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Chapter 34
Sedative-Hypnotic Drugs
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Sedative-Hypnotic Drugs
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Drugs that depress CNS function
Primarily used to treat anxiety and insomnia
Antianxiety agents or anxiolytics
Distinction between antianxiety effects and
hypnotic effects is often a matter of dosage
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Sedative-Hypnotic Drugs
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Benzodiazepines
Benzodiazepine-like drugs
Ramelteon: a melatonin agonist
Barbiturates
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Benzodiazepines
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Drugs of choice to treat insomnia and anxiety
Used to induce general anesthesia
Used to manage seizure disorders, muscle spasm,
panic disorder, and withdrawal from alcohol
Most familiar member: diazepam (Valium)
Most prescribed: lorazepam and alprazolam
Safer than general CNS depressants
Lower potential for abuse
Produce less tolerance and physical dependence
Fewer drug interactions
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Benzodiazepines
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Overview of pharmacologic effects
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Central nervous system
Cardiovascular system
Respiratory system
Molecular mechanism of action
Pharmacokinetics
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Absorption and distribution
Metabolism
Time course of action
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Benzodiazepines
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Therapeutic uses
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Anxiety
Insomnia
Seizure disorders
Muscle spasm
Alcohol withdrawal
Panic disorder
Perioperative applications
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Benzodiazepines
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Adverse effects
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CNS depression
Anterograde amnesia
Sleep driving
Paradoxical effects
Respiratory depression
Abuse
Use in pregnancy and lactation
Other adverse effects
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Benzodiazepines
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Drug interactions
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CNS depressants
Tolerance and physical dependence
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Tolerance
• With prolonged use, tolerance develops to some effects
but not others
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Physical dependence
• Can cause physical dependence, but the incidence of
substantial dependence is low
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Benzodiazepines
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Acute toxicity
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Oral overdose
Intravenous toxicity
General treatment measures
Treatment with flumazenil
Preparations, dosage, and administration
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Preparations and dosage
Routes
• Orally
• Parenterally (IM and IV)
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Benzodiazepine-like Drugs
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Zolpidem (Ambien)
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Zaleplon (Sonata)
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Sedative-hypnotic
Short-term management of insomnia
New class of hypnotics, pyrazolopyrimidines
Short-term management of insomnia
Prolonged use does not appear to cause tolerance
Eszopiclone (Lunesta)
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Is the S-isomer of zopiclone
For treating insomnia
No limitation on how long it can be used
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Ramelteon: Melatonin Agonist
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Brand name: Rozerem
Relatively new hypnotic
Activation of melatonin receptors
Approved for chronic insomnia: difficulty with
sleep onset
Rapid onset (about 30 minutes)
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Barbiturates
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Three classifications
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Ultrashort-acting (thiopental)
Short- to intermediate-acting (secobarbital)
Long-acting (phenobarbital)
Mechanism of action
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Binds to the GABA receptor–chloride channel
complex
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Barbiturates
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Pharmacologic effects
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CNS depression
Cardiovascular effects
Induction of hepatic drug-metabolizing enzymes
Tolerance and physical dependence
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Tolerance
• Develops to many—but not all—of the CNS effects
• Very little tolerance develops to respiratory depression
Physical dependence
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Fig. 34–2. Induction of hepatic microsomal enzymes by barbiturates.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Barbiturates
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Pharmacokinetics
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Lipid solubility has a significant impact
Rapid onset and brief duration
Therapeutic uses
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Seizure disorders
Induction of anesthesia
Insomnia
Other uses
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Barbiturates
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Drug interactions
 CNS depressants
 Interactions resulting from induction of
drug-metabolizing enzymes
 Chloral hydrate
 Meprobamate
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Barbiturates
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Adverse effects
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Respiratory depression
Suicide
Abuse
Use in pregnancy
Exacerbation of intermittent porphyria
Hangover
Paradoxical excitement
Hyperalgesia
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Barbiturates
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Acute toxicity
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Symptoms
• Respiratory depression
• Coma
• Pinpoint pupils
 Treatment
• Removal of barbiturate from the body
• Maintenance of an adequate oxygen supply to the brain
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Administration
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Oral
Intravenous
Intramuscular
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Fig. 34–3. Development of tolerance to the toxic and subjective
effects of barbiturates.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Miscellaneous Sedative-Hypnotics
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Basic pharmacologic profile
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Nonselective CNS depressants
Actions much like those of barbiturates
Acute overdose resembles poisoning with
barbiturates
Avoid during pregnancy and lactation
Chloral hydrate
Meprobamate
Paraldehyde
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Management of Insomnia
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Sleep physiology
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Basic management principles
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Sleep phases
Cause-specific therapy
Nondrug therapy
Drugs used for treatment
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Hypnotic drugs
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Sleep Physiology
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Sleep phases
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Rapid-eye-movement (REM)
Non–rapid-eye-movement sleep (NREM)
• I = Relatively light sleep
• II = Relatively light sleep
• III = Deep sleep
• IV = Deep sleep
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Basic Management Principles
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Cause-specific therapy
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Treatment is highly dependent on the cause
Nondrug therapy
Therapy with hypnotic drugs
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Drugs Used for Treatment
of Insomnia
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Drugs used for treatment
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Benzodiazepines
Benzodiazepine-like drugs: zolpidem, zaleplon,
and eszopiclone
Ramelteon
Trazodone
Doxepin
Antihistamines
Alternative medicines
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