No abstract

Nine deaths involving oxycodone were investigated to assess the contribution of this opiate to these fatalities. All except one of the bodies were subjected to a full autopsy by specialist pathologists with a subsequent thorough toxicological examination. No significant anatomical pathology was found at autopsy. All deaths gave concentrations of oxycodone in femoral blood higher than expected following normal therapeutic use. In three cases no other drug in toxic concentrations was detected. Two cases involved the presence of a high concentration of a benzodiazepine and in a further two cases a high concentration of alcohol in addition to other drugs in therapeutic concentrations were present. One case involved methamphetamine in significant concentrations and another involved high concentrations of oxazepam in combination with pethidine. In all cases the presence of oxycodone was given as a factor contributing to the death. In only one case were there circumstances clearly indicating suicide. Our observations suggest that oxycodone is at least as toxic as other opiates and will cause deaths if misused.

The vasodilator effects of nitroglycerin (NTG) are mediated via activation of guanylate cyclase; this process is believed to require the availability of free sulfhydryl groups. Previous studies in man have shown that the sulfhydryl donor N-acetylcysteine (NAC) potentiates the systemic and coronary vasodilator effects of NTG. Furthermore, interaction of NTG and NAC may lead to the formation of S-nitroso-NAC, which strongly inhibits platelet aggregation. The effects of intravenous NTG combined with intravenous NAC (5 g 6 hourly) were compared with those of intravenous NTG alone in a double-blind trial in 46 patients with severe unstable angina pectoris unresponsive to conventional treatment, which included calcium antagonists and cutaneous nitrates in all but one patient. Treatment with NTG/NAC (24 patients) and that with NTG alone (22 patients) was associated with a similar frequency of episodes of chest pain and of increments in NTG infusion rate for pain control (10 vs 17; p= NS). The NTG/NAC group had a significantly lower incidence of acute myocardial infarction than the NTG/placebo group (three vs 10 patients; p =.013). Symptomatic hypotension occurred frequently in the NTG/NAC group (seven vs 0 patients; p = .006). Lactate-pyruvate ratios and venous NTG concentrations were not significantly affected by NAC. Subsequently, another 20 consecutive patients were treated with intravenous NTG and continuously infused NAC (10 g/day). Seven remained pain free during the first 24 hr of NTG infusion; 11 required increments in NTG infusion rate for pain control. Acute myocardial infarction occurred in one patient, while none developed symptomatic hypotension. It is concluded that combined administration of NTG and NAC may augment the clinical efficacy of NTG, particularly by preventing acute myocardial infarction. However, the risk of development of hypotension with combined NTG/NAC is increased when NAC is administered by rapid intravenous infusion.

The simultaneous identification and quantitation of 15 benzodiazepines and selected metabolites in postmortem blood, serum, or liver homogenate is described. The assay involves extraction with diethylether, followed by an acid clean-up step of the ether. Chromatographic separation was achieved on a Nova-Pak phenyl 18 column using ultraviolet detection at 240 nm. A gradient HPLC system was developed to improve separation of nitro-reduction metabolites from the solvent front and endogenous peaks. The mobile phases consisted of a gradient from 15 to 28% acetonitrile in 40 mM potassium phosphate buffer. Within-run and day-to-day precision were generally 10-15%. The method described is sensitive and reproducible for the analysis of benzodiazepine concentrations in postmortem tissues.