Drug-induced Hepatic Injury Research Articles

肝障害ラットの血清ＧＰＴ値および肝薬物代謝酵素に及ぼすクロルプロマジンの影響

Effects of chlorpromazine (CPZ) on serum GPT (SGPT) and hepatic microsomal drug-metabolizing enzyme activities in the rat with liver injured by CCl4 were studied.Rats were intraperitoneally injected with CCl4 at a dose of 0.2ml/kg every 3 days, and with CPZ at a dose of 5 mg/kg once a day for 48 days. SGPT activity was gradually elevated from the beginning of CCl4-administration and reached to the maximum after 30 days.The elevation of SGPT value induced by CCl4-administration was inhibited by the administration of CPZ.In addition, decreases of cytochrome P-450 and cytochrome b5 by CCl4-administration were observed.However, CPZ restored the decrease of cytochrome P-450.These results indicate that CPZ protects liver cell damage induced by CCl4, resulting in that the effect of CPZ on cytochrome P-450 may be important for protecting from drug-induced hepatic injury.

Drug-induced hepatic injury

Drug-induced hepatic injury

9 Drug-induced cholestasis

Acute, drug-induced hepatocellular cholestasis (either pure or cholestatic hepatitis) is a common manifestation of drug-induced hepatic injury. The drugs most frequently responsible are hormonal steroids and psychopharmacological agents (in particular phenothiazines and some antidepressants). Cholestasis usually subsides without sequelae in less than six months. Acute, drug-induced ductular or ductal cholestasis is uncommon and can resemble biliary tract obstruction. Complete recovery occurs promptly after the withdrawal of the causative drug in most cases. The pathogenetic mechanism may be immunoallergic. Prolonged ductular or ductal cholestasis can follow drug-induced acute hepatitis despite prompt withdrawal of the offending drug. This syndrome, observed mainly with chlorpromazine and uncommonly with twenty other drugs, is characterized by the progressive disappearance of small bile ducts and by manifestations mimicking primary biliary cirrhosis. However, its prognosis appears to be better than that of primary biliary cirrhosis, the condition being reversible in the majority of cases or even subsiding completely. The mechanism is still unknown, but several features suggest some form of autoimmunity. Extrahepatic cholestasis related to sclerosing cholangitis is a frequent and long-term complication of intra-arterial infusion of floxuridine in patients treated for hepatic metastases from colorectal carcinoma. Although it may be reversible, floxuridine-induced sclerosing cholangitis has a poor prognosis and can lead to death in a few patients. The mechanism is probably related to the vascular supply of the common hepatic duct and its relationship to the perfusion territory of floxuridine.

Pharmacological studies of "reiousan" which contains bezoar and ginseng

Pharmacological properties of "Reiousan", a crude drug preparation consisting of bezoar and ginseng, were studied. The hypotensive effect on spontaneously hypertensive rat, inhibition of platelet aggregation, acetic acid-induced writhing, stress ulcer, CCl4 and d-galactosamine-induced hepatic injury, and facilitation of recovery from neuroparalysis and muscular fatigue, protective effect on anoxic brain damages, antipyretic effect, and facilitation of learning in aged mice were observed after administration of "Reiousan". It was suggested that bezoar and ginseng act synergistically in causing the hypotensive effect, acetic acid-induced writhing and drug-induced hepatic injury, and protection from anoxic brain damages and muscular fatigue.

Stricker, B. H. Ch. and Spoelstra, P.: Drug‐induced hepatic injury.

LiverVolume 5, Issue 6 p. 354-354 Stricker, B. H. Ch. and Spoelstra, P.: Drug-induced hepatic injury. Per Buch Andreasen, Per Buch AndreasenSearch for more papers by this author Per Buch Andreasen, Per Buch AndreasenSearch for more papers by this author First published: December 1985 https://doi.org/10.1111/j.1600-0676.1985.tb00259.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume5, Issue6December 1985Pages 354-354 RelatedInformation

肝炎について 歯科医療の立場から

The clinicopathological features of viral hapatitis were reviewed based on the observation of the autospy cases in the Department of Pathology, Tokyo Medical and Dental University. The autopsy cases consisted of 24 cases of acute hepatitis, 16 cases of chronic hepatitis, 40 cases of cirrhosis of the liver, 9 cases of liver cell carcinoma (5 cases with concurrent cirrhosis of the liver) and 4 cases of drug-induced hepatic injuries. The typical cases were presented. In this paper the incidence of persons with elevated tites of HB antigen in the four dental school hospitals in Japan were reported. Data from the general practioners were also presented. According to these reports, dentists and oral hygienists had a higher incidence of viral hepatitis than that in the general population. The role of the saliva in the transmission of the virus was discussed.

薬剤性肝障害を発症し興味ある血清学的変動を示した早期の原発性胆汁性肝硬変症例

薬剤性肝障害を発症し興味ある血清学的変動を示した早期の原発性胆汁性肝硬変症例

Drug-Induced Liver Disease

The large number of chemical agents administered for therapeutic or diagnostic purposes can produce various types of hepatic injury by several mechanism. Acute injury may be cytotoxic, cholestatic or mixed. Cytotoxic injury may consist of necrosis or steatosis. Cholestatic injury may be cholangiolitic (hepatocanalicular) or bland (canalicular). Chronic hepatic lesions caused by medicinal agents include chronic active hepatitis, steatosis, cirrhosis, fibrosis, hepatoportal sclerosis (non-cirrhotic portal hypertension), hepatic vein thrombosis, peliosis hepatis, adenoma, carcinoma, and angiosarcoma. There is a useful relationship between the type of hepatic injury and the chemical setting in which the drugs are employed. Some agents produce the liver damage because they are intrinsic (true, predictable) hepatotoxins. Other (non-predictable "hepatotoxins"), produce hepatic injury only in the rare and unusually susceptible individual (idiosyncratic injury). Hepatotoxic agents can be recognised by their dose-dependent and experimental reproducibility, properties which are not shared by agents which produce hepatic injury only in idiosyncratic hosts. Intrinsic hepatotoxins may be categorised as direct or indirect. Direct hepatotoxins injure the hepatocyte by direct physiochemical alteration and as a consequence produce metabolic defects. Indirect hepatotoxins selectively block metabolic pathways and, by producing a precise biochemical lesion, lead to structural changes. They may lead to hepatic steatosis or necrosis (cytotoxic indirect hepatotoxins) or block bile flow (cholestatic indirect hepatotoxins). Direct hepatotoxins are rarely encountered as drugs. Overdoses of some drugs and antineoplastic agents appear to be indirect cytotoxic hepatotoxins, and the C-17 alkylated anabolic and contraceptive steroids are indirect, cholestatic hepatotoxins. Idiosyncracy of the host is the mechanism for most types of drug-induced hepatic injury. It may reflect allergy to the drug or a metabolic aberration of the host permitting the production of hepatotoxic metabolites.

Two cases of drug-induced hepatic injury probably due to Glyclopyramide

Two cases of drug-induced hepatic injury probably due to Glyclopyramide

Drug-Induced Hepatic Injury

Drug-Induced Hepatic Injury

Various Forms of Chemically Induced Liver Injury and Their Detection by Diagnostic Procedures

A large number of chemical agents, administered for therapeutic or diagnostic purposes, can produce various types of hepatic injury by several mechanisms. Some agents are intrinsically hepatotoxic, and others produce hepatic injury only in the rare, uniquely susceptible individual. Idiosyncrasy of the host is the mechanism for most types of drug-induced hepatic injury. It may reflect allergy to the drug or a metabolic aberation of the host permitting the accumulation of hepatotoxic metabolites. The syndromes of hepatic disease produced by drugs have been classified hepatocellular, hepatocanalicular, mixed and canalicular. Measurement of serum enzyme activities has provided a powerful tool for studies of hepatotoxicity. Their measurement requires awareness of relative specificity, knowledge of the mechanisms involved, and knowledge of the relationship between known hepatotoxic states and elevated enzyme activities.

Various forms of chemically induced liver injury and their detection by diagnostic procedures.

A large number of chemical agents, administered for therapeutic or diagnostic purposes, can produce various types of hepatic injury by several mechanisms. Some agents are intrinsically hepatotoxic, and others produce hepatic injury only in the rare, uniquely susceptible individual. Idiosyncrasy of the host is the mechanism for most types of drug-induced hepatic injury. It may reflect allergy to the drug or a metabolic aberation of the host permitting the accumulation of hepatotoxic metabolites. The syndromes of hepatic disease produced by drugs have been classified hepatocellular, hepatocanalicular, mixed and canalicular. Measurement of serum enzyme activities has provided a powerful tool for studies of hepatotoxicity. Their measurement requires awareness of relative specificity, knowledge of the mechanisms involved, and knowledge of the relationship between known hepatotoxic states and elevated enzyme activities.

Drug-induced Hepatic Injury

Drug-induced Hepatic Injury

Iatrogenic disorders of the liver: Drug-induced hepatic injury

Iatrogenic disorders of the liver: Drug-induced hepatic injury

Hepatotoxicity After Methoxyflurane Administration

METHOXYFLURANE (Penthrane) is a shortchain halogenated ether which was developed as a general anesthetic by Van Poznak and Artusio1and has been in clinical use since 1959. Although chemically an ether, this compound has organic chloride and fluoride substituents similar to that of halothane. In view of this structural similarity it might be expected that increasing use of methoxyflurane will be associated with rare reports of drug-induced hepatic injury. To our knowledge, this is the first nonfatal case of suspected methoxyflurane hepatotoxicity with documented hepatocellular necrosis. Report of a Case In June 1965, a 58-year-old Negro woman (NYH 159-803) was seen in the outpatient department complaining of a persistent vaginal discharge. A friable lesion, which on biopsy proved to be a squamous-cell carcinoma was noted in the vaginal vault. She was admitted for treatment in July 1965. She had suffered from attacks of acute pelvic inflammatory disease in 1939 and 1946 with episodic, recurrent lower abdominal pain. A hysterectomy and bilateral salpingo-oophorectomy was performed in 1953.

Electron microscopic observation of thioridazine-induced hepatitis.

The introduction of new drugs for clinical practice in recent years, has causedan increasing number of drug-induced hepatic injuries, which are currently receiving much attention because of their iatrogenic nature . As one of the approaches to the study of pathogenesis, electron microscopic studies have been undertaken. This report is concerned with an electron microscopic observation of the liver of a thioridazine-induced hepatitis patient with special reference to the bile canalicular alterations.

DRUG-INDUCED LIVER DISEASE: A PENALTY FOR PROGRESS.

DRUG-INDUCED hepatic injury, particularly that associated with jaundice, is becoming more frequent because of the increasing use of potent drugs. Nevertheless, its pathogenesis remains mysterious, and its classifications is difficult. Initially, drug-induced hepatic injury followed use of established hepatotoxins as exemplified by diethylene glycol, the vehicle of an early sulfonamide preparation which proved to be a fatal poison.1Subsequently, new disease entities were recognized after patients were exposed to drugs. For instance, intrahepatic cholestasis, then called intrahepatic biliary obstruction, following the administration of organic arsenicals, was reported by Hanger and Gutman.2This led to the appreciation of intrahepatic cholestasis caused by agents other than drugs.3Today, however, confusion about the many hepatic changes associated with drug therapy produces apprehension on the part of the physician when prescribing which sometimes protects the patient but almost as frequently prevents beneficial treatment or causes senseless testing for hepatotoxicity. The

Drug-induced hepatic injury: Marplan hepatitis.

tion. The indications that aescin has a generalized antiedematous action suggests that it may be of more value in situations where edema of the brain plays a pathological role, e.g., acute brain trauma, early cerebral vascular accidents and perhaps epilepsy. In summary, the administration of 34, 2 mg. I.V. injections of aescin to 10 patients with psychoses of the senium produced no significant beneficial effect on their mental function. Evaluation in other conditions, includling uropathy with pyuria, should be considered.

PROBABLE HEPATIC ALLERGY TO CHLORPROMAZINE AND DELIBERATE DESENSITIZATION

Excerpt This report issues from studies concerning the pathogenesis of hepatic dysfunction due to chlorpromazine, the prophylactic and therapeutic influence thereon of synthetic adrenocortical horm...

Drug-induced hepatic injury.

Excerpt Drug-induced hepatic injury poses many problems. Establishment of a causal relation between a hepatic disease, usually with jaundice and preceding intake of a drug, is often difficult. This...