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Sedative & Hypnotic Drugs Part II
The document discusses sedative and hypnotic drugs, focusing on sleep neurochemistry and various hypnotic classes, including benzodiazepines and melatonin agonists. It presents insights on insomnia epidemiology, neurobiology of sleep, and compares the effectiveness and safety profiles of different sleep medications. Additionally, it includes details on drug actions, potential adverse effects, and a self-test question related to overdose management.
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Sedative & Hypnotic Drugs Part II
- 1. Sedative & HypnoticDrugs II Brian J. Piper, Ph.D., M.S. January 23, 2013
- 2. Goals • Sleep Neurochemistry •Hypnotic Pharmacy – benzodiazepines – “Z” drugs – melatonin agonists
- 3. Sleep Across theLifespan Roffwarg, Muzio, & Dement (1966). Science, 152(3722), 604-619.
- 4.
- 5. Epidemiology of Insomnia Sex: 2 F: 1 M 5% of adults Age: 50% of elderly Other conditions: smoking or drinking anxious or depressed chronic pain Ohayon (2002) Sleep Medicine Reviews, 67(2), 97-111.
- 6. Neurobiology of Sleep • Hypothalamus – Suprachiasmatic Nucleus (SCN): pacemaker • Pineal Gland (Melatonin) • Reticular Formation (5-HT, DA, NE, ACh)
- 7. Arousal Spectrum Stahl (2008).Essential Psychopharmacology, p. 817.
- 8. Perfect Hypnotic • On/Off •Non-habit forming
- 9. Stahl (2008). EssentialPsychopharmacology, p. 840.
- 10. Stahl (2008). EssentialPsychopharmacology, p. 835.
- 11. Half-Life ≈ 6hours Stahl (2008). Essential Psychopharmacology, p. 841.
- 12. FDA Approved For Insomnia (t1/2) Estazolam (17) Flurazepam (70) Quazepam (39) Temazepam (25) Triazolam (2) Stahl (2008). Essential Psychopharmacology, p. 841.
- 13. Benzodiazepine Dependence Stahl (2008).Essential Psychopharmacology, p. 841.
- 14. “Z Drugs” • Examples: zolpidem, zaleplon • MOA: α1 GABAA POM • Indications: insomnia • Adverse Events – Allergic reaction – Automatic behaviors (non-remembered) Min 1 to 3: http://www.youtube.com/watch?v=FDK1TAkmHjs Daley et al. (2011). Journal of the American Academy of Psychiatry & the Law, 39, 535-542.
- 15. Idealized (?) Stahl (2008).Essential Psychopharmacology, p. 838.
- 16. Benzo versus “Zdrug” • Insomniacs were randomized to receive 28 days of zolpidem (10 mg/day, N = 79) or temazepam (20 mg/day, N = 84). Double-blind • Sleep diaries were completed for 1 week post- hypnotics temazepam zolpidem ↓ total sleep time (40%+) 26% 27% ↑ sleep onset latency (40%+) 58% 53% Voshaar et al. (2004). European Neuropsychopharmacology, 14, 301-306.
- 17. Modified from Stahl(2008). Essential Psychopharmacology, p. 838.
- 18. Melatonin Rhythm Reiter, R.J. (1995). Experimental Gerontology, 30(3/4), 199-212.
- 19. Ramelteon • MOA: Melatonin (M12) agonist • Indication: insomnia (sleep onset) • Half-life: 2 hours • Adverse effects: limited • Schedule: not controlled Bonus (3 min): http://www.youtube.com/watch?v=rIpjfTbCHJ8
- 20. Summary Benzo Z drug Melatonin Agonist Diazepam Zolpidem Ramelteon MOA GABAA α1,2,3,5 GABAA α1 M1,2 Year 1963 1986 2005 Developed Indication Insomnia (onset & Insomnia (onset) Insomnia (onset) maintenance) Long-term Half-Life 50 3 2 (hours) Withdrawal Yes Yes? No Issues
- 22. Stahl (2008). EssentialPsychopharmacology, p. 819.
- 23. Self-Test #1 • PatientC.D. appears to have over-dosed on Zolpidem. What agent would be appropriate in this situation? – A) zaleplon (Sonata) – B) flumazenil (Romazicon) – C) pentobarbital (Nembutal) – D) ramelteon (Rozerem) – E) eszopiclone (Lunesta)
Editor's Notes
- #6 Other factors: marital status (higher for divorced) and lower income have been less consistently observed.
- #7 The term "reticulum" means "netlike structure," which is what the reticular formation resembles at first glance. RF includes raphe and locus coeruleus and projects to thalamus.
- #10 Half-life< 3 hours is too short.
- #11 A half-life of 15-30 hours is too long (e.g. estazolam or ProSom).
- #13 Half-lifes includes half-life of major metabolites and are from Katzung.
- #14 Do a search for benzodiazepine addiction in youtube for videos of people ranting about their benzo experience.
- #15 Complex automatic behaviors occur in 1-5% of patients.
- #17 Rebound insomnia (compared to placebo baseline) does not differ between these agents. Interestingly, this study was funded by the manufacturer of zolpidem (Sanofi-Synthelab).
- #20 Adverse reactions from PDR.net include dizziness, somnolence, fatigue, nausea, and exacerbated insomnia.
- #23 Excessive stimulants (amphetamine) can go beyond arousal and result in hallucinations.