Therapeutics Exam 4 (Liver) Flashcards
Blood enters the liver through via what?
hepatic artery AND portal vein
Blood leaves the liver through what
hepatic vein (central vein)
Drug metabolism usually happens in the liver:
Typically ______ medications but can sometimes _____ medications (______)
typically inactivates CAN activate (prodrugs)
Liver Drug Metabolism:
What are phase 1 reactions
oxidation, reduction, or hydrolysis (activating or deactivating medications)
Liver Drug metabolism:
what are phase 2 reactions
conjugation (making a drug more water soluble— thus easier to excrete)
Liver Drug metabolism:
CYP enzymes seen in phase 1 or phase 2 reactions
phase 1
what is 1st pass metabolism
portion of medication that is metabolized BEFORE reaching systemic circulation….
what is extraction ratio
fraction of drug that is removed by the liver….
If a medication has a high ER it will have _____ bioavailbility
low
what are “pairs” of LFTs to look at for interpreting the liver
AST & ALT
Alk Phos & GGT
bilirubin (total, conjugated, unconjugated)
INR & Albumin
Normal Ranges:
AST
ALT
0 - 50 IU/L for both
Normal Ranges:
Alk Phos
GGT
Alk Phos: 30 - 120 IU/L
GGT: 0 - 50 IU/L
Normal Ranges:
Bilirubin Total:
Bilirubin (conjugated):
Bilirubin (unconjugated):
Total: 0 - 1.4 mg/dL
Conjugated: 0 - 0.3 mg/dL
Unconjugated: 0 - 1.1 mg/dL
Normal Ranges:
INR:
Albumin:
INR: 0.9 - 1.2
Albumin: 3.6 - 5 g/dL
AST or ALT
which one is more specific to the liver
ALT
AST and ALT can be elevated by what things?
viral infections
medications
ischemia
Ratio of ____ to ____ if > 2 = alcoholic liver disease
AST: ALT
if GGT and Alk Phos are elevated = what?
biliary tract injury
what things can elevate GGT and Alk Phos?
cholecystitis (inflammation of gall bladder)
obstruction (gallstone)
Bilirubin = the breakdown of _____
hemoglobin
Bilirubin is conjugated in the _____ to make it ______
in liver
to make it water soluble for excretion
_______ bilirubin is NOT assoc. with liver disease
unconjugated
elevated ______ bilirubin is associated with liver disease
conjugated
Unconjugated bilirubin is NOT assoc. with liver disease – it can be high when?
can be high when hemolysis is high (RBC/heme breakdown is high)
GGT or Alk Phos:
which one is more specific to the liver
GGT
INR will ______ in liver dysfunction - and why
increase because the liver is not making clotting factors = higher chance of bleeding
Albumin will ______ in liver dysfunction and why
decrease – because liver makes albumin…
______ and _____ are used as liver function indicators
INR and albumin
how to interpret LFTs?
look at how many times bigger the value is compared to the UPPER limit of normal
Cirrhosis:
reversible or irreversible
irreversible
Signs and Sxs of Cirrhosis
fatigue wt loss pruritis -- itching from built up bilirubin jaundice hepatomegaly/spleomegaly encephalopathy (pts can be asymptomatic)
what are some complications from cirrhosis/things that lead to increased morbidity and mortality
portal HTN hepatic encephalopathy ascites Esophageal varices spontaneous bacterial peritonitis hepatorenal syndrome
5 things that could cause cirrhosis
Chronic alcohol consumption Chronic viral hepatitis (Hep B and C) Metabolic liver disease Cholestatic liver disease Drugs
what drugs can cause cirrhosis
amiodarone
methotrexate
what are some specific metabolic liver diseases that can lead to cirrhosis
hemochromatosis (high iron) nonalcoholic steatohepatitis (fatty liver)
what is Child-Pugh Classification vs what is MELD Score
Child Pugh - classifies severity of cirrhosis
MELD: predicts mortality of pts with liver disease in next 3 months – helps rank pts on transplant list!!!
Child-Pugh Classification:
If mild disease: Class ___ and a score of ____
A
< 7
Child-Pugh Classification:
If moderate disease: Class ___ and a score of ____
B
7 - 9
Child-Pugh Classification:
If severe disease: Class ___ and a score of ____
C
10 - 15
what things are looked at/considered when finding the Child-Pugh Classification system
Bilirubin Albumin Ascites encephalopathy Prothrombin time
what does MELD score stand for
model for end stage liver disease score
what 3 things does MELD look at for predicting mortality
total bilirubin
SCr
INR
idea behind portal HTN
blood wont flow thru liver bc it is hard/fibrotic (thx cirrhosis) that the blood backs up and creates pressure
what is hepatic encephalopathy (HE)?
essentially confusion —
brain dysfunction due to liver insufficiency
why/how does hepatic encephalopathy occur?
Ammonia is produced by protein breakdown (normal thing to happen in body, dur)
liver NORMALLY makes ammonia –> urea but since liver sucks ammonia builds up
ammonia can cross BBB and cause neurotoxicity
Hepatic Encephalopathy:
FYI: Can be classified by type and severity, and its time course
(Type A,B,C and Grade I, II,III,IV, episodic, recurrent, persistent)
if ammonia level is _____ then it probably is NOT HE
ammonia level is normal - then probs not HE
what is asterixis
flapping tremor seen when the hands/arms are stuck out
Can be classified by what things?
by type and severity, and its time course, and if precipitated or not
(Type A,B,C and Grade I, II,III,IV, episodic, recurrent, persistent)
Treating Hepatic Encephalopathy:
when should you treat it?
always!! (doesn’t matter if spontaneous or precipitating)
what things could precipitate hepatic encephalopathy
infections electrolyte disorder GI bleeding diuretic overdose constipation
when do prophylaxis treatment for HE?
do secondary prophylaxis (aka if they ever get it - do prophylaxis…)
Contaminant drugs to avoid when treating someones hepatic encephalopathy
benzos! (drugs that worsen confusion…)
drugs used to treat hepatic encephalopathy (2 that are commonly used vs 2 that are not used as commonly)
commonly used: lactulose and rifaximin
not commonly used: neomycin and metronidazole
MOA for lactulose to be used for hepatic encephalopathy
it increases ammonia elimination (via laxative effect)
makes environment more acidic = NH3 –> NH4- which means it cannot be absorbed
Rifaximin MOA
eliminates ammonia producing bacteria
Rifaximin or lactulose which one is more tolerated by patients
rifaximin
Issues with lactulose?
they are pooping a lot
unpleasant taste
may cause dehydration, gas and bloating
For acute or chronic treatment of hepatic encephalopathy:
titrate til you get to how many bowel movements a day?
2 - 4 / day
Neomycin sucks for HE treatment why?
long term use = concern for ototoxicity or nephrotoxicity
Metronidazole sucks for HE treatment why?
long term use = concern for neurotoxicity
Ascites:
fluid (lymph) accumulation in the _______
peritoneal space
what is SAAG stand for and why is it relevant to liver disease
SAAG = serum ascites albumin gradient
the SAAG score can help determine the cause of ascites
how to find the SAAG value?
(albumin in serum) - (albumin in ascitic fluid)
the SAAG value needs to be ____ to be cirrhosis
high or (> 1.1)
how does a high SAAG value happen
portal HTN = more pressure = drive fluid into peritoneal space
since albumin is large it cannot pass the membrane
1st line options for treating Ascites:
avoid alcohol Na+ restriction avoid NSAIDs (leads to more Na+ and fluid retention) diuretics asses for liver transplant
2nd line options for treating ascites
serial paracentesis
shunt
what diuretics are used for ascites treatment
spironolactone
furosemide
ratio of spironolactone and furosemide for treating ascites
100: 40
spironolactone and furosemide:
which is superior by itself compared to the other
sprironolactone is superior alone
combo is superior is better overall
Max doses of spironolactone and furosemide for ascites
spirono: 400 mg
furosemide: 160 mg
if pt develops gynecomastia from spironolactone – what drugs can be used to replace it
eplerenone
amiloride
triamterene
what is paracentesis
literally removing fluid straight from the ascites area
Albumin and paracentesis:
give albumin when in relation to it?
AFTER
Albumin and paracentesis:
use what ___ albumin
25% (more concentrated = less fluid you’re giving back)
When is it indicated to give albumin to patients in relation to paracentesis
when over 5 L of fluid is removed!!
how much albumin to give patients after paracentesis
6 - 8 g of albumin PER LITER of fluid removed
what is SBP
spontaneous bacterial peritonitis
Patients are at a higher risk of SBP if the have ______ in ascitic fluid
low protein
Diagnosing SBP:
Done by taking a sample of ascitic fluid —
need to see an elevated _________ of (______ cells/mm3)
PMN count
(polymorphonuclear leukocyte)
> 250 cells/mm3
Common abx for treating SBP
and treat for how long?
Cefotaxime and Olfloxacin
treat for 5 - 10 days
For prevention of SBP:
do when recurrence rate is high —- what patients are high risk
if pts have low protein (<1.5 g/dL)
variceal hemorrhage
or
prior SBP
For prevention of SBP:
Discontinue _________ because it is associated with increase rate of SBP
unnecessary PPIs
what antibiotics can be used for SBP prevention and how often do you take them
Ciprofloxacin or SMT-TMP(bactrim)
take once daily
In Cirrhosis — we will see (decreased or increased) INR - and what would make sense to give for this issue but we do not give it because it wasn’t actually effective…?
INCREASED INR – bc liver is not making clotting factors
do not give vitamin K
Esophageal Varicies:
________ veins in the esophagus that leads to high risk of ______
enlarged
bleeding
Esophageal Varicies: Treatment options?
blood transfusions (when Hgb hellla low) Octreotide EVL aka banding Ceftriaxone (sorta PPIs)
Esophageal Varicies Treatment:
Give Blood transfusions when?
to make sure Hgb stays above 7 g/dL
Esophageal Varicies Treatment:
Octreotide is a ________ analogue
start when?
works by reduce _______ by causing ______
somatostatin analogue
start IMMEDIATELY if you suspect a variceal bleed
reduces portal pressure by causing vasoconstriction
what is EVL? and another name for it?
and use it for what?
endoscopic variceal ligation aka BANDING
for treating esophageal varicies
Esophageal Varicies Prohpylaxis options?
NSBB (non selective beta blockers)
EVL (the banding)
or TIPS – last line!
Esophageal Varicies Prohpylaxis:
what to do for preprimary prophylaxis?
no treatment
Esophageal Varicies Prohpylaxis
what to do for primary prophylaxis
NSBB OR EVL (not both!!)
definitely no TIPS
Esophageal Varicies Prohpylaxis
what to do for secondary prophylaxis
NSSB + EVL = 1st line
TIPS = 2nd line
T or F: for secondary prophylaxis of Esophageal Varicies Prohpylaxis once TIPS occurs you need to continue NSBB and EVL
false!! do not need them anymore
what beta blockers are used for Esophageal Varicies Secondary Prohpylaxis
propranolol (BID
naldolol (QD)
carvedilol (QD to BID)
For Esophageal Varicies Prophylaxis:
target a HR of ______ BPM
55 - 60
For Esophageal Varicies Prophylaxis:
Hold or decrease dose when the SBP goes below _____
90 mmHg
what is NASH stand for and what is it as a disease?
Non-alcoholic steatohepatitis
it is essentially “fatty liver”
Risk factors for NASH?
metabolic diseases — obesity, T2DM, hyperlipidemia
Treatment options for NASH?
lifestyle modification!! (wt loss and exercise)
possibly pioglitazone…?
what does ALD stand for/what is
alcoholic liver disease — can be any injury ranging form steatosis to cirrhosis
what are some additional risk factors that increase chance of ALD (other than large alcohol consumption)
type of alcohol (beer and liquor >wine) timing (worse when not around mealtime) binge drinking (4 -5 at a time) obesity genetics
questionnaire for seeing if alcoholism
CAGE questionnaire (cut down, annoyed, guilty, eye opener)
Prognostic score for ALD? it will give a sense of what?
MDF – maddrey discriminant function
predicts mortality
ALD treatment?
abstain from alcohol - duh
supportive care
or prednisone or pentoxyfylline
ALD Treatment:
if MDF Score < 32 give ________
supportive care only
ALD Treatment:
if MDF Score > 32 give _____________
prednisone or pentoxifylne
Signs and Symptoms of Alcohol Withdrawal
HA tremors/SEIZURES (grand mal seizures) elevated body temp increased HR N/V irritability hallucinations
T or F: delirium tremens is life threatening
true!!
what is score is found in alcohol withdrawal based on symptoms
CIWA score (clinical institute withdrawal assessment)
Drugs for treatment for alcohol withdrawal
Folic acid/Thiamine
Multivitamin
Benzo – PRN is best
Definition of Acute Liver Disease: Evidence of \_\_\_\_\_\_ abnormality & any degree of \_\_\_\_\_\_in a pt without preesxisting cirrhosis & illness is < \_\_\_\_\_ in duration
coagulation (INR of 1.5 or above)
degree of encephalopathy
< 26 weeks
what drugs are direct toxins to the liver (she gave us a list of top 7)
APAP! ASA Niacin Vit. A Buprenorphine Methylprednisolone Tetracycline
APAP posioning treatment:
3 things to possibly give?
activated charcoal
NAC (N-acetylcysteine)
Acetadote
How does activated charcoal work for APAP toxicity
it binds to it in the STOMACH and prevents absorption
wont affect the APAP already absorbed tho :’(
When to give NAC for APAP toxicity
all the time!!
even if you just suspect it, just give it!
How does NAC work for APAP toxicity
NAC increases glutathione
*sometimes APAP –> NAPQI (which is toxic)
glutathione binds/detoxifies NAPQI
T or F: NAC is not recommended if activated charcoal has already been given
false!!
give it still
When adjusting a patients medications because of liver disease consider:
Extent of ________ of the med
Extent of liver disease (dose adjust recommended by _______ class)
Is the medication highly ______
avoid ______ meds
extent of hepatic extraction
child pugh class
highly protein?
avoid hepatotoxic
Highly protein bound meds:
in liver disease —
____ protein/albumin = ____ unbound drug = ____ therapeutic effect
(each blank is high or low)
low albumin
high unbound drug
high effect
