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Tizanidine double dose. In addition to a decrease T3 level (Figure 6), no major changes or were observed in the other parameters measured (data not shown). No major change was also seen in the renal markers after addition of the double dose tizanidine (Data not shown). DISCUSSION Our results show that, in healthy adult volunteers, administration of the dual dose lorazepam (5 mg) was sufficient to enhance subjective effects of cocaine. These the double dose were not influenced by the pharmacological dose of drug, which was not reported Tetracycline 250mg $116.01 - $0.32 Per pill in a number of reports [18, 19]. This study also showed a statistically significant effect of the double dose lorazepam on psychomotor alertness and performance measured by the psychomotor vigilance task, and these effects persisted during the next day. Previous studies demonstrated that benzodiazepines, when co-administered with an opiate, produce enhanced response of the analgesic effect after administration of these drugs, with the greatest increase in this response seen when opioids and benzodiazepines were administered together [20–23]. In particular, studies of the combination morphine hydrochloride (15 or 30 μg) and benzodiazepines showed an increase in analgesia after the administration of morphine, but this effect was eliminated when morphine and benzodiazepines were administered separately [18, 23, 24]. A similar decrease in pain sensitivity with the double dose of benzodiazepines and morphine in healthy volunteers has also been measured in some studies [18, 24]. The analgesic effect of oxycodone (0.5mg/kg) and diazepam (5–15 mg) was increased by diazepam in doses that were not found to produce significant subjective alterations (5–15 mg/kg) [3, 5]. A study of the interaction between oxycodone and diazepam did not confirm these findings [5]. The double dose of both oxycodone and diazepam in healthy volunteer subjects also induced some subjective euphorigenic effects [5], which may be due, among other factors, to the higher doses used increase analgesic effect by diazepam. Further studies on this topic are needed. In general, a reduction the dose and simultaneous increase in the length of administration time used to induce a subjective effect (for example, 5 mg/kg of oxycodone in the study by Pacheco and co-workers [1] or 1-mg/kg of diazepam in the study by Pacher and co-workers [2]) should be avoided in patients with chronic pain. This study also provided additional evidence that the subjective euphoria induced by chronic cocaine may produce a drug-placebo interaction. The double dose of oxycodone and diazepam caused a reduction in ratings of "physical effects," but the subjective alterations observed in "psychological effects" subscale were unaffected. These findings are consistent with recent studies in healthy volunteers where administration of the dual dose diazepam and oxycodone did not influence ratings of "physical effects," but did cause a subjective reduction in these ratings [19], [23]. one study, diazepam produced a reduction in "psychological effects," but the effect was not affected by the addition of double dose diazepam and oxycodone to drug treatment [5]. However, in the other study that used oxycodone but not diazepam, "psychological effects" ratings were decreased by diazepam when compared to the effects of single doses diazepam, but the reduction remained significant when diazepam was administered alone [5]. These data show that subjective effects, which were influenced by the placebo factor or other drugs [1, 5], may be influenced by the effect of chronic cocaine on subjective euphoria. In conclusion, some studies have demonstrated that the euphoric effect of opiates and benzodiazepines may also be influenced by their combination. This finding may account for some adverse or unexpected actions reported by some subjects receiving these substances together with co-administration of cocaine. The double dose of lorazepam caused dose-dependent changes in plasma lorazepam, clonidine and norfloxacin levels did not alter a significant portion of these parameters in relation to the changes basal level. lack of a dose-dependent effect on the levels of these drugs suggests that lorazepam did not modify the response of these drugs to the cocaine. In contrast to the increased basal levels of lorazepam and clonidine observed in our subjects, healthy volunteers diazepam also increased plasma levels at all dose tested (data not shown). This is consistent with previous reports [25] where, in healthy volunteers, co-administration of the main benzodiazepine, clon.

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