Pain perception of intravenous heroin users on maintenance therapy with levomethadone.

Methadone is a very potent analgesic drug. Accordingly, maintenance therapy of heroin addicts with methadone may conceal pain producing processes. Here we report on the pain perception of 42 patients on a levomethadone maintenance treatment for intravenous heroin users. Pain perception was measured by single-blind, non-invasive pressure stimulation of the nociceptors located in the dorsal extension aponeurosis and the underlying periosteum of the middle phalanx of a digit before and respectively 1,2, and 4 hours after oral routine drug administration. Measures were related to the individual levomethadone plasma levels. Under steady-state conditions, the pain perception of the patients did not differ from a drug-free placebo control group and was not related to individual levomethadone plasma levels, although an analgesic effect in the reabsorption phase was observed. It is concluded that the individual pain perception of maintained patients is adapted to a normal response range and that even prolonged opioid consumption does not diminish dynamic analgesic responsiveness to levomethadone.

Pharmacokinetic and pharmacodynamic interactions in an outpatient maintenance therapy of intravenous heroin users with levomethadone.

The plasma levels of 42 patients on a levomethadone maintenance treatment programme for intravenous heroin users were measured before and, respectively, 1, 2 or 4 hours after oral routine administration and related to the individual additional drug usage (detected by urine drug screening), liver function, side-effects and withdrawal symptoms. In general, accelerated levomethadone metabolism induced by additional misuse of benzodiazepines, barbiturates and opiates resulted in significantly lower plasma levels of the substitute. In particular, high gamma-glutamyltransferase activity was related to benzodiazepine consumption. On the other hand, an impaired liver function reflected by increased beta-globulins resulted in an insufficient body clearance and drug accumulation. Major side effects, such as sweating, were not related to plasma levels whereas withdrawal symptoms like diarrhoea or "feeling cold" correlate with lower plasma concentrations. It is concluded that polydrug misuse in the methadone maintenance therapy creates a vicious circle of enzyme induction, thus increasing "instrumental drug utilization". However, underestimated maintenance dosage may lead to additional drug consumption resulting, finally, in therapeutic failure.