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Pharm Exam 4 > Antiviral drugs > Flashcards

Antiviral drugs Flashcards

1
Q

Drug for:

HSV1/HSV2/VZV/CMV?

A
  • acyclovir
  • valacyclovir
  • ganciclovir
  • valganciclovir
  • foscarnet
  • trifluridine
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2
Q

Drugs for influenze viruses?

A
  • osteltamivir
  • zanamivir
  • amantadine
  • rimantadine
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3
Q

Drugs for Respiratory syncytial virus?

A

-aerosolized ribavarin

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4
Q

Drugs for Chronic HCV

A
  • ribavarin
  • pegylated interferon
  • sofosbuvir
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5
Q

Which viral enzyme does oseltamivir inh

A

(-activated by liver esterases)
-binds to active site of neuraminidase = inh function
==> stops spread of progeny virons through respiratory tract

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6
Q

Which viral enzyme does zanamivir inh?

A

-(-activated by liver esterases)
-binds to active site of neuraminidase = inh function
==> stops spready of progeny virons through respiratory tract

SAME AS OSELTAMIVIR JUST INHALATION ROUTE NOT ORAL

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7
Q

Which viral enzyme does amantadine inh?

A

1) symmetric tricyclic amine
2) MOA
- inh activity of **INFLUENZA A M2 PROTEIN*
- its an ion channel forming protein needed for nucleocapsid release

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8
Q

Which viral enzyme does rimantadine inh?

A

1) symmetric tricyclic amine
2) MOA
- inh activity of **INFLUENZA A M2 PROTEIN*
- its an ion channel forming protein needed for nucleocapsid release

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9
Q

Virus life cycle

A
  • Attachment
  • Entry
  • mRNA production
  • Protein and genome synthesis
  • viron assembly
  • Egress
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10
Q

Herpes virus - genome type?

A

DNA viruses that encode own polymerase

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11
Q

Therapeutic target for Herpes virus drugs?

A

Herpes own encoded DNA polymerase

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12
Q

Which herpes stage is suppresed by antivirals?

A

lytic (productive/contagious) stage

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13
Q

Herpes tx goals?

A
  • speed healing

- inc time bw outbreaks

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14
Q

Which herpes virus diseases almost exclusively occur in immunocompromised patients?

A

1) HSV1&2
- Disseminated herpes infections
2) cytomegalovirus (only immnocomp individuals)
- pneumonia
- gastroenteritis
- retinitis

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15
Q

Acyclovir

  • *-MOA?
  • Resistance development?
A
  • -MOA:
    1) phosphorylated by viral thymidine kinase**
    2) competitive inh of viral DNA polymerase**
    3) chain termination upon incorporation into viral DNA
  • Resistance:
    1) mutation in thymidine kinase gene
    2) cross-resistance with other antivirals with similar mech
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16
Q

Acyclovir

*-therapeutic indications?

A

1) oral
- genital herpes
- varicella zoster
2) IV
- severe disesminated mucocutaneous disease
- neonate infections
- HSV encephalitis
- VZV in immunocomp

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17
Q

Acyclovir

*-special adverse effects?

A

-reversible crystalline nephrotox and neurological effects ESPECIALLY WHEN PATIENT IS DEHYDRATED

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18
Q

Cautious use of this drug in dehydrated or pt already on nephrotoxic drug?

A

acyclovir

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19
Q

Valacyclovir

  • MOA?
  • Why use this drug?
A
  • Same as acyclovir - Vala is a PRODRUG of acyclovir activated in the liver and intestines
  • MOA:
    1) phosphorylated by viral thymidine kinase**
    2) competitive inh of viral DNA polymerase**
    3) chain termination upon incorporation into viral DNA*
  • BETTER BIOAVAILABILTY
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20
Q

Valacyclovir

-Therapeutic indications:

A

GREAT ORAL ROUTE

  • primary and recurrent genital herpes
  • varicella in older children and adults
  • zoster
  • orolabial herpes
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21
Q

**-What is the difference bw foscarnet and acyclovir/valacyclovir?

A
  • ***-Foscarnet does NOT need to be phosphorylated by thymidine kinase for activity
  • How would resistance be developed to fosc—> in DNA Poly (Rare)
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22
Q

**Foscarnet route of administration?

A

ONLY IV!**

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23
Q

Foscarnet MOA?

A
  • No activation required by thymidine kinase

- acts directly on DNA POL - binds where pyrophosphate binds so no adding new nucleotides

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24
Q

-When to use foscarnet?

A
  • If patient infection shows resistance to acyclovir or valacyclovir
  • good for all CMV infections
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25
Q

Patient has CMV retinitis, CMV colitis or CMV esophagitis - give which antiviral drug?

A
  • foscarnet

- ganciclovir

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26
Q

Foscarnet - adverse:

A

-DO NOT USE foscarnet when patient is on othe rnephrotoxic drugs (acyclovir/valacyclvir only need to use caution with nephrotox drugs)

27
Q

Ganciclovir

  • Similar to what drug?
  • MOA?
  • why better?
A
  • nucleoside analog like acyclovir
  • initial phosphorylating by viral kinase CMV UL97 –> much more efficient than acyclovir ===> 100x more active than acyclovir
  • competitive inh of viral DNA POL = chain termination
28
Q

Direct Inh of viral DNA POL via binding to pyrophosphate binding area so virus cant add new nucleotides??

A

-foscarnet

29
Q

Competitive inh of DNA poly by acting as nucleotide analogs that terminate the chain when added?

A
  • acyclovire
  • valacyclovir
  • ganciclovir
30
Q

Ganciclovir

  • Bioavailability?
  • Route of administration?
A
  • Poor oral

- given IV, oral, or intraoccular

31
Q

Ganciclovir

-Therapeutic indication:

A

1) IV=
- CMV retinitis (AIDS)
- CMV colitis, pneumonitis, esophagitis
2) IV then ORAL=
- reduce risk of CMV disease in transplant patients
3) Intraoccular=
- CMV reitinitis

32
Q

Ganciclovir

-Adverse:

A
  • myelosuppression
  • CNS tox

many IV adverse rxns

33
Q

Valganciclovir

  • MOA?
  • why use this drug over ganciclovir?
A

1) PRODRUG OF GANCICLOVIR
2) MOA
- nucleoside analog like acyclovir
- initial phosphorylating by viral kinase CMV UL97 –> much more efficient than acyclovir ===> 100x more active than acyclovir
- competitive inh of viral DNA POL = chain termination

Better oral bioavailabilty than ganciclovir

34
Q

Valganciclovir

-Therapeutic indications:

A
  • CMV retinitis (AIDS)

- prevent CMV in transplant patients (prophylactic)

35
Q

Trifluridine

  • type of drug?
  • MOA?
A

1) fluorinated nucleoside (nucleotide mimic)
2) MOA
- phosphorylated by cellular enzymes
- competitive inh of thymidine for incorporation into newly synthesized genomes

36
Q

Trifluridine

-Therapeutic indications:

A
  • low selectivity = not for systematic administration (can insert into HOST DNA=not good)
  • OCCULAR addministration for keratoconjunctivtis and recrrent epithelial ketatitis due HSV1&2
37
Q

Different bw Trifluridine and the other -vir antivirals?

A
  • trifluridine is activated by HUMAN CELLULAR ENZYMES

- other -vir antivirals are activated by viral enzymes

38
Q

INfluenza virus

  • genome type
  • which serotypes and which we worry about?
  • protection/prophyaxis?
A
  • segmented RNA virus
  • orthomyxovirus family
  • A B and C serotypes
  • A and B are serious ones

-We have vaccines - injectable inactivated & attenuated

39
Q

How to tx influenza?

A

antivirals must be given within first 48 hours or no effect on disease progression

40
Q

Oseltamivir

  • type
  • MOA?
A

1) sialic acid analogue
-administered as prodrug - activated by HUMAN liver esterases
2) binds to active site of neuraminidase - cleaves sialic moities = inh function
==> stops spready of progeny virons through respiratory tract

41
Q

Oseltamivir

  • Therapeutic indications
  • adverse effects?
A
  • ok for children 1+ yo and up
  • effective against A and B serotypes
  • must be given within first 48 hours for effect in uncomplicated

-usual - headahce, nausea, faituge….
RARELY =rash and neuropsychiatric events

42
Q

Zanamivir

  • type
  • MOA?
A

-just like oseltamivir
1) sialic acid analogue
-administered as prodrug - activated by HUMAN liver esterases
2) binds to active site of neuraminidase - cleaves sialic moities = inh function
==> stops spready of progeny virons through respiratory tract

43
Q

Zanmivir

-administration

A

INHALATION (POWER)

44
Q

oseltamivir vs zanamivir - use in children

A
  • oseltamivir good for children 1+

- zanamivir good for children 7+

45
Q

Zanamivir

-adverse effects:

A
  • cough
  • bronhcospasm
  • temp decrease in pulmonary function
  • irritation nose and throat
  • DO NOT GIVE TO PATIENTS WITH PULMONARY DISEASE
46
Q

Amantadine & Rimantadine

  • type drug?
  • MOA?
A

1) symmetric tricyclic amine
2) MOA
- inh activity of INFLUENZA A M2 PROTEIN
- its an ion channel forming protein needed for nucleocapsid release

47
Q

Amantadine & Rimantadine

-therapeutic indications?

A
  • must be given within 48 for INFLUENZA A VIRUS INF to decrease illness by ~1 day… awesome
  • not really used = HIGH LEVELS OF RESISTANCE
48
Q

Respiratory syncytial virus (RSV)

  • type of virus/family?
  • Who gets this/what happens?
A
  • enveloped
  • RNA
  • paramyxovirus family
  • children under 1 year = bronchilitis and pneumonia
  • immunosuppressed get
  • common cold in everyone else
49
Q

RSV -

Tx? When treat?

A

Ribavirin - only in infants and immunocomp infection

50
Q

Ribavirin

  • type of drug?
  • MOA?
A

1) guanosine analogue
2) phosphorylated by HUMAN adenoside kinase –> interferes with synthesis of guanosine triphos ==> inh viral mRNA capping

51
Q

Which drug INH RNA depependent RNA pol for RSV and HCV

A

Ribavirin

52
Q

Ribavirin

-route of administration:

A
  • AEROSOL ROUTE FOR RSV

- ORAL for HCV (with pegylated interferon for chronic)

53
Q

Which drugs can be administered by inhalation?

A
  • Ribavirin (aerosol for RSV)

- zanamivir (fine power)

54
Q

Ribavirin

-Adverse:

A

-hemolytic anemia
-depression
fatigue
rash
cough
insomnia
…

55
Q

Ribavirin

-contraindication:

A
  • pregnancy
  • anemia
  • ischemic vascular disease
  • severe renal disease
56
Q

HCV

  • type virus/family?
  • genotypes and significance?
  • transmission?
A
  • ssRNA / flavivirus
  • 6 genotypes where #1 is the least responsive to antiviral tx
  • parenteral - close contact
57
Q

Acute & Chronic HCV?

A
  • acute is mild

- 70% progress to chronic = cirrhosis and HCC

58
Q

*Treatment for CHRONIC HCV genotypes 1, 4, 5, and 6?

A

COMBO THERAPY

  • Ribavirin
  • pegylated interferon
  • sofosbuvir
59
Q

*Treatment for CHRONIC HCV genotypes 2 and 3?

A

COMBO THERAPY

  • sofosbuvir
  • ribavirin
60
Q

Ribavirin administration for chronic HCV?

A

oral

61
Q

Interferon

  • MOA?
  • administration?
A
  • binds interferon receptors on immune cells and Jak/Stat paths ==> invoked antiviral state is cells
  • IV
62
Q

Sofosbuvir

  • type of drug?
  • MOA?
  • administration?
A

1) nucleic acid prodrug
2) MOA
- incorporated into synthesized RNA via RNA dependent RNA poly = premature chain termination
- ORAL

63
Q

Do not give sofosbuvir with what stuff?

A

-do not with inducers of p-glycoproteins - St johns wort, rifampin (TB drug)

64
Q

Sofosbuvir

-therapeutic indications?

A
  • HCV 1,4,5,6 give triple therapy (sofos, ribavirin, peg-interferon)
  • HCV 2,3 give dual or triple therapy (sofos, ribavirin +/-peg-interferon)’

NEVER MONOTHERAPY

Pharm Exam 4 (10 decks)

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