Summary Pha 415 - Exam 2 study guide

Therapeutics Unit 2!!
DILI
 Identify biochemical liver tests consistent with DILI
o AST/ALT, ALP, TBL increased
o Use GGT and LDH to determine differential diagnosis
o Serum albumin + PT or INR to determine severity
o Definition of DILI: any 1 of the following + med that can cause DILI
 ALT >5X ULN
 ALP >2x ULN
 ALT >3X ULN + TBL >2X ULN
o Moderate: above + symptomatic hepatitis
o Severe: above + INR>1.5, ascites, encephalopathy, or other organ failure
 Calculate the R value to determine the pattern of liver injury
o Hepatocellular
 ALT >5x ULN
 R>5
o Cholestatic
 ALP >2x ULN
 R<2
o Mixed
 R 2-5
o Calculation of R value
 [pt ALT/ULN]/ [pt ALP/ULN]
 Recognize signs and symptoms of liver injury
o Often asymptomatic/ mild
o Typically – acute hepatitis-like syndrome (N, fatigue, jaundice, abdominal
discomfort)
o If cholestatic: pruritus and asthenia, QoL limiting
o Immunoallergic features: fever, rash, arthralgia, lymph node enlargement
o Skin reactions: nonspecific rash, DRESS, SJS, or TEN
o Diagnosis of DILI
 Suspicion + pharmacologic hx
 Evaluate temporal relationship, hepatotoxicity potential, and signature
 Withdraw any suspected drug or HDS
 Exclude any other causes
 LiverTox is helpful website to determine likelihood of med causing DILI
 Recall common drugs that can cause DILI
o Risk factors (host)
 Age
 Gender

,  Race
 Alcohol consumption
 Pregnancy
 Comorbidities
o Risk factors (drug-dependent)
 Lipophilicity + daily dose >100mg
 Concomitant drugs
 Reactive metabolites
 Oxidative stress
 Mitochondrial hazards
 Hepatobiliary transport inhibition
o Intrinsic
 Acetaminophen!!
 Amiodarone
 Divalproex sodium/ valproic acid
 Statins
o Idiosyncratic
 Allopurinol
 Amiodarone
 Amoxicillin/clavulanate
 Diclofenac
 Fenofibrate
 Isoniazid
 Ketoconazole
 Minocycline
 Nitrofurantoin
 Phenytoin
 Statins
 Sulfonamides
o Acetaminophen-induced intrinsic DILI
 N-acetylcysteine
 150 mg/kg/h x 1h followed by taper
 Adults with idiosyncratic drug-induced ALF should receive NAC early in
the course
 Adjunct therapies: BAS for pruritus, CS for hypersensitivity
o Valproate toxicity
 Levocarnitine 100 mg/kg IV x1
Liver, Gallbladder, Pancreas
 Recall key organs and accessory structures in the hepatobiliary system

, o
 Review key functions of the structures within the hepatobiliary system
o Liver functions
 Bile synthesis/storage
 Glucose and glycogen synthesis/storage- essential for blood glucose
homeostasis
 /s of clotting factors, vitamins/minerals, albumin/plasma proteins
 Elimination of bilirubin
 Metabolism of steroid hormones, drugs, carbohydrates, fats, proteins (urea
formation from ammonia)
 Elimination of bacteria and toxins from the blood
 Cholesterol synthesis, recycling, elimination
o Gallbladder
 Receives bile from the liver via the common hepatic duct
 Stores and concentrates bile
 Maintains the solubility of cholesterol
 Release of bile stimulated by CCK
 Regulates pressure in the common bile duct
o Pancreas
 Exocrine functions
 Acinar cells secret digestive enzymes
 Mainly trypsin, chymotrypsin, amylase, and lipase
 CCK and parasympathetic NS stimulate production and secretion
of pancreatic enzymes and zymogens
 Acidic chyme stimulates the release of secretin which stimulates
release of watery pancreatic juice with bicarb and phos
 Acid/base are kept separate
 Endocrine functions
 Pancreatic hormones secreted by beta cells: insulin, amylin