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PHCL-3720/5720 Pharmacology II: 

PHCL-3720/5720 Pharmacology II Dr. William Messer Department of Pharmacology Office: WO2243 Phone: 419-530-1958 Email: wmesser@utnet.utoledo.edu

Syllabus: 

Syllabus Topics Exams

PHCL-3720/5720 Website: 

PHCL-3720/5720 Website Home page http://www.neurosci.pharm.utoledo.edu/PHCL3720.htm Presentations http://www.neurosci.pharm.utoledo.edu/PHCL3720/Lectures.htm Location of lectures http://www.neurosci.pharm.utoledo.edu/PHCL3720/Lecture01.ppt Will not load directly Save as .ppt file

Insomnia Overview: 

Insomnia Overview Characteristics of sleep Electroencephalogram Sleep patterns Neurochemistry Sleep deprivation Sleep deprivation implications Sleep disorders Hypnotic drugs

Characteristics of Sleep: 

Characteristics of Sleep Decrease in metabolic rate Decrease in arterial blood pressure Slower pulse rate Lower sympathetic nervous system activity Relaxation of skeletal muscle

Electroencephalogram: 

Electroencephalogram EEG provides insight into neural activity associated with different phases of sleep Four stages of slow wave sleep REM sleep Dream sleep Similar in some ways to wakefulness

Sleep and EEG Patterns: 

Sleep and EEG Patterns

Sleep patterns: 

Sleep patterns Change throughout life Newborns sleep > 50 % of time REM sleep occupies roughly 50 % of sleep time Sleep gradually decreases with age to approximately 8 hours per day Sleep levels are especially low in the elderly

Neurochemistry: 

Neurochemistry Prostaglandins Prostaglandin E2 promotes wakefulness Prostaglandin D2 induces sleep Serotonin Decreases sleep through inhibition of reticular activating system 5-HT2 agonists prevent sleep, yet produce REM-like symptoms

Neurochemistry: 

Neurochemistry Acetylcholine Acetylcholine enhances sleep (parasympathetic tone) May help entrain circadian rhythm Histamine Drowsiness associated with H1 antagonists Histamine important for wakefulness

Sleep deprivation: 

Sleep deprivation Symptoms Difficulty in thinking, concentrating, learning Anxiety and irritability Over-eating Decreased seizure threshold Behavioral disturbances Psychosis

Sleep deprivation: 

Sleep deprivation Associated with increased risk of psychiatric illness Insomnia affects 30% of population (most prevalent in the elderly) Effects serious in 17% of the population Individuals with less than 6 hours of sleep per night have a 70% higher mortality rate

Insomnia: 

Insomnia Transient Less than three days Associated with brief stressor Brief use of hypnotics may help Short-term Associated with grief or ongoing stress Intermittent use of hypnotics (~1 week) Long-term (over 3 weeks)

Insomnia/Psychiatric Illness: 

Insomnia/Psychiatric Illness

Sleep Disorders: 

Sleep Disorders Disorders of initiating or maintaining sleep (DIMS) Associated with psychiatric illness Also linked to drug and/or alcohol abuse May be associated with withdrawal from CNS drugs Sustained use or withdrawal from other drugs Alcoholism

Sleep Disorder Causes: 

Sleep Disorder Causes Psychological factors Sleep apnea (Respiratory impairment) Myoclonus (Involuntary muscle contractions) Ideopathic (Unknown)

Treatment of Insomnia: 

Treatment of Insomnia Therapy Counseling Drug intervention

Sleep Hygiene: 

Sleep Hygiene Minimize use of caffeine, cigarettes, stimulants and other medications Recognize that alcohol may cause fragmentation of sleep Maintain regular sleep schedule Exercise regularly, not too close to bedtime Avoid napping (after 2 p.m.)

Stress Management: 

Stress Management Recognize association between stressful events and sleeplessness Ventilate conflicts and anger to avoid internalization Address daily worries a few hours before bedtime Be tolerant of occasional sleeplessness Avoid rumination over sleep difficulty Try relaxation techniques

Sedatives and Hypnotics: 

Sedatives and Hypnotics Approximately $700M spent per year in U.S. Between $1.6-12B per year world-wide Initially barbiturates were used as sedatives in the treatment of anxiety Drugs for sleep disorders Hypnotics vs. Anxiolytics

Sedatives and Hypnotics: 

Sedatives and Hypnotics Sedatives Decrease activity Moderate excitement Calms recipient Hypnotics Produce drowsiness Facilitate onset and maintenance of sleep

Ideal Hypnotics: 

Ideal Hypnotics Induce sleep rapidly Increase total sleep time Decrease sleep awakening Normal sleep patterns Sense of well-being Low side effect profile No day-time after effects Devoid of tolerance or dependency No drug interactions Low toxicity

Benzodiazepines: 

Benzodiazepines All benzodiazepines have sleep-inducing effects Not all benzodiazepines are ideal hypnotics

Hypnotics: 

Hypnotics Flurazepam Temazepam Triazolam Quazepam Estazolam Zolpidem Zaleplon Dalmane® Restoril® Halcion® Dorval® ProSom® Ambien® Sonatal®

Effects on Sleep Patterns: 

Effects on Sleep Patterns Shorten slow wave sleep, REM cycle Increase total sleep time (stage 2) Increase number of REM cycles (total REM increases) Sense of deep, refreshing sleep Decrease in sleep latency No significant REM rebound on withdrawals