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GEMS > GI Pharm IV: HBV & HCV > Flashcards

GI Pharm IV: HBV & HCV Flashcards

1
Q

Interferon alfa 2A

MOA

Uses

A

Immune modulator & inhibitor of viral processes

Type 1 interferons lead to the activation of Jak/Stat pathway –> transcribes specific mRNAs to help cells respond to viruses

Uses: HBV & HVC

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2
Q

Interferon alfa 2A

ADME/Use

A

Use: younger pts
-Well compensated cirrhosis
-Pts who don’t want long-term tx

-IV for acute Hep B
-SubQ weekly for chronic Hep B
-Pegylated –> longer half-life (1x/wk)

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3
Q

Interferon alfa 2A

Adverse Effects

A

BB: May cause or aggravate fatal or life-threatening neuropsych, autoimmune, ischemic, and infectious disorders (worse in elderly)

Flu-like symptoms (fatigue)

long term use can cause neurotoxicity, myelosuppression, fatigue

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4
Q

Interferon alfa 2A

Contraindications/Monitor

A

DONT USE in PREGNANACY

Monitor:
CBC
TSH
Serum HCV RNA levels

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5
Q

Entecavir

MOA

A

Guanine nucleoside analog – inhibits HBV DNA Polymerase

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6
Q

Entecavir

Adverse Effects

A

HA, fatigue, dizziness, nausea.

Black Box- lactic acidosis and severe hepatomegaly with steatosis, and exacerbations of HBV when discontinued

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7
Q

Entecavir

Contraindications
Monitor

A

Don’t use if Lamivudine resistance

*Lactic acidosis by most nucleotide analogs occurs by inhibiting mitochondrial polymerase γ inside the liver and muscle cells

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8
Q

Tenofovir

1st line in HBV infection

MOA

A

Adenosine nucleotide analog (NRTI)

Interferes with the viral RNA dependent DNA polymerase resulting in inhibition of viral replication

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9
Q

Tenofovir

ADME/Use

A

Can also treat HIV

Two formulations, disoproxil fumarate and alafenamide

Alafenamide has fewer adverse effects on renal function and bone density

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10
Q

Tenofovir

Adverse Effects

A

GI effects (formulated with lactose so lactose intolerance increases these effects)

Renal tubulopathy → calcium and phosphate loss → monitor bone density in long-term use

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11
Q

Tenofovir

Contraindications
Monitor

A

Active against strains of HBV that are resistant to entecavir or lamivudine

Monitor: Serum phosphorus & creatinine, urine glucose & protein, LFTs, Bone density

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12
Q

Lamivudine

MOA

A

HBV –incorporated into the viral DNA by hepatitis B virus polymerase, resulting in DNA chain termination (cytidine analog)

NRTI in HIV therapy

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13
Q

Lamivudine

ADME/USE

A

Can also treat HIV

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14
Q

Lamivudine

Adverse Effects

A
  • Headache, dizziness, insomnia
  • GI effects
  • Respiratory effects (cough, sore throat, nasal effects)

Black Box Warnings
- Lactic acidosis and severe hepatomegaly
- Exacerbations of hepatitis B on discontinuation

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15
Q

Ribavirin

MOA

A

Guanosine analog

Interferes with viral mRNA capping, inhibits synthesis of guanosine, inhibits viral RNA-dependent polymerase

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16
Q

Ribavirin

ADME/USE

A
  • Needs phosphorylation to become active (triphosphate form)
  • Oral v inhalation (RSV)
17
Q

Ribavirin

Adverse Effects

A

Black Box Warning
-Don’t use as monotherapy (used in combination with interferon)
- Hemolytic Anemia (oral)
- HIGHLY teratogenic

o Central nervous system: Fatigue, headache, insomnia
o Gastrointestinal: Nausea, anorexia
o Hematologic: Anemia

For inhalation form, healthcare works experience- (Respiratory syncytial virus [RSV]) Headache (51%); conjunctivitis (32%); rhinitis, nausea, rash, dizziness, pharyngitis, and lacrimation (10% to 20%).

18
Q

Ribavirin

Contraindications

A

Also treats RSV

VERY TERATOGENIC – DO NOT USE IN PREGNANCY. If using in women of childbearing age, must use TWO forms of birth control during + 6 months after termination of drug

19
Q

Sofosbuvir

MOA

A

NS5B Inhibitor - (buvir)

Nucleotide analog (uracil) that inhibits the RNA-dependent RNA polymerase found in genotypes 1-6 (NS5B)

Pangenotypic

20
Q

Sofosbuvir

Adverse Effects

A

CNS – Fever, HA, insomnia, chills, irritability
Dermatitis – Pruritus, skin rash
Hem/Onc – Decreased Hgb, anemia, neutropenia, decreased neutrophils
Neuromuscular: Weakness, myalgia
Respiratory: Flu-like sxs

Amiodarone: symptomatic bradycardia drug i/a

21
Q

Sofosbuvir

Contraindications
Monitor

A

NS = nonstructural protein

22
Q

Velpatasvir

MOA

A

Inhibits NS5A, likely viral transcription factor that might be involved in the induction of the viral RNA-dependent RNA polymerase

23
Q

Velpatasvir

ADME
Uses

A

-Oral
-Half-life 15 hr
-Fixed dose with sofosbuvir for once per day dosing

Approved to be used in combination with sofosbuvir & effective w/o interferon/ribavirin

24
Q

Velpatasvir

Adverse Effects

A

w/ sofobuvir- package alert HBV reactivation-check all patients for current or prior HBV infection

Diabetes – Caution for improvement of glucose metabolism, leading to hypoglycemia in pts taking antidiabetic agents

25
Q

Glecaprevir

MOA

A

Potent pan genotypic inhibitor of HCV NS3/4A protease, necessary for the proteolytic cleavage of HCV-encoded polyprotein (into mature forms of the NS3, NS4A, NS4B, and NS5B proteins)

Essential for viral replication. Typically found in combo with pibrentasvir

26
Q

Glecaprevir

ADME
Adverse Effects

A

Half-life 6 hr

AE: Fatigue, HA, nausea are most common
BB: HBV reactivation on discontinuation

27
Q

Glecaprevir

Monitoring

A

LFTs
Sx of liver dysfunction (N/V, weakness, jaundice, elevated bilirubin, alkaline phosphase, INR)

Diabetic pt: monitor bloo glucose
Sx of hypoglycemia

Pt on warfarin: INR during/post therapy

28
Q

Interferons

A

Upregulate MHC to make cells more obvious/more apparent to immune system to get destroyed

29
Q

HVC Tx Options

A

Interferon & Ribavirin

Dual:
NS5A inh + NS5B inh
HS5A inh + Protease inh

Triple/Quad:
NS5A inh + NS5B inh + protease inh +/- CYP3A4 inh (Ritonavir)

30
Q

Extraction Ratio

A

ER = (Cb - Ca)/ Cb

b=before liver
a=after liver

Range: 0-1

31
Q

Low Numbers ER

A

-Very little drug extraction –> low first pass effect

-Liver perfusion rate is not that important

Not metabolized by phase 1 or 2 enzymes

Needs induction of metabolizing enzyme –> less predictable extraction

High serum protein binding –> low free drug conc.

32
Q

Examples of Low ER Drugs

A

Phenytoin
Diazepam
Digitoxin, Chlorpropamide
Theophylline
Tolbutamide
Warfarin

33
Q

High ER numbers

A

Extensive drug extraction –> high first pass

Clearance is significantly affected by changes in blood flow to liver

34
Q

Examples of HIGH ER drugs

A

Morphine
Nitroglycerin Desipramine Imipramine Meperidine Propranolol Amitriptyline
Izonizid

35
Q

Hepatic clearance

A

HC = Q x ER

Vol of blood x Extraction Ratio = hepatic clearance

GEMS (20 decks)

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