Sedative & Hypnotic Drugs Part II
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This PPT is part 2 of 2 lectures given to second year pharmacy students in a pharmacology & toxicology class.
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Sedative & Hypnotic Drugs Part II
- 1. Sedative & Hypnotic Drugs 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 the Lifespan Roffwarg, Muzio, & Dement (1966). Science, 152(3722), 604-619.
- 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). Essential Psychopharmacology, p. 840.
- 10. Stahl (2008). Essential Psychopharmacology, p. 835.
- 11. Half-Life ≈ 6 hours 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 “Z drug” • 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). Essential Psychopharmacology, p. 819.
- 23. Self-Test #1 • Patient C.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)
Hinweis der Redaktion
- Other factors: marital status (higher for divorced) and lower income have been less consistently observed.
- 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.
- Half-life< 3 hours is too short.
- A half-life of 15-30 hours is too long (e.g. estazolam or ProSom).
- Half-lifes includes half-life of major metabolites and are from Katzung.
- Do a search for benzodiazepine addiction in youtube for videos of people ranting about their benzo experience.
- Complex automatic behaviors occur in 1-5% of patients.
- Rebound insomnia (compared to placebo baseline) does not differ between these agents. Interestingly, this study was funded by the manufacturer of zolpidem (Sanofi-Synthelab).
- Adverse reactions from PDR.net include dizziness, somnolence, fatigue, nausea, and exacerbated insomnia.
- Excessive stimulants (amphetamine) can go beyond arousal and result in hallucinations.