Anxiolytic ,
Sedative and
Hypnotic Drugs-1
Anxiolytic ,
Sedative and
Hypnotic Drugs-1
SEDATIVE
Drugs that have an
inhibitory effect on the
CNS
to the degree that they reduce:
Nervousness
Excitability
Irritability without causing sleep
Drugs that have an
inhibitory effect on the
CNS
to the degree that they reduce:
Nervousness
Excitability
Irritability without causing sleep
HYPNOTICS
Calm or soothe the CNS to the point
that they
cause sleep
A hypnotic drug should produce
drowsiness and encourage the onset
and maintenance of a state of sleep
resembles the natural sleep state.
Calm or soothe the CNS to the point
that they
cause sleep
A hypnotic drug should produce
drowsiness and encourage the onset
and maintenance of a state of sleep
resembles the natural sleep state.
Anxiolytics: reduce anxiety
Sedatives: decrease activity,
calming effect
Hypnotics: induce sleep
Some drugs have anxiolytic
and sedative/hypnotic effects.
Anxiolytics: reduce anxiety
Sedatives: decrease activity,
calming effect
Hypnotics: induce sleep
Some drugs have anxiolytic
and sedative/hypnotic effects.
Most anxiolytic and sedative –hypnotic
drugs produce dose – depended
depression of the central nervous system
function
Anxiolytic, Sedative and
Hypnotic Drugs
CNS Depression
CNS Depression
Sedation
Hypnosis
General Anesthesia
Poisoning
Death
Sedation
Hypnosis
General Anesthesia
Poisoning
Death
the patient
calm
drug should
anxiolytic
The ideal
and
sedation
causing too much day time
without
producing physical or
without
and
drowsiness
dependence
psychological
the patient
calm
drug should
anxiolytic
The ideal
and
sedation
causing too much day time
without
producing physical or
without
and
drowsiness
dependence
psychological
sleep
Summary of anxiolytic and hypnotic drugs
Barbiturates.
Benzodiazepines.
Other anxiolytic drugs: buspirone,
hydroxyzine, antidepressants.
Other hypnotic agents: antihistamine,
chloral hydrate, ethanol, ramelteon,
zolpidem
Anxiolytic, Sedative and
Hypnotic Drugs
Summary of anxiolytic and hypnotic drugs
Barbiturates.
Benzodiazepines.
Other anxiolytic drugs: buspirone,
hydroxyzine, antidepressants.
Other hypnotic agents: antihistamine,
chloral hydrate, ethanol, ramelteon,
zolpidem
Barbiturates
They have been largely replaced by the
benzodiazepines, because Barbiturates:
Induce tolerance
Induce drug-metabolizing enzymes
Physical dependence and
Very severe withdrawal symptoms
Narrow therapeutic index
Certain barbiturates, such as the very short-acting
thiopental, are still used to induce anesthesia
Anxiolytic, Sedative and
Hypnotic Drugs
Barbiturates
They have been largely replaced by the
benzodiazepines, because Barbiturates:
Induce tolerance
Induce drug-metabolizing enzymes
Physical dependence and
Very severe withdrawal symptoms
Narrow therapeutic index
Certain barbiturates, such as the very short-acting
thiopental, are still used to induce anesthesia
Barbiturates are classified according to
their duration of action into:
Ultra-short acting :thiopental (20
minutes)
Short acting: pentobarbital, secobarbital,
amobarbital(3-8)hours
Long acting: phenobarbital (1-2 days)
Anxiolytic, Sedative and
Hypnotic Drugs
Barbiturates are classified according to
their duration of action into:
Ultra-short acting :thiopental (20
minutes)
Short acting: pentobarbital, secobarbital,
amobarbital(3-8)hours
Long acting: phenobarbital (1-2 days)
Mechanism of action of barbiturates
The sedative-hypnotic action of the barbiturates is due to
their interaction with GABA receptors, which enhances
GABAergic transmission. The binding site is distinct from
that of the benzodiazepines. Barbiturates potentiate GABA
action on chloride entry into the neuron by prolonging the
duration of the chloride channel openings.
In addition, barbiturates can block excitatory glutamate
receptors.
Anesthetic concentrations of pentobarbital also block high-
frequency sodium channels. All of these lead to decreased
neuronal activity.
Anxiolytic, Sedative and
Hypnotic Drugs
Mechanism of action of barbiturates
The sedative-hypnotic action of the barbiturates is due to
their interaction with GABA receptors, which enhances
GABAergic transmission. The binding site is distinct from
that of the benzodiazepines. Barbiturates potentiate GABA
action on chloride entry into the neuron by prolonging the
duration of the chloride channel openings.
In addition, barbiturates can block excitatory glutamate
receptors.
Anesthetic concentrations of pentobarbital also block high-
frequency sodium channels. All of these lead to decreased
neuronal activity.
Actions of barbiturates:
Depression of CNS: At low doses, the barbiturates
produce sedation (calming effect, reducing
excitement). At higher doses, the drugs cause
hypnosis, followed by anesthesia (loss of feeling or
sensation), and finally, coma and death. Thus, any
degree of depression of the CNS is possible,
depending on the dose.
Barbiturates have no analgesic properties.
Anxiolytic, Sedative and
Hypnotic Drugs
Actions of barbiturates:
Depression of CNS: At low doses, the barbiturates
produce sedation (calming effect, reducing
excitement). At higher doses, the drugs cause
hypnosis, followed by anesthesia (loss of feeling or
sensation), and finally, coma and death. Thus, any
degree of depression of the CNS is possible,
depending on the dose.
Barbiturates have no analgesic properties.
Respiratory depression : over dosage cause
respiratory depression and death.
Circulatory collaps (by toxic dose)
Enzyme induction: Barbiturates induce P450
microsomal enzymes in the liver. Therefore,
chronic barbiturate administration diminishes
the action of many drugs that are dependent on
p450 metabolism example ( phenytoin ,
anticoagulants)
Anxiolytic, Sedative and
Hypnotic Drugs
Respiratory depression : over dosage cause
respiratory depression and death.
Circulatory collaps (by toxic dose)
Enzyme induction: Barbiturates induce P450
microsomal enzymes in the liver. Therefore,
chronic barbiturate administration diminishes
the action of many drugs that are dependent on
p450 metabolism example ( phenytoin ,
anticoagulants)
Therapeutic uses of barbiturates:
Anesthesia: The ultra short-acting barbiturates,
such as thiopental, are used intravenously to
induce anesthesia.
Anticonvulsant: Phenobarbital is used in long-
term management of tonic-clonic seizures,
status epilepticus, Phenobarbital has been
regarded as the drug of choice for treatment of
young children with recurrent febrile seizures.
Anxiolytic, Sedative and
Hypnotic Drugs
Therapeutic uses of barbiturates:
Anesthesia: The ultra short-acting barbiturates,
such as thiopental, are used intravenously to
induce anesthesia.
Anticonvulsant: Phenobarbital is used in long-
term management of tonic-clonic seizures,
status epilepticus, Phenobarbital has been
regarded as the drug of choice for treatment of
young children with recurrent febrile seizures.
Anxiety: Barbiturates have been used
as mild sedatives to relieve anxiety,
nervous tension, and insomnia. When
used as hypnotics, they suppress REM
sleep more than other stages. However,
most have been replaced by the
benzodiazepines.
Anxiolytic, Sedative and
Hypnotic Drugs
Anxiety: Barbiturates have been used
as mild sedatives to relieve anxiety,
nervous tension, and insomnia. When
used as hypnotics, they suppress REM
sleep more than other stages. However,
most have been replaced by the
benzodiazepines.
Pharmacokinetics of barbiturates
Barbiturates are absorbed orally and
distributed widely throughout the body.
Barbiturates are metabolized in the liver,
and inactive metabolites are excreted in
the urine.
They readily cross the placenta and can
depress the fetus.
Anxiolytic, Sedative and
Hypnotic Drugs
Pharmacokinetics of barbiturates
Barbiturates are absorbed orally and
distributed widely throughout the body.
Barbiturates are metabolized in the liver,
and inactive metabolites are excreted in
the urine.
They readily cross the placenta and can
depress the fetus.
Adverse effect of barbiturates
1.
CNS: Barbiturates cause drowsiness, impaired
concentration, The CNS depressant effects of
barbiturates synergize with those of ethanol.
2.
Drug hangover: Hypnotic doses of barbiturates
produce a feeling of tiredness well after the
patient wakes. This drug hangover may lead to
impaired ability to function normally for many
hours after waking. Occasionally, nausea and
dizziness occur.
Anxiolytic, Sedative and
Hypnotic Drugs
Adverse effect of barbiturates
1.
CNS: Barbiturates cause drowsiness, impaired
concentration, The CNS depressant effects of
barbiturates synergize with those of ethanol.
2.
Drug hangover: Hypnotic doses of barbiturates
produce a feeling of tiredness well after the
patient wakes. This drug hangover may lead to
impaired ability to function normally for many
hours after waking. Occasionally, nausea and
dizziness occur.
Anxiolytic, Sedative and
Hypnotic Drugs
3. Induce the P450 system and may decrease the
duration of action of drugs that are metabolized by
these hepatic enzymes.
4. Increase porphyrin synthesis, and they are
contraindicated in patients with acute intermittent
porphyria.
5. Physical dependence: Abrupt withdrawal from
barbiturates may cause tremors, anxiety, weakness,
nausea and vomiting, seizures, delirium, and cardiac
arrest.
6. Poisoning: death resulting from drug overdoses
because of severe depression of respiration and
cardiovascular depression.
3. Induce the P450 system and may decrease the
duration of action of drugs that are metabolized by
these hepatic enzymes.
4. Increase porphyrin synthesis, and they are
contraindicated in patients with acute intermittent
porphyria.
5. Physical dependence: Abrupt withdrawal from
barbiturates may cause tremors, anxiety, weakness,
nausea and vomiting, seizures, delirium, and cardiac
arrest.
6. Poisoning: death resulting from drug overdoses
because of severe depression of respiration and
cardiovascular depression.
Note: No specific barbiturate
antagonist is available
Anxiolytic, Sedative and
Hypnotic Drugs
Treatment of patient with barbiturates
poisoning
artificial respiration
purging the stomach of its contents if the
drug has been recently taken
Hemodialysis may be necessary if large
quantities have been taken.
Alkalinization of the urine often aids in the
elimination of phenobarbital .
Anxiolytic, Sedative and
Hypnotic Drugs
Treatment of patient with barbiturates
poisoning
artificial respiration
purging the stomach of its contents if the
drug has been recently taken
Hemodialysis may be necessary if large
quantities have been taken.
Alkalinization of the urine often aids in the
elimination of phenobarbital .