive property
(rarely)
• Half life: 5 – 6 hours

20. ZOLPIDEM
• MOA: Acts on α1 subunit of BZ receptor (hypnotic)
• Shortened sleep latency period, prolongs sleep time – but
no anticonvulsant, antianxiety or muscle relaxant effects
• Minimal residual day time sedation or fading of effects on
repeated use
• Little rebound insomnia on discontinuation
• Absence of tolerance and low abuse potential
• Kinetics: Completely metabolized in liver – half life – 2
hrs
• Uses: short term therapy of sleep onset insomnia – day
time sedation less (short half life)

21. ZALEPLON
• Shortest acting - acts on α1 subunit of BZ receptor
(hypnotic)
• Kinetic: Rapidly absorbed (30% bioavailability) – rapidly
cleared by hepatic metabolism – Half life (1 hr)– no active
metabolite
• Does not prolong total sleep time or reduce the number of
awakenings
• Can be taken late night – no morning sedation, anxiety or
insomnia
• No tolerance or dependence
• Uses: Sleep-onset insomnia (1-2 weeks therapy)

22. BUSPIRONE
• Totally different anxiolytic from BZs, no effects on GABA
systems, partial agonist at 5-HT1A receptors some affinity
for D2 & 5-HT2A
• Indication: Indicated for generalized anxiety disorders but
takes 1 to 2 weeks to exert anxiolytic effects.
• Buspirone lacks anticonvulsant and Muscle relaxant
property and cause minimal sedation.
• No additive CNS depression with other drugs.
• ADRs: hypothermia, increase prolactin, headache,
dizziness, nervousness

23. CHLORAL HYDRATE
• Relatively safe hypnotic, inducing sleep in a half hour
and lasting about 6h.
• Used mainly in children and elder, and in patients
who failed to respond other drugs.

24. THANK YOU