Feb05Sepracor

Information about Feb05Sepracor

Published on November 29, 2007

Author: BAWare

Source: authorstream.com

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Current Concepts in Sleep (Part1): Is insomnia a primary disorder of sleep disturbance…… or just another patient complaint? :  Current Concepts in Sleep (Part1): Is insomnia a primary disorder of sleep disturbance…… or just another patient complaint? Susan M. Skolly, PharmD, DABAT Senior Medical Liaison, Medical Affairs Sepracor, Inc Disclosure:  Disclosure Dr. Susan M. Skolly is a full-time employee of Sepracor, inc. The following information concerns a use that has not been approved by the US Food and Drug Administration Presentation Objectives: :  Presentation Objectives: Understand Primary and Secondary disorders of sleep; sleep and wake mechanisms Understand how sleep disorders are evaluated Discuss definition, epidemiology, and health consequences of chronic insomnia Identify common medications known to interfere with sleep processes Function of Sleep:  Function of Sleep Restoration and recovery Sleep serves to reverse and/or restore biochemical and / or physiological processes degraded during prior wakefulness Energy conservation 10% reduction of metabolic rate below basal level Memory consolidation Thermoregulation Homeostasis Function of Sleep:  Function of Sleep “If sleep does not serve an absolutely vital function, then It is the biggest mistake the evolutionary process ever made” A. Rechtschaffen Total Sleep Requirement:  Total Sleep Requirement Electrophysiologic Tools for Basic Polysomnogram (PSG):  Electrophysiologic Tools for Basic Polysomnogram (PSG) The combined use of the electroencephalogram, electrooculogram and electromyogram can determine between sleep stages and wakefulness Sleep Stages:  Sleep Stages Relaxed wakefulness prior to sleep 80% time in NREM (stages 1-IV), 20% in REM Each cycle is approximately 90-110 minutes 4-6 cycles per night NREM cycles predominate during first 1/3 of night REM cycles increase in duration during last 1/3 of night Normal Sleep Cycles:  Normal Sleep Cycles Children Young Adults Elderly CNS Neurotransmitters promoting wakefulness/ Arousal:  Acetylcholine (cholinergic) Main areas of cholinergic projection: Pedunculo-pontine / Lateral dorsal tegmental nucleus (PPT-LDT) & nuclei of basal forebrain Regulates thalamocortical transmission, Ascending Reticular activating System (ARAS), Initiation of REM sleep: Phasic –PGO waves occur Tonic – hippocampal theta waves Norepinephrine (adrenergic) Localization: Locus Coeruleus in dorso-lateral pons Cortical activation and wakefulness Histamine Location: posterior hypothalamus -- tuberomamillary nucleus (TMN) Inhibits sleep-promoting effects on VLPO through projections to anterior hypothalamus Projects: cerebral cortex, hippocampus, brain stem cholinergic nuclei CNS Neurotransmitters promoting wakefulness/ Arousal CNS Neurotransmitters promoting wakefulness/ Arousal:  CNS Neurotransmitters promoting wakefulness/ Arousal Glutamate (excitatory amino acid NT) Synthesized in large neurons of ARAS & projection neurons of thalamus & cortex Photic information reaches SCN through fibers of retino-hypothalamic tract (RHT) via glutamate neurotransmission Dopamine (catecholamine) Cells located in Ventral Tegmental Area (VTA) of midbrain Role: Behavioral responsiveness: reward & arousal CNS Neurotransmitters promoting wakefulness/ Arousal:  Serotonin (indolamine) Dorsal Raphe brainstem nuclei exhibit tonic firing during wakefulness/ quiescent during REM Sensory modulation and analgesia; Behavioral inhibition Prepares the brain for sleep Hypocretin (Orexin) (peptide NTs) Neurons are contained in posterior lateral hypothalamus Thought to modulate switching mechanism between sleep and wake states Close link between hypocretin receptor dysfunction and narcolepsy CNS Neurotransmitters promoting wakefulness/ Arousal Sleep Promoting CNS Neurotransmitters :  Sleep Promoting CNS Neurotransmitters GABA (inhibitory amino acid) & Galanin (peptide) Ventral Lateral Pre-Optic Nucleus (VLPO) within anterior hypothalamus -- “command & control center” for sleep Inhibitory connections to thalamus, descending projections inhibit cell bodies and dendrites of serotonin, norepinephrine, histamine, acetylcholine-producing inter-neurons Role: Initiation and maintenance of sleep spindles and SWS Melatonin (hormone of darkness) Secreted from pineal gland during darkness// indirectly feedbacks to SCN High levels secreted prior to sleep Levels low during wakefulness MOA and GABAA Receptor Complex:  MOA and GABAA Receptor Complex BZD binding GABA Complaints vary according to the “experience” of inadequate sleep:  Complaints vary according to the “experience” of inadequate sleep It takes me too long to fall asleep I keep waking up throughout the hour I never get deep sleep anymore I haven’t sleep in months I always wake up too early and can’t get back to sleep My mind won’t shut off at night I always have to drag myself out of bed in the morning because my nighttime sleep is so bad I’m tired all day Classification of Sleep Disorders:  Classification of Sleep Disorders Sleep Disorders Primary Disorders Secondary Disorders Sleeping disorder not related to another condition: RLS/PLMS Apnea Narcolepsy Circadian rhythm disorders Primary Insomnia Sleeping disorder resulting from another illness: Psychiatric Condition -depression, anxiety Medical conditions -pain, neurological, CV and GI Substance abuse Behavioral Induced American Psychiatric Association Task Force on DSM-IV-TR. Diagnostic and Statistical Manual of Mental Disorders (DMS-IV). 4th ed. Washington, DC: American Psychiatric Association;1994. Evaluation of Sleep Disorders:  Evaluation of Sleep Disorders Use of patient sleep diary Bed partner interview Review of medical and psychiatric history Sleep inventories SSS – Stanford sleepiness scale ESS- Epworth sleepiness scale (1-24) Polysomnogram (PSG) Full night (baseline) Split-night Multiple sleep latency test (MSLT) Relative measure of sleepiness Maintenance of wakefulness test (MWT) Relative measure of ability to stay awake Slide20:  A neurological movement disorder assoc with daytime sleepiness Unpleasant, tingling, creeping feelings or nervousness in legs during inactivity and sleep Irresistible urge to move legs 12 million people affected; genetic predisposition May be associated with other Neurologic conditions Restless Legs Syndrome Slide21:  Involuntary excessive daytime sleepiness May include sudden loss of muscle tone in response to strong emotion, hallucinations and sleep paralysis 125-200,000 or 1/2000 persons; often diagnosed in 2nd decade of life Impairs ability to engage in daily activities; can lead to injuries if not treated Narcolepsy At the…..Sunshine State Pharmacy:  At the…..Sunshine State Pharmacy Slide23:  Pauses in breathing due to obstruction in airway causing gasps and arousals during sleep 18 million affected --mostly males Risk Factors: Obesity and/or have high blood pressure, persons with upper airway physical abnormality Lowers blood-oxygen levels & increases work of heart Associated with cardiovascular problems and daytime sleepiness Sleep Apnea DSM-IV Definition of Chronic Insomnia:  DSM-IV Definition of Chronic Insomnia Difficulty with initiating sleep, maintaining sleep, or non-restorative sleep for ≥ 1 month Causes distress or impairment in social, occupational, or other areas of functioning Causes life interference American Psychiatric Association Task Force on DSM-IV-TR. Diagnostic and Statistical Manual of Mental Disorders (DMS-IV). 4th ed. Washington, DC: American Psychiatric Association;1994. Insomnia can present as……:  Insomnia can present as…… Insomnia Primary Insomnia Secondary Insomnia Idiopathic Insomnia Hyper-arousal disorder? Insomnia resulting from: Psychiatric: depression, anxiety Medical conditions: including pain, Neurological, CV and GI illnesses Substance abuse Behavioral Co-existing Insomnia Insomnia and other disorder co-existing together Slide26:  Illustration of Normal vs. Insomnia Sleep Pattern Awake Insomnia is Dynamic…:  Insomnia is Dynamic… Change can occur with… The Nature of Symptoms In one study, symptoms changed in 50% of patients over a 4-month period.1 OR The Duration of Insomnia2,3: Transient – several days Chronic – 3x/week & 1 month Recurrent Transient – several times/year 1Hohagen et al. Eur Arch Psych Clin Neurosci. 1993; 242:329. 2Buysse et al. Sleep. 2004; 27:A268., 3Hohagen F et al., Sleep. 1994 Sep;17(6):551-4. Insomnia Symptoms in Elderly:  Insomnia Symptoms in Elderly Bixler et al. Am J Psych 1979;136:1257-62 1979. (n=336) Karacan et al. Sleep wake disorders 1983;37-60. (n=285) Gislason et al. J Intern Med 1993;234:31-9. (n=430) Foley et al. Sleep 1995;18:425-32. (n=9282) NSF Sleep In America 2003;1-46 (n=1506) % Pts with Sleep Complaint Bixler (n=336)1 Karacan (n=285)2 Gislason (n=430)3 Foley (n=9282)4 NSF (n=1506)5 Insomnia Prevalence:  Insomnia Prevalence Ancoli-Israel et al. Sleep. 1999;22(suppl 2):S354-S358. One third of Americans are affected by insomnia N=1000, Ages 18 and over Insomnia Prevalence:  Almost 30% of American adults experience occasional insomnia; 10% on a chronic basis Those most at risk: Women Older adults Pts w/ psychiatric disorders Pts w/ medical disorders incl pain syndromes 2nd / 3rd shift-workers Insomnia Prevalence Reduced Total Sleep Time Impacts Health & Next-day Functioning:  Reduced Total Sleep Time Impacts Health & Next-day Functioning Increased pain in rheumatic diseases1 Increased number (4.5-fold) of serious accidents or injuries2 200,000 MVA each year caused by drowsiness (US DOT) Impaired alertness & memory Impaired psychomotor performance Increased healthcare utilization3 and absenteeism 1Mahowald et al. Sleep Medicine. 2000; 1: 179. 2Balter et al. J Clin Psychiatry. 1992; 53 Suppl: 34 3Simon et al, Am J Psychiatry. 1997; 154: 1417 Insomnia Is Associated With Co-morbid Medical and Psychiatric Disorders:  Chronic sleep loss may be risk factor for insulin resistance and obesity1,2 Increased risk of depression3,4 and anxiety3 Hypersecretion of ACTH and cortisol5 - Decreased growth hormone and prolactin secretion6 Insomnia patients have been shown to have reduced natural killer cell activity- suggesting impaired immune system7 Insomnia Is Associated With Co-morbid Medical and Psychiatric Disorders 1Mander BA, Van Cauter E et al. Unpublished data. 2Spiegel K. Lancet. 1999. 354:1435-1439. 3Breslau et al. Biol Psychiatry. 1996; 39: 411. 4Chang et al. Am J Epidem. 1997; 146: 105. 5 Vgontzas AN. 2001. J Cln Endocrinol. 86(8)3787-3794. 6Van Cauter et al JAMA. 2000;284:861-68 7 Irwin et al, 1995 Insomnia May Be A Risk Factor for New Psychiatric Disorders:  Insomnia May Be A Risk Factor for New Psychiatric Disorders Incidence (%) over 3.5 years * * * Incidence (%) Breslau N et al. Biol Psychiatry. 1996;39:411-418. *95% CI for odds ratio excludes 1 Multiple Factors Affect Sleep :  Multiple Factors Affect Sleep Stress Lifestyle Alcohol prior to bedtime Caffeine late in the day Exercise close to bedtime Life influencers Job change Divorce Financial problem Shift work (20% US employees) Jet lag Psychiatric conditions Depression Anxiety disorder Data Sources: NSF 2001, American Family Physician, 10/99 Diet Circadian Rhythm Disturbances Advanced sleep phase syndrome Delayed sleep phase syndrome Environmental Interference Temperature Noise Lighting Physical Factors Arthritis Back pain/backache Medication Effects Medications Affecting Sleep :  Medications Affecting Sleep Antidepressants SSRIs Bupropion MAOIs Venlafaxine Alcohol (acute/withdrawal) Anticholinergics Ipratropium bromide Diphenhydramine Antineoplastics Goserelin acetate Leuprolide acetate Pentostatin Daunorubicine Interferon Alfa Antihypertensives Clonidine Beta-blockers Propranolol Atenolol Pindolol Alpha-methyldopa Calcium channel blockers Diuretics / reserpine Medications Affecting Sleep:  Medications Affecting Sleep Sympathomimetic amines Bronchodilators Terbutaline Albuterol Salmeterol Metaproterenol Xanthine derivatives Theophylline Decongestants Phenylpropanolamine Pseudoephedrine Hormones OC’s / progesterone Thyroid preps Corticosteroids Neurology agents Phenytoin Topiramate / Lamotrigine Stimulants (amphetamine/methylphenidate) Levodopa Miscellaneous Quinidine Nicotine Caffeine Starbuck’s coffee! Anacin®, Excedrin®, Empirin® Chocolate Conclusions:  Conclusions The function of sleep and sleep mechanisms are not fully understood Insomnia may be a symptom of another illness, may co-exist with another illness or exist or alone as a primary disorder of sleep Insomnia impacts psychiatric and medical illness and next-day functioning Multiple factors affect sleep; particularly, medication use

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