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Clinical Pharm Exam 3 > Antiviral > Flashcards

Antiviral Flashcards

1
Q

Influenza

A

Amantidine
Rimantidine
Oseltamivir
Zanamivir

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2
Q

Amantidine MOA:

A

Inhibit uncoating of the viral RNA within infected host cells, preventing replication

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3
Q

Rimantidine MOA

A

Inhibit uncoating of the viral RNA within infected host cells, preventing replication

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4
Q

Oseltamivir MOA

A

Inhibit neuraminidase of influenza a and b; preventing the release of virons from the host cell and prevents entry into the cell

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5
Q

Zanamivir MOA

A

Inhibit neuraminidase of influenza a and b; preventing the release of virons from the host cell and prevents entry into the cell

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6
Q

Amantidine

A

Crosses BBB –> parkinson’s Disease
Pregnancy category C
CDC DOES NOT recommend use

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7
Q

Rimantidine

A

Pregnancy category C

CDC DOES NOT recommend use

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8
Q

Oseltamivir

A

Pro drug, oral
Indicated: prevention and treatment of Influenza A and B
BEGIN within 2 days of onset (renally dosed)
Pregnancy category C

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9
Q

Zanamivir

A

Oral inhalation
Indicated: prevention and treatment of Influenza A and B
Avoid in Dairy allergy - contains milk protein
Pregnancy category C

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10
Q

Nucleoside analogs MOA

A

synthetic analogs of purines or pyrimidines that inhibit the viral replication through
competitive inhibition of DNA polymerase
incorporation and termination of viral DNA chain
inactivation of viral DNA polymerase

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11
Q

Trifluridine

A

Pyrimidine analogs
Ophthalmic solution
Indications Ocular HSV
Refrigerate

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12
Q

Cidofovir

A

Pyrimidine analogs
IV formulation ONLY
Indication CMV infections, HSC activity (systemic, organs, meningitis)
Renally Toxic –> HYDRATE prior to therapy

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13
Q

Acyclovir

A

Guannine Analogs
ONLY effective against activiely replicating virus
Indications HSV and VZV
Oral, IV (renally toxic), topical
Poor bioavailability –> multiple dosing/day (5X)
Pregnancy category B
Monitor renal function

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14
Q

Valacyclovir

A

Prodrug of acyclovir
Better bioavailability
Indications HSV and VZV
Oral formulation only (1 x day)

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15
Q

Famciclovir

A 
Prodrug of penciclovir
guanine analog
Inhibits viral DNA polymerase
Better bioavailability
Indications: prevention and treatment of HSV and VZV
Pregnancy category B
Oral agent
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16
Q

Penicilovir

A

Guanine analog
Inhibits viral DNA polymerase
Topical formulation ONLY
Indication: treatment of HSV infections (Herpes labialis and facialis)

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17
Q

Ganciclovir

A

Guanine analog
Indications: treatment and prevention of CMV infection
IV formulation renally toxic –> HYDRATE
Monitor: CBC w/ diff, LFTs, Renal function, serum electrolytes
Pregnancy category: C

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18
Q

Valganciclovir

A 
prodrug of ganciclovir
Oral table take with food
renally excreted
Indications: Prevention and treatment of CMV infections
Monitor CBC w/ diff, renal function
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19
Q

Foscarnet

A

Inorganic pyrophosphate analog
inhibits viral-specific DNA polymerases and reverse transcriptase at the pyrophosphate binding site –> preventing DNA synthesis
Indications: prevention and treatment of CMV, treatment of refractory HSV and VZV
Monitor: chem 10 (renal function and electrolyte loss), CBC w/ diff (bone marrow suppression), EKG (AV block, ST wave changes)
Pregnancy category C

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20
Q

HAV Vaccines

A

Vaqta
Havrix
Twinrix

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21
Q

Vaqta

A

HAV only
Indications >12months of age
2 doses series - 1st dose then 2nd dose 6-18 months later

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22
Q

Havrix

A

HAV only
Indications >12 months
2 dose series - 1st dose then 2nd dose 6-12 months later

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23
Q

Twinrix

A

HAV/HBV combination
Indicated >18y/o
3 dose series - 1st dose, then 2nd dose @ 1month, then 3rd dose @ 6months

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24
Q

HBV Agents

A 
Adefovir
Entecavir
Lamivudine
Interferon/peg-interferon
Tenofovir
Telbivudine
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25
Q

Interferon MOA

A

signaling proteins that are released by host cell in response to pathogens; triggering protective defense mechanisms within the immune system.
Interfere with viral replication and activate natural killer cells and macrophages

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26
Q

Peg-Interferon

A

SQ once weekly
ADEs: Anemias (cbc w/ diff), infections (CXR),
arrhythmias (ekg), LFTs, Hypothyrodism (TSH), psych changes (moods), renal function

REFRACTORY HBV

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27
Q

Interferon

A

IV, IM, SQ once daily for 16 weeks
ADE:Anemias (cbc w/ diff), infections (CXR),
arrhythmias (ekg), LFTs, Hypothyrodism (TSH), psych changes (moods)

REFRACTORY HBV

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28
Q

Adefovir

A

Adenosine analog prodrug metabolixed by cellular kinases preventing DNA synthesis
Indications HBV, effective against Lamivudine- resistant HBV
Renally dosed when CrCl<50ml.min
Monitor: Renal function, LFTs, HBV labs (viral load and serologies

NO CO INFECTION COVERAGE
DO NOT USE WITH TENOFOVIR

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29
Q

Entecavir

A

inhibit HBV reverse transcriptase –> suppressing DNA replication (weak toward HIV)
Co-infectioon, lamivudine resistance on tenofovir
Renally dosed when CrC<50ml/min
Monitor: Renal function, LFTs, T.bili, Blood glucose

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30
Q

Lamivudine

A

nucleoside reverse transcriptase inhibitor Resistance via M184V and M184I mutations
Indications: HIV-1, HIV-2: 300mg po 1xday
HBV: 100mg po 1xday
Well tolerated (mostly GI/HA)
Monitor: Blood glucose, CBC with diff, HIV VL/CD4 count

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31
Q

Telbivudine

A 
MOA: inhibits DNA polymerase --> preventing DNA replication
Thymidine analog
Renally dosed when CrCl<50ml/mn
ADE: LFTs
TOO EXPENSIVE
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32
Q

NS5B Polymerase Inhibitor MOA

A

Nucleoside/nucleotide analogs that incorporate into HCV RNA leading to chain termination –> stop HCV replication

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33
Q

NS3/4A Protease Inhibitor MOA

A

Inhibits the cleavage of polyproteins into nonstructural proteins that are essential in HCV replication
Lower barrier of resistance Q80K

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34
Q

NS5A Inhibitor MOA

A

Inhibits the phosphorylation of proteins required for HCV RNA replication –> preventing HCV RNA replication
* need to do genetic resistance testing

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35
Q

Non-Nucleoside NS5B palm Polymerase Inhibitor MOA

A

Inhibits the activity of the NS5B to inhibit HCV RNA replication

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36
Q

NS5B Polymerase Inhibitor Agents

A

Sofosbuvir

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37
Q

NS3/4A Protease Inhibitor Agents

A 
Glecaprevir
Grazoprevir
Paritaprevir
Simeprvir
Voxilaprevir
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38
Q

NS5A Inhibitors Agents

A 
Daclatasvir
Elbasvir
Ledipasvir
Ombitasvir
Pibrentasvir
Velpatasvir
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39
Q

Non-Nucleoside NS5B palm Polymerase Inhibitor Agents

A

Dasabuvir

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40
Q

3A4 PK Booster Agents

A

Ritonavir

41
Q

Sofosbuvir

A 
NS5B RNA nucleotide polymerase inhibitor for Genotype 1,2,3,4
Pro drug
Pangenotypic
No CYP Interactions
Substrate of pgp efflux pump and BCRP
*Tenofovir --> Increase renal toxicity associated with Tenofovir
Pregnancy: Sofosbuvir ONLY - Category B
otherwise Category X
42
Q

Sofosbuvir/Ledipasvir (Harvoni)

A

Ledipasvir - NS5A inhibitor
metabolism via oxidation - no DDI via CYP
elimination via pgp efflux pump and BCRP
ADE: Asthenia, Hyperbilirubinemia, fatigue/headache, GI effects, No hepatic dosing, No renal dosing - caution CrCl<30ml/min
DDI: acid suppressants, Tenofovir –> nephrotoxicity, Amiodarone –> Symptomatic bradycardia

43
Q

Velpatasvir/Sofosbuvir (Epclusa)

A 
NEW GOLD Standard in HCV management
Velpatasvir NS5A inhibitor
Pangenotypic for genotype 1-6
metabolized CYP 2B6, 2C8, 3A4
Eliminated via feces

ADE: anemia, GI, Headache, Fatigue, no hepatic dosing, no renal dosing - caution in GFR<30ml/min

LOTS OF DDI

44
Q

Voxilaprevir/Velpatasvir/Sofosbuvir (Vosevi)

A

Voxilaprevir NS3/4A protease Inhibitor via CYP3A4 –> DDI

Significant DDI with acid suppressants (Antacid, H2Blockers, PPIs)

Renal issues: do not use when GFR<30ml/min

ADE: headache, fatigue, GI, Rash, Depression, Elevated lipase, CPK, t. bili

45
Q

Elbasvir/Grazoprevir (Zepatier)

A

Elbasvir - NS5A Inhibitor
Grazoprevir - NS3/4A Protease Inhibitor

ADE: GI, Fatigue, headache, Anemia, elevated LFTs, Hyperbilirubinemia, No renal or hepatic dosing

LOTS OF DDI

46
Q

Viekira Pak

A

Paritaprevir (NS3/4A protease inhibitory)
- Metabolism 3A4 - MAJOR DDIs
Ritonavir (CYP3A4 Booster)
Ombitasvir (NS5A Inhibitor)
- Metabolized via hydrolysis
+
Dasabuvir (non-nucleoside NS5B palm polymerase inhibitor
- Metabolism via 2C8, 3A4 (possible DDIs)

Must be taken eith food
No renal or hepatic dosing
ADE: GI, rash, LFTs
TO COMPLICATED

47
Q

Viekira XR

A

Genotype 1a and 1b
Paritaprevir/ritonavir/Ombitasvir/Dasabuvir
Must be taken with food - cannot be chewed, crushed, or split
TOO MANY DDI
ADE: GI, rash, LFTs
3 pills once a day

48
Q

Simeprevir

A

NS3/4A Protease Inhibitor for Genotype 1 ONLY

  • Q80K resistance mutation –> reduction in efficacy based on SVR
  • more effective in 1b

Metabolized via 3A4 & 1A2 –> interactions

Take with food
Sulfonamide Allergy
ADE: Rash, LFTs, GI, Hyperbilirubinemia

MUST BE GIVEN WITH Sofosbuvir

49
Q

Daclatavir

A

NS5A Inhibitor
Indications: HCV genotype 3
Must be co-administered with Sofosbuvir

Metabolism
- CYP3A4 - substrate –> DDI
Co-administered with 3A4 inhibitor –> reduce to 30mg QD
Co-administered with 3A4 inducer –> increase to 90mg QD

ADE: Anemia, Fatigue, GI effects, Headache

50
Q

Glecaprevir/Pibrentasvir (Mavyret)

A 
Glecaprevir - NS3/4A Protease Inhibitor
Pibrentasvir - NS5A Inhibitor
Pangenotypic for genotypes 1-6
Dose: 3 tablet once daily with food
Glecaprevir: CYP3A4, eliminated pgp efflux pumps
Pibrentasvir: Biliary-fecal route

No renal dosing
ADE: Headache, Fatigue, GI, Elevated t.bili

51
Q

Pef-Interferon + Ribavirin

A

Refractory HCV

52
Q

Ribavirin

A

MOA: Increase mutation frequency and inhibits HCV polymerase activity
Indications: in combination with PEG-IFN therapy
ADE: pruritus, weight loss, GI symptoms, Neutropenia, Headache, Insomnia, Fatigue, Fever
BBW: hemolytic anemia + Teratogenicity

53
Q

Recommendations for patients with CKD stage 1, 2, or 3

A 
Daclatasvir
Elbasvir/Grazoprevir
Glecaprevir/Pibrentasvir
Ledipasvir/Sofosbuvir
Sofosbuvir/Velpatasvir
Simeprevir
Sofosbuvir/Velpatasvir/Voxilaprevir
Sofosbuvir
54
Q

Recommendations for patients with CKD stage 4 or 5 (GFR<30ml/min)

A

Elbasvir/Grazoprevir

Glecaprevir/Pibrentasvir

55
Q

When to initiate HIV Therapy

A

any time end organ damage, pregnant, co-infection (HBV/HCV)

DO NOT INITIATE THERAPY IF PATIENT IS NOT READY or WILLING

56
Q

What to initiate

A

Integrase inhibitor based Antiretroviral therapy:
- Raltegravir + Emtricitabine/Tenofovir DF or Tenofovir AF
- Elvitegravir/c/TDF/Emtricitabine
- Elvitegravir/c/TAF/Emtricitabine
- Dolutegravir + Emtricitabine/Tenofovir DF or Tenofovir AF
- Dolutugravir/abacavir/lamivudine
HLA-B5701 negative

57
Q

Under special conditions

A

Darunavir/Ritonavir or Darunavir/c + TDF/Emtricitabine or TAF/Emtricitabine or Abacavir/Lamivudine
- epzicom if HLA-B5701 negative
Atazanavir/ritonavir or Atazanavir/c + TDF/Emtricitabine or TAF/Emtricitabine or Abacavir/Lamivudine
Raltegravir + Abacavir/Lamivudine (baseline HIV VL <100K copies/ml) inferior to truvada/descovy

58
Q

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)

A 
Abacavir
Didanosine
Emtricitabine
Lamivudine
Stavudine
Tenofovir
 - TDF
 - TAF
Zidovudine

MOA: competitively inhibits of HIV-1 reverse transcriptase

Renally dosed (except Abacavir)
Mitochondrial toxicity
- due to inhibition of mitochondrial DNA polymerase
- lactic acidosis and hepatic steatosis
- lipoatrophy --> fat wasting
   extremities, buttocks, face
59
Q

Truvada

A

Emtricitabine/Tenofovir DF

60
Q

Dsescovy

A

Emtricitabine/Tenofovir AF

61
Q

Epzicom

A

Abacavir/Lamivudine

62
Q

Combivir

A

Zidovudine/Lamivudine

63
Q

Abacavir

A

ADE: Rash, CVD risk
DO NOT USE baseline HIV VL >100K copies/ml

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

64
Q

Didanosine

A

ADE: Weight-dosed, pancreatitis, peripheral neuropathy

65
Q

Emtricitabine

A

ADE: Hyperpigmentation, well tolerated

Active against HBV

66
Q

Lamivudine

A

ADE: well tolerated, headache

Also reactive against HBV infections

Rapidly selects for mutation - M184V

67
Q

Stavudine

A

ADE: weight-dosed, pancreatitis, peripheral neuropathy

68
Q

Tenofovir

A

TDF - nephrotoxicity, osteomalacia

TAF - Safer, no kidney or bone mineral density

69
Q

Zidovudine

A

ADE: bone marrow suppression (anemias, RBC, WBC, platelets)

High level resistance is generally seen

70
Q

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

A 
1st Generation:
- Efavirenz
- Nevirapine
2nd Generation:
- Etravirine
- Rilpivirine

MOA: binds noncompetitively to allosteric site

baseline genotypic resistance testing is recommended
resistance occurs rapidly with monotherapy and results from single mutation
- lowest genetic barrier resistance
- MOST COMMON MUTATION = K103N (resistant to efavirenz & nevirapine)

71
Q

Efavirenz

A

1st generation NNRTI
take on empty stomach (take at bed)
ADE: CNS effects - somnolence, fatigue, psych changes, SI/SA - rash, LFTs
Metabolized by CYP3A4; induces and inhibits CYP3A4
Pregnancy category: D

72
Q

Nevirapine

A

1st generation NNRTI
DO NOT USE: in female with CD4 > 350cells/mm3; males with CD4 >400cells/mm3
Metavolized by CYP3A4; Induced CYP3A4
ADE: rash, liver toxicity

73
Q

Etravirine

A

2nd generation NNRTI
Active against K103N virus
Metabolized by CYP3A4; Induces and Inhibits CYP3A4\
ADE: rash, LFTs, minor CNS effects

74
Q

Rilpivirine

A

2nd generation NNRTI
active against K103N virus
Must be taken with food; 900kcals (bad for diabetic, heart disease, obese)
Metabolized by CYP3A4; substrate
ADE: rash, LFTs, CNS effects
Do not use: baseline HIV VL > 100K copies/ml

75
Q

Complera

A

Rilpivirine/TDF/Emtricitabine

76
Q

Odefsey

A

Rilpivirine/TAF/Emtricitabine

77
Q

Protease Inhibitors Agents

A 
Atazanavir
Fosamprenavir
Darunavir
Indinavir
Lopinavir/ritonavir
Nelfinavir
Ritonavir
Saquinavir
Tipranavir
78
Q

Protease Inhibitors

A

MOA: Inhibit the activation of immature proteins –> block the GAG-POL region within protease to inhibit the cleavage of proteins

Class Effects: Rash, LFTs, Increases Blood glucose (DM), Increases TG and LDL, Lipodystrophy (central adiposity), Increases CVD risk

All PIs are metabolized by CYP3A4 (most are potent CYP3A4 inhibitors)

High genetic barrier to resistance (difficult to become resistance)

79
Q

Ritonavir

A

Most 3A4 Potent inhibitor
ADE: GI
DO NOT give with nelfinavir
Active against HIV –> as a booster

80
Q

Atazanavir

A

ADE: PR interval prolongation, Hyperbilirubinemia
GI neutral
Lipid neutral

81
Q

Darunavir

A

MUST co-admin w/ ritonavir
Sulfonamide –> cautious with sulfa allergy
GI neutral
Lipid neutral

82
Q

Fosamprenavir

A

Sulfonamide –> cautious with Sulfa allergy

ADE: GI

83
Q

Indinavir

A

Nephrolithiasis, hyperbilirubinemia

84
Q

Lopinavir

A

ADE: GI

85
Q

Saquinavir

A

ADE: GI, CVD risk

86
Q

Tipranavir

A

Only CYP3A4 inducer
MUST Co-admin w/ ritonavir
Sulfonamide –> cautious with sulfa allergy
ADE: Intracranial hemorrhage

87
Q

Cobicistat

A

Similar to ritonavir –> used as 3A4 booster
ONLY with atazanavir and darunavir
NO HIV Activity
DDI/Contraindications = ritonavir
ADE: renal impaitment (don’t use with TDF when CrCl<70ml/min)

88
Q

Evotaz

A

Atazanavir/Cobicistat

1 tablet + 2 NRTIs

89
Q

Prezcobix

A

Darunavir/Cobicistat

1 tablet + 2 NRTIs

90
Q

Fusion Inhibitor

A

Enfuvirtide
ONLY SQ
MOA: inhibits gp41 and prevents the fusion of HIV to CD4 cell surface
ADE: injection site reaction, GI

91
Q

Entry inhibitor

A

Maraviroc
MOA: inhibits HIV co-receptor CCR5-tropic HIV-1 infection
MUST test for co-receptor tropism prior to using
With inhibitor: decrease dose
With inducer: increase dose

ADE: LFTs, Rash, Pyrexia, orthostasis

92
Q

Integrase Inhibitors

A

Raltegravir
Elvitegravir
Dolutegravir
Bictegravir/TAF/Emtricitabine

93
Q

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 CYP450 system
Eliminated via pgp efflux pumps

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

ADE: rash, LFTs, Increase CPK, pyrexia

94
Q

Quad Pill

A

Elvitegravir/COBI/TDF/Emtricitabine
MOA: Blocks the catalytic activity of the HIV-encoded integrase, thus preventing integration of virus DNA into the host

3A4 Substrate, glucuronidation
CrCl > 70ml/min
Treatment naive patients

ADE: new or worsening renal function, bone mineral density losses, GI

TOO MANY C/I and DDI

95
Q

Genvoya

A

Elvitegravir/COBI/TAD/Emtricitabine

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

Safe in pt with CrCl > 30

96
Q

Dolutegravir

A

MOA: Blocks the catalytic activity of the HIV-encoded integrase, thus preventing integration of virus DNA into the host
Metabolism: UGT-1A1, 3A4

ADE: Hypersensitivity reaction, LFTs (especially in HBV or HCV co-infections), Insomnia, Hyperglycemia (>125mg/dl), hypertriglyceridemia

DDI: Polyvalent cations (Mg, Al, Fe, Ca) Space 2hrs before or 6hrs after cations

97
Q

Bictegravir/TAF/Emtricitabine

A 
Integrase Inhibitor
Treatment naive and as SWITCH regimen 
Renal issues CrCl<30ml/min
Metabolism Glucuronidation and Via CYP3A4
ADE: GI &amp; Headache
98
Q

SWITCH regimen

A

a pt on an effective HIV regimen & able to maintain viral suppression for at least 6 months & looking for simple regimen

Clinical Pharm Exam 3 (5 decks)

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