Liver Flashcards
(120 cards)
1
Q
cirrhosis is caused by what two things?
A
chronic hepatic inflammation or cholestasis
2
Q
5 most common causes of chronic liver disease?
A
chronic viral hep C, alcoholic liver disease, non alcoholic fatty liver disease, chronic hep B, autoimmune induced hep
3
Q
what are six complications of liver disease?
A
1) . portal HTN
2) . Ascites
3) . hepatic encephalopathy
4) . esophageal varices
5) . spontaneous bacterial peritonitis
6) . hepatorenal syndrome
4
Q
portal HTN causes what two things?
A
inc pressure within the portal venous system and complications of cirrhosis
5
Q
what is ascites?
A
accumulation of fluid within peritoneal cavity
6
Q
what happens in hepatorenal syndrome?
A
arterial vasodilation in splanchnic circulation, from portal hypertension, decreases GFR and subsequent failure
7
Q
what two things can cause ascites?
A
inc resistance within the liver pushes lymphatic drainage into abdominal cavity OR reduced osmotic pressure (hypoalbuminemia)
8
Q
what are the four tx options for ascites?
A
sodium restriction, diuretics, paracentesis, albumin
9
Q
sodium restriction guidelines for ascites
A
<2000 mg/day; some may need <500 mg/day
10
Q
what happens when sodium is restricted too much? what does this put muscle at risk for?
A
protein and caloric consumption decreases as well; puts muscle at risk for wasting
11
Q
what are the two preferred agents for ascites diuretics? what is the dosing of each
A
furosemide (Na/K+ excretion) and spironolactone (K+ sparing)
**40 mg/100 mg
12
Q
what three things do you need to monitor when giving diuretics for ascites?
A
electrolyte imbalances, renal impairment, and gynecomastia (spironolactone)
13
Q
hepatic encephalopathy: impaired hepatic clearance or portal-systemic shunting leads to (5)
A
accumulation of ammonia or glutamine (leads to swelling), benzodiazepine-like substances activating GABA receptors, zinc deficiency, altered cerebral metabolism
14
Q
if removing >5 L at one time for ascites, what should you administer?
A
albumin (try to correct plasma balance)
15
Q
if a pt still has refractory ascites, what do you add to diuretic combination
A
midodrine (vasopressor-constricting)
16
Q
what group of meds contribute to sodium and water retention (and therefore will stop when having ascites)
A
NSAIDS
17
Q
what two drugs should you avoid to prevent renal failure when a pt has ascites
A
ACEs and ARBs
18
Q
what is important to look for before administering drugs for hepatic encephalopathy?
A
other causes of altered mental states
19
Q
on the child-Turcotte-pugh classification for cirrhosis severity, what is indicated by a pt who scores more points?
A
more cirrhosis, more severe liver disease, more complications
20
Q
covert hepatic encephalopathy is stages ____ through ____ (better); overt is stages ___ and ____
A
covert- 0-2
overt 3&4
21
Q
1st choice agent for hepatic encephalopathy
A
lactulose
22
Q
MOA lactulose
A
colon bacteria convert lactulose to acetic & lactic acid, creating an acidic pH; acidic pH causes GI tract ammonia to be reduced to ammonium ion (inhibits diffusion of ammonia into blood)
23
Q
dosing of lactulose
A
45 mL q 1-2 hr until loose stool AND titrate further until pt has 2-3 BMs per day
24
Q
lactulose can be continued ___ _____ for prevention
A
long term
25
10 gm of Kristalose is ___ mL of lactulose
15 mL
26
what is goal of ABX therapy for hepatic encephalopathy
reduce urease producing bacteria that lead to excess NH3
27
three ABX used for hep encephalopathy
rifaximin, neomycin, metronidazole
28
dose, absorption, tolerance of rifaximin
550 mg BID; minimal, good toleration
29
dose, absorption, and monitoring for neomycin
3-6g/day for 1-2 weeks then 2 g/day maintenance; very little absorption, monitor in renal patients
30
dose for metronidazole; what can it cause
250 mg BID, peripheral neuropathy
31
4 other tx for hepatic encephalopathy besides lactulose and ABX
Miralax, zinc supplementation, nutritional interventions, dietary changes
32
miralax dosing for hepatic enceph and when to use
4L over 4 hrs; use in acute situation to get symptoms under control (faster improvement than lactulose)
33
what are the two specific dietary supplementations given for hepatic enceph?
BCCA or LOLA
34
esophageal varices are often a consequence of ________ _________, commonly due to ________
portal HTN; cirrhosis
35
pts with esophageal varices have a tendency to develop _______ and are associated with ______ mortality rates
develop bleeding and high rates
36
tx options for esophageal varices depend on what three things?
acute bleed vs primary prophylaxis vs secondary prophylaxis after a bleed
37
acute management for esophageal varices: surgical and medication
endoscopy with band ligation or sclerotherapy; octreotide (somatostatin analog) and ceftriaxone
38
primary prevention of bleed (esophageal varices) medication
non selective BB
39
secondary prevention of bleed (esophageal varices): surgical and medication
band ligation; non selective BB +/- nitrates
40
BB MOA (B1 and B2)
Decrease cardiac output (β1)
| Decreasing vasodilation of splanchnic arteries (β2)
41
how do BB help esophageal varices?
slow down their growth and lowers incidence of first bleed or repeat bleed
42
how to use BB for esophageal varices
continue indefinitely; titrate HR to 55 bpm or 25% below baseline (OR until side effects)
43
why do nitrates help with esophageal varices?
used in combo with BBs to potentially decrease bleeding rate
44
what resistance does nitrate use help decrease?
intrahepatic
45
MOA of octreotide
mimics somatostatin by inhibiting release of serotonin, gastrin, VIP, insulin, glucagon, secretin, pancreatic polypeptide, motilin, and growth hormone; inhibition leads to vasoconstriction and dec splanchnic blood flow
46
ADRs of octreotide
bradycardia, hyperglycemia, pruritus, hypersensitivity rxn, fatigue, HA, diarrhea
47
what should you use octreotide in combo with?
ABX- ceftriazone (1 gr qd for a week, crosses the blood brain barrier)
48
what is SBP? what organisms can cause it?
infection of ascetic fluid; organisms are usually GRAM NEG (E coli and Klebsiella), but can be gram pos (strep pneumo, S aureus)
49
dx of SBP depends on...
> 250 polymorphonuclear cells/mm3
50
what are the two options for acute tx of SBP?
ABX (cefotaxime or ceftriaxone) or albumin
51
how long do you administer ABX for acute SBP? dosing of each is?
5-10 days
Cefotaxime (2 g q 8-12 hours)
Ceftriaxone (2 g qd)
52
dosing for albumin for SBP
1.5 g/kg day 1 and then 1 g/kg on day 3
53
when do you consider using albumin for acute SBP tx? (3 things)
1) . SCr >1 mg/dL
2) . BUN >30 mg/dL
3) . total bili >4 mg/dL
54
what are ABX used for SBP prevention?
fluoroquniolones- cipro or norfloxacin
| OR bactrim
55
when does a pt get prophylactic ABX for SBP?
if pt survives the first episode of SBP then get ABX to prevent another episode
56
what do we use to tx patients with alcoholic liver disease? what is specific drug and dosing?
corticosteroids- only thing we can give them; 4 week course of prednisone 40 mg, followed by 2 week taper
57
Hep A virus is what type of virus? this does not result in _________ infection
RNA virus; chronic
58
how is Hep A transmitted? (2 ways)
person to person through fecal-oral or consumption of contaminated food/water
59
Hep A resolves within ___ months of infection because...
2; death of hepatocytes results in elimination of the virus
60
what are the preexposure prophylaxis measures for Hep A?
vaccination- Havrix/Vaqta
| Twinrix (Hep A and B combo)
61
what is postexposure prophylaxis for Hep A? (2)
Hep A immune globulin or HAV vaccine
62
what type of virus is Hep B? what two types of disease can it be?
DNA; acute and chronic
63
chronic infection of Hep B increases risk of what?
hepatocellular carcinoma
64
prevention strategies for Hep B
vaccination:
3 dose schedule (0, 1 & 6 months) of recombivax and Engerix-B
OR HEPLISAV-B for adults only (2 dose series, 2nd dose 1 month later)
65
are alfa interferons good for tx of chronic Hep B virus?
nope, tx lasts for 48 weeks and lots of ADRs so not preferred
66
when are alfa-interferons considered the preferred option for Hep B?
for initial tx of chronic HBV infection in tx naïve adults (never been tx for hep B before)
67
what are the five NRTI drugs for chronic Hep B tx?
```
lamivudine (epivir)
entecavir (baraclude)
telbivudine (tyzeka)
adefovir (hepsera)
tenofovir alafenamide (vemlidy)
```
68
are ABX for hepatic encephalopathy always added to lactulose?
not always, in later stages of disease you might add ABX BUT these ABX are very expensive and isn't the current guidelines
69
what are the two 1st choice options for chronic Hep B tx in tx-naïve adults?
entecavir (baraclude) and tenofovir alafenamide (vemlidy)
70
how long should tx for chronic Hep B be for?
12 months after pts have seroconversion to HBV- negative (some people might need to take indefinitely)
71
which chronic Hep B drug is used less often due to increased resistance within 1st year of use?
lamivudine (epivir-HBV)
72
which chronic Hep B drug should only be initiated if other antivirals are contraindicated or not available?
telbivudine (tyzeka)
73
which chronic Hep B drug should not be used in combination with interferon alpha because of neurologic side effects?
telbivudine (tyzeka)
74
which chronic Hep B drug inhibits DNA polymerase/reverse transcriptase and is effective against lamivudine resistant HBV?
adefovir (hepsera)
75
what is goal of therapy for chronic Hep C?
eradicate virus plus prevent progression of fibrosis and development of cirrhosis
76
what is considered a cure for chronic Hep C?
undetectable HCV RNA for 12 weeks after completing therapy
77
what is the most prevalent HCV genotype?
Type 1- 75% (type 2&3: 20-25%, Type 4,5,6 <2%)
78
what are the three direct acting antivirals used for Hep C tx?
NS3/4A (protease) inhibitors, NS5A inhibitors, and NS5B inhibitors
79
what are the protease inhibitor drugs?
```
"pr" in middle of names*
simeprevir
paritaprevir
grazeoprevir
glecaprevir
voxilaprevir
```
80
what are the NS5A inhibitor drugs?
have "asvir" ending
| ledipasvir, daclatasvir, obitasvir, elbasvir, velpatasvir, pibrentasvir
81
what are the NS5B inhibitor drugs?
have "buvir" ending
| sofosbuvir, dasabuvir
82
how do protease inhibitors and NS5A inhibitors target Hep C virus?
prevent viral replication
83
how do NS5B inhibitors target Hep C virus?
act as a chain terminator so virus cant finish replication cycle
84
when is peginterferon alfa-2b used for chronic Hep C tx?
used in combo with ribavirin with compensated liver disease and/or HIV infection (not used much anymore though)
85
when is ribavirin used for chronic Hep C tx?
combo therapy in interferon alfa with compensated liver disease and /or HIV infection (not used much anymore)
86
what is the boxed warning for ribavirin?
hemolytic anemia
87
can ribavirin be used in pregnancy?
no, its a teratogen; there are two forms of barrier tx during pregnancy and 6 months after (used for men and women)
88
what are the four preferred drugs for tx of HCV?
Epclusa, Harvoni, Zepatier, Mavyret
89
what are the two indications for use of Epclusa?
tx of chronic HCV genotypes 1-6 in adults:
1) . without cirrhosis or with compensated cirrhosis (stage A of cirrhosis)
2) . decompensated cirrhosis (stage B and C) combined with ribavirin
90
how long do you use epclusa for tx? what is dose?
12 weeks; one tab per day (with or without food)
91
main ADR of epclusa
can reactivate HBV
92
what are drug-drug interactions for epclusa?
agents that induce P-gp and CYP3A4 (dec concentration of epclusa)
93
what are two indications of use for Harvoni?
tx of chronic HCV genotypes 1,4,5,6 (tx naive/experience with or without cirrhosis OR tx w cirrhosis) OR tx of chronic HCV in pts coinfected with HIV
94
what is the main drug drug interaction with Harvoni?
amiodarone (levels are increased by Harvoni)
95
what are the two indications of use for zepatier?
tx of chronic HCV genotypes 1 or 4 in adults or tx of patients with HIV coinfection
96
severe potential ADR of zepatier
increase in ALT >5x normal in 1% of subjects
97
2 indications of use for Mavyret
tx-naïve pts with HCV genotypes 1-6 without cirrhosis and compensated cirrhosis OR HCV genotype 1 previously treated
98
can you get an acute or chronic liver injury from drugs?
both
99
what is the most common cause of acute liver failure in the US?
drug induced liver injury
100
what is intrinsic hepatotoxicity associated with?
ingestion of toxic dose (acetaminophen, tetracycline, anabolic steroids)
101
intrinsic hepatotoxicity is _________ and dose ___________
predictable and dose dependent
102
what is the most common type of drug induced liver injury?
idiosyncratic hepatotoxicity
103
idiosyncratic hepatotoxicity is ___________ and has a ________ ________ before sensitivity reaction
unpredictable; latent period (1-3 months usually, can be up to a year)
104
what are the two types of idiosyncratic hepatotoxicity?
non immune mediated and immune mediated
105
how does non immune mediated IH cause injury?
drug metabolites interfere with protein/enzyme activity, which disrupts cell function & leads to cell death
106
how long does it take for toxicity to develop in non immune mediated IH?
weeks or months OR develop several weeks after discontinuing
107
ex of drugs that cause non immune mediated IH
amiodarone, diclofenac, isoniazid, ketoconazole, valproate
108
how does immune mediated IH cause injury?
involves drug, its metabolite and immune system leading to hepatocyte necrosis or apoptosis (cytokines are also released)
109
how long for onset of symptoms for immune mediated IH?
delayed: 1-8 weeks
110
what is the severe condition that can be caused by immune mediated IH?
Stevens-Johnson's syndrome
111
what is symptom recurrence for immune mediated and non immune mediated IH rechallenge
immune mediated- recurrence is quick
| non immune mediated- injury may or may not occur again
112
what are 5 common causative agents of acute hepatocellular injury?
acetaminophen, valproic acid, nefazodone, venlafazine, lovastatin
113
how do drugs cause acute hepatocellular injury?
liver cells are injured by the drug releasing enzymes found primarily in the liver cells in the blood (elevation of enzymes in serum indicates injury)
114
how do drugs cause acute cholestasis injury?
drug interferes with bile metabolism inside the cell, increased bile levels in the cells leads to cell injury
115
how soon after discontinuing the offending agent does acute cholestasis resolve symptoms?
within a few weeks have full resolution
116
what are five common causative agents of acute cholestasis injury?
amoxicillin/clavulanic acid, erythromycin, carbamazepine, chlorpromazine, anabolic steroids
117
what is mixed pattern acute hepatic injury? what are AST/ALT and alkaline phosphatase labs?
combo of hepatocellular and cholestasis; ast/alt >8x and alka phos >3x
118
what are some common causative agents of mixed pattern acute hepatic injury?
```
NSAIDs
Macrolides (azithromycin)
Nitrofurantoin
Sulfonamides (Bactrim)
Amoxacillin/clavulanic acid
Cyclosporine
Carbamazepine
```
119
what are the two steps of dechallenge to determine DILI?
1) . remove current drug from regimen
| 2) . if 50% decrease in AST/ALT in 8 days, you found the offending agent
120
what do you do for acetaminophen toxicity?
administer n-acetylcysteine (which increase glutathione and clears Tylenol from system)
