Medical toxicology最新文献

{"title":"Methanol and ethylene glycol poisonings. Mechanism of toxicity, clinical course, diagnosis and treatment.","authors":"D Jacobsen,&nbsp;K E McMartin","doi":"10.1007/BF03259846","DOIUrl":"https://doi.org/10.1007/BF03259846","url":null,"abstract":"<p><p>Methanol and ethylene glycol poisonings share many characteristics both clinically and biochemically. Both alcohols are metabolised via alcohol dehydrogenase to their toxic metabolites. Methanol is slowly metabolised to formaldehyde which is rapidly metabolised to formate, the metabolite mainly responsible for methanol toxicity. Formate metabolism depends upon the folate pool which is small in primates compared with other animals. Therefore, formate accumulates in primates during methanol intoxication and is mainly responsible for the metabolic acidosis in the early stage of intoxication. In late stages lactate may also accumulate, mainly due to formate inhibition of the respiratory chain. This tissue hypoxia caused by formate may explain the ocular as well as the general toxicity. Ethylene glycol is metabolised more rapidly than methanol, via alcohol dehydrogenase to glycolaldehyde which is rapidly metabolised to glycolate, the metabolite mainly responsible for the metabolic acidosis in ethylene glycol poisoning. Glycolate is metabolised by various pathways, including one to oxalate which rapidly precipitates with calcium in various tissues and in the urine. Ethylene glycol toxicity is complex and not fully understood, but is mainly due to the severe metabolic acidosis caused by glycolate and to the calcium oxalate precipitation. The clinical course in both poisonings is initially characterised by the development of metabolic acidosis following a latent period, which is more pronounced in methanol poisoning and is the time taken for both alcohols to be metabolised to their toxic metabolites. In methanol poisoning there are usually visual symptoms progressing to visual impairment, whereas ethylene glycol victims develop renal and cardiopulmonary failure. Prognosis is excellent in both poisonings provided that there is early treatment with alkali to combat acidosis, ethanol as an antimetabolite, and haemodialysis to remove the alcohols and their toxic metabolites. Ethanol is also metabolised by alcohol dehydrogenase, but has a much higher affinity for this enzyme than methanol and ethylene glycol. Presence of ethanol will therefore inhibit formation of toxic metabolites from methanol and ethylene glycol. Due to competition for the enzyme, the therapeutic ethanol concentration depends on the concentration of the other two alcohols, but a therapeutic ethanol concentration around 22 mmol/L (100 mg/dl) is generally recommended. Most patients are, however, admitted at a late stage to hospitals not capable of performing analyses of these alcohols or their specific metabolites on a 24-hour basis.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 5","pages":"309-34"},"PeriodicalIF":0.0,"publicationDate":"1986-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259846","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14659807","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":"Adverse reactions and interactions with beta-adrenoceptor blocking drugs.","authors":"R V Lewis, D G McDevitt","doi":"10.1007/BF03259848","DOIUrl":"10.1007/BF03259848","url":null,"abstract":"<p><p>beta-Blocking drugs are widely used throughout the world and serious adverse reactions are relatively uncommon. Most of those which do occur are pharmacologically predictable and may be avoided by ensuring that patients who are to be given beta-blockers do not have a predisposition to the development of bronchospasm, cardiac failure or peripheral ischaemia. In some situations, the use of a beta 1-selective blocking drug may reduce the risk of a severe adverse reaction, but there is little evidence that other ancillary properties such as partial agonist activity are of relevance in this context. Long term experience with many of the beta-blockers in current use suggests that unpredictable major adverse reactions such as the practolol oculomucocutaneous syndrome are unlikely to be repeated, although some of these drugs may be associated with immunological disturbances and some have been implicated in the development of retroperitoneal fibrosis. beta-Blocking drugs appear to be associated with a number of subjective side effects including muscle fatigue, peripheral coldness and some neurological symptoms. These side effects are highly subjective and are therefore difficult to quantify and it is not known whether they are of major importance in terms of their effect upon patients' overall well-being. It cannot be assumed that simply because such side effects can be elicited that they do, in fact, matter. However, because beta-blockers are often prescribed for patients who have no symptoms and for whom the benefits of therapy are generally small, such side effects would be of considerable importance if they had an overall effect upon quality of life. There are theoretical reasons to suppose that the incidence and severity of such side effects may be related to the ancillary properties of the individual drugs, but there is little evidence that parameters such as beta 1-selectivity, or partial agonist activity are clinically important determinants of the severity of these side effects. Lipophilicity, however, may be associated with an increased incidence of neurological symptoms. beta-Blocking drugs may cause a variety of metabolic disturbances including an increase in serum VLDL-cholesterol concentrations. However, long term studies have not shown that such disturbances are associated with an increased risk of cardiovascular disease, indicating that such metabolic changes may not be of major importance in practice. beta-Blocking drugs may be involved in a number of interactions with other drugs, but few of these have been shown to be of clinical significance.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 5","pages":"343-61"},"PeriodicalIF":0.0,"publicationDate":"1986-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14013511","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":"Adverse effects associated with the newer inotropic agents.","authors":"M W Webster,&nbsp;D N Sharpe","doi":"10.1007/BF03259847","DOIUrl":"https://doi.org/10.1007/BF03259847","url":null,"abstract":"<p><p>The ideal inotropic agent should be available for both parenteral and oral administration and be potent and effective long term without significant adverse effects. In recent years, numerous new agents have been developed in an attempt to find a more potent, less toxic alternative to digoxin. beta-Agonists, while useful when given parenterally short term, appear to have their long term oral application limited by adverse effects and the development of tolerance. A number of other non-catecholamine agents, most of which have both inotropic and vasodilator actions, have also been studied. Adverse effects have been relatively frequent and occasionally severe. Of these newer agents none has yet been proven in clinical trials to be safe and effective in the long term.</p>","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 5","pages":"335-42"},"PeriodicalIF":0.0,"publicationDate":"1986-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259847","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14015933","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":"Adverse effects of nitrous oxide.","authors":"J B Brodsky, E N Cohen","doi":"10.1007/BF03259849","DOIUrl":"10.1007/BF03259849","url":null,"abstract":"<p><p>Although once considered completely devoid of complications, it is now recognised that the misuse or inappropriate use of nitrous oxide (N2O) often results in adverse side effects. Hypoxia, particularly the entity 'diffusion hypoxia', can occur with the administration of inadequate amounts of oxygen during or immediately after a N2O anaesthetic. N2O will diffuse into air-containing cavities within the body faster than nitrogen diffuses out. This results in a temporary increase in either the pressure and/or volume of the cavity depending upon the distensibility of its walls. The magnitude of the effect is proportional to the blood supply of the cavity, the concentration of N2O inhaled and the length of time the patient is exposed to N2O. Significant morbidity or even death can result from this phenomenon. A property unique to N2O is its ability to oxidise and inactivate the vitamin B12 components of certain enzymes in both animals and man. One such enzyme, methionine synthetase is essential for normal DNA production. Animal and human studies have demonstrated that the haematological, immune, neurological and reproductive systems are each affected. These adverse effects of N2O can occur after both acute (surgical) or long term (occupational) exposure to the gas. Because of its effects on the pressure and volume characteristics of air-containing spaces, N2O should not be used for patients with bowel obstruction, pneumothorax, middle ear and sinus disease, and following cerebral air-contrast studies. Many anaesthesiologists feel that use of N2O should be restricted during the first two trimesters of pregnancy because of its effects on DNA production and the experimental and epidemiological evidence that N2O causes undesirable reproductive outcomes. Since N2O affects white blood cell production and function, it has been recommended that N2O not be administered to immunosuppressed patients or to patients requiring multiple general anaesthetics. Many anaesthesiologists believe that the potential dangers of N2O are so great that it should no longer be used at all for routine clinical anaesthesia. However, the continued use of N2O remains a controversial topic since, at present, a suitable substitute gas is not available.</p>","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 5","pages":"362-74"},"PeriodicalIF":0.0,"publicationDate":"1986-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14660785","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":"Role of the intensive care unit in the management of the poisoned patient.","authors":"P Kulling, H Persson","doi":"10.1007/BF03259850","DOIUrl":"10.1007/BF03259850","url":null,"abstract":"<p><p>By applying a sensible toxicological approach to the general principles of intensive care, an optimum setting for the treatment of poisoning is created. The intensive care unit (ICU) can perform the necessary close observation and monitoring, and thus facilitate rapid detection of symptoms, and the institution of early appropriate treatment. Diagnosis may be complex in poisoning and require continuous qualified interpretation of clinical and analytical data. Antidote therapy and treatment to enhance elimination of the poison must often be dealt with under careful supervision. The capacity of the ICU to counteract various toxic effects in a nonspecific way and to provide optimum symptomatic and supportive care is crucial. However, the ongoing toxic effects on the body must always be considered and allowed to guide symptomatic treatment. Thus, clinical toxicology appears to be a specialised branch of intensive care medicine.</p>","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 5","pages":"375-86"},"PeriodicalIF":0.0,"publicationDate":"1986-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14660783","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":"Adverse reactions to beta 2-agonist bronchodilators.","authors":"K M Lulich,&nbsp;R G Goldie,&nbsp;G Ryan,&nbsp;J W Paterson","doi":"10.1007/BF03259844","DOIUrl":"https://doi.org/10.1007/BF03259844","url":null,"abstract":"<p><p>Beta 2-Agonists are safe and effective bronchodilator drugs. Their major adverse effects of skeletal muscle tremor, tachycardia and various metabolic effects are mediated by beta-adrenoceptor stimulation and are reversible. Skeletal muscle tremor is the most frequent dose-limiting side effect. It may be reduced by commencing treatment with a low dose and if it persists another beta 2-agonist may be tried. Other side effects such as cardiac arrhythmias and reduction in PaO2 are a serious potential problem in some susceptible asthmatics. However, they are infrequent or of a mild degree and are generally outweighed by the good control of asthma produced by beta 2-agonists. Side effects from beta 2-agonist therapy can be minimised by use of the inhaled route which selectively delivers the drug to the airways. Furthermore, selective tolerance develops to their side effects. The dose of a beta 2-agonist should be assessed on the basis of therapeutic effect and the level of tolerance to its side effects. Recommended doses of beta 2-agonists used for long term therapy do not cause clinically significant desensitisation of airway beta-adrenoceptors, although this may become a relevant problem in patients who are regularly receiving very high doses. Intravenous beta 2-agonists have a place in the treatment of severe asthma not responding to nebuliser therapy. In this life-threatening situation with severe airflow obstruction, monitoring of heart rate, PaO2, plasma potassium and the electrocardiogram should be mandatory and supplemental oxygen given so that serious adverse effects are presented.</p>","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 4","pages":"286-99"},"PeriodicalIF":0.0,"publicationDate":"1986-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259844","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14015932","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":"Acute overdose with sustained release drug formulations. Perspectives in treatment.","authors":"A Minocha, D A Spyker","doi":"10.1007/BF03259845","DOIUrl":"10.1007/BF03259845","url":null,"abstract":"<p><p>Acute overdose with sustained release formulations presents special problems for the health care system. Proper management requires a basic understanding of the pharmacokinetic and pharmacodynamic characteristics of the drugs taken in overdose because different techniques employed by the manufacturers to produce sustained release formulations lead to differences in these characteristics in comparison with conventional formulations. In general, with sustained-release formulations, there is a prolongation of the time for the patient to manifest toxicity ('preclinical phase'), as well as the period of high drug concentrations and clinical toxicity ('toxic phase') and the resolution phase (clinical improvement with declining drug concentrations). Continued drug absorption over a prolonged period alters the normal drug concentration-time profile. The prolonged absorption half-life may appear as an increase in elimination half-life, even though the clearance of the drug stays the same. Gastrointestinal decontamination is extremely important in the management of overdose with sustained release formulations. We advocate an aggressive decontamination approach to management, especially in the preclinical phase. With a history of potentially toxic ingestion of an adsorbable drug, a charcoal stool following administration of oral activated charcoal should be a minimum requirement for discharge of the patient. Gastrointestinal decontamination is critical in the preclinical and the toxic phases and may be of value during the resolution phase until the drug concentrations decline to the therapeutic range.</p>","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 4","pages":"300-7"},"PeriodicalIF":0.0,"publicationDate":"1986-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14659802","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":"Drug- and chemical-induced methaemoglobinaemia. Clinical features and management.","authors":"A H Hall, K W Kulig, B H Rumack","doi":"10.1007/BF03259842","DOIUrl":"10.1007/BF03259842","url":null,"abstract":"<p><p>Methaemoglobin is haemoglobin with the iron oxidised to the ferric (Fe ) state from the normal (or reduced) ferrous (Fe++) state. Methaemoglobinaemia refers to the presence of greater than the normal physiological concentration of 1 to 2% methaemoglobin in erythrocytes. Methaemoglobin is incapable of transporting oxygen. It has an intense dark blue colour; thus, clinical cyanosis becomes apparent at a concentration of about 15%. The symptoms are manifestations of hypoxaemia with increasing concentrations of methaemoglobin. Concentrations in excess of 70% are rare, but are associated with a high incidence of mortality. Methaemoglobinaemia may be congenital but is most often acquired. Congenital methaemoglobinaemia is of two types. The first is haemoglobin M disease (several variants) which is due to the presence of amino acid substitutions in either the alpha or beta chains. The second type is due to a deficiency of the NADH-dependent methaemoglobin reductase enzyme. This deficiency has an autosomal dominant transmission, and both homozygous and heterozygous forms have been reported. The heterozygous form is not normally associated with clinical cyanosis, but such individuals are more susceptible to form methaemoglobin when exposed to inducing agents. A wide variety of chemicals including several drugs, e.g. the antimalarials chloroquine and primaquine, local anaesthetics such as lignocaine, benzocaine and prilocaine, glyceryl trinitrate, sulphonamides and phenacetin, have been reported to induce methaemoglobinaemia. An intense 'chocolate brown' coloured blood and central cyanosis unresponsive to the administration of 100% oxygen suggests the diagnosis. A simple bedside test using a drop of the patient's blood on filter paper helps to confirm the clinical suspicion. Methaemoglobin can be quantitated rapidly by a spectrophotometric method.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 4","pages":"253-60"},"PeriodicalIF":0.0,"publicationDate":"1986-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14659800","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":"Poisoning due to tricyclic antidepressant overdosage. Clinical presentation and treatment.","authors":"P Crome","doi":"10.1007/BF03259843","DOIUrl":"10.1007/BF03259843","url":null,"abstract":"<p><p>Tricyclic antidepressants are among the commonest causes of both non-fatal and fatal drug poisoning in the world. Their toxicity is due to effects on the brain, the heart, the respiratory system and the parasympathetic nervous system. Symptoms usually appear within 4 hours of an overdose and all but the most seriously poisoned patients recover within 24 hours. The most common clinical features are dry mouth, blurred vision, dilated pupils, sinus tachycardia, pyramidal neurological signs, and drowsiness. In severe poisoning, there may be coma, convulsions, respiratory depression, hypotension and a wide range of electrocardiographic (ECG) abnormalities. The most frequent findings on the ECG are prolongation of the PR and QT intervals; the tracing may resemble bundle branch block or supraventricular or ventricular tachycardias. Treatment of poisoning due to the tricyclic antidepressants is essentially supportive, there being insufficient evidence at present to recommend the use of methods to increase elimination of the drug from the body. Gastric aspiration and lavage should be performed if more than 750 mg of drug have been taken. There must be regular monitoring for hypoxia, acidosis and hypokalaemia and these complications should be corrected enthusiastically. Convulsions should be treated with diazepam or chlormethiazole. Muscular paralysis and artificial ventilation should be employed if anticonvulsants are ineffective. Hypotension should be treated firstly by fluid replacement and then with sympathomimetic agents (dopamine or dobutamine). Antiarrhythmic drugs should only be employed if there is evidence of circulatory failure which fails to respond to correction of hypotension. Sodium bicarbonate infusions should be given to cardiotoxic patients who are acidotic and are worth trying even if the patient is not acidotic. Although physostigmine salicylate will reverse most of the features of tricyclic antidepressant poisoning, its effects are short-lived in serious toxicity and it can produce dangerous side effects; physostigmine should therefore be reserved for those patients who have complications of coma or who have resistant cardiotoxicity or convulsions. Drug screening and quantitative determination of tricyclic antidepressant serum concentrations are useful in a minority of patients who have severe, unusual or prolonged symptoms.</p>","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 4","pages":"261-85"},"PeriodicalIF":0.0,"publicationDate":"1986-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14659803","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":"Techniques of postmarketing surveillance. An overview.","authors":"J L Carson,&nbsp;B L Strom","doi":"10.1007/BF03259840","DOIUrl":"https://doi.org/10.1007/BF03259840","url":null,"abstract":"","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 4","pages":"237-46"},"PeriodicalIF":0.0,"publicationDate":"1986-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259840","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14660779","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}