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Clinical Pharmacology II > Antivirals > Flashcards

Antivirals Flashcards

1
Q

What is the treatment for Hep C genotype 3 with cirrhosis

A

Mavyret for 12 weeks

Vosevi for 12 weeks

If Y93H is present, add ribavirin Or consider velpatasvir/Sofosbuvir/Voxilaprevir

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2
Q

What is HHV-5 and what does it cause?

A

Cytomegalovirus (CMV)

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3
Q

What are the two CD4 coreceptors of HIV?

A

CXCR4 (X4)

CCR5 (R5)

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4
Q

What is the backbone NRTI of all HIV therapy regimens?

A

Descovy
Truvada
Epzicom

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5
Q

What is interferon for Hep C?

A

Formulations: Intron A, Infergen, Peg-intron, pegasys

MOA: induces the innate antiviral immune response

Dosing: weekly SQ injection

ADRs: FLU-LIKE SYMPTOMS, GI, photosensitivity, hepatitis flare, leucopenia, hypothyroidism, thrombocytopenia, alopecia, arthralgia

BBW: NEUROPSYCHIATRIC, autoimmune, ischemic, and infectious disorders

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6
Q

What is Dolutegravir?

A

Was designed to have different mutation rates for resistance; you can still use it and just increase dose if patient develops resistance

MOA: same as RAL

Metabolism: UGT-1A1 (major) and 3A4 (minor)

ADRs: Hypersensitivity reaction, LFTs (especially in HBV or HCV coinfection), insomnia, hyperglycemia (>125 mg/dL), hypertriglyceridemia

DDIs: space 2 hours before or 6 hours after cations Mg, Al, Fe, Ca

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7
Q

What is Darunavir?

A

MUST co-administer with Ritonavir

Sulfonamide so be cautious in patients with sulfa allergy

ADR: GI

Lipid neutral

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8
Q

What is Havrix?

A

HAV only

Can’t give until patient is 12 months or older

2 dose series = 1st dose then 2nd dose 6-12 months later

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9
Q

Which types of drugs are ineffective against oral or genital herpes?

A

topicals because of scarring associated with blisters

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10
Q

What is Nevirapine?

A

Must be titrated to therapeutic dose:

200 mg once a day for 2 weeks and if there is no rash or significant change in LFTs, you can titrate to 200mg twice a day

Do NOT use in: females with CD4 > 250 cell/mm3
Males with CD4 > 400 cells/mm3

Metabolized by CYP3A4; induced CYP 3A4

ADRs: rash, liver toxicity

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11
Q

How do you diagnose Hep C?

A

Check HCV antibody

RT-PCR RNA viral load

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12
Q

What is the uncoating stage of viral replication?

A

Viral enzymes degrade the capsid, exposing the viral genome inside the host cell

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13
Q

What is Viekira XR?

A

Paritaprevir, Ritonavir, Ombitasvir, and Dasabuvir are all in one drug but they are very large and you must take 3 once a day

MUST BE TAKEN WITH FOOD! cannot be chewed, crushed, or split

Many DDIs

ADRs: GI, rash, LFTs

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14
Q

What is Tenofovir (TDF)?

A

ADRs: NEPHROTOXICITY, OSTEOMALACIA, Faconi Syndrome

OLDEST VERSION

Formulated in lactose so use caution with lactose intolerant patient

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15
Q

What is HCV virus?

A

ss-RNA

Disease: Chronic Hepatitis C virus, cirrhosis, hepatocellular carcinoma

Transmission: Needles (tattoos, piercings, accupuncture), sexual, blood, vertical, razors, toothbrushes

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16
Q

What is HAV virus?

A

ss-RNA

Disease: acute Hepatitis A

Transmission: Fecal-Oral, food and water, blood

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17
Q

What is the most prominent and dominant mutation for Hep C genotype 1A?

A

Y93

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18
Q

What are the two GI neutral protease inhibitors?

A

Atazanovir

Darunavir

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19
Q

What is the treatment for Hep C genotype 3 without cirrhosis?

A

Mavyret for 8 weeks

Vosevi for 12 weeks

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20
Q

What are virustatic agents?

A

antiviral agents that will slow down replication of the virus through competitive inhibition temporarily or non-competitive inhibition permanently

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21
Q

What is the Hep C treatment for Genotype 1A/B if patient doesn’t have cirrhosis?

A

Zepatier for 12 weeks without NS5A RAS

Mavyret for 8 weeks

Harvoni for 12 weeks

Harvoni for 8 weeks if HCV VL <6 million

Vosevi for 12 weeks

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22
Q

What is Famciclovir?

A

Prodrug of penciclovir and guanine analog

MOA: utilizes viral thymidine kinase for activation which inhibits viral DNA polymerase and prevents viral DNA synthesis

Different half lifes depending on herpes virus being treated

Use: VZV and HSV

Monitor renal function

Dosing: 2X a day

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23
Q

What is Epclusa?

A

NEW gold standard in HCV management

pangenotypic for GT 1-6

ADRs: Anemia, GI, headache, fatigue, no hepatic dosing, no renal dosing

MANY DDIs with CYP 450 system

Caution in patients with CrCl < 30 mL/min

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24
Q

What are viruses?

A

microscopic organism that can only replicate inside th cell of a host organism

They are completely dependent on the host

They can mutate and are subject to natural selection

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25
Q

When should you use Epzicom in HIV therapy?

A

When patient is HLA-B5701 negative AND baseline HIV VL <100,000 copies/mL

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26
Q

What is Twinrix?

A

HAV/HBV

Can’t give until patient is 18 years or older

3 dose series = 1st dose, then 2nd dose at 1 month after, then 3rd dose at 6 months after

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27
Q

Which drugs block viral uncoating?

A

Amantadine

Rimantadine

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28
Q

What is Stavudine?

A

WEIGHT DOSED

ADRs: PANCREATITIS, PERIPHERAL NEUROPATHY, lactic acidosis with hepatic steatosis, lipodystrophy

RENAL DOSING

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29
Q

What is HHV-3 and what does it cause?

A

Varicella Zoster Virus (VZV)

Chicken pox and shingles

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30
Q

Which drugs block viral release?

A

Neuraminidase inhibitors

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31
Q

Which type of influenza do we vaccinate against?

A

Influenza A

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32
Q

What two NRTIs are considered “kissing cousins” because they are interchangeable?

A

Lamivudine and Emtricitabine

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33
Q

What are the direct acting agents for Hep C?

A

NS5B Polymerase Inhibitors
NS3/4A protease inhibitors
NS5A inhibitor
Non-nucleoside NS5B Palm Polymerase Inhibitor

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34
Q

What is Vaqta (Merck)?

A

HAV Only vaccine

Can’t give until patient is 12 months or older

2 dose series = 1st dose then 2nd dose 6-18 months later

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35
Q

What is the special consideration with dosing of TamiFLU?

A

Must be given within 48 hours of onset of the flu and taken for 5 days in order to be effective at all

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36
Q

Describe Influenza C

A

Infects humans, pigs, and dogs

Causes mild disease in children

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37
Q

Which drugs block late protein synthesis and processing?

A

Protease inhibitors

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38
Q

What are the NS3/4A mutations?

A

Q80K polymorphism which decreases activity of simeprevir

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39
Q

What is the dosing for Dolutegravir?

A

Treatment Naive = 50 mg PO once daily

Treatment experienced but INSTI naive = 50 mg PO once daily
Coadministered with EFV, fAPV/r, TPV/r, or RIF = 50 mg PO every 12 hours

INSTI-experienced with certain or suspected INSTI resistance = 50 mg every 12 hours

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40
Q

When should you start a patient on HIV therapy?

A

At any CD4 count and if the patient is willing to start antiretroviral therapy (ART)

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41
Q

What is HHV-1 and what does it cause?

A

Herpes Simplex Virus 1

Oral lesions

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42
Q

What is Mavyret?

A

pangenotypic for GT 1-6

Dosing: 3 tablets once a day with food

Made by the same people that made the Viekira Pak

not many DDIs

No renal dosing

ADRs: elevated total bilirubin (must monitor), HA, fatigue, GI

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43
Q

What should you always be monitoring for while patient is on HCV therapy?

A

SVR

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44
Q

What mutations are there for Hep C genotype 3?

A

M28
Q30
L31
Y93

Cause a five fold reduction in NS5A inhibitors

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45
Q

What is the MOA of Amantidine and Rimantidine?

A

inhibits uncoating of the viral RNA within infected host cells, thus preventing its replication

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46
Q

What is the drug of choice for the flu?

A

Oseltamivir (TamiFlu)

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47
Q

What is Foscarnet?

A

inorganic pyrophosphate analog

MOA: inhibits viral specific DNA polymerases and reverse transcriptases at the pyrophosphate binding site which prevents DNA synthesis

Excretion: 72-92% renally

IV ONLY and can accumulate in blood and cartilage and is renally toxic

Use: CMV and resistant refractory CMV and chickenpox

Monitor: Chem 10, CBC, EKG changes

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48
Q

Which NNRTI’s will the K103N mutation effect?

A

First generation

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49
Q

What is Zepatier?

A

Many DDIs; no renal or hepatic dosing required

ADRs: ELEVATED LFTs, hyperbilirubinemia; anemia, HA, fatigue, GI

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50
Q

What is Emtricitabine?

A

ADRs: Hyperpigmentation of palms and bottom of feet seen in clinical trials of African Americans

Fluorinated analog of lamivudine

Active against HBV

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51
Q

What is the HPV virus?

A

ds-DNA

Disease: Genital warts, cervical cancer

Transmission: sexual, vertical, fomites

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52
Q

What is Anti-HBc the marker for?

A

Hep B antibodies to core proteins

infection

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53
Q

What is Anti-HBs the marker for?

A

Hep B antibodies to surface antigen

Indicates recover and/or immunity (after vaccine series)

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54
Q

Which integrase inhibitor has the most DDIs?

A

Elvitegravir

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55
Q

What is the resistance testing in clinical practice for Epclusa regimen for Hep C?

A

NS5A RAS testing is recommended for GT3, treatment especially naive with cirrhosis and treat 12 weeks

If Y93H is present, add wt. based ribavirin

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56
Q

What is HBsAg the marker for?

A

Hep B surface antigen

Marker of infection

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57
Q

What is Daclatasvir?

A

Used for HCV GT3 and must be coadministered with Sofosbuvir

Metabolized by CYP3A4:
if taken with 3A4 inhibitor reduce dose to 30 mg
if taken with 3A4 inhibitor increase dose to 90 mg

Pgp efflux pump substrate and inhibitor

ADRs: anemia, fatigue, GI effects, headache

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58
Q

What is Cidofovir?

A

Acyclic cytidine nucleotide analog

IV ONLY

Use: systemic or severe herpes infections, HSV meningitis, CMV meningitis or gastritis

Highly renal toxic and will accumulate in the kidneys and cause problems

HYDRATE!

Can be given with probenecid to maintain plasma concentrations

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59
Q

Which Hep C GT 1A/B and 3 drugs can be used in patients with Chronic kidney disease that are on dialysis?

A

Elbasvir 50mg/Grazoprevir 100mg for 12 weeks

Glecaprevir 300mg/Pibrentasvir 120mg for 8-16 weeks

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60
Q

What Hep C genotype is found in the US mostly?

A

Genotype 1A

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61
Q

Which Hep C drugs do not require dose adjustment for patients with chronic kidney disease that are not on dialysis?

A 
Daclatasvir
Elbasvir 50mg/Grazoprevir 100mg
Glecaprevir 300mg/Pibrentasvir 120mg
Ledipasvir 90mg/Sofosbuvir 400mg
Sofosbuvir 400mg/Velpatasvir 100mg
Simeprevir 150mg
Sofosbuvir 400mg/Velpatasvir 100mg/Voxilaprevir 100mg
Sofosbuvir 400mg
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62
Q

What should you be monitoring for prior to therapy with Hep C drugs?

A 
CBC
INR
Complete LFT panel
TSH
eGFR
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63
Q

What is the resistance testing in clinical practice for Harvoni regimen for Hep C?

A

NS5A RAS testing for GT1A may be considered for treatment especially without cirrhosis

If > 100 fold resistance present, add wt. based ribavirin and treat for 12 weeks or use a different regimen

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64
Q

How do we treat hepatitis A?

A

with a vaccine

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65
Q

Which drugs block nucleic acid synthesis?

A

NRTI’s
NNRTI’s
Acyclovir
Foscarnet

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66
Q

What is Zanamivir?

A

Administration is by oral inhalation of a dry powder; needs to be coadministered with bronchodilator

Elimination: completely unchanged in urine within 24 hours

Use: prevention and treatment of Influenza A and B

Avoid use in patients with a diary allergy because milk proteins are vehicle

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67
Q

What is HAV?

A

Incubation period: 14-28 days

Accounts for approximately 50% of acute hepatitis in the US

Due to person to person exposure

Does not cause chronic disease

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68
Q

What is Rilpirivine?

A

Active against K103N virus

Dose: 25mg orally once daily and MUST BE TAKEN WITH 900 kcals of FOOD

Metabolized by CYP 3A4; substrate

ADRs: Rash, LFTs, CNS effects

DO NOT USE in patients with baseline HIV VL > 100,000 copies/mL

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69
Q

What is peginterferon alpha-2a?

A

MOA: inhibits viral protein production

Dosing: 180 mg SQ weekly

Hepatic Dosing and some renal dosing

Monitor: LFTs, TFTs, CBCs, triglycerides, EKG, EYE EXAM

ADRs: anemias, infections, arrhythmias, increased LFTs, hypothyroidism, psych changes, renal function

Supresses immune system and patient is at risk for increased secondary infections

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70
Q

What is the MOA of protease inhibitors?

A

Inhibit the activation of immature proteins by blocking the GAG-POL region within protease to inhibit the cleavage of proteins

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71
Q

What must you check for if Abacavir is part of an HIV regimen?

A

HLA-B5701 allele

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72
Q

What are the pyrimidine analogs?

A

Trifluridine

Cidofovir

73
Q

What counseling points should you tell your patients that currently have HCV and are on therapy?

A

Do NOT drink alcohol
Vaccinate against HAV and HBV
Vaccinate against pneumococcal infection in all patients with cirrhosis
Educate on how to avoid giving it to others
Educate on how to reduce liver disease

74
Q

What are the 6 stages of viral replication?

A 
Attachment
Viral Entry
Uncoating
Replication
Assembly
Release
75
Q

How do you diagnose Hepatitis?

A

Full liver panel
Imaging - CT, MRI, and/or US
Liver biopsy

76
Q

What is Fosamprenavir?

A

Sulfonamide so be cautious with sulfa allergy patients

ADRs: GI

77
Q

What is HHV-4 and what does it cause?

A

Epstein Barr Virus (HBV)

Mononucleosis and lymphoma

78
Q

How do you diagnose Hep B?

A

Check serology for antibodies and antigens

RT-PCR DNA viral load

79
Q

What is the MOA of Non-nucleoside NS5B Palm Polymerase inhibitors?

A

Inhibits the activity of the NS5B to inhibit HCV RNA replication

80
Q

What is a SWITCH regimen?

A

Used in patient on a currently effective HIV regimen who was able to maintain viral suppression for at least 6 months and is requesting a simplification of regimen

81
Q

What is the MOA of NRTIs?

A

Completely inhibits HIV-1 reverse transcriptase

82
Q

What are virucidal agents?

A

antiviral agents that will kill the virus and are active only against actively replicating viruses

83
Q

What is Ribavarin?

A

MOA: increase mutation frequency and inhibits HCV polymerase activity

Use: in combo with Peg-IFN therapy

Dosing: 2 divided doses = < 75kg: 1000 mg daily; >75kg: 1200 mg daily

ADRs: GI SYMPTOMS, NEUTROPENIA, headache, insomnia, fatigue, fever, pruritus, weight loss

BBW: HEMOLYTIC ANEMIA and TERATOGENICITY

84
Q

What is HBeAg the marker for?

A

Hep B envelope antigen

Active viral replication

85
Q

What are the NS5A mutations?

A

M28
Q30
L31
Y93

Causes five fold reduction in NS5A inhibitors

86
Q

What genotype is now more difficult to manage thanks to treatment for 1A genotypes?

A

Genotype 3

87
Q

What is the HIV virus?

A

2 ss-RNA

Diseases: HIV, AIDS

Route of transmission: Sexual, IVU, vertical, blood

88
Q

What is Simeprevir?

A

One of the first oral agents developed and approved

ONly for GT1

Metabolized by 3A4 adn 1A2

Take with food

SULFONAMIDE ALLERGY

ADRs: Rash, LFTs, GI, and hyperbilirubinemia

89
Q

Who do we initiate Hep C treatment in?

A

For all patients with chronic HCV except those with short life expectancy (<12 months) that cannot be treated with transplantation or with remediated treatment

90
Q

What are the two categories of antiviral agents effective against herpes?

A

Nucleoside Analogs

Misc. Agents

91
Q

What are the purine analogs?

A 
Acyclovir
Valacyclovir
Famciclovir
Penciclovir
Ganciclovir
Valganciclovir
92
Q

What is Elvitegravir?

A

AKA Quad Pill

MOA: same as RAL, tenofovir, and Emtricitabine

Metabolism: 3A4 substrate; glucuronidation to a lesser extent

Dosing: must be taken daily with food

Caution in treatment naive patients and with TDF Do not use in patients with CrCl > 70 mL/min.

Elvitegravir/COBI/TDF/Emtricitabine

ADRs: New or worsening renal function, bone mineral density losses, GI

93
Q

What is the class effect of protease inhibitors?

A 
Rash
LFTs
Increase BGs causing Diabetes Mellitus
Increased triglycerides and LDL except for two
Lidodystrophy (central adipocity)
Increased CVD risks

Metabolized by CYP 3A4 and most are potent CYP3A4 inhibitors

HIgh genetic barrier to resistance

94
Q

What protease inhibitor should you not use with Nelfinavir?

A

Ritonavir

95
Q

What are the counseling points to prevent transmission of HCV?

A

Do not share toothbrushes, dental, or shaving equipment
Cover any bleeding wounds
Discuss the importance of stopping drug use and entering rehab
Do not donate blood, organs, tissue, or semen
Use condoms
Clean visibly contaminated surfaces with bleach: water at 1:9 ratio; wear gloves

96
Q

What is Zidovudine?

A

ADRs: BONE MARROW SUPRESSION, myelosuppresion, macrocytic anemia, neutropenia

A high level of resistance is usually seen

97
Q

What are interferons?

A

signaling proteins that are released by the host cell in response to pathogens triggering defense mechanisms within the immune system

They interfere with viral replication and activate NKCs and macrophages

98
Q

What is the LIfe Cycle of HIV?

A
  1. Attachment
  2. Coreceptor Binding
  3. Fusion
  4. Uncoating
  5. Reverse Transcription
  6. Integration
  7. Transcription
  8. Translation
  9. Assembly
  10. Budding and Maturation
99
Q

What is Cobistat?

A

Similar to Ritonavir and used as a 3A4 booster

NO HIV activity

DO NOT use with Ritonavir

ADR: Renal impairment

DO NOT use with TDF when CrCL < 70 ml/min.

100
Q

What does IgG and IgM antibodies represent in Hep A?

A 
IgG = exposure to virus, slower
IgM = acute flair, first/faster
101
Q

What is Lamivudine?

A

WELL TOLERATED

ADRs: HEADACHE

Also active against HBV infections

Rapidly selects for mutation - M184V

102
Q

What is Genova?

A

Safe in patients with CrCl > 30 mL/min. Because it has TAF

Elvitegravir/COBI/TAF/Emtricitabine

103
Q

What is the class effect of NRTIs?

A

Regally dosed; except Abacavir

Mitochondrial toxicity due to inhibition of mitochondrial DNA polymerase

Lactic Acidosis and hepatic stratus is

Lipoatrophy = fat wasting in extremities, buttocks, and face (especially seen in older NRTIs)

104
Q

What are the two Rilpivirine FDC products?

A

Complera

Odefsey

105
Q

What is Atazanavir?

A

ADRs: PR interval prolongation, hyperbilirubinemia

GI and Lipid neutral

106
Q

What is the dosing for Acyclovir?

A

200 mg/5X a day

107
Q

What is Anti-HBe the marker for?

A

Hep B antibodies to envelope antigen

Inactive viral replication; natural immunity or through treatment

108
Q

How do you diagnose Hep A?

A

Check HAV IgG/IgM antibodies

RT-PCR RNA viral load

109
Q

What is Ganciclovir?

A

Guanine and Acyclovir analog

Formulations: TOPICAL OPHTHALMIC, Intravitreal implantation, oral, IV is renally toxic

Excretion: 90% in the urine unchanged

Use: CMV

Dosing: IV in large veins slowly over 1 hour

Monitor: CBCs, LFTs, renal function, serum electrolytes

110
Q

What is Sofosbuvir?

A

PART OF EVERY HEP C REGIMEN = pangenotypic

MOA: uridine analog which causes HCV RNA chain terminator

Therapeutic dose is 400 mg orally

Metabolism: hydrolysis = NO CYP 450

Substrate of p-glycoprotein efflux pump and BCRP; no significant DDIs with inhibitors but there are with inducers

111
Q

Which drugs block viral attachment and entry?

A

Enfuvirtide
Maraviroc
Docosanol
Palivisumab

112
Q

What is the drug of choice for herpes treatment?

A

Acyclovir

113
Q

Which two drugs are really old and not typically used anymore to treat influenza?

A

Amantidine

Rimantidine

114
Q

What is Lopinavir?

A

ADRs: GI

115
Q

What is Tipranavir?

A

Only CYP 3 A4 inducer

Must be co-administered with Ritonavir

Sulfonamide so be cautious in patient with sulfa allergy

ADR: Intracranial hemorrhage

116
Q

What is penciclovir?

A

Active metabolite of famciclovir and guanine analog

Topical ONLY

Use: Herpes labialis and facialis; oral herpes

117
Q

HIV therapy will always contain what class of drug?

A

Integrase

118
Q

What is HHV-2 and what does it cause?

A

Herpes Simplex Virus 2

Genital Lesions

119
Q

What is Abacavir?

A

ADRs: RASH, CVD risk in MIs and strokes

Hypersensitivity reactions, occasionally fatal

Do not use: baseline HIV VL > 100,000 copies/mL

Need testing for HLA-B5701 allele before initiation is recommended to identify the patients with an increased risk of an associated hypersensitivity reaction

120
Q

What is Entecavir?

A

Guanosine Analog

Dosing: 1mg/day normally or 0.5 mg/day for renal dosing; oral tablet or solution and they are NOT bioequivalent

Elimination via urine

Renal dosing when CrCl < 50 mL/min.

Monitor: LFTs and renal function, total bilirubin and BGs

TAKE ON EMPTY STOMACH

121
Q

What is Maraviroc?

A

Entry Inhibitor

MOA: Inhibits HIV co-receptor CCR5-tropic-HIV-1 infection

MUST test for co-receptor tropism prior to use

Metabolized by CYP 3A4; substrate

Dose: 300 mg PO every 12 hours
With inhibitor = 150 mg every 12 hour
With inducer = 600 mg every 12 hours

ADRs: LFTs, rash, pyrexia, orthostasis

122
Q

What is Influenza A, B, and C virus?

A

ss-RNA

Disease: the Flu

Transmission: Inhalation (coughing, sneezing), bird droppings

123
Q

Describe Influenza A

A

Most common, most pathogenic type of influenza

Infects: humans, pigs, and horses

124
Q

What is Enfuviritide?

A

Fusion Inhibitor

MOA: inhibits gp41 and prevents the fusion of HIV to CD4 cell surface

Only SQ product and requires refrigeration

ADRs: infection site reactions, GI

Dose: 90 mg every 12 hours

125
Q

Which two protease inhibitors can be given with Cobistat?

A

Atazanavir

Darunavir

126
Q

What is MOA of NS3/4A protease inhibitors?

A

inhibits the cleavage of polyproteins into nonstructural proteins that are essential in HCV replication

Lower barrier to resistance

127
Q

What does a negative Anti-HBs but positive for all other serological markers indicate?

A

Acute infection; highly infectious

128
Q

What is Valacyclovir?

A

prodrug of acyclovir and has better bioavailability which requires less frequent dosing

Oral formulation only

129
Q

What is Didanosine?

A

WEIGHT DOSED

ADRs: PANCREATITIS, PERIPHERAL NEUROPATHY, Lipoatrophy

RENAL DOSING

130
Q

What are the three parts of a virus?

A

Helical Genetic Molecule
Protein Coat
Envelope

131
Q

What is Trifluridine?

A

Thymidine analog

Opthalmic solution ONLY

Use: Ocular herpes

Administration: refrigerated eyedrops

132
Q

WHta is Saquinavir?

A

ADRs: GI, CVD risk

133
Q

What does positive for Anti-HBs and Anti-HBc but negative for all others indicate?

A

Resolved infection or immune due to natural infection

134
Q

What is adefovir?

A

Adenosine Analog

Use: Hep B; effective against lamivudine-resistant HBV

Dosing: 10 mg/day oral

Renal Dosing when CrCl < 50 mL/min.

Monitor: LFTs and renal function

DO NOT USE WITH TENOFOVIR

135
Q

What is Idinavir?

A

ADRs: Nephrolithiasis, Hyperbilirubinemia

136
Q

What should you monitor during therapy with Hep C drugs?

A

Check HCV VL at week 4 and 12 and d/c therapy if detectable at week 6 or later

Check the same routine labs as you did prior to therapy

137
Q

What is Telbivudine?

A

Thymidine analog

Dosing: 600 mg/day orally

Renal dosing when CrCl < 50 mL/min.

Monitor LFTs

Super expensive and not typically used

138
Q

What is the MOA of NS5B Polymerase Inhibitors?

A

nucleoside/nucleotide analogs that incorporate into HCV RNA leading to chain termination which stops HCV replication

139
Q

Who should get tested for Hep C?

A

All persons born between 1945-1965 regardless of risk factors should be tested at least once

Those with risk behaviours, exposures, and/or conditions such as: IVDU, intranasal drug users, long term HD, tattoos in unregulated setting, healthcare providers, children born to HCV mothers, recipients of transfusions or organ donations before 1992, recipients of clotting factors before 1987, incarcerated individuals, HIV, MSM, solid organ donors, or unexplained elevations in ALT

140
Q

What does positive for only Anti-HBs indicate?

A

Immune due to vaccine

141
Q

What is the resistance testing in clinical practice for Zepatier regimen for Hep C?

A

NS5A RAS testing for GT1A

If present, wt. based ribavirin should be added and treat for 16 weeks or use different regimen

142
Q

What does negative Anti-HBs, +/- HBeAg, and positive for all other serological markers indicate?

A

chronic infection

143
Q

What are non-nucleoside reverse transcriptase inhibitors (NNRTIs)?

A

Bind noncompetitively to allosteric site

Baseline genotypes resistance testing is recommended

Extremely long half life = adherence forgiving and 95% adherence rate is required in order to maintain therapeutic concentrations

Resistance occurs rapidly with mono therapy and results from single mutation = they have lowest genetic barrier to resistance

144
Q

What is the resistance testing in clinical practice for Daclatasvir + Sofosbuvir regimen for Hep C?

A

NS5A RAS testing is recommended for GT3 treatment espeically without cirrhosis or naive with cirrhosis and treat for 12 weeks

If Y93H is present, add wt. based ribavirin

145
Q

What is Valganciclovir?

A

prodrug of Ganciclovir

Oral tablet that MUST be taken with food for higher absorption

Renally excreted

Use: CMV

Monitor: CBCs and renal function

146
Q

What is Rimantidine?

A

Use: prevents and treats Influenza A

Excretion: 70-85% in urine

Elimination: 13-65 hours

Dosing: tablets and syrup

RENAL and LFT monitoring

147
Q

What is the MOA of NS5A inhibitors?

A

inhibits the phosphorylation of proteins required for HCV RNA replication which prevents HCV RNA replication

Associated with resistance mutations which decreases its activity

148
Q

What is Oseltavmivir?

A

Prodrug and oral agent that is converted to oseltamivir carboxylate

Excretion: 99% in urine

Use: prevention and treatment of Influenza A and B

Renally dosed

149
Q

What is Harvoni?

A

Combo drugs

Elimination via p-glycoprotein efflux pumps and BCRP

Minimal DDIs: acid suppresants, tenofovir causing nephrotoxicity, amiodarone causes symptomatic bradycardia

ADRs: Asthenia, hyperbilirubinemia, fatigue/headache, GI effects, no hepatic dosing, no renal dosing

DO NOT USE IN PATIENTS WITH CrCl < 30 mL/min.

150
Q

What does negative for all serological markers indicate?

A

Not infected; not vaccinated; susceptible to Hep B

151
Q

What is Etravine?

A

Active against K103N virus

Dose: 200 mg orally every 12 hr.

Metabolized by CYUP 3A4; induces and inhibits CYP 3A4

ADRs: Rash, LFTs, minor CNS effects

152
Q

What is interferon alpha-2b

A

MOA: inhibits viral protein production

Use: refractory Hep B that doesn’t respond to oral agents

IM injection, IV and SQ

Highly toxic

Monitor: LFTs, TFTs, CBCs, triglycerides, and EKG

ADRs: anemias, infections, arrhythmias, LFTs, hypothyroidism, psych changes (mood)

153
Q

What is the MOA of Oseltamivir and Zanamivir?

A

inhibits neuraminidase of influenza a and b, preventing the release of virions from the host cell and prevents entry into the cell

154
Q

What is Acyclovir?

A

Guanine analog that is ONLY effective against actively replicating virus; oldest herpes drug we have

Use: HSV, VZV, limited CMV and EBV

Formulations: oral, IV is renally toxic, and topical

Elimination: 90% renally = renal dosing

Dosing varies for stage of disease

155
Q

What mutations exist for Hep C genotype 1a?

A

NS3/4A mutation

NS5A mutations

156
Q

What is HBV virus?

A

ds-DNA-RT

Disease: Chronic Hepatitis B, cirrhosis, hepatocellular carcinoma

Transmission: blood, sexual, IVU, vertical

157
Q

What is HHV-8 and what does it cause?

A

Kaposi’s Sarcoma typically found on bottom of feet and palms of older sicilian women

158
Q

What must we test for with Hep C and why?

A

we must do resistant testing as part of therapy for Hep C because 75% of patients have resistance to GT1A and 10-15% have mutations to 5A polymerase inhibitor

159
Q

What is Lamivudine?

A

Cytosine Analog and also classified as NRTI

Dosing: 100 mg if only for Hep B and 300 mg if for coinfection with HIV; oral tablet or suspension are bioequivalent to eachother

Use: coinfection with HBV and HIV 1 or 2

Renal dosing if CrCl < 50 mL/min.

Monitor: LFTs and renal function, blood glucose, CBC, HIV VL/CD4 count, HBV VL

ADRs: GI and headache

160
Q

What is the treatment for Hep C Genotype 1A/B if patient has cirrhosis?

A

Same Zepatier, Harvoni (if HCV VL > 6 million), and Epclusa regimens

Not recommended treatment with Harvoni if HCV VL < 6 million

Mavyret for 12 weeks instead of 8

161
Q

What is HHV-6/7 and what does it cause?

A

Roseolavirus

162
Q

Who should be tested yearly or every six months for Hep C?

A

IV drug users
HIV patients
MSM

163
Q

Which drugs block penetration of virus?

A

Interferon-alpha

164
Q

Describe Influenza B

A

infects humans only

165
Q

What part of the influenza virus do we use to classify the subtypes of influenza?

A

surface proteins: Hemagglutinin (H) and Neuraminidase (N)

166
Q

What two NRTIs should you NEVER use together?

A

Didanosine and Stavudine

167
Q

What is Amantadine?

A

Use: treats and prevents Influenza A; PARKINSONS

Crosses BBB and placenta

Excretion: 90% in urine

Elimination: long half life of 7-10 days in renally impaired and 11-15 hours normally

RENAL monitoring

168
Q

What are the HSV, CMV, EBV, VZV, HHV-8 viruses?

A

ds-DNA

Diseases: HSV-1/-2, CMV, mononucleosis, burkitts lymphoma, chicken pox, shingles, Kaposi’s sarcoma

Route of transmission: direct contact, saliva, blodd, sexual, vertical, organ, airborne (VZV)

169
Q

What is the goal of therapy for Hep C?

A

to reduce all-cause mortality and liver-related health complications by achieving sustained virologic response (SVR)

Want to cure it

170
Q

What are the new fixed dosed protease inhibitor agents?

A

Evotaz

Prezcobix

171
Q

What is Efavirenz?

A

Must be taken at bedtime and on an empty stomach

ADRs: CNS effects - somnolence, fatigue, psych changes; rash, LFTs

Metabolized by CYP 3A4, induces and inhibits CYP 3A4

172
Q

What is Biktarvy?

A

Bictegravir/TAF/Emtricitabine

INSTI

Use: treatment Naive and as “SWITCH” regimen

Dose: 1 tablet PO once daily

Renal issues with CrCl < 30 mL/min.

Metabolism: Glucuronidation and via CYP 3A4

ADRs: GI, headache

173
Q

What is Tenofovir Alafenamide Fumarate (TAF)?

A

Safer; improves kidneys and bone marrow suppression

Newer formulation and prodrug of tenofovir

Therapeutic doses depend on the product formulation

174
Q

What is Viekira Pak?

A

Many DDIs and scheduling of dosing is difficult

Paritoprevir, Ritonavir, and Ombitasvir are all in one drug + Dasabuvir

Dosing is 2 of the combo pills + the 1 regular pill twice a day

MUST BE TAKEN WITH FOOD

No renal or hepatic dosing

ADRs: GI, rash, LFTs

175
Q

What are nucleoside analogs?

A

synthetic analogs of purines or pyrimidines that inhibit the viral replication through:

  1. Competitive inhibition of DNA polymerase
  2. Incorporation and termination of viral DNA chain
  3. Inactivation of viral DNA polymerase
176
Q

WHta is Ritonavir?

A

Most 3A4 potent inhibitor

ADRs: GI

177
Q

What is Vosevi?

A

Pangenotypic for GT 1-6

significant DDIs:
acid suppressants = separate dose by 4 hours
H2 blockers = simultaneous or staggered dose
PPIs = omeprazole may be dosed simultaneously

DO NOT USE IF eGFR < 30 mL/min

ADRs: DEPRESSION; ELEVATED LIPASE, CPK, and total bilirubin; HA, fatigue, GI, rash

178
Q

Which two herpesvirus families can be cross transmitted and what is the clinical significance of this?

A

HHV-1 and HHV-2

The antibody test for this would test for both and both would be treated the same

179
Q

What is Raltegravir?

A

MOA: blocks the catalytic activity of the HIV-encoded integrase, thus preventing integration of virus DNA into the host

Metabolized by glucuronidation and does not interact with the cytochrome P450 system

Eliminated via p-glycoprotein efflux pumps

Dose: 400 mg PO every 12 hours

Resistance: Virologic failure has been uncommon in vitro resistance requires only a single point mutation at codons 148 or 155

ADRs: Rash, LFTs, Increase CPK, pyrexia

Clinical Pharmacology II (25 decks)

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