Sleeping Pills, Insomnia, and Medical Practice Report of a Study (1979) / Chapter Skim
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Chapter 1: An Overview of Sleep and Medication
Chapter 1: An Overview of Sleep and Medication
Pages 17-46
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From page 17... ...
currently includes various forms of dependence on benzodiazepines and other minor tranquilizers under the heading of "drug dependence of the the barbiturate type." 3/ When an addicted individual suddenly reduces or discontinues his or her dose of one of these drugs, seizures may result as part of the withdrawal syndrome. The term addiction usually carries the connotation of a physical dependence on an agent, with the liability for withdrawal symptoms.
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From page 18... ...
NREM sleep is usually subdivided into four stages on the basis of relatively distinguishable electroencephalographic brain wave patterns: Stage 1, a brief transitional stage between wakefulness and sleep, is about 5 percent of the total night's sleep, and has a low voltage, mixed frequency EEG pattern. Stage 2, defined on the basis of sleep spindles and K complexes, usually constitutes 40-60 percent of total sleep in the young adult.
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From page 19... ...
The sleep states and stages are not yet well-defined by adult standards, and 50 percent of total sleep time may be spent in REM sleep. As adults enter middle age and old age, Stage 3 and 4 decrease markedly and sleep tends to become progressively more fragmented with brief arousals and longer periods of wakefulness.
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From page 20... ...
B Prescription Drugs Marketed as Hypnotics In addition to the hypnotic drugs marketed specifically for the induction of sleep, a variety of medicines marketed for other uses, such as the antihistamines and antidepressants, are sometimes given to aid sleep because they possess sedating qualities.
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Slow eye movements Stage 2 Sleep spindles Abstract thoughts 40-60% of K complexes total sleep Stage 3 Delta waves:20-507 of given epoch Secretion of growth Abstract thoughts 10-207 of hormone Memory consolida- total sleep Lion (?
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Intermittent Time awake after sleep onset and before final arousal Awake of sleep period; also known as wake after sleep onset or WASO. NREM Sleep Non-Rapid-Eye-Movement Sleep; known also as orthodox sleep, S-sleep, slow-wave sleep.
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Stage 1 A stage of non-REM sleep, defined by low voltage, mixed frequency EEG pattern in absence of rapid eye movements and EMG atonia. Usually seen as brief transition phase lasting 1-3 minutes between wake fulness and other stages of sleep.
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The short-acting hypnotic barbiturates often produce death at lower blood levels than longer acting barbiturates, and may do so more rapidly. Toxicity is worsened by concomitant ingestion of alcohol.
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Fatal doses of secobarbital, for instance, are usually associated with blood levels of 1.1-6.0 mg/100 ml; for ethanol, fatal blood levels are generally thought to be about 400 mg/100 ml. Fatalities have occurred, however, with a combination of respective levels of 0.5 and 100 mg/100 ml.
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From page 26... ...
In two intensive investigations of over 900 cases, however, only two cases of barbiturate overdose associated with genuine amnesia for ingesting the pills were found (and one case was rather dubious) ; all other cases of alleged "automatism" were discovered to be based on retrospective denial of suicidal intent by disturbed individuals who had indeed attempted suicide.
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From page 27... ...
38/ The diazepam blood levels in the two decedents were 5.0 micrograms/ml and 19.0 micrograms/ml -about five and 19 times the therapeutic range, respectively. In 912 combined drug deaths, diazepam was present along with various amounts of other drugs, including alcohol.
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From page 28... ...
17/ Mild withdrawal symptoms may be seen after cessation of therapeutic doses, 42/ and severe withdrawal syndromes, including delirium and seizures, may result from abrupt withdrawal of high doses. 43/ Interaction with ethanol Among 914 drug deaths in which diazepam was present, Finkle reported 51 cases in which the cause of death was attributed only to the combination of diazepam and alcohol.
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From page 29... ...
50/ Although ethanol may inhibit metabolism of benzodiazepines, and in some cases produce increased blood levels, it also appears that there may be behavioral interactions long before maximum blood levels are achieved. 52/ Non-Barbiturate, Non-Benzodiazepine Hypnotics With the exception of chloral hydrate, most of these agents were developed in response to the need for potent hypnotics that do not pose the same liabilities as barbiturates.
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Powerful anticholinergic side effects may be problematic. The lethal dose of glutethimide is thought to be 20-40 times the usual hypnotic dose, but 10 times the hypnotic dose may produce severe intoxication.
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Chronic ingestion of large amounts of methaqualone may lead to dependence. Clinical estimates indicate that ingestion of seven times the hypnotic dose for one month may be sufficient to produce withdrawal seizures.
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Dependence may result from the chronic ingestion of ethchlorvynol in quantities 2-3 times the hypnotic dose.
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When a normal subject takes alcohol for several days, tolerance to the REM-suppressing effect occurs, and amounts of REM sleep return to normal. 80/ Upon cessation of alcohol administration, however, there may be a rebound increase in REM sleep for several days.
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Although L-tryptophan is not a hypnotic approved by the Food and Drug Administration, it is easily obtained as a dietary supplement from natural food stores, and its use as a hypnotic has been advocated in lay publications. Although its mild hypnotic effects have been shown in several studies, 86/-88/ it has yet to be evaluated for clinical use in various types of insomnia, compared to standard drugs.
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From page 35... ...
Phenobarbital IV Luminal(R) NONBARBITURATES Benzodiazepines Flurazepam IV Dalmane(R)
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Abuse of the substance may lead to moderate or low physical dependence or high psychological dependence.
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From page 37... ...
Abuse of the substance may lead to limited physical dependence or psychological dependence relative to the substances in Schedule IV. Requirements Dispensing limits: Security: Manufacturing quotas: OTC or Prescription drugs limited to M.D order Secure storage area No, but some drugs limited by Schedule II quotas Source: U.S.
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From page 38... ...
Liss, Inc., New York 1978~. Guilleminault, C., Malta, J., et al; Asystole and rapid eye movement sleep: a life threatening disease related to phase events?
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A study of hypnotic drugs in patients with chronic diseases, J Chronic Dis.
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and Linnoila, M Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving.
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Benzodiazepine appraisal in death cases in Los Angeles County, 1977. Department of Chief Medical ExaminerCoroner, Los Angeles.
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From page 42... ...
and Mattila, M.J. Drug interaction on psychomotor skills related to driving: diazepam and alcohol.
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From page 43... ...
Effect of treatment with diazepam or lithium and alcohol on psychomotor skills related to driving.
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and Iber, F.L. Comparison of blood clearance of ethanol and tolbutamide and activity of hepatic ethanol-oxidizing and drug-metabolizing enzymes in chronic alcoholic subjects.
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Doxepin Fatalities, Department of Chief Medical Examiner-Coroner, Los Angeles, California, (unpublished)
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From page 46... ...
Gen., Psychiatry 28:146-149, 1973. Baiter, M.B., and Bauer, M.L., Patterns of prescribing and use of hypnotic drugs in the United States in Sleep Disturbance and Hypnotic Drug Dependence (Clif.
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