Therapeutics Exam 4 (Hepatology) Flashcards
What are the functions of the liver?
-Bile production
-Drug/food/toxin metabolism
-Protein synthesis (albumin + coagulation factors)
-Storage/Adjustment of vitamins/gluconeogenesis
What do liver enzymes (AST, ALT, Alk phos) tell us?
These are markers of acute injury
-not true markers of liver function
What 3 proteins does chronic liver disease affect and what effects does it have?
Decreases albumin
Increases INR
Increases bilirubin
What is the main drug that can cause Drug-induced liver injury (DILI)?
Acetaminophen
-high doses (>8g)
How do high doses of acetaminophen cause drug-induced liver injury?
Results in toxic levels of N-acetyl-p-benzoquinone imine (NAPQI)
-this causes direct hepatotoxicity
What is the normal AST range?
0-50 IU/L
What is the normal ALT range?
0-50 IU/L
What is the normal Alk phos range?
30-120 IU/L
What drug can we use to reverse the toxic metabolite (NAPQI) produced by high doses of acetaminophen?
N-acetylcysteine +/- activated charcoal
To give activated charcoal, it must be within what amount of time to the time that the patient ingested acetaminophen?
<1 hour
-only prevents absorption if taken immediately after ingestion
How do we determine if we need to give a patient N-acetylcysteine?
Use the Rumack-Matthew Nomogram
-Hours post-ingestion vs plasma concentration
-Dark grey area= give med
What is the dosage form of N-acetylcysteine?
Oral or IV depending on what they tolerate
What is cirrhosis?
Severe, chronic, irreversible fibrosis of the liver
what are the S/S of cirrhosis?
Fatigue
Weight Loss
Ascites (fluid buildup in abdomen)
Jaundice
Hepatomegaly or Splenomegaly
Encephalopathy (confusion)
What are the causes of cirrhosis?
Alcohol use
Viral hepatitis
Liver disease
Drugs (amiodarone, methotrexate)
What is ascites?
Fluid accumulation in the peritoneal space
What are the non-pharmacologic treatments for ascites?
Sodium Restriction
Assess for liver transplant
What is the first-line therapy for ascites?
Aldosterone antagonist (spironolactone)
+
Loop diuretic (furosemide)
What is the second-line therapy for ascites?
Paracentesis
TIPS (surgery)
If a patient can only tolerate one of the first-line therapies for ascites, which drug class is preferred?
Aldosterone antagonist (spironolactone)
Which drug class should be avoided in patients with cirrhosis due to its ability to increase the risk of ascites and bleeding?
NSAIDs
At what ratio should the diuretics for ascites be initiated?
spiro 100:40 furo
What is the maximum daily dose of diuretics for ascites?
400mg spiro/ 160mg furo
When is a paracentesis indicated for ascites?
Refractory/resistant ascites
Cases of AKI
How much fluid needs to be removed via paracentesis for us to replace albumin?
> 5L
How much albumin should be given to paracentesis patients who need it?
25% IV albumin
Give 6-8g albumin per liter removed*
How does cirrhosis result in esophageal varices?
Portal hypertension causes hepatic/splanchnic vasodilation
-results in decreased perfusion
-compensatory varices (small offshoots) form
Why are esophageal varices dangerous?
Dilation of EV can occur and result in variceal bleeding
-this can be severe
What are the risk factors for variceal bleeding?
-Larger size varices
-Cirrhosis severity
-Red color markings seen on endoscopy
-Active alcohol use
What are the 2 options for variceal bleeding prophylaxis (prevention)?
Non-selective beta-blockers (moderate disease)
Endoscopic variceal ligation
*NOTE that neither of these have mortality benefits
What are the beta-blockers that can be used for variceal bleeding prophylaxis?
Nadolol
Propranolol
Carvedilol
What is the HR goal with beta blockers?
55-60 bpm
Immediately upon presentation of a patient with variceal bleeding, what needs to be done?
-Blood transfusion (Hg>7)
-Give octreotide
-Antibiotic prophylaxis
What is the second thing we do after a patient presents with variceal bleeding?
Endoscopic variceal ligation
After an EVL, what is the third thing we do after a patient presents with variceal bleeding?
Secondary prophylaxis
(indefinitely until compensated)
What is the moa of octreotide?
Inhibits release of vasodilatory peptides
-results in splanchnic vasoconstriction and decreased blood flow
What do we use octreotide for?
Acute variceal bleeds
How long should octreotide be used for?
2-5 days
-or until EVL, then stop 1 day after
What is the gold standard for variceal bleeding cessation?
Endoscopic variceal ligation
What is the goal for how quickly we want patients to have an endoscopic variceal ligation after they appear with variceal bleeding?
Within 12 hours
What is the downside to variceal ligation?
It is not a long-term solution
-bands can break
-new varices can form
What other type of prophylaxis do patients with active variceal bleeding need?
Primary Antibiotic Prophylaxis
-due to increased infection risk
What antibiotic is recommended for primary antibiotic prophylaxis?
Ceftriaxone
-use until the hemorrhage resolves (max 7 days)
What therapy is not recommended in variceal bleeding despite elevated INR?
Vitamin K
-do not give
What therapy do we use as secondary prophylaxis for varices?
Endoscopic variceal ligation (every 1-4 weeks)
Non-selective beta-blockers indefinitely (nadolol, propranolol, carvedilol)
How does cirrhosis cause spontaneous bacterial peritonitis (SBP)?
-Due to bacterial translocation
-bacteria cross the intestinal barrier
What is the clinical presentation of spontaneous bacterial peritonitis?
-Fever
-Abdominal pain/Tenderness
-Leukocytosis
-Encephalopathy
*can be asymptomatic
How do we diagnose spontaneous bacterial peritonitis?
Therapeutic Paracentesis
-If the fluid has >/= 250 cells/mm^3 polymorphonuclear leukocytes (PMN) then diagnose
Note: PMNs= WBC from fluid x % Neutrophils
What is the treatment for spontaneous bacterial peritonitis?
Ceftriaxone
How long do we treat with ceftriaxone for spontaneous bacterial peritonitis?
5-7days
What other drug is used in treatment of spontaneous bacterial peritonitis?
albumin
What is the dosing of albumin for spontaneous bacterial peritonitis?
IV:
Day1: 1.5 g/kg once
Day 3: 1 g/kg once
*use ABW
What agents can be used for secondary prophylaxis of spontaneous bacterial peritonitis?
Sulfamethoxazole/Trimethoprim (Bactrim)
Ciprofloxacin
-not used as much
How long should secondary antibiotic prophylaxis be used in patients with SBP?
Indefinitely!
What is the estimated incidence of drug-induced liver injury (DILI)?
0.02%
