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Ther 201 LE 3 > Antiviral Agents > Flashcards

Antiviral Agents Flashcards

1
Q

Viral Infection Properties/effects

A

(1) Self-limiting disease
(2) significant sequelae
(3) death
(4) latency

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2
Q

How do you activate anti-herpes agents (prodrugs)

A

Phosphorylate thrice

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3
Q

Enzymes used for anti-herpes agent activation

A

Viral thymidine kinase (TK)

G protein kinase (PKG UL97)

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4
Q

Drug activated by Viral thymidine kinase (TK)

A

Valcyclovir (HSV)

Famcyclovir (VZV)

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5
Q

Drug activated by PKG UL97

A

Valgancyclovir (for CMV)

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6
Q

Examples of Anti-herpes agents discussed in class

A

Acyclovir
Valacyclovir
Gancyclovir
Valgancyclovir

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7
Q

mechanism of action: Acyclovir

A

DNA chain terminator:

becomes activated once phosphorylated by the virus and targets polymerase

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8
Q

Acyclovir routes of administration

A

IV

Topical

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9
Q

Indications of IV acyclovir

A

severe/life threatening diseases caused by HSV/VZV
- Encephalitis
- Hepatitis
- Neonatal
- Acute retinal necrosis syndrome
- Mucocutaneous disease
- Zoster (with or without visceral disease)
critically ill patients for the therapeutic dose to be reached right away to avoid sequelae

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10
Q

Indication of Topical acyclovir

A

HSV immunocompromised hosts

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11
Q

Acyclovir + L-valylester

A

Valacyclovir

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12
Q

effect of addition of L-valylester

A

higher bioavailbility, more effects at same dose

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13
Q

Oral Acyclovir vs. Valacyclovir

A

advantage of valacyclovir:

  • reduced viral shedding
  • reduced fever by 1 day
  • dec skin lesion
  • dec time of total crusting by 2 days
  • less side effects
  • higher biovailability (3x higher)
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14
Q

synthetic guanosine analogue

A

Gancyclovir

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15
Q

Gancyclovir mechanism of action

A

suppresses viral DNA polymerase; competes for dGTP for incorporation into viral DNA

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16
Q

Gancyclovir advantage over Acyclovir

A

100X greater activity for CMV

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17
Q

Gancyclovir disadvantage

A

only for life threatening conditions

  • myelosuppresion
  • hepatotoxic
  • carcinogenic
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18
Q

Gancyclovir routes of administration

A

IV

Oral

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19
Q

Gancyclovir IV indications

A

congenital CMV, CMV retinitis, only for emergency

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20
Q

L-valyl ester of ganciclovir

A

Valgancyclovir

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21
Q

What happens after oral ingestion of Valgancyclovir?

A

both diastereomers are hydroyzed by intestinal and hepatic esterases

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22
Q

compare Gancyclovir and Valgancyclovir

A

Valgancyclovir has a higher bioavailability (60%) due to addition of L-valyl ester, longer half life, both are excreted via renal pathway

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23
Q

Factors considered for Varicella treatment

A

(1) host factors
(2) extent of infection
(3) initial response to therapy

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24
Q

Varicella duration of replication in immunocompetent hosts

A

72 hours

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25
Q

routine use of acyclovir is not recommended in

A

healthy children < 12 years

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26
Q

Oral acyclovir is given to

A
  • more than 12 years
  • chronic cutaneous/pulmonary skin disorders
  • long-term salicylate therapy
  • short, intermittent, aerosolized course of corticosteroids
  • pregnant women (2nd/3rd trimesters)
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27
Q

IV acyclovir is given to

A

for immunocompromised patients

  • treated with chronic corticosteriods
  • pregnant women with serious complications
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28
Q

Treatment of neonatal HSV

A

IV - 14 days - skin, eye and mouth disease

IV - 21 days for HSV encephalitis

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29
Q

Treatment of genital HSV

A

primary: oral acyclovir or valacyclovir
severe: IV
recurrent: same as primary + suppression therapy for 1 year (if more than 6 recurrences)

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30
Q

Treatment of mucocutaneous HSV

A

Oral always for immunocompetent

IV for immunocompromised

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31
Q

Treatment of Varicella zoster infections (chickenpox, shingles)

A

Oral always for immunocompetent

IV for immunocompromised

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32
Q

Anti-HSV drugs are given to those treated with immunosuppressant drugs or radiotherapy because

A

due to risk of HSV infection via reactivation of the latent virus

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33
Q

Steps involved in cell entry of HIV

A

attachment
co-receptor binding
fusion

34
Q

converts viral RNA to DNA

A

reverse transcriptase

35
Q

incorporates viral DNA into chromosome

A

integrase

36
Q

Protease importance

A

cleaves viral proteins to several smaller units to activate them (maturation)

37
Q

Target Steps of Drugs

A

(1) entry
(2) reverse transcriptase
(3) integrase
(5) protease

38
Q

process wherein new viruses/virions are formed and released

A

viral budding

39
Q

Classes of Antiretrovirals

A

(1) Nucleoside reverse transcriptase inhibitors
(2) Non-nucleoside RTI
(3) protease inhibitors
(4) entry inhibitors
(5) integrase inhibitors

40
Q

nucleoside reverse transcriptase inhibitors mechanism of action

A

inhibits RT by being incorporated to newly synthesized viral DNA, preventing further elongation

41
Q

nucleoside reverse transcriptase inhibitors adverse effects

A

lactic acidosis
hepatic steatosis
dyslipidemia

42
Q

NRTI pro-drug

A

Zidovudine/Azidothymidine (AZT)

43
Q

AZT adverse effects:

A

macrocytic anemia

44
Q

NRTI examples

A

Zidovudine
Lamivudine
Tenofovir

45
Q

Non-NRTI MOA

A

attaches to a site distant from the RT’s active site to inhibit it

46
Q

NNRTI adverse effects

A

Stevens Johnson Syndrome
nausea
hypersensitivity
Drug interactions *CYP3A3

47
Q

most recommended NNRTI

A

Niverapine

48
Q

Niverapine properties

A

excellent BA (>90%)
not affected by food
effective in preventing maternal-fetal transmission
rash in 20%, mild and selflimiting, 7% severe
liver HT 4%

49
Q

Protease inhibitors MOA

A

inhibits protease preventing maturation (cleavage) of viral peptides

50
Q

Protease inhibitors disadvantage

A

limited CNS penetration
multiple drug-drug interactions as CYP450 metabolizes it
multiple side effeccts

51
Q

Protease inhibitors side effects

A

serum lipid abnormalities, vascular system effects, body fat redistribution (lipodystrophy), glucose intolerance

52
Q

Protease inhibitor in the PH

A

Lopinavir + Ritonavir (combination or not)

53
Q

Ritonavir is a potent inhibitor of

A

CYP3A4

54
Q

Used as a booster of other protease inhibitors

A

Ritonavir. fewer dose but higher effects - synergistic

55
Q

T/F all adults must be given ART regardless of WHO clinical stage and at any CD4 cell count

A

T

56
Q

ART priority given to

A

WHO Stage 3 or 4

CD4 count <= 350 cells/mm3

57
Q

First line ART

A

two NRTIs + one NNRTI

NEVER MONOTHERAPY

58
Q

Monotherapy for ART results to

A

resistance

59
Q

Drugs for HepaB therapy in adults, + children above 12

A

Tenofovir (high barrier to drug resistance)

Entecavir

60
Q

Drugs for HepaB therapy for children 2-11 years of age

A

Entecavir

61
Q

Influenza virus infection symptoms

A 
acute high fever
dry cough
myalgia
arthralgia
severe malaise
sore throat 
runny nose
sever and lasts for more than 2 weeks
62
Q

Influenza Virus latest strain

A

H7N9

63
Q

why is influenza vaccine administered yearly

A

reassortment of H and N variants produces new strains

64
Q

H variant

A

hemagglutinin

65
Q

N variant

A

Neuraminidase

66
Q

Neuraminidase function

A

needed by virus to penetrate and/or escape from the cell, elicits mucus secretion from the host

67
Q

Neuraminidases inhibitors function

A

inhibits release of progeny and/or prevents penetration of virus to the protective mucus of respiratory epithelium

68
Q

Examples of Neuraminidase inhibitors

A

Zanamivir
Oseltamivir
Adamantanes

69
Q

not effective against influenza B

A

Adamantanes - no longer used due to resistance

70
Q

Adamantanes examples

A

Amantadine

Rimantadine

71
Q

Zanamivir vs. Osetalmivir form/route

A

z: inhaled dry powder
o: capsule

72
Q

Zanamivir vs. Osetalmivir effective on which age group

A

z: not for children <7
o: old people (O for Old)

73
Q

Zanamivir vs. Osetalmivir bioavailability

A

z: 4-17%
o: 75%

74
Q

Zanamivir vs. Osetalmivir metab/excretion

A

z: renal
o: liver -> active carboxylate form

75
Q

Zanamivir vs. Osetalmivir halflife

A

z: 2.5-5.1h
o: 6-10h

76
Q

effects of Zanamivir and Osetalmivir

A

relief of symptoms by 1-5 days, decrease viral shedding

77
Q

greatest benefit when antiviral is given within

A

48 hours of influenza illness onset

78
Q

persons with higher risk for influenza complication

A 
<2
>65
person with immunosuppression
with chronic pulmo, CV, renal, hepatic, hema, metab, neuro
<19 receiving long term aspirin therapy
pregnant women
obese
79
Q

recommended anti-influenza treatment duration

A

5 days

80
Q

Zanamivir adverse effects

A 
bronchospasm (not recom for ppl with pulmo disease)
oropharyngeal and facial edema
nausea
diarrhea
ENT infections
81
Q

Oseltamivir

A

transient neuropsych events (reports only for Japanese)

Nausea/vomit (most common)

Ther 201 LE 3 (9 decks)

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