Sweatman Antiviral Drugs Flashcards
1
Q
NRTI’s
A
ABACAVIR
LAMIVUDINE (3-TC)
TENOFOVIR
ZIDOVUDINE (AZT)
2
Q
HIV-1 PROTEASE INHIBITORS
A
ATAZANAVIR
RITONAVIR
3
Q
DNA STRAND TRANSFER INHIBITORS
A
RALTEGRAVIR
4
Q
NNRTI’S
A
EFAVIRENZ
NEVIRAPINE
5
Q
FUSION INHIBITORS
A
ENFUVIRTIDE
MARAVIROC
6
Q
CLASSES OF ANTI-RETROVIRAL DRUGS
A
NRTI's NNRTI's HIV-1 PROTEASE INHIBITORS DNA STRAND TRANSFER INHIBITORS FUSION INHIBITORS
7
Q
ANTIVIRAL DRUGS
A
ACYCLOVIR- (ZOVIRAX) VALCYLOVIR- (VALTREX) RIMANTIDINE PEGINTERFERON ALFA VALGANCICLOVIR BECEPREVIR FOSCARNET GANCICLOVIR OSELTAMVIR (TAMI-FLU) RIBAVARIN TELAPREVIR TRIFLURIDINE ZANAMIVIR
8
Q
REASONS WHY VIRUSES ARE HARD TO TREAT
A
- fewer targets sufficiently different than host cells to exploit
- heterogeneous group of infectious agents (harder to make a broad spectrum drug)
- replicate by co-opting host cell machinery
9
Q
general steps involved in a DNA virus replication
A
- attachment and entry
- uncoating
- genome replication
- RNA synthesis
- protein synthesis
- assembly and maturation
- Eggress and release
10
Q
MOA for most antiviral agents that are currently approved
A
neucleoside analogues that target genome replication (DNA polymerase or reverse transcriptase)
11
Q
Attachment and entry inhibitors and their target
A
Maraviroc
Enfuviritide (t-20)
*attachment and entry
12
Q
Ion channel blockers and their target
A
amantidine
rimantadine
*M2 ion channel–> prevents uncoating
13
Q
polymerase inhibitors and their target
A
acyclovir
zidovudine
efavirenz
*reverse transcriptase or DNA polymerase
14
Q
integrase inhibitor and their target
A
raltegravir
*prevents viral dna from being inserted into the host DNA
15
Q
protease inhibitors and their target
A
saquinavir
ritonavir
*prevents assembly an maturation
16
Q
Neuroaminidase inhibitors and their target
A
zanamavir
oseltamvir
*prevents mature virions from exiting host cell
17
Q
Steps in HIV-1 retrovirus replication
A
- virus attachment
- Fusion
- uncoating
- integration
- transcription and post-transcriptional processing
- translation
- assembly
- proteolytic cleavage—> fully infective virions
18
Q
Virus attachment for HIV depends on
A
gp41-gp120 complex binding to host cell CD4+ T cell receptors and certain chemokine receptors
19
Q
Fusion of HIV virus relies on–>
A
HR1 and HR2 complex forming a fusion pore
20
Q
type of genetic material in HIV virus
A
ssRNA
21
Q
what does uncoating stage of HIV replication accomplish
A
permits ssRNA HIV genome to be copied by RT in to dsDNA
22
Q
integration step relies on
A
HIV encoded protein “integrase”
23
Q
Stages of Influenza A replication
A
- Hemagglutinin bind sialylated glycoprotein receptors on host-cell
- virus enter cell via receptor-mediated endocytosis
- ATP dependent proton pump acidifies cell
- hemagglutinin reminds to endosome, virus-host membranes fuse
- RNP’s now released into cytoplasm
- RNP’s taken to nucleus for replication
24
Q
M2 ion channels are located where?
A
viral membrane
25
M2 channel blockers
amantadine
| rimantadine
26
Neuaraminidase inhibitors
oseltamvir
| zanamivir
27
know why antiviral drugs are limited based on time course of infection-->symptom presentation
by the time someone feels like shit...virus has already proliferated and the virus has spread all over
*this s why tami-flu must be taken in the first 2-3 days of contracting influenza A
28
know the steps involved in HIV infection
too many to type justt know them in your soul
29
Enfuvirtide (t-20) MOA
mimics HR2, binds HRI--> prevents HR1 and Hr2 interaction
| *traps the process at the atachment stage-->no membrane fusion
30
Maraviroc MOA
blocks "other chemokine receptors"
| -->therefore cells that rely on CCR5 for attachment and entry are inhibited
31
M2 ion channel MOA
pH gated ion channel that opens up in response to acidification of endosome--> necessary step for uncoating of Influenza A RNP's and viral genetic material into cytosol
32
Which are HIV-1 specific NRTI's or NNRTI's
NNRTI's
33
Require metabolic activation usually to a triphosphate form
NRTI's
34
Indirectly inhibits polymerization
NRTI's
35
prevents elongation of newly formed nucleic acid by polymerase
NRTI's
36
most common uses of NRTI's
herpes
| HIV
37
MOA of nucleoside analogues
competitive inhibition with endogenous nucleosides for DNA polymerase/reverse transcriptase-->ultimately leading to termination of elongation
38
toxicity associated with NRTI's
*they also inhibit mitochondrial DNA synthesis-->leading to depletion of mitochodnrial DNA
39
MOA for NNRTI's
Direct-Specific inhibition of HIV-1 RT:
| bind to hydrophobic pocket on HIV-1 reverse transcriptase changing its form and function
40
Does NNRTI's require metaoblic activation (ie intracellular phosphorylation)
HELL NAW
41
NNRTI's are innefective against HIV-2, or other retroviruses
binding site is virus strain specific
42
Raltegravir MOA
blocks activity of HIV 1 and 2 integrase
| *cannot insert cDNA into host chromosome
43
HIV-1 protease inhibitors MOA
"inhibit precursors of polypeptide cleavage"
-inhibit ASPARTYL PROTEASE (responsible for HIV gag and pol precursors that go on to make many CRUCIAL prot components required for replication--> enzymes and strcutral
(reverse trasncriptase, proteases, integrases, many structural prots)
44
Some Protease inhibitors used in HIV treatment---WHY?
Some of them inhibit CYP3A4 activity-->(RITONAVIR) in low doses will prolong plasma persistence of drugs broken down by CYP3A4
45
What limits Protein INhibitors presence in Blood Brain Barrer
1. P-gp pump (ABC transporter---> MDresistance)
| 2. strong plasma-protein biding
46
What is unique about peginterferon
log-lasting formulation of interferon that is conjugated to ethylene glycol to increase durability in the circulation of active drug
47
Interferons affect what types of viruses
DNA and RNA
48
Interferon MOA
BInding if an IFN causes cell to produce a series of antiviral proteins MOST OF WHICH ACT TO INHIBIT THE TRANSLATION OF VIRAL PROTEINS
49
Drugs which inhibit release of influenza virus form infected cell
Zanamivir, Oseltamvir
| *selective sialic acid analogue inhibitors
50
MOA for drugs that inhibit Influenza A release
produce conformational changes in active site of influenza A and B NEURAMINIDASES
51
What do neuraminidases do?
destroy terminal sialic acid residues-->which destroys the receptors recorgnized by viral hemagglutinin that are present on the cell surface in progeny virions and respiratory secretions
52
Use of these drugs leads to local aggregation of progeny virions on infected cell surface and results in decreased viral spread within the respiratory tract
neuroaminindase inhibitors
53
Principle of chemo:
| ALL ASPECTS OF THE DISEASE ARE DERIVED FROM VIRAL EFFECTS UPON ______
CD4+ Helper T Cells
54
Principle of HIV chemo:
| Current drugs require ______
actively replicating virus
55
Principle of HIV chemo:
| If the viral genetic material is hiding in quiescent T cells____
it is unlikey that drug treatment will eradicate ALL infected T cells
56
Principle of HIV chemo:
| It is likely that some infected T cells_____
will survive decades if not throughout the life of the patient
57
Principle of HIV chemo:
| Drug therapy does NOT cause mutations
rather it provides selective presure to promote growth of the naturally ocuring mutant viruses
(i'm not following this?)
58
Principle of HIV chemo:
| Clinically beneficial of HIV chemo?
1. long-term suppression (decrease in plasma RNA levels
| 2. replenishment of CD4+ T cells
59
Result of using 3 HIV drugs simultaneously
initial treatment will reduce plasma RNA copies <50copies/mL by 24 weeks
60
Limiting factor in using 4+ drugs?
1. toxicity
| 2. inconveneince (pt's ability to tolerate)
61
If viral resistance is observed?
| *implying RNA levels increase despite continued adherence to the regimen
regimen must be changed
62
Principle of HIV chemo:
| resistant strains remain in?
T lymphocytes forever
63
Principle of HIV chemo:
| the relative "forgiving nature" of a given regimen towards missed doases is based on?
duration of of drug persistence in pt's blood
| longer half lives are better
64
Principle of HIV chemo:
| failed treatment usually resultant of
non-adherence
65
preferred agents used against HBV polymerase
tenofovir disproxil fumarate, and entacavir
66
tx for HCV is defined by?
genotype of the infected virus
67
Genotype 1 HCV is treated with?
peginteferon-alfa + ribavarin + telaprevir + boceprevir HCV NS3/4A
68
Major factor in recent H1N1 resistant to neuraminidase inhibitors?
overuse of drugs and veterinary usage
69
DOC for early events (viral entry of uncoating)
enfurvitide, maraviroc, amantadine, rimantadine
70
DOC for nucleic acid synthesis by herpes viruses
Acyclovir, Ganciclovir, Valcyclovir, Valganciclovir
71
DOC for Nucleic acid synthesis by HIV
| *NRTI's
abacavir, lamivudine (3-tc), tenofivir, disproxil, zidovudine (AZT), emtricitabine, didanosine (ddl), stavudine
72
DOC for Nucleis acid synthesis in HIV
| **NNRTI's
efevirenze, nevirapine
73
DOC for Nuecleic acid synthesis by HBV
adefovir
74
DOC for nucleic acid synthesis for other viruses
ribavarin, trifluridine
75
DOC for HIV integrase inhibition
raltegravir
76
DOC for cleavage (protease) of precursor polypeptides
atazanavir, ritonavir
77
DOC Cleavage of precursor polypeptides of HCV
boceprevir, telaprevir
78
DOC for synthesis directed by viral mRNA
Peginterferon-alfa
79
DOC for release of influenza from infected cell
Oseltamvir, Zanamivir
