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Biomedical subjects

R B Resnick

Publications and source records attributed to R B Resnick.

54 records · Page 3Linked to original sources

Problems of methadone diversion and implications for control.

With the expansion of methadone maintenance there has been an increase in accidental ingestion and related deaths. This is at least partially due to programs involving take-home methadone. The use of 1-alpha-acetylmethadol (LAAM), a congener of methadone that suppresses withdrawal for up to 72 hours, may reduce diversion and accidental overdose.

Heroin Dependence↗

Evaluation of propranolol in opiate dependence.

Among the increasing number of recent reports of the use of beta-adrenergic blocking drugs for a variety of psychiatric disorders is a series concluding that propranolol hydrochloride is efficacious in the treatment of opiate dependence. These reports were based on clinical observations of outpatient addicts in an uncontrolled situation. In order to validate these findings, we carried out a series of controlled, double-blind studies with hospitalized volunteers. The results of our studies do not confirm the previous reports. Propranolol neither relieved nor precipitated opiate withdrawal in subjects dependent either on dihydromorphinone hydrochloride or on heroin. It did not effectively block heroin-induced euphoria in dependent or nondependent subjects. In addition, there was no effect on the pattern of self-administration in opiate-dependent subjects, whether they were maintained on propranolol or placebo.

Adult↗

Naltrexone: disposition, metabolism, and effects after acute and chronic dosing.

The disposition of naltrexone during acute and chronic administration of 100-mg oral dose was studied in 4 subjects. Following an acute dose the mean (X) peak naltrexone plasma level was 43.6 +/- 29.9 ng/ml at 1 hr and for the major biotransformation product, beta-naltrexol, was 87.2 +/- 25.0 ng/ml at 2 hr. Twenty-four hours after the dose the X levels of naltrexone and beta-naltrexol declined to 2.1 +/- 0.47 and 17.6 +/- 5.0 ng/ml, respectively. Following chronic administration and X peak plasma levels of naltrexone and beta-naltrexol rose to 46.4 +/- 18.5 and 158.4 +/- 89.9 ng/ml at 1 hr, but by 24 hr both compounds declined to levels of the same order as in the acute state at 24 hr. Plasma levels of naltrexone and beta-naltrexol measured 24 hr after the daily doses of naltrexone throughout the study indicated that steady-state equilibrium was rapidly attained and that there was no accumulation of naltrexone and beta naltrexol in the plasma after chronic treatment on 100 mg oral doses. Biexponential kinetics were observed for naltrexone and beta-naltrexol in the first 24 hr. The half-life of naltrexone and beta-naltrexol decreased slightly from the acute to thechronic study from 10.3 +/- 3.3 to 9.7 +/- 1.1 hr and from 12.7 +/- 2.6 to 11.4 +/- 2.0 hr. The plasma levels of naltrexone declined slowly from 24 through 72 hr from 2.4 to 1.7 ng/ml, with an apparent half-life of 96 hr. The renal clearance data indicate that naltrexone is partially reabsorbed while beta naltrexol is actively secreted by the kidney. During acute and chronic naltrexone administration the mean fecal excretion was 2.1% and 3.6% while urinary excretion was 38% and 70% of the dose in a 24-hr period. Opiate antagonism to 25 mg heroin challenges was nearly complete through 48 hr after naltrexone. At 72 hr the objective responses reappeared to a greater extent than the subjective ones. Correlation coefficient (r) between naltrexone plasma levels and opiate antagonism was 0.91 and between individual half-life of naltrexone and opiate antagonism it was 0.99.

Adult↗

l-Alpha-acetylmethadol (LAAM): prognostic considerations.

The authors studied the responses of 28 adult male volunteers who were openly changed from methadone to l-alpha-acetylmethadol (LAAM) maintenance. They found that patients who had been receiving middle-range doses (50-70 mg) of methadone required a significantly lower mean increase in LAAM than patients who had been receiving either high or low methadone doses and that the patients who accepted LAAM differed significantly from those who did not in MMPI 2-point-code ratings and mean social adjustment scale scores. These findings may provide prognostic indicators for response to LAAM, a possible alternative to methadone.

Heroin Dependence↗

Short-term effects of naltrexone in 155 heroin ex-addicts.

The narcotic antagonist naltrexone was administered for periods of up to 8 months to a total of 155 patients at a dose of 40-200 mg per day. The antagonistic effect of naltrexone was tested by injections of heroin. Eighty milligrams of natrexone was effective for 48hr. The antagonistic effect decreased at 72 hr after the administration of 120-200 mg of naltrexone. Laboratory tests indicated no signs of toxicity. Naltrexone may elicit an increase in blood pressure and opigastric pain. Neither of these side effects appear clinically important. No signs of dependence on naltrexone were detected. These results suggest that naltrexone may be useful for clinical treatment of opiate dependence.

Abdomen↗

Clonidine in opiate withdrawal: review and appraisal of clinical findings.

Studies in animals and humans have demonstrated that clonidine hydrochloride, an alpha-2-noradrenergic agonist, significantly attenuates the opiate withdrawal syndrome. Inpatient and outpatient clinical studies have shown that clonidine is a reasonably safe, specific, and effective agent for detoxifying opiate addicts. Clonidine seems best suited for use as a transitional treatment between opiate dependence and induction onto the opiate antagonist naltrexone. Dosage regimens of clonidine must be individualized according to symptoms and side effects and closely supervised because of varying sensitivity to clonidine's sedative, hypotensive, and withdrawal-suppressing effects. Clonidine is an important new treatment option for selected opiate addicts and may be the treatment of choice when detoxification using methadone is inappropriate, unsuccessful, or unavailable. Lofexidine, a structural analogue of clonidine, may be safer and more effective as an opiate detoxification treatment. It has similar withdrawal-suppressing actions but causes little hypotension and sedation. Although clonidine and lofexidine may be highly effective in helping opiate addicts achieve initial abstinence, a multi-modality aftercare treatment approach including naltrexone and psychotherapy may be necessary to maintain an abstinent state.

Clinical Trials as Topic↗