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Flashcards in Antiviral Agents Deck (81):
1

Viral Infection Properties/effects

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

2

How do you activate anti-herpes agents (prodrugs)

Phosphorylate thrice

3

Enzymes used for anti-herpes agent activation

Viral thymidine kinase (TK)
G protein kinase (PKG UL97)

4

Drug activated by Viral thymidine kinase (TK)

Valcyclovir (HSV)
Famcyclovir (VZV)

5

Drug activated by PKG UL97

Valgancyclovir (for CMV)

6

Examples of Anti-herpes agents discussed in class

Acyclovir
Valacyclovir
Gancyclovir
Valgancyclovir

7

mechanism of action: Acyclovir

DNA chain terminator:
becomes activated once phosphorylated by the virus and targets polymerase

8

Acyclovir routes of administration

IV
Topical

9

Indications of IV acyclovir

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

10

Indication of Topical acyclovir

HSV immunocompromised hosts

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Acyclovir + L-valylester

Valacyclovir

12

effect of addition of L-valylester

higher bioavailbility, more effects at same dose

13

Oral Acyclovir vs. Valacyclovir

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)

14

synthetic guanosine analogue

Gancyclovir

15

Gancyclovir mechanism of action

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

16

Gancyclovir advantage over Acyclovir

100X greater activity for CMV

17

Gancyclovir disadvantage

only for life threatening conditions
-myelosuppresion
-hepatotoxic
-carcinogenic

18

Gancyclovir routes of administration

IV
Oral

19

Gancyclovir IV indications

congenital CMV, CMV retinitis, only for emergency

20

L-valyl ester of ganciclovir

Valgancyclovir

21

What happens after oral ingestion of Valgancyclovir?

both diastereomers are hydroyzed by intestinal and hepatic esterases

22

compare Gancyclovir and Valgancyclovir

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

23

Factors considered for Varicella treatment

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

24

Varicella duration of replication in immunocompetent hosts

72 hours

25

routine use of acyclovir is not recommended in

healthy children < 12 years

26

Oral acyclovir is given to

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

27

IV acyclovir is given to

for immunocompromised patients
-treated with chronic corticosteriods
-pregnant women with serious complications

28

Treatment of neonatal HSV

IV - 14 days - skin, eye and mouth disease
IV - 21 days for HSV encephalitis

29

Treatment of genital HSV

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

30

Treatment of mucocutaneous HSV

Oral always for immunocompetent
IV for immunocompromised

31

Treatment of Varicella zoster infections (chickenpox, shingles)

Oral always for immunocompetent
IV for immunocompromised

32

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

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

33

Steps involved in cell entry of HIV

attachment
co-receptor binding
fusion

34

converts viral RNA to DNA

reverse transcriptase

35

incorporates viral DNA into chromosome

integrase

36

Protease importance

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

37

Target Steps of Drugs

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

38

process wherein new viruses/virions are formed and released

viral budding

39

Classes of Antiretrovirals

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

40

nucleoside reverse transcriptase inhibitors mechanism of action

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

41

nucleoside reverse transcriptase inhibitors adverse effects

lactic acidosis
hepatic steatosis
dyslipidemia

42

NRTI pro-drug

Zidovudine/Azidothymidine (AZT)

43

AZT adverse effects:

macrocytic anemia

44

NRTI examples

Zidovudine
Lamivudine
Tenofovir

45

Non-NRTI MOA

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

46

NNRTI adverse effects

Stevens Johnson Syndrome
nausea
hypersensitivity
Drug interactions *CYP3A3

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most recommended NNRTI

Niverapine

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Niverapine properties

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

Protease inhibitors MOA

inhibits protease preventing maturation (cleavage) of viral peptides

50

Protease inhibitors disadvantage

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

51

Protease inhibitors side effects

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

52

Protease inhibitor in the PH

Lopinavir + Ritonavir (combination or not)

53

Ritonavir is a potent inhibitor of

CYP3A4

54

Used as a booster of other protease inhibitors

Ritonavir. fewer dose but higher effects - synergistic

55

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

T

56

ART priority given to

WHO Stage 3 or 4
CD4 count <= 350 cells/mm3

57

First line ART

two NRTIs + one NNRTI
NEVER MONOTHERAPY

58

Monotherapy for ART results to

resistance

59

Drugs for HepaB therapy in adults, + children above 12

Tenofovir (high barrier to drug resistance)
Entecavir

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

Entecavir

61

Influenza virus infection symptoms

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

62

Influenza Virus latest strain

H7N9

63

why is influenza vaccine administered yearly

reassortment of H and N variants produces new strains

64

H variant

hemagglutinin

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N variant

Neuraminidase

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Neuraminidase function

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

67

Neuraminidases inhibitors function

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

68

Examples of Neuraminidase inhibitors

Zanamivir
Oseltamivir
Adamantanes

69

not effective against influenza B

Adamantanes - no longer used due to resistance

70

Adamantanes examples

Amantadine
Rimantadine

71

Zanamivir vs. Osetalmivir form/route

z: inhaled dry powder
o: capsule

72

Zanamivir vs. Osetalmivir effective on which age group

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

73

Zanamivir vs. Osetalmivir bioavailability

z: 4-17%
o: 75%

74

Zanamivir vs. Osetalmivir metab/excretion

z: renal
o: liver -> active carboxylate form

75

Zanamivir vs. Osetalmivir halflife

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

76

effects of Zanamivir and Osetalmivir

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

77

greatest benefit when antiviral is given within

48 hours of influenza illness onset

78

persons with higher risk for influenza complication

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

79

recommended anti-influenza treatment duration

5 days

80

Zanamivir adverse effects

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

81

Oseltamivir

transient neuropsych events (reports only for Japanese)
Nausea/vomit (most common)