Pharmacobezoars described and demystified

Introduction.?A bezoar is a concretion of foreign material that forms and persists in the gastrointestinal tract. Bezoars are classified by their material origins. Phytobezoars contain plant material, trichobezoars contain hair, lactobezoars contain milk proteins, and pharmacobezoars contain pharmaceutical products. Tablets, suspensions, and even insoluble drug delivery vehicles can, on rare occasions, and sometimes under specific circumstances, form pharmacobezoars. The goal of this review is to catalog and examine all of the available reports in the English language medical literature that convincingly describe the formation and management of pharmacobezoars. Methods.?Articles included in this review were identified by performing searches using the terms “bezoar,” “pharmacobezoar,” and “concretion” in the following databases: OVID MEDLINE, PubMed, and JSTOR. The complete MEDLINE and JSTOR holdings were included in the search without date ranges. The results were limited to English language publications. Articles that described nonmedication bezoars were not included in the review. Articles describing phytobezoars, food bezoars, fecal impactions, illicit drug packet ingestions, enteral feeding material bezoars, and hygroscopic diet aid bezoars were excluded. The bibliographic references within the articles already accumulated were then examined in order to gather additional pharmacobezoar cases. The cases are grouped by pharmaceutical agent that formed the bezoar, and groupings are arranged in alphabetical order. Discussions and conclusions specific to each pharmaceutical agent are included in that agent's subheading. Discussion.?Patterns and themes that emerged in the review of the assembled case reports are reviewed and presented in a more concise format. Conclusion.?Pharmacobezoars form under a wide variety of circumstances and in a wide variety of patients. They are difficult to diagnose reliably. Rules for suspecting, diagnosing, and properly managing a pharmacobezoar are highly dependent on the pharmaceutical agent or agents involved. Becoming familiar with the sparse data available on pharmacobezoars and maintaining a high index of suspicion in future clinical encounters may be the best way to improve diagnostic sensitivity and accuracy.     

栀子黄色素对四氯化碳肝损伤小鼠的影响

目的 :　研究栀子黄色素 (GY)对 CCl4 肝损伤小鼠的保护作用。方法 :　取健康的雄性昆明种小鼠 (2 0± 2 ) g 5 0只 ,按体重随机分成 5组 ,每组 1 0只 ,即正常组 ,(饲喂正常饲料 ) ,CCl4 肝损伤组 (正常饲料 +CCl4 ) ,低剂量组 (正常饲料 +CCl4 +0 .1 ml GY溶液 /只 ) ,中剂量组 (正常饲料 +CCl4 +0 .2 ml GY溶液 /只 ) ,高剂量组 (正常饲料 +CCl4 +0 .4ml GY溶液 /只 )。GY溶液提前 5 d每天灌胃 ,对照组与肝损伤组灌胃 0 .4ml生理盐水 ,末次灌胃后 2 h给 0 .1 0 % CCl4 0 .4ml致伤。1 8h后摘除眼球取血 ,测定血清谷丙转氨酶 (SGPT)、谷草转氨酶 (SGOT)、乳酸脱氢酶 (LDH)活性 ,破腹取肝脏 ,测定肝脏丙二醛 (MDA)、谷胱甘肽 (GSH)含量及肝脏指数 ,并对肝细胞的组织形态学进行观察。结果 :　预先灌 GY溶液 ,具有显著地抑制 CCl4 引起的小鼠血清 SGPT、SGOT、LDH及肝脏 MDA含量、肝脏指数的升高以及肝脏 GSH含量的降低 ,并能显著地减轻 CCl4 引起的肝小叶内的灶性坏死。结论 :　栀子黄色素对 CCl4 致小鼠肝损伤具有保护作用     

A prospective study of liver function in infants and children exposed to daily isoflurane for several weeks

Eleven infants and children presenting for daily radiotherapy for a period of at least 2 weeks were anaesthetised with isoflurane in 33% oxygen and nitrous oxide. They were unpremedicated and given no other agents to supplement anaesthesia. The average number of exposures was 24 (SD 11; range 10-39) and the total anaesthetic time per exposure varied between 15 and 30 minutes. Liver function was assessed by determining serum total bilirubin, aspartate amino transferase, gamma glutamyl transferase and alkaline phosphatase before the start of treatment and at 5-daily intervals thereafter. There was no measurable change in any of these determinants of liver function. All children accepted daily induction of anaesthesia with isoflurane. Induction, maintenance and recovery from anaesthesia were uncomplicated.     

Cyanamide hepatotoxicity. Incidence and clinicopathological features

ABSTRACT— Ground-glass hepatocytes resembling those seen in HBsAg carriers on hematoxylin and eosin and on trichrome stained sections, but giving a negative reaction to orcein and a positive one to PAS, were found in liver biopsy specimens from nine asymptomatic former alcoholics who were on treatment with cyanamide, in one of four who had been treated with cyanamide several months before the liver biopsy procedure, in none of 15 treated with disulfiram, and in one of eight who had apparently not received aversive drugs. Portal and periportal inflammatory changes and fibrosis were more frequently observed in biopsy specimens containing PAS-positive ground-glass hepatocytes than in those without, but cirrhosis was found with a similar frequency. It is concluded that periportal PAS-positive ground-glass hepatocytes are a histological marker of cyanamide treatment.     

Kava hepatotoxicity: comparative study of two structured quantitative methods for causality assessment

Background and objective: Ingestion of the medicinal herb kava has been associated with hepatotoxicity. We aimed to compare two different quantitative methods of causality assessment of patients with assumed hepatotoxicity by the herb. Methods: We assessed causality in 26 patients from Germany and Switzerland, using two structured quantitative analytical methods: the system of Maria and Victorino (MV) and that of the Council for International Organizations of Medical Sciences (CIOMS). In all 26 patients, regulatory ad hoc evaluation had suggested a causal relationship between liver disease and kava use. Results and discussion: Assessment with the MV scale resulted in no or low graded causality for kava in the 26 patients with liver disease. Causality was probable (n = 1), possible (n = 2), unlikely (n = 7), and excluded (n = 16). Causality for kava was more evident with the CIOMS scale: highly probable (n = 1), probable (n = 2), possible (n = 6), unlikely (n = 2) and excluded (n = 15). However, the results of both quantitative causality assessments are not supportive for most of the regulatory ad hoc causality assessments of the 26 patients. Conclusion: Grades of causality for suspected hepatotoxicity by kava were much lower when evaluated by structured quantitative causality assessment scales than by regulatory ad hoc judgements. The quantitative CIOMS scale is the preferable tool for causality assessment of spontaneous reports of hepatotoxcity involving kava.     

Drug-related hepatotoxicity and hepatic failure following combined androgen blockade

Androgen deprivation therapy has been the mainstay of treatment for metastatic prostate cancer and of less advanced cancers as neoadjuvant and adjuvant treatment. Abnormal liver function test, in particular elevated transaminases, is an adverse reaction more frequently noticed during androgen deprivation therapy with antiandrogen. We report the case of a patient with acute hepatic failure associated with the use of bicalutamide.     

Radioprotective effect of silymarin against radiation induced hepatotoxicity

The radioprotective effect of silymarin using different modes of treatment against radiation (3 or 6 Gy) induced hepatotoxicity 1, 3 and 7 days post-irradiation was studied. Whole-body gamma-irradiation revealed an increase in serum alkaline phosphatase (AP) activity as well as liver glutathione reductase (GR) and glutathione peroxidase (GSH-PX) activities on the first post-exposure day with respect to the control value. However, 3 days after radiation exposure, these parameters showed a significant decrease below the control level which persisted till the end of the experimental time except for serum AP activity that showed another increase on the seventh post-exposure day at 3 Gy dose of radiation. A gradual increase in serum alanine and aspartate aminotransferase (ALT&AST) as well as gamma glutamyl transpeptidase activities were observed due to irradiation throughout the experimental time. Administration of silymarin as single (70 mg kg (-1)), fractionated (490 mg kg (-1)) oral doses or as intravenous (i.v.) injection (50 mg kg (-1)), caused significant protection. Intravenous treatment showed the most pronounced protection. The protective effect of silymarin was attributed to its antioxidant and free radicals scavenging properties.     

Therapeutic Efficacy and Hepatotoxicity of a Composition of Isoniazid and Dialdehyde Dextran Obtained by Radiochemical Oxidation of Dextran

Tuberculous granulomas were found in all parenchymal organs of mice infected with mycobacteria of BCG vaccine. The number and size of hepatic granulomas decreased, while the count of degenerated and necrobiotic hepatocytes in infected animals increased 3 months after the start of therapy with a composition of isoniazid and dialdehyde dextran. The composition of isoniazid and dialdehyde dextran obtained by radiochemical oxidation of dextran had greater therapeutic efficacy and lower hepatotoxicity. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Suppl. 1, pp. 73–75, 2008     

trans‐resveratrol alone and hydroxystilbenes of rhubarb (Rheum rhaponticum L.) root reduce liver damage induced by chronic ethanol administration: a comparative study in mice

The hepatoprotective effects and pharmacokinetics of trans‐resveratrol and hydroxystilbenes of the garden rhubarb (Rheum rhaponticum L., R. rhaponticum) root ethanol extract were studied. Ethanol was administered to male BALB/c mice for 35 days in an inhalation chamber. During this time vehicle, trans‐resveratrol (20 mg/kg per day) or R. rhaponticum extract was intraperitoneally (i.p.) administered and mice were sacrificed for the collection of liver and blood. In an additional experiment, the level of parent compounds and metabolites was estimated in the blood after acute i.p. administration of trans‐resveratrol or R. rhaponticum extract. The levels of hydroxystilbenes, their metabolites and fatty acid oxy‐metabolites (oxylipins) were studied by LC‐tandem DAD‐MS/MS. Ethanol induced hepatotoxicity, as evidenced by histological changes and accumulation of oxylipins in the blood. Both trans‐resveratrol and R. rhaponticum extract reduced the extent of these changes. The pharmacokinetics of trans‐resveratrol was characterized by a rapid removal from the blood and metabolism to sulfates and glucuronides. After the administration of R. rhaponticum extract, in addition to trans‐resveratrol glucoside and its metabolites, several other hydroxystilbenes were found. Inhibition of oxidation of polyunsaturated fatty acids is proposed as a basis of the hepatoprotective effect of both trans‐resveratrol and R. rhaponticum extract. Copyright © 2008 John Wiley & Sons, Ltd.