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

3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Sedative-Hypnotic Drugs

Benzodiazepines Benzodiazepine-like drugs Ramelteon: a melatonin agonist Barbiturates

4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

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

5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

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

6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Benzodiazepines

Therapeutic uses Anxiety Insomnia Seizure disorders Muscle spasm Alcohol withdrawal Panic disorder Perioperative applications

7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Benzodiazepines

Adverse effects CNS depression Anterograde amnesia Sleep driving Paradoxical effects Respiratory depression Abuse Use in pregnancy and lactation Other adverse effects

8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

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

9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

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)

10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

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

11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

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)

12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

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

13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

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

14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Fig. 34–2. Induction of hepatic microsomal enzymes by barbiturates.

15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Barbiturates

Pharmacokinetics Lipid solubility has a significant impact Rapid onset and brief duration

Therapeutic uses Seizure disorders Induction of anesthesia Insomnia Other uses

16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Barbiturates

Drug interactions CNS depressants Interactions resulting from induction of

drug-metabolizing enzymes Chloral hydrate Meprobamate

17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Barbiturates

Adverse effects Respiratory depression Suicide Abuse Use in pregnancy Exacerbation of intermittent porphyria Hangover Paradoxical excitement Hyperalgesia

18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

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

19Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Fig. 34–3. Development of tolerance to the toxic and subjective effects of barbiturates.

20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

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

21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Management of Insomnia

Sleep physiology Sleep phases

Basic management principles Cause-specific therapy Nondrug therapy

Drugs used for treatment Hypnotic drugs

22Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

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

23Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Basic Management Principles

Cause-specific therapy Treatment is highly dependent on the cause

Nondrug therapy Therapy with hypnotic drugs

24Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Drugs Used for Treatment of Insomnia

Drugs used for treatment Benzodiazepines Benzodiazepine-like drugs: zolpidem, zaleplon,

and eszopiclone Ramelteon Trazodone Doxepin Antihistamines Alternative medicines