Analgesic efficacy and tolerability of diflunisal in oral surgery.

A double-blind, completely randomized study was carried out on 169 patients to compare the analgesic efficacy and tolerability of diflunisal with that of Veralgin after surgical removal of impacted third molars. One group received 1000 mg diflunisal (Donobid, MSD) 2 h preoperatively and then 500 mg twice daily for 2.5 days, and the other group Veralgin (aminophenazon. 286 mg, barbital. 114 mg, aethylmorph. hydrochlorid. 20 mg, Orion), a fixed combination widely used in Finland, 1 tablet twice daily beginning 2 h prior to operation. Visual analogue scales were used to estimate pain. Diflunisal was found to be superior in relieving pain in the early postoperative period, the associated frequency of adverse clinical experiences was lower and the final evaluation of analgesic efficacy by both the patients and the investigators, was in its favour. The study confirms that postoperative pain after third molar surgery can be controlled well without the use of mainly centrally acting combination analgesics.

Central nervous system supersensitivity and withdrawal from long-term treatment with barbital

The effects of withdrawal from long-term treatment with increasing concentrations of sodium barbital in the drinking water were studied in rats. Animals were tested 72 h after the removal of the drug. Withdrawal of barbital induced a significant leftward displacement of the dose-response curves obtained for the convulsive effects of strychnine, picrotoxin and 3-mercaptopropionic acid. The removal of the drug also made the rats more sensitive to convulsions elicited by sound. Baclofen and THIP were able to decrease the audiogenic response score of rats, withdrawn from barbital, in a dose-dependent way. These effects were interpreted to be a consequence of changes in the sensitivity of central GABA(A) and/or noradrenergic receptors induced by depression due to long-term administration of barbital.

Treatment of alcohol withdrawal symptoms in hospitalized patients. A randomized, double-blind comparison of carbamazepine (Tegretol) and barbital (Diemal).

Seventy-two hospitalized patients with alcohol withdrawal symptoms were treated with either carbamazepine (Tegretol) or barbital ( Diemal ) in a randomized, double-blind trial. The dose of trial medication as well as the duration of treatment was individual, corresponding to the conventional treatment schedule. During the trial period daily records were kept of target withdrawal symptoms, global evaluation, the patient's subjective feeling and unwanted effects. Sixty patients completed the treatment successfully. The two treatment groups were homogeneous as regards patient characteristics, pre-treatment disease severity and drop-out rate. No statistically significant differences were found in efficacy between the two treatments, and both drugs were well tolerated. It is concluded that carbamazepine is a valuable alternative drug in the treatment of mild and moderate alcohol withdrawal symptoms.

Increased carbon tetrachloride-stimulated chemiluminescence in the in situ liver of barbital-treated mice.

Mice treated with barbital (0.1% in the drinking water) during 15 days showed a 63% increased endoplasmic reticulum mass. The carbon tetrachloride-stimulated chemiluminescence of the in situ liver was 51% increased after barbital treatment. Hydroperoxide-stimulated chemiluminescence of liver homogenates and microsomal suspensions were increased by 140 and 92%, respectively, in the barbital-treated mice. Spontaneous liver chemiluminescence (109 cps/cm2) was found unchanged after barbital treatment. Superoxide dismutase, catalase and glutathione peroxidase activities were 109, 61 and 103%, respectively, increased after barbital treatment. The results are consistent with a primary role of cytochrome P 450 in the biotransformation of CCl4, which initiates a radical chain reaction leading to the production of powerful oxidizing species. Apparently, superoxide dismutase, catalase and glutathione peroxidase are synthetized in a coincident manner with respect to cytochrome P 450.

Delirium tremens. Some clinical features. Part II.

Twenty patients with delirium tremens (grade 3) and a less severe clinical state (grade 2) were investigated thoroughly from the time of admission until recovery from the acute state. A lumbar puncture was performed in the majority of the patients immediately after admission and then repeated after recovery from the acute state. The cerebrospinal fluid was found to be both macroscopically and microscopically normal, as was the spinal fluid pressure. The clinical course was without complication, none of the patients were severely dehydrated. All the patients were treated with barbital, a long acting barbiturate. The duration of the acute state and the total amount of drug necessary in the treatment were equal in the two groups of severity. However, patients with proper delirium tremens needed significantly fewer barbital doses during the first hours after treatment was initiated than did patients with a less severe clinical state. The opposite was seen about 12 hours later. These findings are discussed in relation to the high blood alcohol concentration seen at the time of admission in the majority of the patients with proper delirium tremens, but not in patients with grade 2. It is concluded that barbital exerts its effect due to cross-dependence properties with alcohol. The majority of the patients had moderately elevated blood pressure, pulse rate and rectal temperature at the time of admission; these variables were to a great extent normalized within 48 hours after admission. No differences in those physical signs were seen between patients with fully developed delirium tremens and patients with less severe clinical states. The patients' condition during the acute state was followed by means of a delirium tremens rating scale. Physical symptoms were similar in various degrees of severity of the clinical condition. 18-24 hours after admission the differences in mental symptoms between patients with grade 3 and patients with grade 2 had disappeared, 48 hours after admission the patients' condition was to a large extent normalized. Methodological problems in using a rating scale in conditions as delirium tremens are discussed. The results are discussed in relation to aetiology and pathogenesis of delirium tremens. It is concluded that it may be that a qualitative, and not only a quantitative, difference exists between a severe withdrawal reaction and fully developed delirium tremens, and a hypothesis about a "point of no return" is suggested.

Delirium tremens and related clinical states. Aetiology, pathophysiology and treatment.

Definitions of Delirium Tremens (DT) and related clinical states are discussed together with the concepts of aetiology and pathogenesis in relation to psychiatric disease. The withdrawal theory which considers reduction or cessation of alcohol intake as an important precipitating factor in DT is discussed; this theory is supported by experimental studies of ethanol withdrawal in man and by studies indicating cross dependence between ethanol and several other CNS depressors; the arguments in the literature for and against the withdrawal theory are discussed. Other possible aetiological factors such as type of liquor, hypovitaminosis, liver disease, dysfunction of the adrenals and fat emboli are reviewed, and it is concluded that these factors are unimportant as precipitating or specific aetiological factors in DT. Possible pathophysiological mechanisms are discussed, especially concerning electrolyte metabolism and cerebral blood flow and oxygen consumption. It is concluded that the pathophysiology of the disease is poorly understood, and some possibilities for future research are indicated. The discussion about treatment of DT is concentrated on drug treatment, and the literature concerning antipsychotics and sedatives is reviewed. It is concluded that barbital, a long-acting barbiturate, is the most effective treatment; diazepam can be recommended as an acceptable alternative. Finally, practical recommendations concerning treatment are given.

Barbital and diazepam plasma levels during treatment of delirium tremens.

Plasma concentrations of barbital and diazepam were measured daily during a double-blind study of the efficacy of the two drugs in the treatment of delirium tremens and less severe clinical states. Treatment was estimated as satisfactory in the majority of cases; the present study deals with the satisfactory groups only. Both in the barbital group and in the diazepam group the same plasma level was seen in different clinical states. This result is discussed in relation to the theories about the aetiology of delirium tremens, and it is concluded that the data fits best with the assumption that delirium tremens is released from a withdrawal state, but once established, the delirious state is not interrupted by the drugs. The barbital concentrations were rather high, many at a level where non-alcoholics would show pronounced intoxication symptoms not seen in the present material. The diazepam concentrations on the other hand were low, often below a level where a cerebral effect is measurable in normal subjects. On this basis it is concluded, that the two drugs have different modes of action. Barbital may act by its cross-dependence properties with alcohol and thus diminish the withdrawal reaction, whereas diazepam may act by its anti-anxiety effect, but not in the doses here applied, by cross-dependence properties with alcohol. Finally, this hypothesis is discussed in relation to clinical experience in the treatment of delirium tremens.

Delirium tremens: a double-blind comparison of diazepam and barbital treatment.

The effect of diazepam and barbital in the treatment of delirium tremens and other acute conditions related to alcohol abuse was evaluated in a double-blind trial. 91 patients participated in the study, 44 in the diazepam group, 47 in the barbital group. The choice of diazepam rather than chlordiazepoxide was motivated by its major anticonvulsive properties. Barbital was given by the oral route, diazepam as intramuscular injections. Different ways of drug administration to patients with delirium tremens are discussed. It is concluded that the two different ways used in the study probably did not have a noteworthy influence on the results. All patients were excluded who had taken psychoactive drugs before admission. Nevertheless a considerable part of the patients had diazepam, but not barbital, in the blood before treatment was initiated. This may give support to the use of barbital as a "special purpose drug" in the treatment of these conditions. The patients were divided into three diagnostic categories, according to the severity of the clinical condition. No difference between the two drugs tested was found in the milder conditions, but barbital was found superior to diazepam in the treatment of fully developed delirium tremens.

[The relationship between the activity of microsomal enzymes and pulmonary carcinogenesis in mice]. / Zavisimost' legochnogo kantserogeneza u myshei ot aktivnosti mikrosomal'nykh fermentov

Under study was the effect of phenobarbital, medinal and aminazine on the development of lung tumors in mice, as well as on the content of cytochrome P-450 in rat liver microsomes. Phenobarbital and medinal administration resulted in a 2-8 fold increase in cytochrome P-450 amount. Aminazine would reduce the latter but insignificantly. The number of urethan induced lung adenomas in mice was reduced by 64 per cent in phenobarbital exposure while medinal yielded only the decrease by 25-44 per cent. Aminazine failed to effect urethan carcinogenesis. Medinal would also suppress the development of DMBA induced lung tumors in mice by 34 per cent, but MC-by 50 per cent.