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Gastrointestinal System > Pharmacotherapy of Hepatitis & Cirrhosis > Flashcards

Pharmacotherapy of Hepatitis & Cirrhosis Flashcards

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
Q

What is the MOA of Lamivudine?

A

Ceases viral DNA replication
Nucleoside Reverse Transcriptase Inhibitor

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25
Q

What are the PK of Lamivudine?

A

Excellent bioavailability
Excreted primary in the urine

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26
Q

Which virus is Lamivudine useful for?

A

HBV Infections

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27
Q

What are the side effects of Lamivudine?

A

Cough
Peripheral neuropathy
Diarrhea

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28
Q

What is the main limitation of Lamivudine?

A

Resistance

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29
Q

What are nucleoside analogues for HBV?

A

Entecavir
Tenofovir

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30
Q

What is Entecavir?

A

Analogue of guanosine

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31
Q

What is the function of Entecavir?

A

Inhibitor of HBV reverse transcriptase
Delayed chain termination

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32
Q

In which kind of patients is Entecavir used?

A

Treatment in naive patients

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33
Q

What is the MOA of Entecavir?

A

Incorporation into DNA and leading to termination
Ceases viral DNA replication

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34
Q

What are the PK of Entecavir?

A

Rapidly absorbed
Half-life of 24 hours
Low resistance
High-antiviral efficiency

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35
Q

What is the first line medication for HBV?

A

Entecavir

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36
Q

What are the side effects of Entecavir?

A

Nausea,
Somnolence (strong desire for sleep),
Headache

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37
Q

What is Tenofovir?

A

Analogue of adenosine monophosphate

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38
Q

Tenofovir is exactly the same as which other drug, regarding MOA, function, PK and side effects?

A

Entecavir

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39
Q

Which virus is Ribavirin used for?

A

HCV

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40
Q

What is Ribavirin?

A

Analogue of guanosine

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41
Q

What is the MOA of Ribavirin?

A

Unknown mechanism:
Inhibits viral RNA polymerase and inhibits purine synthesis

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42
Q

What is the range of anti-viral effects of Ribavirin?

A

Wide range of anti-viral effects (DNA / RNA)

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43
Q

What is the half-life of Ribavirin?

A

12 days, stored in the RBCs

44
Q

How is Ribavarin administered?

A

Aerosol
Oral
IV

45
Q

What was Ribavarin administered with?

A

INF - a

46
Q

What are the adverse effects of Ribavarin?

A

Anemia
Fatigue, cough, rash, pruritus (itching), renal impairment

47
Q

When is anemia a side effect of Ribavarin?

A

If Ribavarin is given through IV

48
Q

What is the contraindication of Ribavarin?

A

Conception & Pregnancy

49
Q

Why is Ribavarin contraindicated in pregnancy?

A

It is teratogenic, embryo-toxic, and possibly gonadotoxic (high concentration in the sperm)

50
Q

When was Ribavarin and INF-a the treatment for HCV?

A

From 1998 till the discovery of new treatments

51
Q

What are the SVR rates for HCV with Ribavarin and INF-a?

A

40 to 50% in patients with genotype 1 infection

52
Q

What is the aim of the treatment of HCV?

A
  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
Q

What is SVR for HCV?

A

A sustained virology response is an undetectable HCV RNA level using a sensitivity array at least 12 weeks after completing HCV therapy

54
Q

When did the SVR rates of HCV improve?

A

They improved with the standard therapy combing Peg-IFN and Ribavarin

55
Q

What are the two preparation of Interferon alpha?

A

IFN-alpha 2b
Peg- IFN - alpha 2b

56
Q

Which formulation of INF-alpha is preferred?

A

The Peg one

57
Q

What is the MOA of INF-alpha?

A

Viral suppression and immune modulatory activity for both HBV and HCV

58
Q

What are the PK of INF-alpha?

A

Poor safety record

59
Q

What is the absorption peak for INF-alpha 2b?

A

4.4 hours, clearance of INF-alpha 2b is lower than INF-alpha

60
Q

What are the side effects of INF-alpha?

A

Flu-like symptoms,
Rash,
High levels of transaminases,
Headache

61
Q

What are the 3 proteins that are involved in crucial steps of the HCV cycle?

A

NS3/4A protease
NS5A protein
RNA-dependent RNA polymerase NS5B protein

62
Q

What are DAAs?

A

Combination of 2 to 3 inhibitors of the proteins involved in the HCV cycle

63
Q

What are DAAs usually given with?

A

Ribavarin

64
Q

Who should be treated with DAA?

A

Everyone

65
Q

What is the suffix of the protease inhibitor drugs?

A

Previr

66
Q

What is the suffix of the replication complex inhibitor drugs?

A

Asvir

67
Q

What is the suffix of the polymerase inhibitor drugs?

A

Buvir

68
Q

How many HCV genotypes are there?

A

6 genotypes, 1 to 6

69
Q

What is the combination for each genotype and subtype?

A

Combination of 2 DAA, from 2 different classes of inhibitors

Combination with Ribavarin or not

Addition of Ritonavir

70
Q

What is the purpose of Ritonavir in the combination of drugs?

A

Inactivates CYP3A, to boost the level of the other drugs

71
Q

What is one thing to do prior to prescribing DAAs?

A

Check the status of the patients for other infections, like HIV, HBV and HCV

72
Q

What is the purpose of checking patients for any other infections prior to giving them DAAs?

A

Prevention of resistance to other viruses and good choice of combination therapy

73
Q

What are the drug interactions of DAAs?

A

If given with PPIs, H2 blockers and antacids –> failure to reach SVR

74
Q

What happens if Sofosbuvir is administered with amiodarone (treatment for arrhythmia)?

A

Leads to bradycardia

75
Q

What is the effect of metabolism by CYP3A4 on other drugs?

A

It might decrease the dose, especially with drugs like Atorvastatin so need to change the statin

76
Q

What are the adverse effects of DAAs?

A

Well tolerated for the most part, fatigue, headache, pruritus and anemia

77
Q

What is Primary Biliary Cholangitis (PBC)?

A

Inflammation of the intrahepatic bile ducts which may lead to fibrosis and cirrhosis

78
Q

What is the gender prevalence of PBC?

A

Female > male

79
Q

What are the features of PBC?

A

Often asymptomatic, pruritus, fatigue, abdominal pain, jaundice after years

80
Q

What are the LFTs for PBC like?

A

Cholestatic picture with raised ALP and GGT

81
Q

What is the main complication of PBC?

A

Cirrhosis

82
Q

What is the treatment for PBC?

A

Cholestyramine for pruritus
Ursodeoxycholic acid for improvement of survival and delay transplant
Liver transplantation

83
Q

What is primary sclerosing cholangitis (PCS)?

A

Inflammation of both intra and extra hepatic bile ducts

84
Q

What is the gender prevalence of PCS?

A

Male > female

85
Q

What are the main features of PCS?

A

Pruritus, fatigue and cholangitis

86
Q

What are the LFTs of PCS like?

A

Cholestatic picture with rasied ALP and GGT

87
Q

What is the main complication of PCS?

A

Risk of cholangio and colorectal carcinoma and cirrhosis

88
Q

What is the treatment for PCS?

A

Cholestyramine for pruritus
Ursodeoxycholic acid may improve LFTs but will not improve survival
Liver transplantation

89
Q

What is biliary liver disease?

A

Primary biliary cirrhosis (autoimmune disease) and primary sclerosing cholangitis (inflammation, scarring and narrowing of bile ducts)

90
Q

What could cause biliary liver disease?

A

Biliary duct or biliary inflammation: acute, antibiotics, surgery

91
Q

What drugs are given for biliary liver disease?

A

ATB, bile acids, antibiotics and anti-pain

92
Q

What is the MOA of Obeticholic acid (OCA)?

A

Bile acids bind to farnesoid X receptor on the intestine
OCA is highly potent FXR agonist – > anti-inflammatory

93
Q

What is the main treatment for chronic biliary liver disease?

A

Ursodeoxycholic acid (UDCA) is the main treatment for PBC, decreases inflammation and delay damage

94
Q

When is OCA used in chronic PBC?

A

When there is no improvement with UDCA

95
Q

What are the side effects of UDCA?

A

Skin rash, itching, dryness, redness, dizziness, feeling tired

96
Q

What are the side effects of OCA?

A

Decrease HDL and cardiac PB,

97
Q

Which patient is OCA not given to?

A

Patients with advanced cirrhosis

98
Q

What is the management / treatment methods for NAFLD - NASH?

A

Need to lose about 10% of body weight
Lowering cholesterol and triglycerides
Controlling diabetes
Avoid alcohol
Antioxidants like Vitamin E

99
Q

What is the whole aim of the treatment options for NAFLD - NASH?

A

To lower inflammation and lipogenesis

100
Q

When is the beta-agonist Resmetiron (Rezdiffra) given?

A

When patients have moderate to advance scarring of the liver

101
Q

What is the main objective before initiating treatment for cirrhosis?

A

Know the cause of it

102
Q

What are the treatment/management methods of Cirrhosis? (9)

A

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
Q

Which drugs make up Harvoni?

A

Ledipasvir& Sofosbuvir

104
Q

Which drugs make up Epclusa?

A

Velpatasvir & Sofosbuvir

105
Q

Which drugs make up Zepatier?

A

Elbasvr & Grazoprevir

106
Q

Which drugs make up Vosevi?

A

Sofosbuvir / Velpatasvr/ Voxilepravir

107
Q

Which drugs make up Mavyret?

A

Glecaprevir / Pibrenstavir

Gastrointestinal System (28 decks)

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