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Biomedical subjects

A Kales

Publications and source records attributed to A Kales.

At least 73 records · Page 4Linked to original sources

Clinical neuropharmacology of sleep disorders.

Within the context of the comprehensive treatment of sleep disorders, which includes medical, neurologic, psychiatric, and social interventions, use of medication is often indicated. Among the three benzodiazepine hypnotics that are available in the United States for the treatment of insomnia, flurazepam is effective for both sleep induction and maintenance, and it retains most of its efficacy over a 4-week period of nightly administration; temazepam is effective only for sleep maintenance, and triazolam improves both sleep induction and maintenance with initial but not with continued administration. Rebound phenomena are more frequent and intense with the more rapidly eliminated drug, triazolam, and to a lesser degree with temazepam. Also, with triazolam, certain behavioral side effects, such as amnesia and psychotic-like symptoms, have been reported. With flurazepam, which is a slowly eliminated benzodiazepine, daytime sedation is more frequent than with the other two drugs. When insomnia is secondary to major depression, antidepressant medication should be administered. Methylphenidate, amphetamines, or other stimulant medications are used for the symptomatic treatment of the sleepiness and sleep attacks of narcolepsy and hypersomnia. For cataplexy and the other two auxiliary symptoms of narcolepsy, imipramine or other tricyclics are the drugs of choice. Protriptyline and medroxyprogesterone have been used in treating mild cases of obstructive sleep apnea, but their efficacy is limited. Similarly, for the treatment of central sleep apnea, medroxyprogesterone and acetazolamide have shown only limited effects. Medication for patients with sleepwalking, night terrors, or nightmares should be prescribed judiciously, and primarily when treatment of an underlying psychiatric condition is desired. The neuropharmacology of sleep should also consider drugs that may cause sleep disorders. Medications with sleep disturbing effects include various antihypertensives, bronchodilators, and the energizing antidepressants. Withdrawal of REM-suppressant drugs, such as the barbiturates, may cause nightmares in association with a REM rebound. Occasionally, a drug or a combination of drugs may produce somnambulistic-like activity in some patients.

Antidepressive Agents↗

Uvulopalatopharyngoplasty as a treatment of obstructive sleep apnea precipitated by uvular prolapse.

Two patients are discussed in whom obstructive sleep apnea was precipitated by uvular prolapse into the larynx and successfully treated by uvulopalatopharyngoplasty. Although tracheostomy has been the definitive treatment for obstructive sleep apnea, uvulopalatopharyngoplasty has also been used as an alternative surgical procedure. However, indications for its successful use have not been clearly defined. Our experience illustrates that the surgical approach to obstructive sleep apnea is dependent on a thorough diagnostic evaluation that includes a sleep history, head and neck examination, hypnopolygraphic recording and, if indicated, nocturnal fiberoptic endoscopy.

Endoscopy↗

Narcolepsy/cataplexy. IV: Diagnostic value of daytime nap recordings.

Sleep and wakefulness patterns in daytime naps of 50 patients with narcolepsy/cataplexy were compared with those of 50 controls. Each subject was monitored polygraphically during 2 one-hour nap periods. A sleep-onset REM period in either of the 2 daytime naps was observed to have a higher diagnostic sensitivity (78%) than an abnormally shortened sleep latency (68%). However, the specificities of a sleep-onset REM period (88%) or abnormally shortened sleep latency (90%) were quite similar. When the occurrence of either a sleep-onset REM period or a shortened sleep latency was evaluated in either of the two naps, the overall sensitivity was increased to 84% while the specificity was decreased only to 80%. The limitations of and indications for the use of testing for sleep and REM latencies in the diagnosis of narcolepsy in clinical practice are discussed.

Adult↗

Adverse reactions to benzodiazepine hypnotics: spontaneous reporting system.

The rates of reported adverse drug reactions involving the central nervous system were compared among patients taking any of three benzodiazepine hypnotics: flurazepam, temazepam, and triazolam. These rates, based upon data collected through the spontaneous reporting system of the Food and Drug Administration, were controlled for the number and size of new prescriptions for each drug. In general, triazolam had much higher overall rates than did the other two drugs. Hyperexcitability and withdrawal effects were greatest for triazolam and least for flurazepam. Amnesia was reported almost exclusively with triazolam. Rates for other cognitive as well as affective and other behavioral effects were also much greater for triazolam and about equal for the other two drugs. Finally, daytime sedation was reported slightly more for flurazepam than triazolam and least for temazepam which was also reported most frequently as lacking hypnotic effect.

Adult↗

Pharyngeal size and resistance in obstructive sleep apnea.

Although anatomic and physiologic abnormalities of the upper airway are thought to be important in the pathogenesis of obstructive sleep apnea (OSA), the relative contributions of these factors have not been elucidated. We therefore measured pharyngeal cross-sectional area (PCSA) and pharyngeal air-flow resistance (Rp) in 12 overweight men with severe symptomatic OSA (mean apnea plus hypopnea index [AHI], 66.9 +/- 6.0 events per hour) and in 17 age- and weight-matched control subjects without spontaneous complaints of OSA symptoms (mean AHI, 4.9 +/- 1.6 events per hour). During wakefulness, PCSA was assessed during breath cessation at FRC by computed tomography (CT) and Rp by measuring inspiratory air-flow resistance between the choanae and epiglottis. No measure of PCSA differed significantly between patients and control subjects, and only 1 measure of PCSA, minimal pharyngeal area, correlated with AHI in all subjects (r = -0.38, p less than 0.05). In contrast, Rp was significantly higher (p less than 0.05) in patients (6.9 +/- 1.0 cm H2O/L/s) than in all control subjects (4.2 +/- 0.5 cm H2O/L/s) and correlated significantly with AHI (r = 0.53, p less than 0.01). We conclude that increased inspiratory resistance to air flow in the naso-oropharynx is present during wakefulness in overweight men with OSA, when compared with matched control subjects without symptomatic OSA, and is associated with disordered breathing during sleep. This occurs even though computed tomography is unable to demonstrate that pharyngeal size during wakefulness at FRC is significantly different between patients and control subjects. These observations suggest that the ability to dilate the pharynx during inspiration may be defective in patients with OSA.

Airway Resistance↗

Further clinical experience with the silicone tracheal cannula in obstructive sleep apnea.

We report on the perioperative and postoperative course of 47 patients with severe obstructive sleep apnea, who underwent tracheostomy by use of a silicone tracheal cannula developed by Dr. William Montgomery. Our initial experience with the first 20 of these patients (presented in 1982) was quite favorable because of the ease of insertion and care, a high degree of patient acceptance, and infrequent complications. With our current sample, larger experience, and more prolonged follow-up, we noted that symptomatic granulation tissue formation, with or without wound infection, occurred more frequently than was initially appreciated. In 21% (10 of 47) of the cases, the only way to resolve this problem was to remove this device and replace it permanently with a metal (or other type) tracheostomy tube. Other complications included tracheal narrowing and cannula malpositioning and fragmentation. This full report lists in detail the incidence of complications associated with our use of this cannula and modifications which may lessen these.

Adult↗

Effects of oral narcotics on sleep-disordered breathing in healthy adults.

Alcohol and benzodiazepines may increase sleep-disordered breathing by decreasing activity of pharyngeal dilating muscles, favoring the development of obstructive apneas and hypopneas. Narcotics cause greater depression of wakeful respiration than the previously mentioned drugs; however, the influence of narcotics on the upper airway and breathing during sleep has not been studied. We, therefore, examined, in 12 healthy adults, the effects of oral hydromorphone hydrochloride (2 and 4 mg) on breathing during sleep and on a variety of awake respiratory variables (minute ventilation, gas exchange, and chemoresponsiveness). In addition, awake pharyngeal inspiratory airflow resistance was determined before and after narcotic administration to assess the drug's influence on patency of the upper airway. Following both doses, minute ventilation decreased, and carbon dioxide pressure increased. The 4-mg dose of hydromorphone hydrochloride also produced a significant decrement in the hypoxic ventilatory response, whereas hypercapnic responsiveness and pharyngeal resistance did not change following either dose of the drug. Despite the respiratory depression during wakefulness described previously, no significant change was observed in any measure of sleep-disordered breathing after either dose of narcotic. We conclude that in healthy individuals without suspected sleep apnea, oral hydromorphone in standard dosages does not significantly increase sleep-disordered breathing. This result may be due to a lack of selective depression of upper-airway muscular function by the doses of narcotic used.

Adult↗

Sleep disorders: sleep apnea and narcolepsy.

Symptoms of obstructive sleep apnea, a potentially life-threatening disorder, include excessive daytime sleepiness and sleep attacks, nocturnal breath cessation, and snorting and gasping sounds. These symptoms usually become manifest before age 40 and cluster within a few years. Most patients are obese, hypertensive men who eventually develop cardiovascular abnormalities. If sleep apnea is suspected based on clinical information, a sleep laboratory evaluation is indicated. For severe obstructive sleep apnea, tracheostomy is the most effective treatment. Narcolepsy, another sleep disorder, is a life-long and usually disabling condition. In most narcoleptic patients the first symptoms develop during childhood or adolescence, yet many years pass before the proper diagnosis is made. The presence of sleep attacks together with auxiliary symptoms, particularly cataplexy, is diagnostic. Treatment of narcolepsy includes stimulants in combination with therapeutic naps for sleep attacks and tricyclic drugs for cataplexy.

Humans↗

Sleep disorders: insomnia, sleepwalking, night terrors, nightmares, and enuresis.

All five sleep disorders reviewed in this article can be adequately evaluated in the physician's office by taking a sleep history and conducting a careful general medical and psychiatric assessment. Insomnia, the commonest sleep disorder, is more prevalent among women and elderly and psychosocially disadvantaged persons. Personality factors such as a tendency toward the internalization of emotions and the occurrence of stressful life events also play a major role in the development of chronic insomnia. A multidimensional approach is indicated for the treatment of chronic insomnia; hypnotic drugs should be used only as an adjunct to this treatment. In children, sleepwalking and night terrors (two manifestations of the same pathophysiologic substrate), nightmares, and enuresis are commonly related to developmental factors; counseling and reassurance of the parents is indicated. Psychopathologic disorders are usually present in secondary enuresis, as well as in sleepwalking, night terrors, and nightmares that occur in adulthood. Psychotherapy and the occasional use of psychotropic drugs may be necessary in the treatment given adults with these disorders.

Dreams↗

Comparison of short and long half-life benzodiazepine hypnotics: triazolam and quazepam.

Two benzodiazepine hypnotics, triazolam, 0.25 mg, with a short elimination t1/2, and quazepam, 15 mg, with a long t1/2, were evaluated in 22-night sleep laboratory studies. Quazepam improved sleep significantly during both short- and intermediate-term use. Daytime sleepiness, which decreased with continued use, was the side effect most often associated with quazepam dosing. In contrast, triazolam dosing did not significantly improve any of the major sleep efficiency parameters, and there was a rapid development of tolerance for the drug's slight initial effectiveness. In addition, there were a number of behavioral side effects including amnesia, confusion, and disinhibition. Withdrawal of triazolam was associated with sleep and mood disturbances (rebound insomnia and rebound anxiety), whereas quazepam exerted carryover effectiveness. Thus the data in this study show that the 0.25 mg dose of triazolam, which is being prescribed increasingly, has a profile of side effects that is similar to that of the 0.5 mg dose.

Adult↗

Quazepam and temazepam: effects of short- and intermediate-term use and withdrawal.

Two benzodiazepine hypnotics, one with an intermediate elimination t1/2 (temazepam, 15 mg) and the other with a long t1/2 (quazepam, 15 mg), were evaluated in 22- night sleep laboratory studies. The effectiveness and side effects of these benzodiazepines were assessed during short- and intermediate term use. Subjects were also assessed for the presence of rebound insomnia after abrupt withdrawal. Quazepam, 15 mg, was significantly effective in improving sleep both with short- and intermediate-term use, but the effectiveness of temazepam was considerably less. Although temazepam was effective for maintaining sleep with short-term use, there was rapid development of tolerance for this effect with intermediate-term use. Temazepam did not produce any behavioral side effects during either drug condition. The only side effect associated with quazepam was a significant degree of daytime sleepiness. After its withdrawal, temazepam was associated with some sleep and mood disturbance on the first withdrawal night, whereas quazepam had carryover effectiveness.

Adult↗

Lorazepam: effects on sleep and withdrawal phenomena.

Lorazepam, an anxiolytic drug, was evaluated in a 2-mg dose using a 16-night protocol including 7 nights of drug trial. Initially and with continued use the drug was moderately effective in inducing and maintaining sleep. Side effects included episodes of memory impairment and confusion in 2 subjects and group mean increases in daytime anxiety and tension with continued drug use. Following drug withdrawal, there was a marked and significant worsening of sleep above baseline levels (rebound insomnia) on the third night as well as significant increases in tension and anxiety the next day. The peak degree of withdrawal sleep disturbance was several times the peak degree of sleep improvement with drug administration.

Adult↗

Narcolepsy/cataplexy. III: Nocturnal sleep and wakefulness patterns.

Nocturnal sleep and wakefulness patterns of 50 patients with narcolepsy and cataplexy were compared to those of 50 control subjects. A sleep onset REM period (SOREM) occurred in 22 (44%) of the patients but in none of the controls. Comparisons among patients showing a SOREM, patients without this abnormality, and controls demonstrated that the timing, number and duration of the remaining REM periods did not differ across the three groups. Thus, the basic REM sleep disturbance in narcolepsy appears to relate to the timing of onset of the initial REM period. This finding lends further support to the theory of dual control of REM-NREM cycling. While narcoleptics took significantly less time to fall asleep, they had significantly more awakenings, wake time after sleep onset and total wake time. The disturbed sleep experienced by patients could not be accounted for by the presence of a sleep onset REM period or the use of medication. Nocturnal wakefulness appeared to be distributed in a regular oscillating manner throughout the recording period similar to the pattern of daytime vigilance previously reported in normal subjects. Thus, typical nocturnal dampening of daytime ultradian vigilance rhythms may be lost in the narcoleptic patient.

Adult↗

Rebound insomnia and elimination half-life: assessment of individual subject response.

Following abrupt withdrawal of five benzodiazepine hypnotics, the presence of rebound insomnia on individual subject nights was evaluated in comparison to a placebo group. During the first three nights of withdrawal, the frequency of occurrence of rebound insomnia for drugs with relatively rapid rates of elimination (triazolam, midazolam, and lormetazepam) was significantly higher than that for the placebo control group. In contrast, the frequency of withdrawal sleep difficulty for two slowly eliminated hypnotics (flurazepam and quazepam) was similar to that of the placebo control group during each of five successive three-night segments of a 15-night withdrawal period. These findings, based on individual subject-night data, confirm and extend previous reports using group mean values that demonstrate a frequent, immediate, and intense degree of rebound insomnia following abrupt withdrawal of relatively rapidly eliminated hypnotic drugs and an infrequent, delayed, and milder degree of sleep difficulty following withdrawal of slowly eliminated drugs.

Adult↗