Study Notes on Sleep and Sedative-Hypnotic Drugs

SLEEP & OVERVIEW OF SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

  • Definition: Drugs that depress central nervous system (CNS) function.
  • Primary Uses:
    • Treatment of anxiety.
    • Treatment of insomnia.
  • Types:
    • Antianxiety agents or anxiolytics.
  • Distinction between Effects:
    • Antianxiety effects vs. hypnotic effects often depend on dosage.
  • Sleep Disorders:
    • Insomnia: Inability to sleep.
    • Hypersomnia: Excessive sleepiness.
    • Narcolepsy: Sudden sleep attacks.
    • Sleep Apnea: Fragmented sleep due to lack of oxygen.
  • Types of Sedative Drugs:
    • Benzodiazepines: Target GABA receptors, CNS activity, treat insomnia and anxiety.
    • Barbiturates: Rarely used today, enhance GABA function, higher addiction potential.
    • Importance of maintaining a sleep routine.

BENZODIAZEPINES

  • Overview:
    • Drugs of choice for treating insomnia and anxiety.
    • Used for inducing general anesthesia, managing seizure disorders, muscle spasms, panic disorders, and withdrawal from alcohol.
  • Examples:
    • Diazepam (Valium) - most familiar member.
    • Lorazepam and alprazolam - most prescribed.
  • Advantages:
    • Safer compared to general CNS depressants.
    • Lower potential for abuse.
    • Less tolerance and physical dependence develops.
    • Fewer drug interactions.

PHARMACOLOGIC EFFECTS OF BENZODIAZEPINES

  • Central Nervous System Effects:
    • Reduce anxiety and promote sleep.
  • Cardiovascular System Effects:
    • Effects vary between oral and intravenous administration.
  • Respiratory System Effects:
    • Weak respiratory depressants, decreasing risks of arrhythmias and hypotension.

MECANISM OF ACTION AND PHARMACOKINETICS

  • Molecular Mechanism:
    • Increase GABA activity in the CNS, leading to sedation.
  • Pharmacokinetics:
    • Absorption and distribution vary.
    • Metabolism impacts efficacy.
    • Time course of action differs among drugs.

THERAPEUTIC USES OF BENZODIAZEPINES

  • Indications:
    • Anxiety management.
    • Insomnia treatment.
    • Seizure disorder management.
    • Muscle spasms and alcohol withdrawal handling.
    • Applications during perioperative periods.

ADVERSE EFFECTS OF BENZODIAZEPINES

  • Central Nervous System Depression:
    • Possible anterograde amnesia and 'sleep driving.'
    • Paradoxical effects including increased anxiety and aggression.
  • Respiratory Depression:
    • Risk of overdose and serious complications.
  • Abuse Potential:
    • Use caution in pregnancy and lactation.
  • Drug Interactions:
    • Increased risk of CNS depression with other depressants.
  • Tolerance and Physical Dependence:
    • Prolonged use can lead to tolerance, less on respiratory depressant effects.

ACUTE TOXICITY

  • Effects of Overdose:
    • Oral: drowsiness, lethargy, confusion.
    • Intravenous: life-threatening reactions such as hypotension and respiratory/cardiac arrest.
  • Treatment Measures:
    • Oral: Gastric lavage or activated charcoal.
    • Flumazenil: Competitive benzodiazepine receptor antagonist used for treatment, noting it may not reverse respiratory depression.

ADMINISTRATION DETAILS

  • Routes of Administration:
    • Oral.
    • Parenteral (intramuscular and intravenous).

BENZODIAZEPINE-LIKE DRUGS

  • Zolpidem (Ambien):
    • Most widely used hypnotic for short-term insomnia management.
    • No apparent tolerance or increase in adverse effects with long-term use; possible side effects: daytime drowsiness, dizziness.
  • Zaleplon (Sonata):
    • Short-term insomnia management with less tolerance development; side effects include headache, nausea, and drowsiness.
    • Notable use recommendation: Take around 9-10 PM to avoid hangover effects.
  • Eszopiclone (Lunesta):
    • Used for insomnia without limitation on treatment duration; common side effect: bitter aftertaste and headaches.

RAMELTEON (MELATONIN AGONIST)

  • Brand Name: Rozerem.
  • Characteristics:
    • New hypnotic, not classified as a controlled substance.
    • Activates melatonin receptors, suitable for chronic insomnia (difficulty with sleep onset).
    • Rapid onset (around 30 minutes), but effects may diminish over prolonged use.

OTHER SEDATIVE OPTIONS

  • Antihistamines (e.g., Diphenhydramine):
    • Off-label for inducing drowsiness, may cause anticholinergic effects.
  • Melatonin:
    • Naturally produced by the body, available over-the-counter.
    • Recommendation against daily use.

BARBITURATES

  • General Properties:
    • Promote tolerance and dependence, high potential for abuse.
    • Multiple drug interactions present.
    • Can cause fatal respiratory depression in overdose.
  • Classification by Duration:
    • Ultrashort-acting (e.g., Thiopental).
    • Short-to-intermediate acting (e.g., Secobarbital).
    • Long-acting (e.g., Phenobarbital).
  • Mechanism of Action:
    • Binds to GABA receptor-chloride channel complex.

PHARMACOLOGIC EFFECTS OF BARBITURATES

  • CNS effects include depression and induction of hepatic drug-metabolizing enzymes.
  • Tolerance and Physical Dependence:
    • Variable tolerance to CNS effects; minimal tolerance to respiratory effects.

THERAPEUTIC USES OF BARBITURATES

  • Indications:
    • Seizure disorders, anesthesia induction, insomnia, and other specialized uses.

ADVERSE EFFECTS OF BARBITURATES

  • Risks include:
    • Respiratory depression leading to coma and pinpoint pupils.
    • Acute toxicity noted with potential treatments via activated charcoal and maintenance of oxygen supply.
    • Both oral and intravenous routes available, intravenous being safer.

SLEEP PHYSIOLOGY

  • Nature of Sleep:
    • Active, multiphase process restoring function and consolidating memory.
  • Sleep Regulation:
    • Hypothalamus acts as the major sleep center.
    • Hypocretins (orexins) promote wakefulness and REM sleep.
  • Sleep Phases:
    • Rapid Eye Movement (REM): 20-25% of sleep time, occurs every 90 minutes, involving heightened parasympathetic activity and vivid dreams.
    • Non-Rapid Eye Movement (NREM): 75-80% of sleep time with decreased sympathetic tone, reflecting reduced metabolic activity.

MANAGEMENT OF INSOMNIA

  • Insomnia: Defined as a condition requiring specific management principles.
  • Treatments include both non-drug therapies and drug treatments utilizing hypnotic drugs.

DRUGS USED TO TREAT INSOMNIA

  • Antidepressants:
    • Trazodone (Oleptro): Sedative with no tolerance build-up.
    • Doxepin: Tricyclic antidepressant effective for sleep maintenance.
  • Antihistamines:
    • E.g., Diphenhydramine and Doxylamine available OTC but develop tolerance quickly and have side effects.

DYSSOMNIAS

  • Defined as difficulties in falling or staying asleep, linked to fatigue and performance challenges.
  • Common types include:
    • Obstructive sleep apnea syndrome.
    • Hypersomnia.
    • Narcolepsy.
    • Circadian rhythm sleep disorders.

OBSTRUCTIVE SLEEP APNEA SYNDROME

  • Characterized by episodes of apneic breathing lasting over 10 seconds.
  • Symptoms include gasping and loud snoring caused by upper airway obstruction.
  • Risk factors include obesity, male sex, advancing age, and postmenopausal status.
  • Consequences of untreated include serious health risks like hypertension and stroke.

NARCOLEPSY

  • Defined as primary hypersomnia disruptive to usual sleep-wake cycles, involving hallucinations and sleep paralysis.
  • Associated with destruction of hypocretin secreting cells in the hypothalamus.

CIRCADIAN RHYTHM SLEEP DISORDERS

  • Disorders affecting the natural 24-hour sleep-wake schedule, leading to long-term health implications.
  • Causes may be intrinsic (e.g., delayed sleep phase) or extrinsic (e.g., rapid time zone change).

PARASOMNIAS

  • Abnormal behaviors during NREM stage 3 sleep including:
    • Sleepwalking, night terrors, violent actions, and rearranging of objects.
  • Often observed in children and may relate to trauma or brain injuries; therapy recommended for management.

REFERENCES

  • Burcham, J. & Rosenthal, L.D. (2019). Lehne’s Pharmacology for Nursing Care (10th Ed.). St. Louis: Elsevier Saunders.
  • Huether, S. & McCance, K. (2020). Understanding Pathophysiology (7th ed.). St. Louis: Elsevier Saunders.

QUESTIONS

  1. Question on teaching effectiveness regarding eszopiclone: The patient should recognize side effects like a bitter taste.
  2. Emergency preparedness for alprazolam overdose: Flumazenil is the supportive treatment choice.
  3. Proper assessment before administering ramelteon: Observation for potential drug interactions is critical for patient safety.