copyright © 2013, 2010 by saunders, an imprint of elsevier inc. chapter 34 sedative-hypnotic drugs
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Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Chapter 34
Sedative-Hypnotic Drugs
2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Sedative-Hypnotic Drugs
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
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Sedative-Hypnotic Drugs
Benzodiazepines Benzodiazepine-like drugs Ramelteon: a melatonin agonist Barbiturates
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Benzodiazepines
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
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Benzodiazepines
Overview of pharmacologic effects Central nervous system Cardiovascular system Respiratory system
Molecular mechanism of action Pharmacokinetics
Absorption and distribution Metabolism Time course of action
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Benzodiazepines
Therapeutic uses Anxiety Insomnia Seizure disorders Muscle spasm Alcohol withdrawal Panic disorder Perioperative applications
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Benzodiazepines
Adverse effects CNS depression Anterograde amnesia Sleep driving Paradoxical effects Respiratory depression Abuse Use in pregnancy and lactation Other adverse effects
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Benzodiazepines
Drug interactions CNS depressants
Tolerance and physical dependence Tolerance
• With prolonged use, tolerance develops to some effects but not others
Physical dependence• Can cause physical dependence, but the incidence of
substantial dependence is low
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Benzodiazepines
Acute toxicity Oral overdose Intravenous toxicity General treatment measures Treatment with flumazenil
Preparations, dosage, and administration Preparations and dosage Routes
• Orally• Parenterally (IM and IV)
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Benzodiazepine-like Drugs
Zolpidem (Ambien) Sedative-hypnotic Short-term management of insomnia
Zaleplon (Sonata) New class of hypnotics, pyrazolopyrimidines Short-term management of insomnia Prolonged use does not appear to cause tolerance
Eszopiclone (Lunesta) 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
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
Three classifications Ultrashort-acting (thiopental) Short- to intermediate-acting (secobarbital) Long-acting (phenobarbital)
Mechanism of action Binds to the GABA receptor–chloride channel
complex
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Barbiturates
Pharmacologic effects CNS depression Cardiovascular effects Induction of hepatic drug-metabolizing enzymes
Tolerance and physical dependence 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.
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Barbiturates
Pharmacokinetics Lipid solubility has a significant impact Rapid onset and brief duration
Therapeutic uses Seizure disorders Induction of anesthesia Insomnia Other uses
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Barbiturates
Drug interactions CNS depressants Interactions resulting from induction of
drug-metabolizing enzymes Chloral hydrate Meprobamate
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Barbiturates
Adverse effects Respiratory depression Suicide Abuse Use in pregnancy Exacerbation of intermittent porphyria Hangover Paradoxical excitement Hyperalgesia
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Barbiturates
Acute toxicity Symptoms
• Respiratory depression• Coma• Pinpoint pupils
Treatment• Removal of barbiturate from the body• Maintenance of an adequate oxygen supply to the brain
Administration Oral Intravenous Intramuscular
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Fig. 34–3. Development of tolerance to the toxic and subjective effects of barbiturates.
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Miscellaneous Sedative-Hypnotics
Basic pharmacologic profile 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
Sleep physiology Sleep phases
Basic management principles Cause-specific therapy Nondrug therapy
Drugs used for treatment Hypnotic drugs
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Sleep Physiology
Sleep phases 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
Cause-specific therapy Treatment is highly dependent on the cause
Nondrug therapy Therapy with hypnotic drugs
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Drugs Used for Treatment of Insomnia
Drugs used for treatment Benzodiazepines Benzodiazepine-like drugs: zolpidem, zaleplon,
and eszopiclone Ramelteon Trazodone Doxepin Antihistamines Alternative medicines