Sedative-Hypnotic drugs *30 hours ++ ( chlordiazepoxide, clorazepate , diazepam

, phenobarbital)
Sedation : reduction of anxiety
Mechanisms of Action :
Anxiolytic : a drug that reduces anxiety a sedative 1. Benzodiazepines = receptors for BZD are present in
thalamus; limbic structures, & cerebral cortex.
Hypnosis : induction of sleep >BZD receptors form part of a GABAᴬ receptor-chloride
ion channel macromolecular complex.
REM sleep : phase of sleep assoc. with rapid eye > BZD increase the frequency of GABA-mediated
movement, most dreaming takes place during REM chloride ion channel opening.
sleep Flumazenil = reverses the CNS effects of BZD.
(antagonist at BZD receptors.)
Tolerance : reduction in drug effect requiring an Certain beta-carbolines have a high affinity for BZ
increase in dosage to maintain the same response receptors & can elicit anxiogenic and convulsant effects.
( inverse agonist )
Physiologic dependence: the state of response to a
drug whereby removal of the drug evokes unpleasant 2. Barbiturates :
symptoms, usually opposite of the drug’s effect. > depress neuronal activity in the midbrain reticular
formation, facilitating and prolonging the inhibitory
Psychological dependence : the state of response to a effects of GABA and glycine.
drug whereby the drug taker feels compelled to use the > barbiturates also binds to multiple isoforms of the
drug & suffers anxiety when separated from the drug. GABAᴀ receptors, but at different sites from which BZD
interact.
Anesthesia : loss of consciousness assoc. with absence > it increases the duration of GABA-mediated chloride
of response to pain ion channel opening.
>blocks excitatory transmitter glutamic acid, & at high
Sedative-hypnotics drugs: conc. blocks sodium channels.
> chemically heterogenous class of drugs > action is not antagonized by Flumazenil
>dose-dependent CNS depressant effects
3. Other Drugs :
PHARMACOKINETICS: Hypnotics : Zolpidem, Zaleplon, and Eszopiclone; are
Absorption and Distribution : not BZD, but exerts CNS effects via interaction with
Most are lipid-soluble & are absorbed well from the certain BZD receptors.
GIT , with good distribution to the brain.( induction > bind more selectively and interact only with GABAᴀ
agents in anesthesia) receptor isoforms that contain alpha subunits.
> CNS depressant effects can be antagonized by
Metabolism and Excretion : Flumazenil.
> metabolized by hepatic enzymes before elimination
from the body. Pharmacodynamics :
> metabolic rates & pathways vary among different > CNS effects of most sedative-hypnotics depends on
drugs. dose.
* BZD’s are converted initially to active metabolites with > Effects range from sedation and relief of anxiety
long half-lives. Accumulation of active metabolites (anxiolysis)- hypnosis ( facilitation of sleep) – anesthesia
excessive sedation. & coma.
*Barbiturates are extensively metabolized > Depressant effects are additive when 2 or more drugs
> duration of CNS action of S/H drugs ranges from; are given together.
*Few hours ( zaleplon < zolpidem = triazolam =
eszopiclone < chloral hydrate )
 A. Sedation : > Psychological dependence occurs frequently with
> Sedative action, with relief of anxiety occur with all most S/H , manifested by compulsive use of drugs to
drugs in this class. reduce anxiety.
Anxiolysis is usually accompanied by some impairment > Physiological dependence, constitute to an altered
of psychomotor functions, and behavioral disinhibition state that leads to an abstinence syndrome ( withdrawal
may also occur. state )when the drug is discontinued.
B. Hypnosis :
> promote sleep onset and increase duration of the *CLINICAL USES:
sleep state. A. Anxiety states
 Rapid eye movement (REM) sleep >* BZD for the treatment of acute anxiety states
duration is usually decreased at high & rapid control of panic attacks.
doses. > It is difficult to demo superiority of one drug
 Rebound increase in REM sleep may over the other; Alprazolam & Clonazepam = have
occur on withdrawal from chronic drug greater efficacy than other BZD’s in long term
use. treatment of panic and phobic disorder.
> Effects on sleep patterns occurs infrequently with
newer hypnotics (zaleplon & zolpidem) B. Sleep Disorders :
> BZD,s including estazolam, flurazepam, and
C. Anesthesia: triazolam = widely used in primary insomnia & other
> *at high doses loss of consciousness may occur., with sleep disorders.
amnesia & suppression of reflexes. Anterograde * lower doses for elderly ( more
amnesia more common with BZD than with other S/H sensitive to the CNS depressant effects)
> Anesthesia can be produced by most barbiturates > Recent use of zolpidem, zaleplon and
(thiopental) & certain BZD (midazolam) eszopiclone in insomnia = cause less
daytime cognitive impairment, & minimal
D. Anticonvulsant Actions : effects on sleep patterns.
>suppression of seizure activity occur with high doses of ** Note: BZD’s and S/H’s are not
most barbiturates & some BZD. With marked sedation. recommended for breathing- related sleep
> High doses of IV diazepam, lorazepam or disorders.
phenobarbital used in status epilepticus.
C. Other Uses :
E. Muscle Relaxation : > induction of anesthesia ( thiopental); & certain BZDs
> skeletal muscle relaxation occurs at high doses of S/H. (diazepam,midazolam).
> Diazepam is effective at sedative dose levels for > management of seizure disorders ( clonazepam,
specific spasticity states, including cerebral palsy. phenobarbital) ;
> Meprobamate – has selectivity as muscle relaxant > bipolar disorders (clonazepam)
> muscle spasticity (diazepam)
F. Medullary Depression : > Longer-acting BZDs ( chlordiazepoxide, diazepam ) =
> high doses of conventional S/H, esp. alcohol & used in mgt. of withdrawal states in person
barbiturates, can cause depression of medullary physiologically dependent on ethanol & other S/H
neurons, leading to respiratory arrest, hypotension &
cardiovascular collapse.
> cause of death in suicidal overdose.

G. Tolerance and dependence:

Tolerance = a decrease in responsiveness- occurs when
S/H are used chronically or in high dosage.
= cross-tolerance may occur among different
chemical subgroups.
TOXICITY : B. Ramelteon:
A. Psychomotor dysfunction : > novel hypnotic drug, activates melatonin receptors
> cognitive impairment, located at the suprachiasmatic nuclei of the CNS.
> decreased psychomotor skills & > decrease the latency of sleep onset, with minimal
> unwanted daytime sedation.. rebound insomnia or withdrawal symptoms.
=more common with BZD’s that have active > minimal abuse liability and is not a controlled
metabolites with long half-lives. (diazepam & substance
flurazepam). > adverse effects; dizziness, fatigue and endocrine
= *Reduced dosage in elderly* changes. ( decreased testosterone & increased
> anterograde amnesia (BZD’s) at high doses* prolactin)
*** All prescription drugs used as sleep aids may cause
functional impairment , including “ sleep-
driving”, with no memory of the event.
** Excesssive daytime sedation in elderly has been
shown to increase the risk of falls & fractures
* Forms the basis for their criminal use in cases of
“date rape”.

B. Additive CNS depression:

> occurs when S/H are used with other drugs in the
class, as well as with alcoholic beverages,
antihistamines, antipsychotic drugs, opioid analgesics, &
tricyclic antidepressants.*

C. Overdosage:
> Severe respiratory and cardiovascular depression.;
more likely to occur with alcohol, barbiturates and
carbamates; than with BZD’s or the newer hypnotics.
> management of intoxication requires;
a). Patent airways
b). Ventilatory support
c). Flumazenil, reverse CNS depressant effects
of BZDs, eszopiclone, zolpidem, & zaleplon , but has
no beneficial actions in overdosage with other S/D’

Atypical Sedative-Hypnotics :
A. Buspirone = selective anxiolytic, with minimal
CNS depressant effects, does not affect driving
skills, has no anticonvulsant or muscle
relaxant properties.
= it interacts with 5-HT, subclasss of brain
serotonin receptors as partial agonist.
= used in generalized anxiety disorder (GAD)
= tolerance development is minimal; slow onset
of action;
= minimal abuse liability & is not a scheduled-
controlled drug.