SEDATIVE : Drugs that clam the patient and reduce anxiety
without inducing normal sleep.
Site of action is on the limbic system which regulates thought
and mental function.
HYPNOTICS : Drugs that initiate
and maintain the normal
Site of action is on the midbrain and ascending RAS which
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.
depress excitatory neurotransmitter actions
Na+ & K+ transport across cell membranes
(reticular activating system inhibition).
All barbiturates are weak acids
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-
metabolized in the liver to inactive metabolites
Excreted in the urine.
Alkalinization increases excretion (NaHCO3)
Cross the placenta ( pregnancy).
CENTRAL NERVOUS SYSTEM: In a dose-dependent fashion.
Anesthesia in large dose
Coma and death.
suppress hypoxic and chemoreceptor response to CO2
Large doses leads to respiratory depression & death.
Healthy patient: at low doses, they have insignificant effects.
Hypovolemicstates, CHF: normal doses may cause
circulatory collapse due to medullary vasomotor
Anesthetic dose reduce muscle contraction by depressing
excitability of neuromuscular junction
INDUCTION OF ANESTHESIA: thiopentone and
HYPERBILIRUBINEMIA AND KERNICTERUS :
Hangover: residual sedation after awakening.
Precipitation of acute attack of porphyria.
Many drug interactions.
Allergic reaction: urticaria and skin rash.
Toxicity : Respiratory depression, Cardiovascular collapse, coma
MECHANISM OF ACTION
Bzs bind to the α subunit of the GABA receptor.
facilitation of GABA action on GABA receptors
chloride channels opening
chloride influx to the cell
inhibition of propagation of
inhibitory effect on different sites of the brain
especially motor cortex, and limbic system.
most of them are well absorbed orally.
Bzs are lipid soluble and widely distributed
Redistribution from CNS to skeletal muscles, adipose tissue.
barrier during pregnancy and are excreted
in milk (Fetal & neonatal depression).
Highly bound to plasma protein.
All Bzs are metabolized in the liver
Phase I: ( liver microsomal system)
Phase II: glucouronide conjugation and excreted in
Many of Phase I metabolites are active : Incresae
elimination half life of the parent compound , cumulative
effect with multiple doses.
EXCEPT No active metabolites are formed for (LEO)
Lorazepam, Estazolam, Oxazepam.
ANXIETY DISORDERS :
alprazolam, lorazepam, oxazepam, diazepam and
Alprazolam has anxiolytic-antidepressant effect.
Diazepam is preferred in acute panic-anxiety.
Chlordiazepoxide is preferred in chronic anxiety states.
INSOMNIA : in ability to sleep.
Triazolam, lorazepam is effective in treating individuals who
have difficulty in going sleep.
Flurazepam, temazepam & nitrazepam is useful for insonia
caused by inability to stay asleep.
Normal sleep consists of distinct stages,based on three
physiologic measures: the electroencephalogram, the
electromyogram, and the electronystagmogram.
Non-rapid eye movement(NREM) sleep: 70%-75%.
Rapid eye movement(REM) sleep.
To control withdrawal symptoms of alcohols
Treatment of epilepsy
Diazepam – Lorazepam: Status epilepticus
Clonazepam-Clorazepate: absence , myoclonic seizures.
Muscle relaxation: in spastic states (Diazepam) .
In anesthesia :
Preanesthetic medication diazepam
Induction of balanced anesthesia (Midazolam)
Ataxia (motor incoordination), cognitive impairment.
Hangover Sleep tendency, drowsiness, confusion especially in
long acting drugs.
Physical and Psychological dependence
Rebound Insomnia, anorexia, anxiety, agitation, tremors and
A selective competitive antagonist of BZD receptors (Bz1).
Blocks action of benzodiazepines, zaleplon and zolpidem but
not other sedative /hypnotics.
Blocks psychomotor, cognitive and memory impairment of
Has short duration of action T 1 /2 = 1 hour.
Absorbed orally .
Undergoes extensive first pass metabolism.
NO active metabolites.
Should be used IV .
Repeated doses are necessary.
Acute BZD toxicity (comatose patients).
Reversal of BZD sedation after endoscopy, dentistry.
Precipitate withdrawal symptoms.
WHY BENZODIZEPINES HAS
SUPRESSED BARBITURATES ?
They do not produce anesthesia in
Produce loss of consciousness and
high doses & patient can be
These are not enzyme inducers,
Very low abuse liability.
Lesser distortion of normal
Bzs have no hyperalgesia.
Bzs can be used as day time
Do not effect respiratory or cvs
There is a specific antagonistFlumazenil.
have low margin of safety
High abuse liability.
Marked suppression of REM
Unacceptable drowsiness is seen.
Causes respiratory and depression
No specific antagonist.
acts on benzodiazepine receptors (BZ 1) & facilitate GABA
mediated neuronal inhibition.
Its action is antagonized by flumazenil.
rapidly absorbed from GIT and metabolized to
metabolites via liver CYT P450.
Short duration of action ( 2- 4 h).
Only hypnotic effect
Its efficacy is similar to benzodiazepines.
Minor effect on sleep pattern, but high doses suppress REM.
Respiratory depression occur at high doses in combination
with other CNS depressant as ethanol.
has no muscle relaxant effect.
has no anticonvulsant effect.
Minimal psychomotor dysfunction
Minimal tolerance & dependence.
Minimal rebound insomnia.
THERAPEUTIC USES AND
a hypnotic drug for short term treatment of insomnia
Dose should be reduced in hepatic or old patients.
rapid onset of action
Short duration of action (1 hr)
Metabolized by liver microsomal enzymes
metabolism is inhibited by cimetidine.
Only hypnotic effect
decreases sleep latency
Little effect on sleep pattern
Potentiates action of other CNS depressants (alcohol).
Dose reduction as before.
Used as hypnotic drug
ADVANTAGES : Less impairment of pyschomotor performance
than BZs or zolpidem.