Disulfiram and erythrocyte aldehyde dehydrogenase inhibition.

During disulfiram therapy erythrocyte aldehyde dehydrogenase (ALDH) was fully inhibited. The time for total loss of erythrocyte ALDH activity ranged from 36 to 120 hr. In contrast to the 85% recovery of in vitro disulfiram-inhibited ALDH activity, this in vivo disulfiram-ALDH inhibition could not be reversed by mercaptoethanol. It is proposed that the in vivo and in vitro mechanisms of ALDH inhibition by disulfiram differ. Erythrocyte ALDH activity can be readily monitored to determine patient compliance and is an accessible model for investigations of in vivo mechanisms of drug inhibition. Because the disulfiram-inhibited erythrocyte ALDH is not regenerated until new erythrocytes are made (120 days), a significant portion of the extrahepatic acetaldehyde metabolic capacity remains inhibited for long periods after disulfiram is discontinued. Thus, the recidivistic patient who discontinues disulfiram and waits several days (to regenerate liver ALDH activity) before drinking will be exposed to even higher ethanol-derived blood acetaldehyde levels than usual, which may induce further alcohol-associated organ damage and alcohol dependence.

Clinical comparison of propoxyphene napsylate and methadone in the treatment of opiate dependence.

In this double-blind comparison of propoxyphene napsylate (PN) 800 mg in two divided doses versus methadone 20 mg, methadone 10 mg or placebo methadone, it was found that PN: 1) did not alleviate withdrawal symptoms in patients previously maintained on methadone 20 mg; 2) produced a slightly overmedicated effect in the detoxified group of exmethadone patients; and 3) compared favorably to methadone 10 mg in suppressing withdrawal symptoms without producing evidence of overmedication in those patients previously stabilized on a methadone maintenance dose of 10 mg.

Initial methadone dose in treating opiate addiction.

Intramuscular administration of naloxone was used to precipitate the narcotic withdrawal syndrome in opiate-dependent patients. Objective signs of withdrawal were rated according to a previously developed scale. Based upon naloxone-induced withdrawal scores, 76 patients were given a dose of methadone, either low, medium, or high, in a randomized double-blind manner on 2 consecutive days. The adequacy of the methadone dose was evaluated by assessing the patients' physical responses after each treatment. Results indicate that the medium dose of methadone in each naloxone-induced withdrawal score range provides optimal control of narcotic deprivation. It is concluded that a correct initial dose of methadone can be administered when the degree of opiate dependence is established by the naloxone test.

Propoxyphene napsylate compared to methadone for opiate dependence.

When high single doses of propoxyphene napsylate (PN) were given to patients on a methadone maintenance program, results indicated that, to avoid undesirable side effects, the dose should not exceed 600 mg. However, when PN was given in divided doses (800 mg/day in two equal doses), no significant adverse reactions were noted. In the double-blind comparison of 800 mg PN in two divided doses versus 20 mg methadone, 10 mg methadone, or placebo methadone, it was found that PN (1) did not alleviate withdrawal symptoms in patients previously maintained on 20 mg methadone, (2) produced a slightly overmedicated effect in the detoxified group of ex-methadone patients, and (3) compared favorably to 10 mg methadone in suppressing withdrawal symptoms without producing evidence of overmedication in those patients previously stabilized on a methadone maintenance dose of 10 mg. It is concluded that on a mg for mg basis, PN at a dose of 80-times that of methadone will relieve withdrawal symptoms in the treatment of mildly addicted patients requiring 10 mg methadone or less per day.