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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
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
47
most recommended NNRTI
Niverapine
48
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
60
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
65
N variant
Neuraminidase
66
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)

Ther 201 LE 3 (9 decks)

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