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Cellular Week 2 > Antivirals > Flashcards

Antivirals Flashcards

1
Q

3 general areas to block with antivirals

A

1) viral attachment
2) stages internally (ex. NRTI, proteases)
3) block release

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2
Q

Resistance is higher with antivirals!! Also we don’t have a backup like in antibacterials

A

..

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3
Q

Which drugs work on virus specific enzyme thymidine kinase?

A

acyclovir
penciclovir
ganciclovir

leads to chain termination

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4
Q

Which drug works on triphosphates for competitive inhibition of viral DNA polymerase?

A

Foscarnet

leads to inhibition of viral DNA synthesis

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5
Q

The host cell uses its own phosphates to get it from monophosphate that the virus specific enzyme created to triphosphate (where foscarnet acts).

A

…

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6
Q

What works on host kinases? (2)

A

cidofovir

Trifluiridine

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7
Q

Acyclovir name?

A

Zovirax

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8
Q

Valacyclovir name?

A

Valtrex

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9
Q

Famciclovir name?

A

Famvir

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10
Q

What are acylcovir, valacyclovir, and famciclovir techinically?

MOA?

mechanisms of resistance?

A

guanosine analogs! (synthetic purine nucleosides) NOT ENZYMES.

Chain termination

  • activated by viral specific thymidine kinase to mono phosphate
  • host enzymes convert to di/triphosphates
  • triphosphate analog inhibits viral DNA polymerase by inhibiting DNA chain elongation! (30x more specific for viral vs cellular DNA polymerase - why not as toxic)

MOR:

  • deficient or mutant thymidine kinase
  • mutant DNA polymerase
  • cross resistance among agents
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11
Q

What do Acyclovir, Valacyclovir, and Famciclovir work on?

A
  • HSV-1/2>VZV

**do not work for CMV!!

  • Used in genital herpes (initial, recurrent, and supprision)
  • used in varicella zoster (chicken pox/shingles)
  • HSV encephalitis (inflame of brain)

**decreases the duration/severity of sx, time to lesion healing, viral shedding, and transmission!!

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12
Q

10 fold more drug is needed for VZV when using acyclovir - generally just less effective

A

…

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13
Q

Shedding is what?

A

The contagious period!
Not necessarily having symptoms though in the individual
It is a period of rapid replication.

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14
Q

Formulations/Kinetics of topical acyclovir?

A

less effective than oral for primary infection; not effective for recurrent

Dosing is based on indication, severity, and immune function. (if immunodepressed give IV of full dose for ex)

Acyclovir is only given with an IV!!!

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15
Q

Formulations/kinetics for valcyclovir/famciclovir?

A

valcyclovir: acyclovir prodrug
famciclovir = penciclovir prodrug

Higher levels, less frequent dosing - only available orally! (really only once a day)

better pharmacokinetics

Dosing is based on indication, severity, and immune function.

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16
Q

Adverse effects of Acyclovir, Valcyclovir, and Famciclovir?

A

Well tolerated (HA - headache, GI side effects possible)

Renal (5%) - crystalline nephropathy with IV acyclovir —- REVERSIBLE WITH HYDRATION.

Neurologic (IV 1-4%) - lethargy, tremors, delirium, hallucinations, seizures.

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17
Q

Antiviral for cytomegalovirus (CMV)?

3

A

Ganciclovir/Valganciclovir
Foscarnet
Cidofovir (Vistide)

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18
Q

How can ganciclovir be given?

A

PO, IV, intravitreal injection, or implant

similar in structure to acyclovir

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19
Q

what is the prodrug of ganciclovir?

A

valganciclovir (PO) - this is generally given

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20
Q

activity for ganciclovir?

A

CMV»HSV-1, HSV-2, VZV

100x greater than acyclovir for CMV

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21
Q

Ganciclovir/Valganciclovir is generally way more toxic and will see more black box warnings!!

A

…

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22
Q

Regular effects of Ganciclovir/Valganciclovir?

A

GI: NVD, pain
CNS: insomnia, HA, confusion
RASH!

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23
Q

Black box warnings for Ganciclovir/Valganciclovir?

A
  • Bone Marrow Toxicity! (actual black box)
    neutropenia (40%), thrombocytopenia (20%), and anemia (20%)

-Mutagenic, Embryotoxic - contraception 90 days post tx (use two diff types)

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24
Q

Potential interactions with ganciclovir/valganciclovir?

A

other myelosuprressive agents

Increased seizure potential with imipenem

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25
Q

Chemistry and MOA of Foscarnet

A

Pyrophosphate analog

Inhibits viral DNA polymerase

  • competes for pyrophosphate binding site on DNA polymerase
  • does not require activation by viral kinases!!
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26
Q

What is Foscarnet used for?

A

CMV

Acyclovir resistant HSV

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27
Q

How is Foscarnet given?

A

poorly absorbed, given IV, intravitreal

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28
Q

Adverse reactions for Foscarnet? (3 big ones - 2 smaller)

A
  • NEPHROTOXCITY (50%)
  • BONE MARROW TOXICITY
  • ELECTROLYTE IMBALANCES
  • GI (30-40%)
  • CNS (fever, HA, hallucinations, seizures)
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29
Q

Drug Interactions with Foscarnet?

A
  • nephrotoxic agents

- imipenem (seizures increased), ciphroflaxin (also increase seizures)

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30
Q

Other name for cidofovir?

A

Vistide

31
Q

Chemistry/MOA of cidofovir?

Used for?

A

cytosine nucleotide analog
inhibits viral DNA polymerase (like foscarnet)

Used for CMV/acyclovir-resitant HSV

32
Q

How is cidofovir given?

A

IV with probenecid (blocks tubular secretion)

33
Q

Adverse side effects of Cidofovir (Vistide) (3)?

A
  • Nephrotoxicity (BLACK BOX!)
    concentration dependent, proximal tubule
    requires, pre and post hydration AND probenecid
    avoid other nephrotoxic agents
  • Bone marrow toxicity
  • carcinogenic/mutagenic (avoid getting pregnant 3 mos post administration!)
34
Q

Brincidofovir… what is it? what is it used for?

A

Lipid conjugate of cidofovir

phase 3 for CMV, Emergency IND - investigational new drug -for Ebola virus

35
Q

cidofovir/foscarnet are virus non specific!!

A

…

36
Q

Cidofovir/foscarnet/ganciclovir are used in CMV disease in immunosuppressed pts.

A

..

37
Q

Cidofovir is given IV only for retinitis.

A

…

38
Q

foscarnet is given IV only for intravitreal.

A

…

39
Q

Infleunza meds that only work on Infleunza A?

Must be given 1-2 before symptoms start! or may be given prophylatically

A

Rimantidine (Flumadine)
Amantadine (Symmetrel)

THESE ARE RARELY USED ANYMORE - OLDER MEDS.

40
Q

Chemistry/MOA for Rimantidine and Amantidine?

A

Work on viral uncoating

Adamantanes

41
Q

Kinetics of amantadine and rimantidine?

A

Rimantidine is extensively metabolized! (less SE)

Well absorbed, high nasal, salivary, lung levels

42
Q

ADRs of amantadine/rimandtidine?

A

(lower with rimantidine)
CNS (5-33%) - alters dopamine transmission
- HA, dizziness, nervousness, dificulty concentrating, insomnia, depression, fatigue
GI/GU (1-10%) nvd, dry mouth, urinary retention

TERATOGENIC, EMBRYOTOXIC!!

43
Q

Influenza A is more common early in the flu season.

A

…

44
Q

Antivirals for Influenza A and B?

must be given within 1-2 days of symptoms but also may be given prophylatically

A

Oseltamvir (Tamiflu)
Zanamivir (Relenza)
Peramivir (Rapivab)

45
Q

Oseltamivir, Zanamivir, and Peramivir…. MOA/Chemistry/MOR?

A

silica acid analogs
inhibit viral neuraminidase (causes clumping of virions preventing release from respiratory epithelial cells)

MOR = aa changes to viral neuraminidase

46
Q

Kinetics (how are they given) for influenza A/B drugs?

ADRs for each?

A

Oseltamivir (tamiflu) - orally - GI

Zanamivir (Relenza) - Nasally
-cough, bronchospaasm, may exacerbate asthma/COPD (give bronchodilator before use!)

Peramivir (Rapivab) - IV
skin reactions

47
Q

viral turnover is greatest at 1-2 days!!

We stretch this number for elderly patients.

A

…

48
Q

There is high resistance in amantadine/rimantidine!!! They are poorly tolerated also…. why we don’t use them anymore!

A

…

49
Q

Baloxavir marboxil (Xofluza) - FDA approved in October 2018.

MOA?
USes?
Adverse effects?
How often?

A

polymerase acidic endonuclease inhibitor

post exposure prophylaxix/A and B strains/Avian and swine flues

GI (n/d)

single oral dose!

useful for strains resistant to neuraminidase inhibitors

50
Q

Antivirals used against Hep B (3)

A

Inteferons
-peglyated interferon - MULTIPLE TOXICITIES

Nucleoside Reverse Transcriptase Inhibitors (given orally) - works on DNA pol

  • Lamivudine (Epivir HBV) - restance
  • Telbivudine (tyzeka) - resitance/$$
  • Entecavir (Baraclude) - most commonly used

Nucleotide Reverse Transcriptase Inhibitors (given orally) - works on DNA poly

  • Adefovir (Hepsera) - nephrotoxicity
  • Tenofovir (Viread) - most commonly used
51
Q

Interferons have to be injected! - subcutaneous injection

A

…

52
Q

Which two drugs are most commonly used for Hep B?

A

Entecavir (Barclude) - nucleoside - oral

Tenofovir (Viread) - nucleotide - oral

53
Q

What is the MOA of interferons…normally?

A
  • small glycoproteins released by macrophages, lymphocytes, and tissue cells infected with a virus
  • diffuse to surrounding cells and bind receptors on the cells
  • produces antiviral proteins

(this works in paracrine manner… normally!)
(interfere with spread of virus from one cell to another)

54
Q

Why are interferons pegylated?

A

longer half life

55
Q

Interferon alpha….

A

recombinant version of one or more proteins that are naturally produced by the body in response to a viral infection

antiviral, antiproliferative, immunomodulatory, and antifibrotic

MOA - not well defined

resistance is low because it is not well tolerated!

56
Q

Most common interferon used?

A

Pegylated IFN alpha-2a (pegasys)

Given SQ once weekly for 48 weeks

57
Q

Other interferons are used for cancer, MS, and granulomatous disease. Oral interferons are being developed…

A

…

58
Q

Adverse effects of Peg-interferon alpha-2a (pegasus)?

A
  • flu like illness, fever, HA, myalgia, fatigue
  • bone marrow suppression - leukpenia and thrombocytopenia
  • hair loss
  • change in mood

**Side effects worse than the Hep B disease itself

59
Q

Follow renal function for Tenofovir… (Hep B) - If renal dysfunction, do not use!

A

..

60
Q

Entecavir and Tenofovir can almost cure patients! Reduces viral load by 67-90/80-95

Have little viral resistance

A

..

61
Q

Increased serum creatinine in what drug?

A

Tenofovir! - why watch renal?

62
Q

Entecavir/Adefovir/Telbivudine.Tenofovir/Lamivudine class effects?

A

lactic acidosis
hepatic steatosis
rebound hepatitis

63
Q

HCV agents…
Immunomodulator?
Inhibit RNA poly?
Direct acting antiviral (DAA) agents? (3) - when using this target two areas to avoid resistance - medical miracle

A

peg-interferon

Ribavirin (rebetol,copegus)

NS 3/4 A protease inhibitor
NS5B polymerase inhibitior
NS5a replication complex inhibitor

64
Q

NS 3/4 A protease inhibitors for HCV

A

simeprevir
paritaprevir
telaprevir
boceprevir

65
Q

NS 3/4 A protease inhibitors for HCV

they inhibit cleavage of non-functional polypeptides into functional proteins

A

simeprevir
paritaprevir
telaprevir
boceprevir

have a lot of p’s!

66
Q

NS5B polymerase inhibitors for HCV?

binds to polymerase actie site (chain termination!)

A

sofosbuvir
dasabuvir

Have b’s!!!! NS5B!!!!

67
Q

NS5A replication complex inhibitor for HCV?

prevents creation of new sites of RNA synthesis! (inhibits assembly)

well tolerated!!! (fatigue, GI, HA, anemia)

A

ledipasvir
daclatasvir
ombitasvir
velpatasvir

have a’s!!! NS5A

68
Q

Oral Ribavirin (Rebetol, Copegus)
Chemistry?
Use?
MOA?

HCV tx

A

Oral guanosine analog
in combination with interferons and other drugs
MOA:
-phosphorylated intracellular by host enzymes
- inhibits viral RNA dependent RNA polymerases
- inhibits replication of DNA and RNA viruses

69
Q

Oral Ribavirin (Copegus, Rebetol) Adverse effects? (2)

HCV tx

A

1) Hemolytic anemia
- decline in hemoglobin within 1-2 weeks of initiation
- hemoglobin decrease usually approx 3.0 g/dl
- contraindicated in patients with significant or unstable cardiac disease

2)teratogencity and embryotoxicity

70
Q

Ribavarin Inhalation (virazole)

Used for what disease?

A

Used for RESPIRATORY SYNCYTIAL VIRUS (RSV) - seen primarily in children

inhalation with a small particle aerosol generator (1.3 microns)

71
Q

Adverse effects of Ribavarin Inhalation (Virazole) used for respiratory syncytial virus seen in children?

for person?
healthcare workers?
precautions taken for eye?

A

Rash, wheezing, eye irritation

Healthcare workers:

  • HA (51), conjunctivitis (32)
  • Rhinitis, dizzines, nausea, lacrimation (10-20)
  • MUTAGENIC, TERATOGENIC, EMBRYOGENIC - PREGNANT WOMEN SHOULD NOT RECEIVE OR GIVE CARE

-precautions - may absorb in contact lenses

72
Q

NS-5B polymerase inhibitors have what adverse effects?

black box warning?

A

Well tolerated (fatigue, GI, HA, anemia) - same as NS-5A

Interaction with Amidarone (fatal arrhythmias)

73
Q

NS3/4A
adverse effets?
black box warning?

A

SE: not well tolerated! - flu-like symptoms, serious liver injury
(also anemia, leukopenia, rash, pruritus, photosensitivity)

Black box:
hyperlipidemia, fat redistribution
CONTRAINDICATED IN MODERATE - SEVERE LVIER IMPAIRMENT. POTENT P450 3A4 INHIBITOR (many interactions)

74
Q

Should screen all patients for HBV before starting DAA (direct-acting antivirals) for HCV! There is a risk of HBV reactivation

A

…

Cellular Week 2 (9 decks)

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