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MVST1B MODA > Chemotherapy L4 > Flashcards

Chemotherapy L4 Flashcards

1
Q

amantadine is used to treat what?

A

Flu

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2
Q

what does amatadine act on?

A

M2 proton channel

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3
Q

role of NA in flu?

A

The neuraminidase helps prevent viral aggregation, facilitates release from the host cells, and may have a role as a virulence factor.

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4
Q

Two major drugs used against Influenza A are ,…..

A

Two major drugs used against Influenza A are amantadine and rimantadine.

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5
Q

how do amantadine and rimantadine work?

A

Both drugs possess a dual mechanism of action. At an early step in viral replication, they block the function of the M2 channel protein. At a later stage, they interfere with hemagglutinin processing

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6
Q

The neuraminidase (also termed sialidase) of Influenza A and possibly B is inhibited by

A

The neuraminidase (also termed sialidase) of Influenza A and possibly B is inhibited by oseltamivir and zanamivir;

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7
Q

how do oseltamivir and zanamivir wokr?

A

inhibit neuraminidase

enhance viral aggregation and inhibit release from the host cells. In addition, they reduce movement of the virus particles through the upper respiratory tract

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8
Q

Zanamivir is an _____ drug whereas oseltamivir is an ethyl ester ____-drug, which is cleaved by esterases in the plasma and in cells of the gut upon the adsorption of oseltamivir.

A

Zanamivir is an active drug whereas oseltamivir is an ethyl ester pro-drug, which is cleaved by esterases in the plasma and in cells of the gut upon the adsorption of oseltamivir.

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9
Q
A
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10
Q

how does Ribavirin work?

A
  • taken up as guanosine analogue.
  • phosphorylated by cellular kinases to Ribavirin-MP, DP, and TP.
  • Ribavirin-MP causes a decrease in intracellular [GTP] due to inhibition of inosine monophosphate dehydrogenase -> inhibition of GTP biosynthesis, and ultimately of DNA/RNA synthesis.
  • Ribavirin-TP inhibits dGTP-dependent 5’-cap formation on mRNA.
  • Ribavirin-TP inhibits Influenza RNA polymerase, and hence, inhibits initiation
  • and elongation of viral mRNA synthesis.
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11
Q

bad efects of ribavirin

A

Drug is teratogenic and causes hemolytic anemia in up to 10% of patients due to drug accumulation in erythrocytes.

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12
Q

how do Zanamivir/Oseltamivir inhibit neuraminidase

A

competitively

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13
Q

All available anti-herpesvirus agents target the…..

A

All available anti-herpesvirus agents target the virally encoded DNA polymerases that replicate the double-stranded DNA genome of these viruses.

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14
Q

t or F

Viral DNA polymerases operate in the same manner as cellular DNA polymerases

A

T

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15
Q

how does Aciclovir work?

whats it used to treat?

A

Herpes simplex and Herpes zoster

purine analogue

Aciclovir triphosphate competitively inhibits viral DNA polymerase.

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16
Q

why is aciclovir selective against virally infected cells

A

• Aciclovir (=prodrug) is only monophosphorylated by the viral thymidine kinase

  • Viral thymidine kinase is only expressed in infected cells
  • Aciclovir-TP preferentially interacts with the viral DNA polymerase (30 x more potent with viral enzyme)

• Acts as competitive substrate and is incorporated in viral DNA, causing termination of DNA replication

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17
Q

aciclovir is administers?

A

The drug is used topically, orally and i.v.

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18
Q

Ganciclovir and penciclovir are also competitive inhibitors of DNA polymerase, but …

A

Ganciclovir and penciclovir are also competitive inhibitors of DNA polymerase, but they have 3’-OH moieties and will permit chain extension.

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19
Q

will Ganciclovir and penciclovir permit chain extension?

(theyre antiherpes drugs - purine alalogues)

A

Ganciclovir and penciclovir are also competitive inhibitors of DNA polymerase, but they have 3’-OH moieties and will permit chain extension.

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20
Q

Ganciclovir is more effective that aciclovir against ….

A

Ganciclovir is more effective that aciclovir against CMV-infected cells.

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21
Q

Pyrimidine analogues - give an example

22
Q

describe Cidofovir

A

Cidofovir is a nucleoside phosphonate analogue of cytosine, which is converted to a diphosphoryl derivative that selectively inhibits the DNA polymerase of CMV

23
Q

Foscarnet is an analogue of what?

A
  • Organic analogue of pyrophosphate
  • Binds selectively to viral DNA polymerase, does not require intracellular metabolism
  • Prevents cleavage of PPi from NTP during DNA synthesis
    *
24
Q

when is foscarnet used?

A

Is used when aciclovir resistance occurs

25
problems with foscarnet
Nephrotoxic, proteinuria
26
how is foscarnet administered?
i.v. administration required
27
How does Enfuvirtide (Fuzeon) inhibit viral entry into host cells?
This drug blocks the conformational change of the HIV envelope spike required to expose the fusogenic domain of gp41. The virus cannot fuse with the host cell membrane and thus cannot enter the cell. blocks viral entrty to the cell
28
2 classes of reverse trancriptase inhibitors?
non nucleoside and nucleoside
29
how do Non-nucleoside reverse transcriptase inhibitors (NNRTI) work? give an exmaple
Non-nucleoside reverse transcriptase inhibitors (NNRTI), such as **nevirapine**, *bind to the target enzyme near the catalytic site and denature it.*
30
how do Nucleoside reverse transcriptase inhibitors (NRTI) work?
Nucleoside reverse transcriptase inhibitors (NRTI), such as zidovudine (azidothymidine, AZT) bind to the target enzyme by mimicking naturally occurring nucleosides. NRTIs (but not NNRTIs) must be phosphorylated by host cell enzymes before becoming active. They inhibit HIV reverse transcriptase but are also substrates
31
AZT is a ______ analogue.
AZT is a **thymidine** analogue.
32
When incorporated into DNA, NRTIs terminate synthesis because t.....
When incorporated into DNA, NRTIs terminate synthesis because these compounds lack 3’-OH groups.
33
Reverse transcription is an early event in the replication cycle, what does this mean about the action of zidovudine and AZT
these agents have no effect on a cell in later stages of viral infection.
34
how to incfreae AZT bioavailability
**Valyl ester of AZT** increases bioavailability
35
label AZT and thmidine
36
Hydroxyurea is often co-administered with pyrimidine analogues (such as AZT) why?
Hydroxyurea is often co-administered with pyrimidine analogues (such as AZT) to inhibit ribonucleotide reductase. This **decreases the intracellular pool of pyrimidine nucleotides**, and thereby potentiates the effect of pyrimidine analogues.
37
There are currently six protease inhibitors (HIV treatment) what are they
1. Saquinavir 2. Indinavir 3. Amprenavir 4. Lopinavir 5. Nelfinavir 6. Fitonavir
38
which HIv protesase do the 6 protease inhibitors target?
aspartic protease used to cleave the polypeptides this protease does not occur in the host Without these cleavages, the newly produced virus is not infectious.
39
HIV protease contains ____ aspartyl residues in its active site
HIV protease contains **two** aspartyl residues in its active site
40
Interferons are....
Interferons are cytokine proteins that bind to receptor on the cell surface
41
interferons are synthesized in response to?
viral infection and cause biochemical changes that inhibit viral propagation (referred to as “viral interference”
42
There are three classes of interferons: what are they
IFN-a, IFN-b, and IFN-gamma.
43
which interferons have antiviral activity
alpha beta
44
which interferones have anti tumour activity?
interferon alpha
45
interferons bind to ....what?
hey bind to specific ganglioside receptors on host cell membranes and promote in host cell ribosomes the production of enzymes that inhibit the translation of viral mRNA
46
IFN-a-2a is used in the treatment of.....
IFN-a-2a is used in the treatment of **hepatitis B** infections and **AIDS** related **Kaposi sarcomas**
47
T or f People infected with human immunodeficiency virus (HIV) — the virus that causes AIDS — have the highest risk of Kaposi's sarcoma.
T
48
IFN-a-2b is used for treatment of ...
IFN-a-2b is used for **hepatitis C.**
49
T ir F ## Footnote Interferons also activate immune cells, such as macrophages, T lymphocytes and natural killer cells
T
50
α and β interferons are produced by all cells in response to ....
α and β interferons are produced by all cells in response to viral infections
51
γ interferons are produced only by ,....
γ interferons are produced only by T lymphocytes and natural killer cells in response to cytokines
52
fat
mamba

MVST1B MODA (22 decks)

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