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Sixteen hours after the infusion was commenced he developed ventricular tachycardia, from which he was resuscitated and made an uneventful recovery.Case A yearold man was admitted with severe facial bone fractures following an assault outside a bar.His clinical state was stable although biochemical studies revealed raised serum enzymes and low serum albumin.Soon after admission he became increasingly restless, parenteral diazepam and chlorpromazine again proving ineffectual.Necropsy revealed an insignificant pulmonary embolus and fatty hepatic degeneration consistent with chronic alcoholism.These cases demonstrate that potentially lethal cardiac dysrhythmias may complicate chlormethiazole infusion at the manufacturers recommended maintenance dose. At the times of cardiac arrest the infusion rates were mgh and mgh respectively.Presumably as a result of agerelated changes in hepatic clearance, the terminal phase halflife of chlormethiazole is longer in the elderly than in healthy young adults.Acute ingestion of alcohol, which accompanied the overdose in at least six of the subjects reported, might also be expected to inhibit the metabolism of drugs with high presystemic extraction, such as chlormethiazole, when they are taken orally.Chlormethiazole is a useful drug which may be employed successfully in the management of the acute symptoms of alcohol withdrawal when other drugs are less satisfactory, as in our cases.However, this report and other recent case studies i emphasise that the drug should be administered with caution.Particular attention should be paid not only to the patients respiratory function and age but also on to alcohol <a href="http://www.targetmol.com/compound/8-Hydroxyquinoline">Targetmol's Hydroxyquinoline</a> intake and hepatic and cardiac function when chlormethiazole is prescribed for oral or intravenous use.The patients who received oral premedication and intravenous sedation with chlormethiazole were invariably elderly with some degree of pulmonary dysfunction and at no time have I experienced any untoward respiratory complication.Even in combination with narcotics the degree of respiratory depression has never exceeded that expected from the narcotic alone.Since azathioprine was given simultaneously, it is highly questionable whether the warning against metronidazole in connection with neutropenia has a shred of evidence to support it.Azathioprine is well known as an agent capable of inducing neutropeniaalone.We believe that a combination of metronidazole and fluorouracil may also give rise to such an effect.In a trial of adjuvant chemotherapy with fluorouracil in this department,   patients with colorectal cancer have received mgkg fluorouracil intravenously after surgery and on the first two postoperative days followed by weekly fluorouracil at a dose of mgkg.An initial pilot study performed one year ago demonstrated no adverse side effects of this regimen in the patients included.However, of the patients admitted to the present trial four have developed a leucopenia with leucocyte counts of x or less.The only difference in therapy between the two studies has been our recent use of metronidazole at a dose of mg orally three times daily for three days before surgery and mg intravenously three times daily for five days after surgery.However, we have not observed a greater incidence of neutropenia in patients who have received in addition to fluorouracil and metronidazole mg of levamisole on the first three postoperative days.In addition, a combination of levamisole and fluorouracil has not, in our hands, been found to cause neutropenia.

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Union Party Of Canada
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