Antivirals Flashcards

1
Q

What is most common form of herpes that is resistant to acyclovir? what do you give these patients?

A

Thymidine kinase (TK)-deficient HSV

give them foscarnet

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2
Q

When acyclovir is given orally, how can we improve its absorption in the gut?

A

valyl ester increases oral absorption

so valylcyclovir is better

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3
Q

Ganciclovir is active in vitro against all herpesviruses, but has the greatest activity against ____. it is also used for ___.

A

CMV. also used for HHV 6

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4
Q

How does ganciclovir work?

A

It’s not chain terminating, but in triphosphate form, it competitively inhibits CMV DNA polymerase.

requires phosphorylation

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5
Q

Non nucleotide inhibitor example

A

Foscarnet: inhibits HSV/CMV DNA polymerase

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6
Q

Will ribivarin treat hepatitis C?

A

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7
Q

what do we use ribivarin against? what does it do?

A

RSV, hepatitis C

inhibits part of guanosine synthesis pathway

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8
Q

Influenza neuraminidase inhibitors two types? how do they work?

A

when virus is budding out of the host cell, NA cleaves away junk so virion can bud

zanamavir
oseltamavir

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9
Q

When influenza enters, there’s a __ change to pH. What inhibitors block influenza A coating, thereby preventing nucleocaspid release in cytoplasm, fusion of viral and endosomal vesicle membranes?

What ion channel do they bind to?
Why don’t we use these drugs much?

A

acidification (lowering)

amantadine, rimantadine

M2 ion channel

amantadine is associated with CNS side effects, not rimantadine

but resistance problems

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10
Q

What are interferons? What are the three types? which has the most antiviral activity, and what cell types naturally secrete it

A

class of natural proteins produced by cells of immune system (glycoproteins, cytokines)

alpha, beta, gamma

alpha (B and T cells)

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11
Q

do we use interferons? what would we use it for?

A

chronic hepatitis C (with ribivarin, obsolete now in DAA era)
chronic hepatitis B
intralesional injection for HPV induced lesions

but adversely: influenza like symptoms, depression, bone marrow suppression

so we only use it if necessary (no other drugs)

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12
Q

what is palivuzimab?

A

it’s a monoclonal antibody

which binds F protein of RSV

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13
Q

What is immune globulin? What is monoclonal antibody?

A

Immunoglobulin (also called gamma globulin or immune globulin) is a substance made from human blood plasma. The plasma, processed from donated human blood, contains antibodies that protect the body against diseases.

Monoclonal antibodies (mAb or moAb) are antibodies that are made by identical immune cells that are all clones of a unique parent cell. (single epitope, very conserved one that virus usually can’t evolve to be resistant to)

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14
Q

How do we treat HBV?

A

HBV-nucleoside (RT) inhibitors

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15
Q

How do we treat HCV?

A

nucleoside inhibitors, NS5A inhibitors, protease inhibitors

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16
Q

What is acyclovir? Does it need anything for activation? How specific is its toxicity?
How is it delivered?

A

Guanosine derivative with an acyclic side chain

prodrug that requires VIRUS SPECIFIC thymidine kinase for activation (gets phosphorylated by herpes thymidine kinase, also cellular kinases add the second two)

Acyclovir triphosphate is then incorporated into DNA by DNA pol, and is an obligate chain terminator

minimal toxicity to non-infected cells

17
Q

What is the order of hte herpesviruses that can be treated by Acyclovir?

A

HSV - 1 > HSV- 2 > VZV > CMV > EBV

mostly stick to the first three, or intravenously for CMV prophylaxis

18
Q

how does acyclovir get administered?

A

oral therapy (mild HSV-1, HSV-2, VZV in immunocompetent patients; HSV/VZV prophylaxis)

or

intravenous (for severe disease, disease in immunocompromised patients, CMV prophylaxis in immmunocompromised patients)

all neonatal disease needs IV therapy
all CNS disease needs IV therapy

19
Q

what is ribivarin

A

synthetic nucleoside, structure similar to guanosine. it is a prodrug, gets phosphorylated and has unclear method of action

can be used against RNA and DNA viruses; used for RSV, hepatitis C, lassa fever