Effect of feeding graded doses of Citrinin on clinical and teratology in female Wistar rats.

Citrinin is the one of the well-known mycotoxins, which is possibly spread all over the world. The graded doses of citrinin (1, 3 and 5 ppm CIT in feed) in female Wistar rats 10 weeks prior to mating, during mating and during organogenesis resulted in resorptions and post implantation losses, decreased fetal body weights and crown-rump lengths in fetuses of all groups. Various developmental anomalies recorded in fetuses of treated rats included gross (wrist drop, curled tail, stretched forelimb, subcutaneous haematoma), skeletal (incomplete ossification of skull bones, incomplete fusion of vertebral bodies, complete and partial agenesis of sternaebrae, metacarpals, metatarsals and phalanges, fused ribs and swing out ribs) and visceral (internal and external hydrocephalus, cerebellar hypoplasia, microphthalmia, roundening of heart, contracted kidneys, dilated renal pelvis and cryptorchid testes). The results suggest that CIT has adverse effects on fetal development which may be due to the longer bioavailability of citrinin in the animals.

Daño hepático inducido por drogas

Drug induced liver disease is responsible of 5 percent of hospital admissions for jaundice in USA, and 10 percent of acute hepatitis in France and North Europe. In addition, 20 to 50 percent of the cases of fulminant hepatic failure in USA are due to drugs. Tradicionally drug induced liver disease has been divided in two groups : 1. Non predictable toxicity (idiosyncratic reaction). 2. Predictable toxicity (Intrinsec toxicity). From the clinical point of view, most of the patients present jaundice associated with elevation of aminotransferases and alkaline phosphatase. However, some patients presents acute liver failure and death. Te duration of illness permit another classification in two groups : acute, frequently characterized by microvesicular steatosis; a picture similar to acute viral hepatitis or biliary obstruction (cholestasic jaundice) with elevated alkaline phosphatase and pruritus. Chronic, manifested by different presentations such as acute hepatitis, chronic hepatitis, (autoimmune), sclerosing cholangitis, phospholipidosis and non cirrhotic or cirrhotic portal hypertension. Histologically drug toxicity can induce the following morphologic changes : a) Pure cholestasis more frequently seen with estrogens. b) Viral hepatitis like. c) Fulminant hepatic failure more commonly seen with halotane, acetaminophen, phenytoin and methyldopa shows multilobular necrosis frequently asssociated with hypersensitivity features (fever, pruritus, eosinofilia)...

Prescripción de medicamentos en enfermos hepáticos

A common problem in patients with liver disease, is chronic administration of drugs. The presence of abnormalities in hepatic metabolism and the splanchnic circulation, makes drug presciption a very special situation. Cirrhosis induces a significant diminituion of the portal venous flow which is compensated by the hepatic artery. The hepatic clearance of drugs depends directly of the hepatic flow and the hepatic extraction of each medication. Consequently, hepatic clearance is equal to the hepatic flow multiplied by the hepatic extraction. drugs efficiently removed by the liver can be affected by a reduction of liver flow, good examples are : lidocaine, nitroglycerin, isosorbide dinitrate, propranolol, verapamil and indocyanine green. This group of medications have a very low bioavailability. In the normal situation the liver removes all of the compound in the first pass, leaving a small amount to the systemic circulation. Tha capacity to remove a drug when the liver flow is not the limiting factor has been defined as intrinsec clearance. High extraction drugs have a high intrinsec clearence and their bioavailability is also very high in cirrhosis. The main two reasons are : a reduced intrinsec clearence and the presence of spontaneous porta-systemic shunts, that derived blood from the splanchnic circulation directly into the systemic one bypassing the liver. As a result of these abnormalities a reduction of the dosage is usually neccesary. A clasic example is propranolol in the treatment of portal hypertension, where dosage of 20-60 mg are usually sufficient, in contrast with higher dosage in the treatment of arterial hypertension. In general drugs that depends on phase I of hepatic metabolism (oxidation, desmetylation) are more affected as far a biotransformation than those depending on phase II (glucuronidation). The impact of this reduction will be more important for low extraction drugs nor affected by changes in the hepatic flow. Examples of these are : aminophyline, caffeine and aminopyrine. Other factors such as cholestasis, low albumin levels and a special sensitivity to the toxic effects of some compounds by some organs such as the stomach (non steroidal anti-inflammatories), kidney (aminoglycosides), and brain (benzodiazepines), are of paramount importance.