Prescripción de medicamentos en enfermos hepáticos

Abstract

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 prescription a very special situation. Cirrhosis induces a significant diminution 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 most of the compound in the first pass, leaving a small amount to the systemic circulation. The capacity to remove a drug when the liver flow is not the limiting factor has been defined as intrinsic clearance. High extraction drugs have a high intrinsic clearance and their bioavailability is also very high in cirrhosis. The main two reasons are: a reduced intrinsic clearance 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 classic example is propranolol in the treatment of portal hypertension, where dosage of 2060 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 as biotransformation than those depending on phase II (glucuronidation). The impact of this reduction will be more important for low extraction drugs not 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.