Medical toxicology and adverse drug experience最新文献

{"title":"Drug-induced sexual dysfunction.","authors":"D E McWaine,&nbsp;W R Procci","doi":"10.1007/BF03259941","DOIUrl":"https://doi.org/10.1007/BF03259941","url":null,"abstract":"<p><p>A large body of data, as well as clinical experience, link prescribed medications and substances of abuse with sexual dysfunction. This review surveys the relevant literature and summarises key points relating various classes of medications and their possible sexual side effects. Surprisingly, there were very few carefully designed, well organised, systematic studies of the effects of medication upon sexual performance. The preponderance of data is in the form of either case studies or collections of patient reports of side effects. As a result, there are great variations in the reported rates of sexual disturbances associated with the administration of a given medication. A further difficulty is the lack of precision in the use of terms which describe the various sexual disorders. A final problem is the almost total lack of data concerning both disordered and normal sexual functioning in females.</p>","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":"3 4","pages":"289-306"},"PeriodicalIF":0.0,"publicationDate":"1988-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259941","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14187475","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":"Prenatal adverse effects of various drugs and chemicals. A review of substances of frequent concern to mothers in the community.","authors":"M Bologa-Campeanu,&nbsp;G Koren,&nbsp;M Rieder,&nbsp;M McGuigan","doi":"10.1007/BF03259942","DOIUrl":"https://doi.org/10.1007/BF03259942","url":null,"abstract":"<p><p>Using the number of calls to the Canadian Motherisk Program as an indicator of the drugs and chemicals frequently of concern to mothers during pregnancy, the risks to the fetus of exposure to these compounds have been reviewed. The drugs which were of concern, and have been proven to be teratogenic, included alcohol, alkylating and antimetabolite agents, stilboestrol, disulfiram, heparin, lithium carbonate, phenytoin, tretinoin (retinoic acid), troxidone and valproic acid. For other compounds studied, there was either no data in the literature or no clear evidence of teratogenicity. The combination of doxylamine and pyridoxine, for example, has been associated with limb reduction defects in isolated case reports: cohort and case-control studies have failed to show a higher-than-baseline risk of malformations. In some cases of exposure to compounds with no known teratogenic potential, other adverse effects to the fetus are possible, and these effects are discussed in detail. In conclusion, when advising a pregnant woman about the potential teratogenic effect of a particular drug or chemical exposure, the health professional should also discuss other factors such as age, obstetric and medical history and the history of other exposures (including alcohol and smoking). In every pregnancy there is a 1 to 5% risk of mayor malformations, and even if the exposure does not appear to increase the teratogenic risk, such a risk still exists.</p>","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":"3 4","pages":"307-23"},"PeriodicalIF":0.0,"publicationDate":"1988-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259942","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14187479","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 digoxin-specific antibodies in the treatment of digitalis poisoning.","authors":"B S Stolshek,&nbsp;S K Osterhout,&nbsp;G Dunham","doi":"10.1007/BF03259880","DOIUrl":"https://doi.org/10.1007/BF03259880","url":null,"abstract":"","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":"3 3","pages":"167-71"},"PeriodicalIF":0.0,"publicationDate":"1988-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259880","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14524406","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 ethanol poisoning and the ethanol withdrawal syndrome.","authors":"B Adinoff,&nbsp;G H Bone,&nbsp;M Linnoila","doi":"10.1007/BF03259881","DOIUrl":"https://doi.org/10.1007/BF03259881","url":null,"abstract":"<p><p>Ethanol, a highly lipid-soluble compound, appears to exert its effects through interactions with the cell membrane. Cell membrane alterations indirectly affect the functioning of membrane-associated proteins, which function as channels, carriers, enzymes and receptors. For example, studies suggest that ethanol exerts an effect upon the gamma-aminobutyric acid (GABA)-benzodiazepine-chloride ionophore receptor complex, thereby accounting for the biochemical and clinical similarities between ethanol, benzodiazepines and barbiturates. The patient with acute ethanol poisoning may present with symptoms ranging from slurred speech, ataxia and incoordination to coma, potentially resulting in respiratory depression and death. At blood alcohol concentrations of greater than 250 mg% (250 mg% = 250 mg/dl = 2.5 g/L = 0.250%), the patient is usually at risk of coma. Children and alcohol-naive adults may experience severe toxicity at blood alcohol concentrations less than 100 mg%, whereas alcoholics may demonstrate significant impairment only at concentrations greater than 300 mg%. Upon presentation of a patient suspected of acute ethanol poisoning, cardiovascular and respiratory stabilisation should be assured. Thiamine (vitamin B1) and then dextrose should be administered, and the blood alcohol concentration measured. Subsequent to stabilisation, alternative aetiologies for the signs and symptoms observed should be considered. There are presently no agents available for clinical use that will reverse the acute effects of ethanol. Treatment consists of supportive care and close observation until the blood alcohol concentration decreases to a non-toxic level. In the non-dependent adult, ethanol is metabolised at the rate of approximately 15 mg%/hour. Haemodialysis may be considered in cases of a severely ill child or comatose adult. Follow-up may include referral for counselling for alcohol abuse, suicide attempts, or parental neglect (in children). The ethanol withdrawal syndrome may be observed in the ethanol-dependent patient within 8 hours of the last drink, with blood alcohol concentrations in excess of 200 mg%. Symptoms consist of tremor, nausea and vomiting, increased blood pressure and heart rate, paroxysmal sweats, depression, and anxiety. Alterations in the GABA-benzodiazepine-chloride receptor complex, noradrenergic overactivity, and hypothalamic-pituitary-adrenal axis stimulation are suggested explanations for withdrawal symptomatology.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":"3 3","pages":"172-96"},"PeriodicalIF":0.0,"publicationDate":"1988-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259881","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14173704","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":"Hepatotoxicity of methotrexate in rheumatic diseases.","authors":"S Kevat,&nbsp;M Ahern,&nbsp;P Hall","doi":"10.1007/BF03259882","DOIUrl":"https://doi.org/10.1007/BF03259882","url":null,"abstract":"<p><p>Methotrexate-induced hepatotoxicity is well recognised in the treatment of leukaemia, psoriasis and rheumatoid arthritis. The pathological lesions are non-specific, consisting of fatty change, nuclear pleomorphism, hepatocyte necrosis, portal chronic inflammatory infiltrate, fibrosis and cirrhosis. The mechanism of liver injury is poorly understood; intracellular accumulation of methotrexate polyglutamate and consequent folate depletion are suspected to play a role. Early studies in psoriasis clearly established a relationship of the hepatic injury with the frequency of methotrexate administration. With weekly low dose therapy, however, consensus is lacking regarding the incidence of hepatotoxicity because studies have had disparate control groups, used variable dosage regimens and often failed to document pre-existing liver disease or categorised patients at risk, i.e. elderly patients, alcoholics and obese diabetics. Moreover, current methods of assessing the degree of hepatic injury are subjective, relying on interpretation by an experienced histopathologist. Preliminary evidence suggests less frequent and less severe hepatotoxicity occurs in patients with rheumatoid arthritis, probably as a result of lower methotrexate doses and better patient selection. Nevertheless, until the risk of serious liver disease is better defined it is recommended that patients have a pretreatment liver biopsy, a follow-up biopsy after a cumulative dose of 1500 mg, and then biopsies approximately every 2 years in the absence of other evidence of liver disease or risk factors.</p>","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":"3 3","pages":"197-208"},"PeriodicalIF":0.0,"publicationDate":"1988-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259882","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14173706","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 drug reaction reporting and retrospective phenotyping for oxidation polymorphism.","authors":"D W Clark,&nbsp;I R Edwards","doi":"10.1007/BF03259884","DOIUrl":"https://doi.org/10.1007/BF03259884","url":null,"abstract":"<p><p>A genetically determined impairment in the ability to oxidase sparteine and debrisoquine also affects the oxidation of several other drugs. This impairment in oxidation may result in accumulation of the associated drugs and in an increased susceptibility to adverse reactions from these drugs. Dunedin houses the New Zealand national centre for the collation and study of adverse drug reactions. Included among the reporting schemes is an intensified monitoring system for newly released drugs, in which physicians report all clinical events occurring during treatment with the drugs under surveillance. The centre thus has available extensive records of names and addresses of prescribers and patients who have been reported as experiencing an adverse event while receiving drug therapy. We investigated the association between genetically poor oxidation of sparteine and adverse reactions to drugs selected as possibly sharing the sparteine/debrisoquine oxidation pathway; these included perhexiline, metoprolol, debrisoquine, piroxicam, mianserin and nifedipine. A kit containing instructions, a sparteine capsule and a container for urine collection was sent to physicians who reported adverse reactions or events to one of the above drugs for forwarding to the patient. It appeared possible, after assays of returned urine for sparteine and its metabolites, that adverse reactions to nifedipine were associated with genetically poor oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":"3 3","pages":"241-7"},"PeriodicalIF":0.0,"publicationDate":"1988-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259884","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14524408","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":"Exchange of cerebrospinal fluid in accidental intrathecal overdose of cytarabine.","authors":"P Lafolie,&nbsp;J Liliemark,&nbsp;O Björk,&nbsp;J Aman,&nbsp;L Wranne,&nbsp;C Peterson","doi":"10.1007/BF03259885","DOIUrl":"https://doi.org/10.1007/BF03259885","url":null,"abstract":"<p><p>Intrathecal cytarabine (cytosine arabinoside) is included in many protocols for the treatment of acute lymphoblastic leukaemia of childhood. We report here the accidental administration of 200mg cytarabine intrathecally to a 4-year-old boy with CNS relapse. After the overdose the patient had dilated pupils during the first hour. One month later an unsteady gait and mild intention tremor in the hands were noted. By the exchange of cerebrospinal fluid with isotonic saline started 1 hour after overdose through a lumbar needle, about 27% of the administered dose was recovered. The estimated recovery in view of the time elapsed between overdose and start/end of the exchange procedure was 36%. This indicates that this procedure is of value in managing patients with heavy overdose of intrathecal cytarabine in hospitals without neurosurgical facilities.</p>","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":"3 3","pages":"248-52"},"PeriodicalIF":0.0,"publicationDate":"1988-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259885","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14296490","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. Adverse effects associated with 'inactive' ingredients in drug products (Part II).","authors":"L K Golightly,&nbsp;S S Smolinske,&nbsp;M L Bennett,&nbsp;E W Sutherland,&nbsp;B H Rumack","doi":"10.1007/BF03259883","DOIUrl":"https://doi.org/10.1007/BF03259883","url":null,"abstract":"","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":"3 3","pages":"209-40"},"PeriodicalIF":0.0,"publicationDate":"1988-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259883","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14173720","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":"Valproate-associated hepatotoxicity and its biochemical mechanisms.","authors":"M J Eadie,&nbsp;W D Hooper,&nbsp;R G Dickinson","doi":"10.1007/BF03259935","DOIUrl":"https://doi.org/10.1007/BF03259935","url":null,"abstract":"<p><p>Intake of the anticonvulsant drug valproic acid, or its sodium salt, has been associated with occasional instances of severe and sometimes fatal hepatotoxicity. Probably at least 80 cases have occurred worldwide. The syndrome affects perhaps 1 in 10,000 persons taking the drug, and usually develops in the early weeks or months of therapy. Most instances have involved children, usually those receiving more than 1 anticonvulsant. Multiple cases have occurred in 2 families. The typical presentation is of worsening epilepsy, increasing depression of consciousness, and progressive clinical and biochemical evidence of liver failure. The liver has sometimes shown hepatocyte necrosis, and on other occasions widespread microvesicular steatosis, while cholestatic changes have also occurred. The appearances are interpreted as consistent with a drug toxicity reaction. During the hepatotoxicity increased amounts of unsaturated metabolites of valproate, notably 4-en-valproate, have been found in blood and urine. In 4 cases there has been evidence of impaired beta-oxidation of valproate with, in 1 case, accumulation of isomers of valproate glucuronide caused by intramolecular rearrangement of the conjugate. There are molecular structural similarities between 4-en-valproate and 2 known hepatotoxins (4-en-pentanoate and methylenecyclopropylacetic acid, the latter being responsible for hypoglycin poisoning). There are also clinical and histopathological similarities between valproate hepatotoxicity and both hypoglycin poisoning and certain spontaneous disorders of isoleucine metabolism (one pathway of valproate metabolism is analogous to oxidative degradation of isoleucine). Unsaturated metabolites of valproate, in particular 4-en-valproate, may contribute to the hepatotoxicity of the drug. However, since the hepatotoxicity appears to involve an element of idiosyncrasy, the primary defect in some cases may be an inherited or acquired deficiency in the drug's beta-oxidation. This defect may divert valproate metabolism towards omega-oxidation, with increased formation of the toxin 4-en-valproate, but may also allow increased formation of a toxic metabolite derived from isoleucine, since beta-oxidation of isoleucine derivatives will also be impaired.</p>","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":"3 2","pages":"85-106"},"PeriodicalIF":0.0,"publicationDate":"1988-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF03259935","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14262465","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. Adverse effects associated with inactive ingredients in drug products (Part I).","authors":"L K Golightly,&nbsp;S S Smolinske,&nbsp;M L Bennett,&nbsp;E W Sutherland,&nbsp;B H Rumack","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Excipient reactions have resulted from the use of clearly toxic substances (e.g. diethyleneglycol), the use of certain excipients in a susceptible group (e.g. very low birthweight neonates, patients with large surface area burns, patients with a history of asthma or contact dermatitis), the alteration of an excipient mixture resulting in altered bioavailability (e.g. phenytoin), and the deliberate or inadvertent extradural administration of preserved medications intended for intravenous use. Inadvertent excipient overdose has also occurred when unusually large doses of a drug containing a preservative were used [chlorbutol in morphine, ethanol in glyceryl trinitrate (nitroglycerin)]. Most excipient problems are preventable with knowledge of the currently available formulation. Government drug regulatory agencies have largely prevented introduction of a new toxic excipient; however, the new use of previously approved (but not adequately studied) excipients continues to result in unfortunate tragedies (e.g. the E-ferol incident). Populations at risk should be monitored carefully. Very low birthweight infants (less than 100g) have a well-demonstrated intolerance to many excipients, particularly during the first 2 weeks of life. Research should be directed toward development of non-preserved medications and safer diluents for this population. Drugs and excipients which have previously been demonstrated to be safer in other populations (e.g. doxapram) should be meticulously studied in this age group before widespread use is recommended. Asthmatic patients comprise another population that are frequently sensitive to excipient toxicity. In some cases, as in sulphiting agents, which are ubiquitous in foods as well as in medications, total avoidance may not be possible and prophylactic therapy may be beneficial. Inactive ingredients are clearly not consistently inert in their biological activity and therefore should not be listed as such. A more useful and concise term is excipient. It is highly recommended that all pharmaceutical manufacturers list all their excipients and make this available to practitioners and drug information centres. Alternatively or additionally, the package insert should list these excipients in accordance with good manufacturing procedures. This disclosure will help to determine the relative frequency and magnitude of problems (bioequivalence, toxicity, etc.) that excipients may have in the population, as well as enabling susceptible patients to avoid inadvertent exposure.</p>","PeriodicalId":77748,"journal":{"name":"Medical toxicology and adverse drug experience","volume":"3 2","pages":"128-65"},"PeriodicalIF":0.0,"publicationDate":"1988-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14415134","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}