Self-administration of cocaine, alfentanil, and nalbuphine under progressive-ratio schedules: consumer demand and labor supply analyses of relative reinforcing effectiveness.

Progressive-ratio (PR) schedules of intravenous (i.v.) drug self-administration are useful for establishing the relationships between reinforcing effectiveness and pharmacological actions of abused drugs. The authors compared the reinforcing effects of the high-efficacy opioid alfentanil, the low-efficacy opioid nalbuphine, and cocaine using a PR schedule of i.v. drug injection in rhesus monkeys in which the response requirement increased during the experimental session and the initial response requirement (IRR) was varied. Analyses based on either consumer demand or labor supply models of behavioral economics revealed that the relative reinforcing effectiveness of cocaine and alfentanil was greater than that of nalbuphine. These results suggest that PR schedules with varying IRRs can provide meaningful estimates of the relative reinforcing effectiveness of abused drugs.

Treatment of intrathecal morphine-induced pruritus following caesarean section.

PURPOSE: To compare both the efficacy and cost of nalbuphine and diphenhydramine in the treatment of intrathecal morphine-induced pruritus following Caesarean section. METHODS: Eighty patients, undergoing elective Caesarean section under spinal anaesthesia, were randomized, in a prospective, double-blind trial, to receive either nalbuphine (Group NAL) or diphenhydramine (Group DIP) for the treatment of SAB morphine-induced pruritus. All patients received an intrathecal injection of 10-12 mg hyperbaric bupivacaine 0.75% and 200 micrograms preservative free morphine. Postoperative pruritus was assessed, using a visual analogue scale (VAS), for 24 hr. Pruritus treatment was administered upon patient request and by a nurse blinded to the treatment given. Patients who failed to respond to three doses of the study drug were deemed treatment failures. Patient satisfaction was assessed with a questionnaire given 24 to 48 hr after surgery. Direct drug costs were calculated based on the pharmacy provision costs as of April 1996. RESULTS: Eighty patients were enrolled and 45 requested treatment for pruritus. Patients treated with NAL (n = 24) were more likely to achieve a VAS score of zero with treatment (83% vs 43%, P < 0.01), had a higher delta VAS following treatment (4 +/- 2 vs 2 +/- 2, P < 0.003), and experienced fewer treatment failures (4% vs 29%, P < 0.04), than those treated with DIP (n = 21). Group NAL patients were also more likely to rate their pruritus treatment as being good to excellent (96% vs 57%, P < 0.004). Direct drug costs were higher for NAL than for DIP ($6.4 +/- 3.1 vs $1.7 +/- 0.7, respectively, P < 0.0001). CONCLUSION: Nalbuphine is more effective than diphenhydramine in relieving pruritus caused by intrathecal morphine and the cost differences are small.

Normalized demand for drugs and other reinforcers.

The concepts of behavioral economics have proven to be useful for understanding the environmental control of overall levels of responding for a variety of commodities, including reinforcement by drug self-administration. These general concepts have implications for the assessment of abuse liability and drug abuse intervention and the formulation of public policy on drug abuse. An essential requirement is the ability to compare the demand for different drugs directly in order to assess relative abuse liability, and to compare demand for the same drug under different environmental and biological interventions to assess their ability to reduce demand. Until now, such comparisons were hampered by the confounding effect of varying drug doses and potencies that prevent quantitative comparisons of demand elasticity--sensitivity of consumption and responding to the constraint of price (effort). In this paper we describe a procedure to normalize demand-curve analysis that permits dose- and potency-independent comparisons of demand across drugs. The procedure is shown to be effective for comparing drug demand within and across the drug classes. The technique permits a quantitative ordering of demand that is consistent with the peak levels of responding maintained by the drugs. The same technique is generalized for the comparison of other types of reinforcers under different biological conditions.