Medical toxicology and adverse drug experience最新文献

{"title":"Adverse reactions and interactions of cyclosporin.","authors":"J P Scott,&nbsp;T W Higenbottam","doi":"10.1007/BF03259936","DOIUrl":"https://doi.org/10.1007/BF03259936","url":null,"abstract":"<p><p>Cyclosporin is a potent, widely used specific immunosuppressive agent which affects T-helper cells, and has little myelotoxicity. Its pharmacokinetics are complex and many of its actions remain poorly understood. Numerous side effects have been reported, affecting most organs. Most troublesome have been renal injury, systemic hypertension and vascular changes. Oral use is more effective than intramuscular and safer than the intravenous route. Interactions with other drugs include those which affect hepatic metabolism and those which reduce clearance. Aminoglycosides, macrolide antibiotics, imidazole derivatives, calcium channel blockers, sulphonamides and steroids are included in such interactions. Other metabolic effects of cyclosporin are more subtle and include hyperchloraemic alkalosis, changes in serum potassium and magnesium and effects on testosterone and prolactin levels. Acute poisoning with cyclosporin has been reported, again without myelosuppression. Cyclosporin is an important agent with multisystem toxicity, which requires precise monitoring of drug concentrations, liver and renal function, haemoglobin levels and plasma electrolytes. Cyclosporin pharmacodynamics and interactions with other drugs need to be carefully considered if lower rates of toxicity are to be achieved.</p>","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1988-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259936","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14415138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole bowel irrigation as a gastrointestinal decontamination procedure after acute poisoning.","authors":"M Tenenbein","doi":"10.1007/BF03259934","DOIUrl":"https://doi.org/10.1007/BF03259934","url":null,"abstract":"","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1988-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259934","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14415141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical features and management of lithium poisoning.","authors":"A Amdisen","doi":"10.1007/BF03259929","DOIUrl":"https://doi.org/10.1007/BF03259929","url":null,"abstract":"<p><p>Lithium salts, in particular the carbonate and citrate, were formerly in widespread use, forming part of alkaline salt mixtures which were used for treatment of the many disorders belonging to the uric acid diathesis. Among these disorders were mania, depression, acute mania, acute melancholia and periodic depression. Satisfactory prophylactic effects on periodic depression were directly claimed. Daily doses of 3 to 26 mmol of lithium were recommended as standards. Only slight or moderate symptoms of poisoning were reported in a very few cases during the period in question (1860 to 1930), when the popularity of these lithium-containing prophylactic drugs with a favourable therapeutic index was at its peak. Lithium intoxication was not a serious clinical problem until 1949 when Cade introduced his fortuitously effective, but nevertheless high, dosage regimen which was continued until signs of recovery from mania appeared. For the maintenance dose, Cade in principle recommended, but seldom adhered to, 17 mmol/day. Chronic lithium intoxication starts insidiously with silent affliction of the kidneys followed by 'prodromal' symptoms, and when moderate severity has been reached, an accelerating renal vicious circle with decreasing kidney function is imminent. After this point the chronic intoxication resembles acute intoxication. Active detoxification at this, or an earlier stage, leaves the patient with a good chance of recovery. At a later stage, with the occurrence of oliguria, semi-coma or coma, and latent convulsive movement, recovery is less certain. There is no specific antidote for the toxic effects of lithium. Haemodialysis is the most effective treatment for acute lithium poisoning. For patients with impaired, or potentially impaired renal function, peritoneal dialysis may be an alternative, but less effective, treatment. Forced diuresis demands unimpaired renal function, and is little more effective than withdrawal of treatment, supplemented with correction of water and electrolyte balance. Sodium overloading is not recommended. Patients on lithium prophylaxis are treated on an outpatient basis. Prevention of intoxication depends on cooperation between patient and clinician, and possibly on the use of smaller, low risk dosages in most patients.</p>","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1988-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259929","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14413074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"'Designer drugs'. A problem in clinical toxicology.","authors":"J F Buchanan,&nbsp;C R Brown","doi":"10.1007/BF03259928","DOIUrl":"https://doi.org/10.1007/BF03259928","url":null,"abstract":"<p><p>'Designer drugs' are substances intended for recreational use which are derivatives of approved drugs so as to circumvent existing legal restrictions. The term as popularised by the lay press lacks precision. Contrary to the popular belief that 'designer drugs' are original creations, the majority of these agents are 'borrowed' from legitimate pharmaceutical research. They merely represent the most recent developments in the evolution of mind-altering chemicals. The most extensively studied class of psychoactive compounds is the phenylethylamines (mescaline analogues). This class includes catecholamines, therapeutic agents and numerous illicit derivatives. Subtle alterations of the phenylethylamine molecule give rise to a spectrum of pharmacological properties ranging from pure sympathomimetic stimulation to primarily psychoactive effects. Although most of these compounds are only of historical interest, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA) continue to be used recreationally. Many deaths have been ascribed to this class of compounds. In overdose the differences between these compounds blur and the clinical presentation is similar to that of amphetamine overdose characterised by tachycardia, hypertension, hyperthermia, diaphoresis, mydriasis, agitation, muscle rigidity, and hyper-reflexia. Death usually results from arrhythmias, hyperthermia or intracerebral haemorrhage. Treatment is aggressive and supportive with careful attention to temperature, blood pressure and seizure control. Synthetic opioid derivatives, which represent the second major class of 'designer drugs', are derivatives of fentanyl (e.g. alpha-methylfentanyl, 3-methylfentanyl) or pethidine (meperidine) and are extremely potent compounds responsible for numerous overdose deaths. Attempts to synthesise pethidine have resulted in the accidental production of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a compound which is metabolised in the brain by the monoamine oxidase system to a toxic intermediate (MPP+) which selectively destroys the sustantia nigra, resulting in the rapid onset of severe Parkinsonian symptoms. Naloxone will antagonise the opiate effects of this drug class, although high doses may be required. Arylhexylamines constitute the third class of 'designer drugs'. The predominant member of this class is phencyclidine (PCP), a derivative of the anaesthetic ketamine. This unique class of psychoactive agents exhibits broad and complex pharmacological effects.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1988-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259928","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14414072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation and administration of chemotherapy. Haematological consequences for hospital-based nurses.","authors":"P R Jochimsen,&nbsp;M P Corder,&nbsp;P A Lachenbruch,&nbsp;M E Spaight","doi":"10.1007/BF03259931","DOIUrl":"https://doi.org/10.1007/BF03259931","url":null,"abstract":"<p><p>This study examined the question of whether previous exposure to cytostatic drugs by oncology nurses was sufficient to lead to haematological phenotypical subclinical abnormalities which had previously been identified in a population of patients who had received chemotherapy as an adjuvant to breast surgery. A comparison of baseline haematological parameters, and the results of a prednisolone stimulation test, was made between nurses regularly coming into contact with such agents and age-adjusted group of nurses who had not been exposed. Although there is a persistent trend toward lower neutrophils, platelets, monocytes and neutrophil reserves in the nurses who handled antineoplastic agents, a statistically significant decrement in these parameters was not identified. Such a finding should help to reassure individuals who have had similar exposure, but does not negate the importance of following published recommended guidelines for the handling and dispensing of antineoplastic agents.</p>","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1988-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259931","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14493931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pemoline-induced choreoathetosis and rhabdomyolysis.","authors":"J G Briscoe,&nbsp;S C Curry,&nbsp;R D Gerkin,&nbsp;R R Ruiz","doi":"10.1007/BF03259933","DOIUrl":"https://doi.org/10.1007/BF03259933","url":null,"abstract":"<p><p>Pemoline is an indirectly acting sympathomimetic with actions similar to amphetamine and methylphenidate. While choreoathetosis is a well-recognised complication of acute or chronic amphetamine abuse, only 3 previous case reports have implicated pemoline in such a movement disorder. We report a 49-year-old man who developed severe choreoathetosis with rhabdomyolysis after markedly increasing his intake of pemoline. Abnormal movements responded to diazepam and completely resolved over 48 hours. He made a complete recovery with supportive care. This is only the second case of pemoline-induced choreoathetosis in an adult reported in the English literature, and the first case of rhabdomyolysis and myoglobinuria complicating choreoathetosis.</p>","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1988-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259933","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14494716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmaceutical Excipients","authors":"L. Golightly, S. Smolinske, M. Bennett, E. Sutherland, B. Rumack","doi":"10.1007/BF03259937","DOIUrl":"https://doi.org/10.1007/BF03259937","url":null,"abstract":"","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1988-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259937","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52283848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Failure of haemoperfusion and haemodialysis to prevent death in paraquat poisoning. A retrospective review of 42 patients.","authors":"E C Hampson,&nbsp;S M Pond","doi":"10.1007/BF03259932","DOIUrl":"https://doi.org/10.1007/BF03259932","url":null,"abstract":"<p><p>In this review the efficacy of haemoperfusion in the treatment of paraquat poisoning is addressed. 42 reports containing sufficient information of paraquat-poisoned patients were evaluated. These reports, from 35 patients reported in the literature and 7 new cases, were chosen for the following reasons: the timed plasma paraquat concentrations were known, patient outcome was known, and details of haemoperfusion were available. In some cases, haemodialysis was also performed. The plasma paraquat concentrations and the specific times post-ingestion were plotted on a contour graph that predicts the probability of survival. Comparison of the predicted probability of survival versus the actual outcome showed that haemoperfusion, single or repeated, did not affect patient survival. None of the patients whose initial plasma concentrations were greater than 3 mg/L paraquat survived, regardless of the time after ingestion that the concentrations were measured, and despite haemoperfusion. Therefore, such patients might not be considered for haemoperfusion because of their uniformly bad prognosis, despite the procedure being used, and because of the morbidity, discomfort and cost associated with it. Clearly, the need for better techniques to remove paraquat and to prevent the consequences of the metabolic effects of the compound are required urgently before the treatment of the paraquat-poisoned patient will be successful.</p>","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1988-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259932","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14413078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral activated charcoal in the treatment of intoxications. Role of single and repeated doses.","authors":"P J Neuvonen,&nbsp;K T Olkkola","doi":"10.1007/BF03259930","DOIUrl":"https://doi.org/10.1007/BF03259930","url":null,"abstract":"<p><p>Activated charcoal has an ability to adsorb a wide variety of substances. This property can be applied to prevent the gastrointestinal absorption of various drugs and toxins and to increase their elimination, even after systemic absorption. Single doses of oral activated charcoal effectively prevent the gastrointestinal absorption of most drugs and toxins present in the stomach at the time of charcoal administration. Known exceptions are alcohols, cyanide, and metals such as iron and lithium. In general, activated charcoal is more effective than gastric emptying. However, if the amount of drug or poison ingested is very large or if its affinity to charcoal is poor, the adsorption capacity of activated charcoal can be saturated. In such cases properly performed gastric emptying is likely to be more effective than charcoal alone. Repeated dosing with oral activated charcoal enhances the elimination of many toxicologically significant agents, e.g. aspirin, carbamazepine, dapsone, dextropropoxyphene, cardiac glycosides, meprobamate, phenobarbitone, phenytoin and theophylline. It also accelerates the elimination of many industrial and environmental intoxicants. In acute intoxications 50 to 100g activated charcoal should be administered to adult patients (to children, about 1 g/kg) as soon as possible. The exceptions are patients poisoned with caustic alkalis or acids which will immediately cause local tissue damages. To avoid delays in charcoal administration, activated charcoal should be a part of first-aid kits both at home and at work. The 'blind' administration of charcoal neither prevents later gastric emptying nor does it cause serious adverse effects provided that pulmonary aspiration in obtunded patients is prevented. In severe acute poisonings oral activated charcoal should be administered repeatedly, e.g. 20 to 50g at intervals of 4 to 6 hours, until recovery or until plasma drug concentrations have fallen to non-toxic levels. In addition to increasing the elimination of many drugs and toxins even after their systemic absorption, repeated doses of charcoal also reduce the risk of desorbing from the charcoal-toxin complex as the complex passes through the gastrointestinal tract. Charcoal will not increase the elimination of all substances taken. However, as the drug history in acute intoxications is often unreliable, repeated doses of oral activated charcoal in severe intoxications seem to be justified unless the toxicological laboratory has identified the causative agent as not being prone to adsorption by charcoal. The role of repeated doses of oral activated charcoal in chronic intoxication has not been clearly defined.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1988-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259930","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14413079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flumazenil in benzodiazepine antagonism. Actions and clinical use in intoxications and anaesthesiology.","authors":"R Amrein,&nbsp;B Leishman,&nbsp;C Bentzinger,&nbsp;G Roncari","doi":"10.1007/BF03259876","DOIUrl":"https://doi.org/10.1007/BF03259876","url":null,"abstract":"<p><p>In anaesthesia and in the intensive care unit, benzodiazepines have proven safe and effective agents for the induction and maintenance of sedation for a variety of therapeutic goals. However, in these contexts, or in benzodiazepine overdose, it is often desirable to be able to terminate or interrupt sedation without waiting for the effect of the benzodiazepine to become dissipated by normal metabolism and excretion. Flumazenil, a 1,4-imidazobenzodiazepine, is a highly effective, specific benzodiazepine antagonist which is indicated for use when the effect of a benzodiazepine must be attenuated or terminated at short notice. It acts by displacing other benzodiazepines from the receptor site by competitive inhibition. The onset of effect after intravenous administration occurs within 1 to 3 minutes. The optimal dosage is determined for each patient by a dose titration procedure and lies in the range 0.2 to 1.0mg in anaesthesiology, and 0.1 to 2.0mg in intensive care use. Despite its short elimination half-life of around 1 hour, after general anaesthesia or conscious to moderate sedation for short procedures, a single dose of flumazenil is usually sufficient to attain and maintain the desired level of consciousness. After intoxication with high benzodiazepine doses, the duration of effect of a single dose of flumazenil is not expected to exceed 1 hour. In such cases, the period of wakefulness can be prolonged as necessary by repeated low intravenous doses of flumazenil or by infusion (0.1 mg/hour). Flumazenil is well tolerated both systemically and locally. The only adverse events seen with greater frequency after flumazenil compared with placebo were nausea and/or vomiting after general anaesthesia, although the incidence of actual vomiting was not significantly different between the 2 groups. Since these effects were virtually absent in studies of intensive care patients and after sedation for short procedures, and were not seen in tolerability studies in healthy volunteers receiving intravenous bolus doses of up to 100mg, there may be a link between these symptoms and the other agents used in general anaesthesia, some of which have well-known emetic properties. Thus, flumazenil provides a safe and effective means of attenuating or reversing the CNS-depressant effects of benzodiazepines whenever indicated, e.g. following benzodiazepine-induced general anaesthesia, conscious sedation, or after benzodiazepine overdose, either alone or in combination with other agents.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259876","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14029135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}