4/3/2014. Elizabeth Thompson, PharmD April Understand the importance of the liver and basic physiology.

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1 Liver Disease Elizabeth Thompson, PharmD April 2014 Objectives Understand the importance of the liver and basic physiology. Review hepatic disorders Recognize liver function scoring systems used to determine treatment plans. Recognized medications related to liver diseases Appreciate the implications of these medications in hepatic disorders What does the liver do? 1

2 Liver Physiology 1 Stomach, small intestine, large intestine, spleen and pancreatic veins drain into the liver. The liver filters the blood and helps in protein synthesis How the liver works 1 Hepatocyte is the main functional unit of the liver How a damaged liver works: o Damaged cells in the liver start producing protein o Permanent scaring of liver tissue o Disrupted blood flow o Backed up blood flow results in portal hypertension Liver Function Tests 2

3 Laboratory Abnormalities Liver enzymes o Aminotransferase: AST and ALT o Enzymes located in the hepatocytes are elevated when injury occurs Bilirubin o Product of the breakdown of hemoglobin Albumin o Marker of hepatic synthetic activity therefore a estimation of hepatocyte activity PT and INR o Clotting factors are synthesized in the liver o PT and INR is prolonged in liver injury Child Pugh Score or Meld Score: What are these measuring? Table for Scoring 3

4 Liver Disorders Cirrhosis Hepatitis Hepatic Disorders Coagulation Disorders Alcoholic Liver Disease Acetaminophen Hepatotoxicity 4

5 Cirrhosis Cirrhosis is the 8 th leading cause of death. Cirrhosis 2,3,5 Cirrhosis Defined o Presence of fibrosis o Usually a result of years of continuous injury to the liver Causes of Cirrhosis o Excessive alcohol abuse o Hepatitis B and C Classification 3 Compensated Cirrhosis Preserved hepatic synthetic function No evidence of complications Decompensated Cirrhosis Reduced hepatic synthetic function Evidence of complications include: o Portal Hypertension Ascites Varices Hepatic Encephalopathy o Jaundice 5

6 No cure Treatment 2,3 Treat the underlying condition o Hepatitis Avoid substances that could injury the liver Liver transplant Treat complications Portal Hypertension 2,3 Due to the excessive fibrosis in the liver blood flow is backed up resulting in portal hypertension Complications: o Build up of fluid upstream from the liver o Stomach, small intestine, large intestine, spleen and pancreatic veins Conditions include: o Ascites o Hepatic Encephalopathy o Varices Ascites 2,3 Most common presentations of cirrhosis. o Over 50% of compensated cirrhosis patients will develop ascites within 10 years Pathophysiology o Ascites is the accumulation of lymph fluid within the peritoneal cavity. Treatment: o Sodium Restriction o Combo of furosemide 40 mg and spironolactone 100 mg Paracentesis o Albumin dose of 6-8 g/l of fluid removed 6

7 Spontaneous Bacterial Peritonitis 4 Infection of the ascitic fluid Antibiotics o Cefotaxime 2 g q8-12 hours, Ceftriaxone 2 g/day or Fluoroquinolones o Duration 5-10 days Albumin o 1.5 g/kg on admission and 1 g/kg on day 3 o Use if poor kidney function and high bilirubin Hepatic Encephalopathy 2,4 Liver dysfunction results in abnormal brain function. Ammonia is a neurotoxin associated with this condition o Ammonia is a by-product of protein metabolism done by the liver to urea, which is then renally eliminated Treatment goal targets ammonia levels: o Limit protein intake o Lactulose o Neomycin o Rifaximin: (cost ~ $1500) Gastroesophageal Varices 4 Varices: o Collateral vessels formed secondary to increased resistance to blood flow within the liver Medical Management o Octreotide/Somastatin o Antibiotic: Norfloxacin or Cipro x 7 days Alternative: Ceftriaxone 1 gram/day 7

8 Prevention of Variceal Bleeds 4 Primary prevention o Small varices + high bleeding risk o Medium/Large varices o Non selective beta blockers Secondary prevention o All patients with history of bleeding o Non selective beta blockers o Endoscopic (band ligation) Hepatitis Viral Hepatitis 4 Hepatitis A Hepatitis B Hepatitis C Hepatitis Defined; o Liver inflammation Acute hepatitis: infection < 6 months Chronic Hepatitis: infection >6 months 8

9 Hepatitis Overview 2,4,6 Type Hepatitis A Hepatitis B Hepatitis C Signsand symptoms Transmission Fecal-oral route Fever, fatigue, jaundice, N/V, abdominal pain, Dark Urine 30% asymptomatic 30% asymptomatic IV, bodily fluids, sexual contact, perinatal Duration Acute Acute and Chronic Chronic Preventative Treatment Vaccine or Immune Globulin Supportive care Vaccine Pegylated interferon or Entecaviror Tenofovir Transfusion, IV drug abuse, transplant No Vaccine Pegylatedinterferon & ribavirin and sofosbuvir +/- simeprevir(boceprevir Or Telaprevir) Hepatitis Summary 2 Hepatitis A: o Get vaccinated if you are at high risk o Supportive Care o Wash your hands! Hepatitis B: o Get vaccinated o Vaccinate your children o Treatment is available Hepatitis C o Treatment is available o 65% of infected people will develop chronic liver disease or liver cancer Coagulation Disorder 9

10 Coagulation Disorder 4 Clotting factors synthesized in the liver are not decreased in liver disease Prolonged PT and INR o Regularly INR=1 o More prone to bleed Thrombocytopenia o Platelet count less than 150,000 o 30-65% of cirrhosis patients o Primary caused by portal hypertension resulting in a backflow or pooling of platelets in the spleen. Alcohol Induced Liver Disease Alcoholic Liver Disease 2,4 Heavy Alcohol Ingestion o Men: 40-80g/day for years o Women: 20-80g/day for years Types of Liver Disease o Fatty Liver Fatty infiltration in the liver Hepatomegaly and mild liver enzyme elevation Potentially reversible if alcohol is stopped o Alcoholic Hepatitis Hepatic inflammation with necrosis o Cirrhosis Fibrosis 10

11 Alcoholic Liver Disease 2,4 Signs and Symptoms o Fatigue, anorexia, weight loss, nausea, vomiting, jaundice, right upper quadrant pain MELD Score: Maddrey Discriminant Function (MDF) 4.6 (PT control PT)+ total bilirubin Scores >32 have a poorer prognosis Treatment of ALD 2,4 Alcohol Abstinence When to consider therapy: o MDF >32 or MELD Score >18 o Prednisolone 40 mg/day 4 weeks course followed by a 2 week taper 30% decrease in risk ratio of short term death o Pentoxifylline 400 mg TID If steroids are contraindicated 40% lower hospital mortality Approximately 75% of patients will ultimately need a liver transplant. Acetaminophen Hepatotoxcity 11

12 Tylenol Overdose 2 Acetaminophen overdose o Leading cause of acute liver disease Dose related toxin Mechanism: o Glutathione in the liver normally detoxifies a metabolite of Acetaminophen, N-acetyl-p-benzoquinone imine(napqi) o At large doses there is not enough glutathione to detoxify NAPQI which can cause hepatocellular necrosis o Levels of Acetaminophen can be tested Tylenol Toxicity 2 Presentation o Nausea and vomiting o Right upper quadrant pain o Elevated Liver enzymes o Possible Elevation in bilirubin and INR o If untreated progression to multi-organ failure Treatment o Activated Charcoal Given within 1 hours of ingestion (up to 3-4 hours post ingestion) o N-Acetylcysteine Precursor of glutathione (increase the livers glutathione stores) Dose not reverse damage to liver already suffered to the liver Treat within 8 hours, may be beneficial within 48 hours How does all of this apply to us? 12

13 Review of Disorders and Medications Cirrhosis Hepatitis Coagulation Disorder Ascites and SBP: Furosemide Spironolactone Albumin Antibiotics Encephalopathy: Lactulose Neomycin Rifaximin Varacies: Octreotide- Somastatin Antibiotics Non-selective Beta blockers Hepatitis A: Vaccine Supportive Care Hepatitis B: Vaccine Treatment Hepatitis C: No vaccine Treatment Increased bleeding risk Aspirin and Coumadin??? ALD Alcohol Abstinence Steroids Pentoxifylline Tylenol OD Charcoal N-Acetylcystiene Summary The liver can impact almost every other organ in the body and if it is not functioning correcting it can have devastating affects to our bodies. It is important to avoid toxins, high risk behaviors or excess amounts of alcohol to prevent liver disease. Summary Continued Treatment or management of liver disease is available. Pharmacy personnel are a large part of getting the right medications to the patients in a timely matter. At the end of the day every medication we touch is going to be used by a person and therefore it deserves our best efforts. 13

14 Reference 1. Boron WF, Boulpaep EL: Medical Physiology: a cellular and molecular approach. Saunder Elsevier: Second edition Shargel L, Mutnick AH, Souney PF, Swanson LN: Comprehensive Pharmacy Review for Naplex. Wolters Kluwer: Lippincott Williams& Wilkins. Eighth Edition Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: a pathophysiologic approach. Mcgraw Hill Medical. Seventh Edition Hemstreet, Brian A. Gastrointestinal Disorders. ACCP Updates in Therapeutics 2013: The Pharmacotherapy Preparatory Review and Recertification Course 5. Bruce A. Runyon, M.D Management of Adult Patients with Ascites Due to Cirrhosis: Update AASLD PRACTICE GUIDELINE. HEPATOLOGY, February Recommendations for Testing, Managing, and Treating Hepatitis C. American Associated for the study of liver diease and Infectious Disease Socity of American. March 12 th 2014 Learning Objectives 14

15 Understand the importance of the liver and basic physiology. What is the basic function of the liver: A. Digest food B. Filter the blood C. Provide pancreatic enzymes D. Helps in bone marrow formation Understand the importance of the liver and basic physiology. What is the basic function of the liver: A. Digest food B. Filter the blood C. Provide pancreatic enzymes D. Helps in bone marrow formation Recognized medications related to liver diseases. If a patient has hepatic encephalopathy all of the medication below which except one could be considered for treatment: A. Lactulose B. Neomycin C. Rifaximin D. Albumin 15

16 Recognized medications related to liver diseases. If a patient has hepatic encephalopathy all of the medication below which except one could be considered for treatment: A. Lactulose B. Neomycin C. Rifaximin D. Albumin Appreciate the need for meds in liver disease. You are talking to a friend who just found out they had hepatitis C. They think their life is over. What is a possible conversation you could have with them. A. You can get vaccinated for that. B. There are treatments available. C. That will blow over in a couple of weeks. D. Your life is over, there is no hope. Appreciate the need for meds in liver disease. You are talking to a friend who just found out they had hepatitis C. They think their life is over. What is a possible conversation you could have with them. A. You can get vaccinated for that. B. There are treatments available. C. That will blow over in a couple of weeks. D. Your life is over, there is no hope. 16

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