CHAPTER 22

Hepatic and Pancreatic Disorders Brian A. Hemstreet, PharmD, BCPS

LEARNING OBJECTIVES KEY TERMS AND DEFINITIONS After completing this chapter, you should be able to Ascites— abnormal accumulation of fl uid in the abdominal cavity. This 1. Defi ne the following: is a common complication of cirrhosis. ● Hepatitis Cirrhosis — a chronic liver disease ● Cirrhosis that is a result of longstanding or repeated damage to the liver. Scar ● Ascites tissue replaces tissue resulting in ● Encephalopathy many complications related to loss of ● Jaundice normal liver function. Cirrhosis is often ● Esophageal varices referred to as end stage liver disease. ● Portal hypertension Hepatic encephalopathy ● Pancreatitis (HE)— dysfunction of the brain and nervous system that occurs in ● Malabsorption patients with cirrhosis. This disorder is ● Pseudocyst thought to be due to the presence of 2. Recall common causes and complications of chronic liver disease waste products in the blood stream, such as ammonia, that are normally 3. Review the role and mechanism of common drug treatments for cirrhosis detoxifi ed by the liver. 4. Review adverse effects and drug interactions for medications used in the treatment Hepatitis — hepatitis means of chronic liver disease infl ammation of the liver and may be caused by a variety of diseases, 5. Identify key patient counseling points for medications used to treat complications toxins, and drugs. Hepatitis may by PART of chronic liver disease acute or chronic and patients may 6. Describe the anatomy and normal physiology of the liver and pancreas exhibit symptoms, such as abdominal pain, jaundice, or nausea. Hepatitis 7 7. Recognize common medications used in the management of acute pancreatitis may also be severe enough to require 8. Review adverse effects, drug interactions, and key patient counseling points for hospitalization. medications used in the treatment of chronic pancreatitis Jaundice— yellow discoloration of the skin, whites of the eyes, and mucous membranes that occurs in patients with hepatitis or cirrhosis. epatic disorders are those that directly affect the liver. Given that the liver This is due to accumulation of a substance called bilirubin that H is a vital organ that is involved in many important functions in the human is normally detoxifi ed by the liver. body, diseases of the liver can result in very serious consequences for patients. Malabsorption — the inability There are many different causes of both acute and chronic liver disease. These to absorb nutrients from the GI include infections, such as those due to hepatitis B virus or hepatitis C virus, tract. This is often seen in patients with chronic pancreatitis who lose exposure to drugs, alternative medications or other toxins, inherited or genetic the ability to digest orally ingested disorders, autoimmune disorders (where the body’s immune system attacks its food (maldigestion) due to a lack of pancreatic enzymes. own organs), and metabolic disorders, among others. In 2009 chronic liver dis- Pancreatitis — infl ammation of ease or cirrhosis was the twelfth leading cause of death in the United States.1 the pancreas due to toxins, drugs, This makes prevention and treatment of liver disease and its complications a trauma, structural abnormalities, signifi cant area of healthcare focus and utilization. or other causes. Pancreatitis can be acute or chronic.

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Portal hypertension— increased The most common causes of chronic liver disease in the United States are alcohol pressure in the portal vein, due to abuse and hepatitis C virus infection. 1, 2 While some drug treatments may target the acute back up of blood fl ow as a result of processes involved in liver disease, such as those caused by viruses or autoimmune con- the presence of cirrhosis. ditions, much of the drug management revolves around management of chronic liver Pseudocyst — a large fl uid collection that forms in or around the pancreas disease and its associated complications. Therefore, this chapter will focus on com- as a result of infl ammation due to mon medications used in the chronic management of advanced nonviral associated liver pancreatitis. diseases and its complications. Varices— enlarged veins located in the lower part of the esophagus CASE STUDY or the stomach that are close to the surface. The veins become so large John Hardy is a 55-year-old male who is 5 feet 10 inches tall and weighs 200 lb. He has that that may burst, leading to a history of alcohol abuse and reports drinking 10 – 15 beers on a daily basis over the life-threatening bleeding. last 20 years. He was seen today at the clinic with complaints of abdominal swelling, swollen ankles, mild shortness of breath, and a 10-lb weight gain over the last 3 weeks. The whites of his eyes and his skin are turning yellow. He currently takes no medications and reports no allergies to medications or foods. After review of his physical exam and laboratory tests his healthcare provider told him that he has cirrhosis.

Anatomy and Physiology of the Liver

The liver is a large organ that consists of two major sections, called lobes, and is located in the right upper portion of abdominal cavity (Figure 22-1). It performs many important functions, including metabolism of drugs and nutrients, detoxifi cation of metabolic waste products and toxins, synthesis of proteins, cholesterol, and bile, as well as excretion of waste products and participation in host immunity. The blood fl ow coming into the liver is unique in that comes mostly from a large blood vessel called the portal vein. A small portion of blood fl ow comes also from the hepatic artery, which carries oxygen-rich blood to the liver. The portal vein drains blood from the stomach and intestines and de- livers it to the liver. Therefore, any nutrient or drug that is orally ingested passes through the portal vein and goes to the liver fi rst before making its way to the systemic circula- tion. Thus the liver is able to act as a fi lter to help metabolized or detoxify any potential harmful substances that are orally absorbed before they reach the bloodstream. Once blood enters the liver it slowly passes through small cavities called sinusoids. As the blood passes through the sinusoids it is exposed to the various types of cells located in the liver. The largest number of cells are called hepatocytes. These cells per- form most of major the detoxifi cation and metabolic processes within the liver. The hepatocytes also produce important pro- teins, such as albumin and various pro- Liver teins involved in the normal blood clotting Stomach process. Specialized cells, called Kupffer Common cells, help to remove any bacteria that may bile duct Gallbladder have entered the liver through the portal vein. Once fi ltered, the blood then leaves Small intestine the liver and enters the systemic circula- Pancreas tion through the hepatic veins. The liver also produces a substance cal- Figure 22-1. Position of liver and pancreas. led bile, which helps to remove fat soluble

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