Medical toxicology最新文献

{"title":"Management of acute iron poisoning.","authors":"A T Proudfoot, D Simpson, E H Dyson","doi":"10.1007/BF03259830","DOIUrl":"10.1007/BF03259830","url":null,"abstract":"<p><p>Acute iron poisoning is most common in children below the age of 5 years. While there is no doubt that it may be fatal, recent surveys show that death occurs in only a very small percentage of cases and that iron salts are responsible for a small minority of fatalities due to overdosage with drugs. Similarly, the proportion of severe cases seems to have fallen over the last thirty years, possibly due to earlier and more aggressive treatment but more probably due to an increase in the number of minor exposures reported. Iron salts are directly toxic to the gastrointestinal tract causing vomiting, diarrhoea, abdominal pain and occasionally significant blood loss. They also cause metabolic acidosis by interfering with intermediary metabolism and producing shock and reduced tissue perfusion. The clinical course of acute iron poisoning is divided into 4 phases. Features of acute gastrointestinal irritation dominate the period up to 6 hours after ingestion and most patients do not develop other features or progress beyond this stage. Rarely, blood loss may be sufficient to cause hypotension. Severe poisoning is characterised by impairment of consciousness, convulsions and metabolic acidosis. The second phase, 6 to 12 hours after ingestion, is one of remission of features. Phase 3 comprises the period 12 to 48 hours from ingestion and is reached only by a small minority of patients. Recurrence or development of shock, and metabolic acidosis are usual and renal failure and features of extensive hepatocellular necrosis may develop. The last (fourth) phase, 2 to 6 weeks after ingestion, is only likely to develop in young children and is characterised by recurrence of vomiting due to gastric or duodenal stenosis caused by healing of iron-induced mucosal ulcers. Acute iron poisoning in humans has not been adequately studied and is unlikely to be so now because of the infrequent and sporadic occurrence of cases. The evidence for many conventional aspects of management is therefore unsatisfactory. Assessment of severity of poisoning is an essential prerequisite to optimum management but is difficult. The amount of elemental iron ingested is unacceptable since it is seldom known with accuracy and absorption is unpredictable because of vomiting and diarrhoea. The commonly encountered clinical features are also unreliable although it is generally accepted that coma, shock and metabolic acidosis indicate severe poisoning.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 2","pages":"83-100"},"PeriodicalIF":0.0,"publicationDate":"1986-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14902894","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":"Diagnosis of acute drug-induced liver injury. Usefulness of clinicopathological patterns and biochemical indices.","authors":"M Døssing, P B Andreason","doi":"10.1007/BF03259829","DOIUrl":"10.1007/BF03259829","url":null,"abstract":"","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 2","pages":"77-82"},"PeriodicalIF":0.0,"publicationDate":"1986-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14902891","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":"Renal toxicity of non-narcotic analgesics. At-risk patients and prescribing applications.","authors":"P Kincaid-Smith","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Acute and chronic renal damage may occur with many analgesics. Acute effects on the kidney occur mainly with aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs). One of the most obvious effects in healthy individuals is fluid retention which is thought to be mediated through inhibition of the renal effects of prostaglandins. Aspirin and NSAIDs also cause a decrease in glomerular filtration rate and renal blood flow and although these changes may occur in healthy individuals they are more pronounced in high renin states and in patients with pre-existing renal disease. Clinical syndromes associated with the renal effects of NSAIDs include oedema, acute renal failure and the nephrotic syndrome. Advanced age, dehydration, concurrent diuretic use and pre-existing renal disease are risk factors for these syndromes. Chronic effects of non-narcotic analgesics on the kidney were suspected before their acute effects became apparent. The key chronic renal lesion in the kidney attributed to prolonged ingestion of non-narcotic analgesics is renal papillary necrosis. The incidence of analgesic-associated renal papillary necrosis in different countries has generally paralleled the national regular use of analgesics. Although phenacetin was widely implicated as the cause of renal papillary necrosis, there is now increasing evidence that aspirin and other NSAIDs may cause renal papillary necrosis in patients who have not taken phenacetin. There is some evidence that this problem is reduced by legislative control of over-the-counter sales. Uroepithelial tumours have also been attributed to chronic abuse of analgesic mixtures. Such tumours are characterised by a reversal of the usual sex ratio, being more common in females.</p>","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 Suppl 1 ","pages":"14-22"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14669908","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":"Comparative pharmacology of 'non-opioid' analgesics.","authors":"K Brune","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Pain is the most prominent symptom of disease in man and analgesics are the most widely used drugs. More than 90% of the analgesics used belong to the so-called peripherally acting, non-opioid (non-narcotic) or mild analgesics. They all derive from 3 types of compounds: aspirin and other acidic non-steroidal anti-inflammatory drugs (NSAIDs), aniline derivatives such as paracetamol (acetaminophen) and non-acidic pyrazole drugs like propyphenazone and dipyrone (metamizole). These compounds and all of their derivatives differ in their analgesic activity and their typical profile of side effects. While NSAIDs are particularly useful in the treatment of pain related to inflammation these compounds are well known to cause gastrointestinal, haematological and kidney side effects. Aniline derivatives such as paracetamol are not very effective analgesics, but reasonably good antipyretics. These compounds, unlike aspirin-like drugs, do not interfere with inflammatory pain. Their main side effects are allergic but, particularly at overdose, they cause liver and kidney damage. Rarely, they have also been associated with kidney damage and malignomas of the urinary system after long term administration. Non-acidic pyrazole drugs are supposedly particularly active in pain originating from spasms of smooth muscles. They are not very effective anti-inflammatory drugs but are good antipyretics. Their major side effects consist of mild allergic reactions. They have also rarely been associated with agranulocytosis and shock. In addition to these differences in therapeutic application and side effect profile the major representatives of the groups of analgesics mentioned differ in their pharmacokinetic behaviour in the human body. Aspirin shows non-linear pharmacokinetics not seen with ibuprofen, a more modern NSAID.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 Suppl 1 ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14669905","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":"Gastrointestinal toxicity. Role of prostaglandins and leukotrienes.","authors":"B M Peskar,&nbsp;A Kleine,&nbsp;F Pyras,&nbsp;M K Müller","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Gastrointestinal tissues have a high synthesising capacity for prostaglandins. As exogenous prostaglandins protect the gastrointestinal mucosa against potentially noxious agents, it has been suggested that the generation of prostaglandins plays a crucial role in the maintenance of mucosal integrity. Analgesic and anti-inflammatory drugs with a potent inhibitory action on gastrointestinal cyclo-oxygenase, such as indomethacin, induce gastric and intestinal ulcerations in experimental animals and frequently lead to gastrointestinal side effects in man. However, drugs that do not reduce gastrointestinal prostaglandin formation, such as paracetamol (acetaminophen), are devoid of gastrointestinal toxicity. Various factors, e.g. tissue-specific differences in the sensitivity of cyclo-oxygenase against inhibition and pharmacokinetic properties, modify the inhibitory activity of analgesic and anti-inflammatory drugs on gastrointestinal prostaglandin formation. As leukotriene C4 is a potent gastric vasoconstrictor, increased metabolism of arachidonic acid via the 5-lipoxygenase pathway in the presence of inhibition of cyclo-oxygenase could possibly contribute to drug-induced gastrointestinal damage.</p>","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 Suppl 1 ","pages":"39-43"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14669909","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":"Blood dyscrasias secondary to non-steroidal anti-inflammatory drugs.","authors":"P A Miescher","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Drug reactions may be classified into 2 categories. The first category comprises reactions to the pharmacological properties of the drug which is given either in excessive amounts or to a subject who is highly susceptible to a given pharmacological action (e.g. G6PD-deficient subjects with regard to oxidants and patients with von Willebrand's disease with regard to drugs which inhibit platelet aggregability). The second category concerns reactions caused by a drug-dependent immune mechanism. By far the largest proportion of NSAID-induced side effects belong to the second category. The sensitising potential of a drug is probably connected to its protein-binding capacity. The clinical aspect depends on the type of immune reaction as well as its localisation within the organism. Cellular immunity usually leads to erythematous skin rashes. However, it is possible that some of the haematological side effects may be caused by T-lymphocytes reacting specifically with haematopoietic cells to which a drug adheres. Antibody-mediated immune reactions are more common. Today, we can distinguish 5 different mechanisms: IgE-mediated drug reactions usually lead to eosinophilia, sometimes with eosinophilic infiltrates in the lung. In such cases, patients frequently develop urticarial rashes. In a number of drug-induced cytopenias the underlying mechanism resides in the action of soluble immune complexes on red cells, leucocytes or platelets as in the case of agranulocytosis secondary to medication with pyrazoles. IgG and/or IgM may be implicated in the formation of the immune complexes. In this system, blood cells are affected when incubated with the serum of an allergic subject previously incubated with the offending drug or one of its metabolites. Some drugs or drug metabolites have a strong affinity for certain blood cells to which they become attached. If a patient develops antibodies to these drugs, an antibody interaction with the drug-coated cells can lead to the destruction of the cells. This mechanism may be operative not only in the periphery but also within the bone marrow. In the serological testing, preincubation of the serum with the offending drug will inhibit the reaction of the antibody to drug-coated cells. This mechanism may coexist with the immune complex type of blood cell damage. Today it appears established that patients may develop antibodies the specificity of which depends on a drug as well as on a membrane component of blood cells. The haematological specificity of the immune reaction would then be explained by the autoantigenic constituent of the drug-autoantigen complex.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 Suppl 1 ","pages":"57-70"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14669912","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":"The regulatory challenge.","authors":"P K Lunde","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The concepts of drug regulation should ideally be derived from an appropriately defined and broadly agreed national drug and health policy, according to health needs, relevant criteria and the local circumstances. The major long term challenge emerging from these concepts is how to establish a sufficiently comprehensive and functional drug and therapeutic audit as a basis for regulatory and other decisions within the health chain that strike a balance between sociomedical and economic requirements. Such an audit involves three sequential phases: collection and compilation of all relevant facts and premises; data organisation and analyses by competent auditors and decision, implementation, and re-evaluation with subsequent adjustments. Despite extensive international and national efforts during recent years, only fragmentary solutions exist, and only in a few countries. Thus, another major challenge still remains: how to weight and integrate the sometimes quite conflicting interests and scopes of politicians, administrators, the teaching institutions, the health professions, the pharmaceutical manufacturers--and the consumers. All the partners involved have to emphasise that the problems behind the present miseries of global drug use are basically of political and economic nature, although there are considerable limitations imposed by widely varying attitudes and deficient knowledge and criteria. Thus there is a need for joint action and a strengthening of collaboration and communication combined with the best possible elements of professional skills and common sense.</p>","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 Suppl 1 ","pages":"121-4"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14938009","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 repeated oral doses of activated charcoal in clinical toxicology.","authors":"S M Pond","doi":"10.1007/BF03259824","DOIUrl":"10.1007/BF03259824","url":null,"abstract":"","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 1","pages":"3-11"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14903142","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":"The role of prostaglandin synthesis inhibition in the renal syndromes associated with non-narcotic analgesics.","authors":"C Patrono","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prostaglandin (PG) synthesis in the kidney is localised to specific sites and is not uniformly present throughout the nephron. It is generally accepted that the regional heterogeneity of PGs, as well as the lack of vascular communications between the medulla and cortex, dictate that PGs [primarily prostacyclin (PGI2)] synthesised in the cortex (glomeruli and vasculature) regulate cortical function, while PGs (primarily PGE2) synthesised in the medulla (collecting tubule and medullary interstitial cells) regulate medullary function. Measurement of urinary unmetabolised PGs, or their stable hydration products, provides the best clinical assessment of the state of renal PG production. Under physiological circumstances, renal function is not critically dependent upon the integrity of PG synthesis, possibly because other regulatory mechanisms can compensate for PG synthesis inhibition. However, when renal PG synthesis is activated in response to altered haemodynamics (e.g. cirrhosis with ascites) or is pathologically reduced (e.g. chronic glomerular disease) then the consequences of pharmacological inhibition can become clinically apparent and measurable. In these circumstances, drugs that inhibit renal cyclo-oxygenase activity can acutely reduce glomerular filtration rate and renal blood flow by 30 to 50%. These functional changes are usually reversible upon discontinuing the drug. The long term consequences of renal PG synthesis inhibition are more difficult to assess. Theoretically, chronic inhibition of renal PG synthesis might be responsible for medullary ischaemia, possibly contributing to the picture of so-called analgesic nephropathy. Selective sparing of renal cyclo-oxygenase activity can be obtained by at least 3 mechanisms: differential 'sensitivity' of the glomerular cyclo-oxygenase; selective intra-renal inactivation of an active metabolite of the drug; differential rate of recovery of glomerular cyclo-oxygenase following irreversible acetylation by aspirin. The recent demonstration of a functional correlate of such biochemical selectivity suggests novel strategies for reducing the chronic renal toxicity of cyclo-oxygenase inhibitors.</p>","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 Suppl 1 ","pages":"23-33"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14234334","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":"Regulatory decisions. Emphasis on safety issues.","authors":"K Strandberg,&nbsp;B E Wiholm","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Effective post-marketing surveillance of drugs calls for an approach tuned to the individual problem. In Sweden, the combined use of spontaneous adverse drug reaction (ADR) reporting data and different registers has yielded much valuable information on safety problems with different drugs. However, the raw data must be interpreted with care and often be supplemented by in-depth studies. The advantage with registers is that they comprise the whole or a random sample of the population and that the reporting routines are fairly simple. Since much of the information is collected primarily for other purposes (like health care planning or budgeting) the cost of the information is low. The potential of spontaneous ADR reporting for detecting new rare ADRs is exemplified by the zimeldine case. Limitations of the system besides low and selective reporting are that the physicians must suspect the clinical manifestation to be drug-induced and that patient compliance is unknown. The greatest disadvantage with the patient- and disease-oriented registers is the frequent inaccuracy of the diagnoses and the delay in the appearance of the data. Improved education and more resources for updating the registers are required. The ICD-code should be adapted to the needs of drug monitoring. Since the registers contain sensitive information about individual patients, the confidentiality of the data must be secured. As a logical complement to these sources of information, systems for case control studies, to be adopted ad hoc when problems arise, should be instituted. Moreover, for certain kinds of long term drug reactions, record-linkage systems are probably the only means to disclose risks (e.g. of cancer) after long term drug exposure. In this respect, the computerisation of Swedish pharmacies offers unique possibilities for the retrieval of prescription data on individual patients.</p>","PeriodicalId":77871,"journal":{"name":"Medical toxicology","volume":"1 Suppl 1 ","pages":"137-49"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14085476","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}