Kinetics of ethanol and methanol in alcoholics during detoxification.

We investigated the kinetics of ethanol and methanol in 20 dependent alcoholics (16 men and four women) during the first 24 hr after admission to hospital for detoxification. The blood-ethanol concentration (BEC) on admission ranged from 238 to 489 mg/dl (mean 386 mg/dl). The mean rate of ethanol disappearance from the blood was 23 mg/dl/hr with a spread from 13 to 36 mg/dl/hr. The concentrations of methanol in blood at the start of detoxification ranged from 0.16 to 2.8 mg/dl (mean 1.15 mg/dl) and these levels remained more or less unchanged until the BEC had dropped below 30 mg/dl. The concentrations of ethanol and methanol in blood at the start of detoxification were not correlated (r = 0.032, P > 0.05). The results of this study do not support the notion that the metabolism of methanol in chronic alcoholics proceeds independently of the prevailing BEC. We found a three-fold difference in the rate of disappearance of ethanol from blood in alcohol-dependent subjects.

Carbamazepine kinetics and adverse effects during and after ethanol exposure in alcoholics and in healthy volunteers.

The influence of ethanol on the single-dose kinetics of carbamazepine (400 mg syrup) was assessed in 7 alcoholics after a debauche (mean daily consumption 240 g ethanol) and after 9 days of controlled abstinence, and in 8 healthy volunteers after intake of the drug with and without a single dose of ethanol (25 g). Twelve h after the first test dose of carbamazepine the alcoholics were treated with the drug for 4 days (200 mg tablet b.d.). Carbamazepine was then withheld until a single test dose was given on day 9. Serum levels of carbamazepine and its 10,11-epoxide metabolite were measured by liquid chromatography. Carbamazepine absorption appeared to be delayed in alcoholics, both after debauche and withdrawal, but its bioavailability did not seem to be reduced. Carbamazepine levels were higher and those of its metabolite lower in alcoholics after a debauche than after 9 days of controlled abstinence, but neither was changed in healthy volunteers after the ingestion of carbamazepine together with a single dose of ethanol. The difference may have been due to inhibition of carbamazepine metabolism by ethanol at the high levels attained in alcoholics but not in volunteers. However, it could also be an expression of the unmasking of enzyme induction after ethanol withdrawal. None of the alcoholics had any withdrawal seizures. Despite similar carbamazepine levels, side effects occurred in all volunteers but in none of the alcoholics, indicating that long-term ethanol exposure may promote central nervous adaptation to the acute untoward effects of carbamazepine.(ABSTRACT TRUNCATED AT 250 WORDS)

Anxiolytic-hypnotic drugs: relationships between prescribing, abuse and suicide.

In 1978 the third largest Swedish city, Malmö, known to have the highest suicide frequency in the country, was found to have a higher prescription rate (defined daily doses (DDD) per 1,000 inhabitants per day) of anxiolytic-hypnotic drugs (AHD) than the country, the corresponding county, other counties, and other cities, including the largest (Stockholm) and second largest (Göteborg = Gothenburg) cities. Barbiturate prescribing in Malmö was 40% higher than in Stockholm and 90% higher than in Göteborg, and the frequency of suicide due to barbiturates was three-times higher than in Göteborg. A small proportion (2.4% of all AHD-prescribing doctors) of private practitioners wrote a large percentage (24%) of all AHD prescriptions. Prescription surveillance and an information campaign in Malmö were accompanied by a 4-year decrease in AHD prescribing (12%), in AHD abuse (40%), in barbiturate prescribing (45%), and in barbiturate suicides (70%). The total suicide rate was reduced by 25%. There was no corresponding 4-year increase in suicide due to other drugs, or by other means, but after 5 to 7 years there was an increase in suicide by non-pharmacological means. The contribution of benzodiazepines to the frequency of suicide was very small, whereas their contribution to AHD abuse was considerable. In Göteborg, where no corresponding intervention was carried out, there was also a reduction in barbiturate prescribing (34%) and in barbiturate suicides (45%), but in contrast there was a continuous increase both in overall AHD and benzodiazepine prescribing, surpassing Malmö after 5 years. Far from a reduction there was a 7-year increase in the overall frequency of suicide. Apparently, AHD abuse and suicide can be greatly reduced by restricted prescribing of AHD, and this may but need not be accompanied by an increase in suicide by other means. Targeted drug information campaigns may assist in changing prescription patterns and their medical and social impact.

Reduction in early alcohol abstinence fits by administration of carbamazepine syrup instead of tablets.

All convulsive fits during ethanol abstinence in the acute ward of a Department of Alcohol Diseases were recorded during two 11-month periods. The patients and the treatment given were similar during the 2 periods, except that the initial dose of carbamazepine was given as tablets during the first period and as syrup during the second period. The rate of withdrawal fits between 2 and 10 h after the initial dose of carbamazepine was significantly lower in the group given the syrup, which is suggestive of greater efficacy. This is probably due to faster absorption of carbamazepine from the syrup, promoting more rapid attainment of an anticonvulsant concentration.