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.
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.
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.
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
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.
