Barbiturates and lung cancer in humans.

In a hypothesis-generating study looking for possible carcinogenic effects of drugs in humans, each of three barbiturates (pentobarbital sodium, phenobarbital, and secobarbital sodium) showed a statistically significant association with the subsequent development of lung cancer, with relative risks ranging from 1.5 to 2.8. Further analysis showed that the association was not explained by the increased prescription of barbiturate drugs shortly before the diagnosis of lung cancer or by an association of barbiturate use with cigarette smoking. Much of the data did not support a causal relationship. Neither a relation of lung cancer to duration or intensity of use not one between barbiturate use and a specific histologic type could be demonstrated.

Screening prescription drugs for possible carcinogenicity: eleven to fifteen years of follow-up.

Using computerized pharmacy records from 1969 to 1973 for a cohort of 143,574 members of the Kaiser Permanente Medical Care Program, we have been testing associations of 215 drugs or drug groups with subsequent incidence of cancer at 56 sites. This paper presents findings with follow-up through 1984. There were 227 statistically significant (P less than 0.05, two-tailed) associations: 170 positive, 57 negative. Some were undoubtedly chance findings; others were likely due to confounding by unmeasured covariables. However, several associations suggested hypotheses for further studies and/or the need for continued observation. Most notable among findings not previously reported were associations of several antibiotics, both oral and topical, with lung cancer. These associations could not be explained by indications for drug use or by differences in smoking habits between users and nonusers, and suggest a possible link between the occurrence of bacterial infections and risk for cancer. In general, our results continue to suggest that most medications used during that period did not affect cancer incidence substantially. However, for less frequently prescribed medications, our power to detect moderate increases in cancer risk was quite low.

Clinical implications of warfarin interactions with five sedatives.

The intensity, uniformity and time course of anticoagulant interference by phenobarbital, secobarbital, glutethimide, chloral hydrate and methaqualone were systematically investigated in 16 patients receiving coumarin therapy. Each subject received an individualized fixed daily dose of warfarin and served as his own pre- and postsedative treatment control. Prothrombin times were measured four times weekly during five long-term experiments. Anticoagulant inhibition was observed during the administration of phenobarbital, secobarbital and glutethimide; there was no significant change in prothrombin test results during the trials of chloral hydrate and methaqualone. Barbiturates and glutethimide should not be administered to patients receiving coumarin drugs. The concurrent use of drugs from these groups is decreasing according to a survey of 200 hospital medical records. Chloral hydrate and methaqualone interact pharmacologically with orally administered anticoagulant agents, but the effect is not clinically significant. It is concluded that chloral hydrate and methaqualone may be administered safely without additional caution in prothrombin test monitoring during oral anticoagulant therapy.

Efficacy and side effects of flurazepam and a combination of amobarbital and secobarbital in insomniac patients.

Flurazepam, 30 mg, was not more effective in inducing sleep than placebo. Barbiturates (100 mg amobarbital plus 100 mg secobarbital) were more effective in inducing and maintaining sleep than flurazepam or placebo. Contrary to work conducted in the sleep laboratory, the barbiturate hypnotics were still effective on the 14th night. Insomniacs performed poorly on psychomotor tests, but as a group they did not show statistically significant psychomotor impairment after the use of the hypnotics.

Paediatric sedation for CT scanning: the safety and efficacy of quinalbarbitone in a district general hospital setting.

The aim of this study was to review retrospectively the safety and efficacy of a paediatric sedation protocol in a district general hospital radiology department. 256 children attended for CT scanning over a 40-month period. 40 children required sedation and were given quinalbarbitone. 34 (85%) of this group were adequately sedated. Of the children who received quinalbarbitone, 35 were under 5 years of age. 32 of this group (91.4%) were adequately sedated. Failures in children under 5 years were all caused by problems with administration whilst failures in the older children were due to paradoxical excitement. No problems with respiratory depression were encountered. Sedation can be safely performed in a district general hospital radiology department if a structured protocol is adhered to. Quinalbarbitone is a safe, effective oral agent in children under the age of 5 years.

A clinical comparison of triazolam with placebo and with secobarbital in insomniac patients.

Seventy-six out-patient insomniacs participated in three different two-night, double-blind crossover trials investigating the hypnotic efficacy andsafety of triazolam. Triazolam 0.5 mg was compared to placebo in one trial conducted K Kay Okawa, MD, and triazolam 0.5 mg was compared to secobarbital 100 mg in trials conducted by K Kay Okawa, MD and George S Allen, MD. The results of the later two studies were combined and the data analyzed jointly. Triazolam 0.5 mg was found to be preferred and to be significantly better than both placebo and secobarbital 100 mg in the treatment of insomnia. Analysis of sleep questionnaire data showed triazolam to be superior to either placebo or secobarbital on the following parameters: how much the medication helped the patients sleep; onset of sleep; duration of sleep; and number of nocturnal awakenings. No differences were observed between treatments in any trial with regard to the patient's feeling of alertness the next morning. The side-effects reported for all treatments did not significantly interfere with the patient's ability to function.

Rectal absorption and disposition of secobarbital in epileptic children.

The absorption and disposition of rectally administered secobarbital was studied in ten epileptic children, ages 2-13 yrs. Five subjects received secobarbital rectally in solution, and the other five received secobarbital suppositories. Concentration of secobarbital in serum was serially determined during 48 hrs after a single rectal dose of about 5 mg/kg. The rate of absorption of secobarbital, as measured by the time to reach peak serum concentration, was much more rapid from the solution than the suppository (0.92 +/- 0.47 hr vs 4.60 +/ 2.30 hr). The peak serum concentration of secobarbital in the solution group was consistently higher than in the suppository group (2.26 +/- 0.37 micrograms/ml vs 1.35 +/- 0.24 microgram/ml). None of the individual peak serum concentrations exceeded 3 micrograms/ml, which is well below the previously reported minimum toxic concentration of secobarbital (ie, 6 microgram/ml). The elimination half-life of secobarbital varied over a wide range, from 2.7 to 13.5 hr, and is, on the average, shorter than estimates previously reported for adult volunteers or poly-drug abusers. Also, the mean elimination half-life did not differ between the solution and the suppository groups. The extent of rectal absorption of secobarbital, as assessed by the area under the serum concentration time curve, was not significantly different between the solution and the suppository treatments. If rectal secobarbital is considered for treatment of prolonged seizure, a rectal solution may offer a more rapid and consistent onset of action than with the suppository preparation.

Prolonged sedation associated with secobarbital in newborn infants receiving ventilatory support.

Newborn infants receiving ventilatory support often require sedation. Secobarbital is commonly used in these patients, but dosage guidelines to avoid prolonged sedation are not available. Seventeen infants (gestational age, 30 to 40 weeks; postnatal age, 0 to 3 days) with hyaline membrane disease or persistent pulmonary hypertension on mechanical ventilation were studied. These patients received secobarbital, 4 to 14 mg/kg/day intravenously for 1 to 10 days to produce sedation. Sedation was considered prolonged if it lasted more than 24 hours after the last dose. Nine of 17 infants experienced prolonged sedation. The mean daily secobarbital dose was 11.2 mg/kg/day in patients with prolonged sedation and 6.9 mg/kg/day in those patients without (p less than 0.05); the cumulative mean dose in the respective groups was 33.3 and 21.3 mg/kg (p less than 0.05). Four infants were sedated for 3 to 4 days after stopping secobarbital; the mean daily and cumulative dose was 13 mg/kg/day and 53 mg/kg in these patients. Duration of sedation was related to both daily and cumulative doses of secobarbital. Based on our results, the daily dose of secobarbital should not exceed 7 mg/kg/day to avoid prolonged sedation in infants. Frequent monitoring appears necessary to ensure efficacy with the lowest cumulative dose of secobarbital in newborn infants.

The antiemetic efficacy of secobarbital and chlorpromazine compared to metoclopramide, diphenhydramine, and dexamethasone. A randomized trial.

The efficacy of secobarbital sodium plus chlorpromazine (SC) in the prevention of cisplatin induced emesis was compared to the combination of metoclopramide, diphenhydramine, and dexamethasone (MDD). Twenty-three patients were entered onto protocol. Eighteen were evaluable. Good to excellent antiemetic prophylaxis was obtained in 72% with MDD versus 17% with SC (P less than 0.01). Sedation and anticholinergic side effects were more common with SC. Extrapyramidal reactions were more commonly seen with MDD. Significantly more patients preferred the combination of metoclopramide, diphenhydramine, and dexamethasone (P less than 0.05).

Midazolam in the treatment of sleep disorders in geriatric patients.

The use of hypnotics in the elderly must be approached with special care in view of possible changes in pharmacokinetic behaviour and drug interactions in older patients. In a randomized, double-blind study in a large geriatric department, midazolam was compared with the barbiturate combination Vesparax with regard to efficacy and safety. The comparison of the efficacy of the 2 hypnotics showed them to be almost identical in this respect. Side-effects, however, were more frequent with Vesparax. Furthermore, in the Vesparax group, unlike in the midazolam group, a troublesome cumulation of effect was observed, together with relatively frequent signs of hangover. It is concluded that, in appropriately titrated dosage, midazolam is an effective and well-tolerated hypnotic for use in the elderly.

Comparative study of midazolam and vesparax in moderate or severe insomnia in female surgical patients.

A double-blind study was conducted in 60 female patients with moderate or severe insomnia, hospitalized for gynaecological surgery. After an initial 2-day placebo selection phase, 30 subjects received 15 mg midazolam and the remaining 30 received 1 tablet Vesparax (= 50 mg hydroxyzine, 150 mg secobarbital, 50 mg brallobarbital) for 5 nights. This verum phase was immediately followed by a 2-day placebo withdrawal phase in order to study the occurrence of rebound phenomena. Both verum compounds were effective in hastening sleep onset, increasing sleep duration, and improving sleep quality, without causing residual effects on the following day. There was no difference in effect between the two agents. Neither active drug caused rebound effects on withdrawal.

Efficacy and safety of midazolam and vesparax in treatment of sleep disorders.

In a double-blind parallel study in which a placebo phase preceded and followed the double-blind verum phase, midazolam 15 mg and Vesparax (150 mg secobarbital, 50 mg brallobarbital, 50 mg hydroxyzine) were administered to 30 female patients aged 20-76 years, suffering from insomnia secondary to neuromuscular disease. Both products were shown to be efficient hypnotics maintaining a constant level of effect. Midazolam proved to be better tolerated and, in contrast to Vesparax, did not cause hangover, nor did rebound phenomena ensue after its withdrawal.