In a previous study' a surprising finding was that patients premedicated with diazepam (Valium) 10 mg orally were better sedated during the first 90 minutes following administration than when the same dose was given by intramuscular injection into the buttock. This was confirmed in a 'double-blind, double-dummy' study involving 200 comparable patients in whom the drugs were given by the nursing staff.' Plasma diazepam levels were estimated to seek an explanation for these clinical findings, the study being carried out to show the influence of the route of administration on the plasma diazepam levels following a single 10 mg dose. Method Plasma diazepam estimationsThese were done by gas-liquid chromatography following benzene e~traction.~ The method of estimation, its reliability and reproducibility has been described in detail in another paper from this d e~a r t m e n t .~ SubjectsThese were fit young women scheduled for morning minor gynaecological operations who had fasted overnight. Patients who had had diazepam in the previous 4 weeks were excluded as were any patients who, despite the screening, were found to have diazepam or its metabolite in the control plasma sample. Table 1 shows the number of patients. The four groups studied were broadly comparable with respect to average age and weight. The preliminary results following the injection of diazepam into the buttocks by nurses, who normally used a 23 swg (3 cm) needle, led us to repeat part of the investigation when the drug was given into the upper outer quadrant of the buttock by one of the authors using a large 21 swg (4 cm)
It is generally agreed that absorption of drugs occurs more rapidly following their intramuscular injection than when given by mouth.'-3 This is the basis for the giving of premedicants by injection, which although challenged by Inglis & Barrow in 1965,4 is still widely practised.Recently, in a pilot study, McCaughey & Dundee' found better sedation when 10 mg diazepam was given by mouth than following its intramuscular injection, but their investigation was carried out on a small number of patients. In view of the importance of this finding a large-scale study was undertaken involving both the oral and intramuscular routes, in which neither the patient nor the observer knew whether the capsule or injection was the active drug. As a result of this, and studies of blood diazepam levels, a further smaller investigation was initiated when injections were all given by a doctor.The findings involve many aspects of the action of diazepam and this presentation is designed to show the relative merits and demerits of the two routes of administration. No attempt was made to compare the action of diazepam with that of other premedicants or a placebo. Method PatientsThe patients were fit adult women from one hospital unit, scheduled for morning minor gynaecological operations. They were first questioned as to their use of tranquillisers or sedatives, and if they had been on long-term therapy within the previous month or had been given a hypnotic on the night prior to operation they were excluded from the study. DrugsEach patient was given one capsule by mouth and a 2 ml injection about 90 minutes
Toxic leukoencephalopathy (TL) is characterised by an insult to the myelin of the cerebral white manner which can be attributed to a number of offending agents, including drugs of abuse. We report a case of a fit and well young man presenting to hospital with an altered mental state. It was subsequently determined that the patient inhaled a significant volume of nitrous oxide recreationally. Nitrous oxide is easily accessible and the second most consumed drug among young adolescents (16–24 years old). Following extensive investigations and brain imaging, the patient was subsequently diagnosed with TL. After a prolonged hospital admission, he went on to make a complete neurological recovery.
When given with pethidine 100 mg or morphine 10 mg as preanaesthetic medication, 10 and 20 mg of metoclopramide cause a reduction in postoperative nausea and vomiting in women undergoing a standard operation with a standard anaesthetic technique. The preoperative emetic effects of pethidine are almost completely abolished by metoclopramide. An additional 10-20 mg of metoclopramide, given i.m. at the end of the operation markedly reduces the emetic effects of pethidine premedication but has less effect when morphine has been given. The evidence suggests that the ineffectiveness of metoclopramide, relative to other antiemetics, is because of its brevity of action.
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