Contraceptive agents hepatitis

Important alterations in hepatic drug excretion and metabolism also occur. Estrogens in the amounts seen during pregnancy or used in oral contraceptive agents delay the clearance of sulfobromophthalein and reduce the flow of bile. The proportion of cholic acid in bile acids is increased while the proportion of chenodeoxycholic acid is decreased. These changes may be responsible for the observed increase in cholelithiasis associated with the use of these agents. 

Materials and Methods. Subjects ranging in age between 21-89 years were randomly selected from the Domiciliary Care Veterans Facility at the Central State Hospital. Determination of copper and ceruloplasmin was made on venous blood drawn from 180 males and 44 females. We have made no attempt to exclude from this study patients with chronic illnesses since it would be highly unlikely that such aged populations would be completely free of these conditions. However, patients with acute intercurrent illnesses and hepatic renal or symptomatic cardiovascular diseases were eliminated from this study. Individuals with acute illnesses as well as pregnant females or females on oral contraceptive agents also have been excluded. Some of the older patients did have evidence of atherosclerosis, mild diabetes mellitus, or compensated heart failure. 

The factors leading to the development of pulmonary hypertension are unclear, although associations with portal hypertension and pregnancy have been detected. Obesity by itself may double the risk of pulmonary hypertension. Additionally, the use of cocaine or oral contraceptives, infection with the human immunodeficiency virus (HIV), the use of anorexic agents, hepatic cirrhosis, genetic susceptibility, and female sex in the third to fourth decades of life also have been implicated as predisposing factors. Exposure of patients to fenfluramine or dexfenfluramine has been associated with 20% of all diagnosed cases of pulmonary hypertension. ... 

Griseofulvin induces hepatic CYPs and increases metabolism of warfarin, sometimes necessitating dose adjustment it also may reduce the efficacy of low-estrogen oral contraceptive agents. 

Veno-occlusive disease (VOD) describes the occlusion of small hepatic veins and is defined as a radicular form of the Budd-Chiari syndrome. A variety of endotheliotoxic noxae, particularly phytotoxins, are responsible for this clinical picture. In 1951 reports were simultaneously published for the first time both in South Africa (G. Selzer et al.) and Jamaica (K. R. Hill) dealing with this disease of the small venous branches, which results from chronic intoxication with pyrrolizidine alkaloids, (s. pp 548, 571) Similar morphological and clinical effects can also be caused by cytostatic agents (6-mercaptopurine, dacarbazine, thioguanine), azathioprine, contraceptives and exposure to X-rays. Since 1957, the term Stuart-Bras syndrome has also been used to describe the occlusion of the small hepatic veins, (s. p. 832)... 

Medicinal agents (such as contraceptives) may result in proliferations of the intima in the hepatic artery and its branches. In some cases, these arterial alterations were associated with thrombosis in the hepatic veins. Phar-macons can trigger three different forms of damage to the sinusoids (7.) dilation of the sinusoids (e.g. by contraceptives), (2.) perisinusoidal fibrosis (e.g. by azathio-prine, vitamin A and cytostatic agents), and (i.) peliosis hepatis (e. g. by contraceptives, anabolic and androgenic steroids, azathioprine, chenodesoxycholic acid). (13, 28, 130) (s. p. 398) (s. fig. 21.8)... 

The hepatic veins may be affected by xenobiotic-induced occlusion resulting from thrombosis or from proliferation starting in the intima and subsequently producing (secondary) thrombosis. An occlusion of the large hepatic veins is known as the Budd-Chiari syndrome. There are two distinct types, the truncular and the radicular form, the latter corresponding to veno-occlusive disease, (s. p. 249) Contraceptives (J.A. Ecker et al., 1966) and cytostatic agents are held responsible. Women develop this type of hepatic disease more than twice as often as men. (s. fig. 29.9)... 

Rifampin induces the activity of the hepatic microsomal enzyme, metabolizing numerous drugs including acetaminophen, anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, clofibrate, contraceptives, corticosteroids, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, mexiletine, quinidine, sulfones, sul-fonylureas, theophyllines, tocainide, and verapamil. The plasma levels and effectiveness of these agents may be decreased. 

With the introduction of RiF in 1967, the duration of combination therapy for the treatment of TB was significantiy reduced (from 18 to 9 months). Rifampin is nearly always used in combination with one or more other antitubercuiin agents. The drug is potentially hepatotoxic and may produce Gl disturbances, rash, and thrombocytopenic purpura. Rifampin is known to induce hepatic microsomai enzymes (cytochrome P450) and may decrease the effectiveness of oral contraceptives, corticosteroids, warfarin, quinidine, methadone, zidovudine, clarithromycin, and the azoie antifungai agents (see Chapter 10) (33). 

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