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Gastrointestinal System > Pharmacotherapy of Hepatitis & Cirrhosis > Flashcards

Pharmacotherapy of Hepatitis & Cirrhosis Flashcards

(108 cards)

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1
Q

What can cause acute hepatitis?

A

Infectious and non-infectious causes

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2
Q

What are the infectious causes that could lead to acute hepatitis?

A

Infections: virus and bacterial

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3
Q

What are the non-infectious causes that could lead to acute hepatitis?

A

Toxic: Alcohol, toxins, drugs
Immune
Acute Biliary Disease

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4
Q

What could lead to chronic hepatitis?

A

Sustained and repetitive injury

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5
Q

What are possible causes that could lead to chronic hepatitis? (7)

A

Autoimmune
Hereditary (Wilson or Hemochromatosis)
HBV or HCV
Non-alcoholic steatohepatitis
Primary biliary cholangitis
Primary sclerosing cholangitis
Persistance alcohol liver disease

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6
Q

What could be the complications of chronic hepatitis?

A

Fibrosis, Cirrhosis, Hepatocarcinoma, Liver Failure

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7
Q

What is hepatitis?

A

Inflammation of the liver

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8
Q

How does hepatitis evolve?

A

Liver damage will lead to liver inflammation –> acute hepatitis

Sustained aggression of the liver and inflammation will lead to fibrosis

If the cause of liver damage is not removed, fibrosis will develop –> cirrhosis –> hepatocarcinoma and then liver failure

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9
Q

What are the different targets for the management of liver disease?

A

Eliminate the source
Inflammation
Fibrosis
Survival

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10
Q

Is Hepatitis B acute or chronic?

A

Acute then chronic

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10
Q

Is Hepatitis A acute or chronic?

A

Acute

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11
Q

Is Hepatitis C acute or chronic?

A

Acute then chronic

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12
Q

Which hepatitis classes is there a vaccine for?

A

Hep A and Hep B

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13
Q

What is the treatment for Hep. A?

A

Care

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14
Q

What is the treatment for Hep. B?

A

Tefonovir, Entecavr, Lamivudine, Interferon alpha

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15
Q

What is the treatment for Hep. C?

A

DAA & other Interferon alpha, Ribavirin

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16
Q

What % of Hep. B virus patients will be cleared from the virus?

A

95% and the 5% will be treated

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17
Q

What is the approach of treatment of chronic HBV?

A

Viral suppression

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18
Q

What is the goal of the treatment of HBV?

A

To prevent progression to sustained liver inflammation

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19
Q

What factors does the choice of agents or regiment depend on for the treatment of HBV?

A

Mutations, because of the fact that HBV replicated at a high rate

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20
Q

What are the clinical consequences of the emergence resistance?

A

Resistance leads to therapeutic failure and rapid resurgence of viral replication

Predispose patients to hepatic decompensation

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21
Q

What are the treatment options for HBV?

A

Lamivudine
Entecavir
Tenofovir
IFNa
PEG-INFa

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22
Q

What is a nucleotide analogue for HBV?

A

Lamivudine –> first class amongst nucleosides

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23
Q

What is Lamivudine?

A

An analogue of cytosine

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24
What is the MOA of Lamivudine?
Ceases viral DNA replication Nucleoside Reverse Transcriptase Inhibitor
25
What are the PK of Lamivudine?
Excellent bioavailability Excreted primary in the urine
26
Which virus is Lamivudine useful for?
HBV Infections
27
What are the side effects of Lamivudine?
Cough Peripheral neuropathy Diarrhea
28
What is the main limitation of Lamivudine?
Resistance
29
What are nucleoside analogues for HBV?
Entecavir Tenofovir
30
What is Entecavir?
Analogue of guanosine
31
What is the function of Entecavir?
Inhibitor of HBV reverse transcriptase Delayed chain termination
32
In which kind of patients is Entecavir used?
Treatment in naive patients
33
What is the MOA of Entecavir?
Incorporation into DNA and leading to termination Ceases viral DNA replication
34
What are the PK of Entecavir?
Rapidly absorbed Half-life of 24 hours Low resistance High-antiviral efficiency
35
What is the first line medication for HBV?
Entecavir
36
What are the side effects of Entecavir?
Nausea, Somnolence (strong desire for sleep), Headache
37
What is Tenofovir?
Analogue of adenosine monophosphate
38
Tenofovir is exactly the same as which other drug, regarding MOA, function, PK and side effects?
Entecavir
39
Which virus is Ribavirin used for?
HCV
40
What is Ribavirin?
Analogue of guanosine
41
What is the MOA of Ribavirin?
Unknown mechanism: Inhibits viral RNA polymerase and inhibits purine synthesis
42
What is the range of anti-viral effects of Ribavirin?
Wide range of anti-viral effects (DNA / RNA)
43
What is the half-life of Ribavirin?
12 days, stored in the RBCs
44
How is Ribavarin administered?
Aerosol Oral IV
45
What was Ribavarin administered with?
INF - a
46
What are the adverse effects of Ribavarin?
Anemia Fatigue, cough, rash, pruritus (itching), renal impairment
47
When is anemia a side effect of Ribavarin?
If Ribavarin is given through IV
48
What is the contraindication of Ribavarin?
Conception & Pregnancy
49
Why is Ribavarin contraindicated in pregnancy?
It is teratogenic, embryo-toxic, and possibly gonadotoxic (high concentration in the sperm)
50
When was Ribavarin and INF-a the treatment for HCV?
From 1998 till the discovery of new treatments
51
What are the SVR rates for HCV with Ribavarin and INF-a?
40 to 50% in patients with genotype 1 infection
52
What is the aim of the treatment of HCV?
1. Improve the long-term prognosis of chronic liver disease associated with persistent HCV infection 2. Prevent mortality associated with hepatocellular carcinoma and chronic liver disease
53
What is SVR for HCV?
A sustained virology response is an undetectable HCV RNA level using a sensitivity array at least 12 weeks after completing HCV therapy
54
When did the SVR rates of HCV improve?
They improved with the standard therapy combing Peg-IFN and Ribavarin
55
What are the two preparation of Interferon alpha?
IFN-alpha 2b Peg- IFN - alpha 2b
56
Which formulation of INF-alpha is preferred?
The Peg one
57
What is the MOA of INF-alpha?
Viral suppression and immune modulatory activity for both HBV and HCV
58
What are the PK of INF-alpha?
Poor safety record
59
What is the absorption peak for INF-alpha 2b?
4.4 hours, clearance of INF-alpha 2b is lower than INF-alpha
60
What are the side effects of INF-alpha?
Flu-like symptoms, Rash, High levels of transaminases, Headache
61
What are the 3 proteins that are involved in crucial steps of the HCV cycle?
NS3/4A protease NS5A protein RNA-dependent RNA polymerase NS5B protein
62
What are DAAs?
Combination of 2 to 3 inhibitors of the proteins involved in the HCV cycle
63
What are DAAs usually given with?
Ribavarin
64
Who should be treated with DAA?
Everyone
65
What is the suffix of the protease inhibitor drugs?
Previr
66
What is the suffix of the replication complex inhibitor drugs?
Asvir
67
What is the suffix of the polymerase inhibitor drugs?
Buvir
68
How many HCV genotypes are there?
6 genotypes, 1 to 6
69
What is the combination for each genotype and subtype?
Combination of 2 DAA, from 2 different classes of inhibitors Combination with Ribavarin or not Addition of Ritonavir
70
What is the purpose of Ritonavir in the combination of drugs?
Inactivates CYP3A, to boost the level of the other drugs
71
What is one thing to do prior to prescribing DAAs?
Check the status of the patients for other infections, like HIV, HBV and HCV
72
What is the purpose of checking patients for any other infections prior to giving them DAAs?
Prevention of resistance to other viruses and good choice of combination therapy
73
What are the drug interactions of DAAs?
If given with PPIs, H2 blockers and antacids --> failure to reach SVR
74
What happens if Sofosbuvir is administered with amiodarone (treatment for arrhythmia)?
Leads to bradycardia
75
What is the effect of metabolism by CYP3A4 on other drugs?
It might decrease the dose, especially with drugs like Atorvastatin so need to change the statin
76
What are the adverse effects of DAAs?
Well tolerated for the most part, fatigue, headache, pruritus and anemia
77
What is Primary Biliary Cholangitis (PBC)?
Inflammation of the intrahepatic bile ducts which may lead to fibrosis and cirrhosis
78
What is the gender prevalence of PBC?
Female > male
79
What are the features of PBC?
Often asymptomatic, pruritus, fatigue, abdominal pain, jaundice after years
80
What are the LFTs for PBC like?
Cholestatic picture with raised ALP and GGT
81
What is the main complication of PBC?
Cirrhosis
82
What is the treatment for PBC?
Cholestyramine for pruritus Ursodeoxycholic acid for improvement of survival and delay transplant Liver transplantation
83
What is primary sclerosing cholangitis (PCS)?
Inflammation of both intra and extra hepatic bile ducts
84
What is the gender prevalence of PCS?
Male > female
85
What are the main features of PCS?
Pruritus, fatigue and cholangitis
86
What are the LFTs of PCS like?
Cholestatic picture with rasied ALP and GGT
87
What is the main complication of PCS?
Risk of cholangio and colorectal carcinoma and cirrhosis
88
What is the treatment for PCS?
Cholestyramine for pruritus Ursodeoxycholic acid may improve LFTs but will not improve survival Liver transplantation
89
What is biliary liver disease?
Primary biliary cirrhosis (autoimmune disease) and primary sclerosing cholangitis (inflammation, scarring and narrowing of bile ducts)
90
What could cause biliary liver disease?
Biliary duct or biliary inflammation: acute, antibiotics, surgery
91
What drugs are given for biliary liver disease?
ATB, bile acids, antibiotics and anti-pain
92
What is the MOA of Obeticholic acid (OCA)?
Bile acids bind to farnesoid X receptor on the intestine OCA is highly potent FXR agonist -- > anti-inflammatory
93
What is the main treatment for chronic biliary liver disease?
Ursodeoxycholic acid (UDCA) is the main treatment for PBC, decreases inflammation and delay damage
94
When is OCA used in chronic PBC?
When there is no improvement with UDCA
95
What are the side effects of UDCA?
Skin rash, itching, dryness, redness, dizziness, feeling tired
96
What are the side effects of OCA?
Decrease HDL and cardiac PB,
97
Which patient is OCA not given to?
Patients with advanced cirrhosis
98
What is the management / treatment methods for NAFLD - NASH?
Need to lose about 10% of body weight Lowering cholesterol and triglycerides Controlling diabetes Avoid alcohol Antioxidants like Vitamin E
99
What is the whole aim of the treatment options for NAFLD - NASH?
To lower inflammation and lipogenesis
100
When is the beta-agonist Resmetiron (Rezdiffra) given?
When patients have moderate to advance scarring of the liver
101
What is the main objective before initiating treatment for cirrhosis?
Know the cause of it
102
What are the treatment/management methods of Cirrhosis? (9)
Avoid alcohol Clear the virus Quit smoking Lose weight if necessary Do regular exercise to reduce muscle loss Practice good hygiene Annual flu and ravel vaccines Avoid decompensation Control for hepatocellular carcinoma
103
Which drugs make up Harvoni?
Ledipasvir& Sofosbuvir
104
Which drugs make up Epclusa?
Velpatasvir & Sofosbuvir
105
Which drugs make up Zepatier?
Elbasvr & Grazoprevir
106
Which drugs make up Vosevi?
Sofosbuvir / Velpatasvr/ Voxilepravir
107
Which drugs make up Mavyret?
Glecaprevir / Pibrenstavir

Gastrointestinal System (29 decks)

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