John E. Peachey

Lack of difference in blood acetaldehyde of alcoholics and controls after ethanol ingestion

Ethanol and acetaldehyde (AcH) metabolism were studied in male Caucasian alcoholic subjects and matched controls following 1 g/kg ethanol, which was administered after a 10 day, ethanol-free period. The rate of ethanol elimination was higher (p greater than 0.05) in the alcoholics (0.120 g/kg/hr) than in controls (0.108 g/kg/hr). Blood AcH concentrations were measured in either the supernatants of whole blood deproteinized with perchloric acid (PCA) or from the supernatants of PCA-treated plasma obtained from blood added to isotonic semicarbazide. There was no differences between the alcoholic and control subjects for AcH in blood dripped directly into the PCA. The blood AcH concentrations decreased from 22 microM (controls) and 23 microM (alcoholics) to 7 microM (controls) and 3 microM (alcoholics) at 1 and 7 hours after the start of drinking, respectively. No significant AcH was found in blood first taken into heparinized tubes before deproteinization with PCA, after correction for artifactual AcH formation was made. As well, no significant AcH was measured by the semicarbazide method after correction for artifactual AcH. These results suggest that elevated blood AcH levels after ethanol ingestion cannot be taken as a general marker of alcoholism.

Clinical observations of agonist-antagonist analgesic dependence

The agonist-antagonist opioids are clinically effective analgesics with generally low abuse potential. Four agonist-antagonists are currently available for use as analgesics. Pentazocine, butorphanol and nalbuphine produce morphine-like effects in low doses and, to varying degrees, dysphoric effects as the dose is increased. Buprenorphine, an antagonist opioid of slow onset but long duration of action, produces morphine agonist effects at lower doses, and as the dose is increased, antagonist effects with minimal or no dysphoria. Clinical experience with pentazocine indicates that abuse is possible and consists of two main types: misuse (and abuse) of the drug alone by patients during treatment for pain and, abuse of the drug, often taken together with other psychoactive agents, as a substitute for the preferred drug of abuse. Few reports of abuse have appeared for butorphanol, nalbuphine and buprenorphine; however, considerable care is recommended in their use in patients, especially where there is the possibility for abuse as might occur in patients who require long-term treatment, with a history of drug abuse, and where the drug is easily obtained.

The Use of Disulfiram and Other Alcohol-Sensitizing Drugs in the Treatment of Alcoholism

The alcohol-sensitizing drugs are used with the expectation of deterring alcoholics from further drinking. Even though many drugs are available, only disulfiram (tetraethylthiuram disulfide®, Antabuse, Abstinyl®) and possibly calcium carbimide (citrated calcium carbimide, Temposil®, Abstem®) have current therapeutic applications in primary* alcoholics (Sellers et al., 1981). Disulfiram is available in many countries, whereas calcium carbimide is prescribed less frequently and is not available in the United States. Notwithstanding the many claims for the effectiveness of these drugs, their continued use in alcoholism treatment has been questioned (Fried, 1977) because of reports of drug-induced toxicity (Peachey et al., 1981a) and lack of experimental evidence that they are efficacious in exerting a positive treatment outcome (Mottin, 1973; Naranjo, 1983).