Opioid tolerance and dependence: an inevitable consequence of chronic treatment?

Although opioids provide effective analgesia, largely unsubstantiated concerns about opioid-induced tolerance, physical dependence and addiction have limited their appropriate use. As a consequence, many patients receive inadequate treatment for both malignant and non-malignant pain. However, it has been shown that analgesic tolerance develops less frequently during chronic opioid administration in a clinical context than in animal experiments, and that instituting an appropriate dosing regimen can minimise withdrawal symptoms.

Partial versus full agonists for opioid-mediated analgesia--focus on fentanyl and buprenorphine.

In contrast to other opioids, fentanyl and buprenorphine share a number of physicochemical properties that render both agents potentially suitable for transdermal delivery. However, there are significant differences between them in terms of their pharmacological profiles, as fentanyl is a full mu opioid receptor agonist capable of exerting a maximal response in certain tissues, while buprenorphine is a partial agonist unable to exert this maximum effect even at high doses. This review examines the hypothesis that partial opioid agonists would confer a number of benefits over full agonists, namely effective analgesia with a better tolerability and a lower propensity for addiction, with respect to fentanyl and buprenorphine.

Fentanyl delivery from an electrotransport system: delivery is a function of total current, not duration of current.

This open-label, parallel study of 28 men was conducted to evaluate the pharmacokinetics and safety of fentanyl delivered by the E-TRANS (fentanyl) electrotransport transdermal system (ALZA Corporation, Palo Alto, CA). The E-TRANS (fentanyl) system provided electrically assisted, transdermal, continuous delivery of fentanyl. Treatments consisted of no current (group A); a constant current of 100 microA for 26 hours plus 4 additional doses at varying currents for varying times during hour 25 (groups B, C, D); a constant current of 100 microA for 26 hours plus 4 additional doses at 1,200 microA over 2.

Investigation of the pharmacokinetics and analgesic effects of an intramuscular injection of sustained-release sufentanil for postoperative pain: an open study.

Study Objectives: To investigate the pharmacokinetics after an intramuscular (IM) injection of sufentanil in thin vegetable oil in postsurgical patients and to determine whether sustained-release IM sufentanil can provide safe and sufficient analgesia of long duration in these patients.

Design: Open study.

Setting: University hospital.

Hydroxypropyl-beta-cyclodextrin can modulate the activity of spinally administered sufentanil.

Hydroxypropyl-beta-cyclodextrin increased the effectiveness of sufentanil after epidural and intrathecal administration in rats, both in terms of a longer duration of analgesia after a fixed dose of sufentanil, and in a reduction of the lowest ED50s to produce analgesia. There was also an increase in specificity, as indicated by the greater dissociation between the ED50s for analgesia and for supra-spinal side-effects. Maximal activity was measured after inclusion complexation of sufentanil in 10% hydroxypropyl-beta-cyclodextrin.