Antivirals

Question 1

What is the relationship between:
HSV thymidine kinase
HSV DNA Polymerase
Acyclovir?

Answer 1

Acyclovir needs to be activated by thymidine kinase, then it is a competitive inhibitor of viral DNA Polymerase

Question 2

What is the most common mechanism for the development of resistance to acyclovir?

Answer 2

Mutation of thymidine kinase gene, which means no activation. this also effects other drugs that rely on activation via this enzyme.

Question 3

Acyclovir
MOA:
Admin route:
Indications:

Answer 3

MOA: competitive inhibitor of viral DNA polymerase, chain terminator, nucleoside analogue
Admin route: Oral, IV in kids
Indications: Genital herpes, varicella zoster

Question 4

Valacyclovir
MOA:
Admin route:
Indications:

Answer 4

MOA: Prodrug (added valine) of acyclovir, converted in liver.
Admin route: better oral bioavailability
Indications: Genital herpes, Varicella, zoster, orolabial herpes

Question 5

Trifluridine
MOA:
Admin route:
Indications:

Answer 5

MOA: comp inhib of thymidine kinase
Admin route: Intraocular
Indications: Conjunctivitis and Keratitis caused by HSV 1/2

Question 6

Ganciclovir
MOA:
Admin route:
Indications:

Answer 6

MOA: initial phosphorylation by UL97 enzyme, more active, competitive inhib of DNA polymerase
Admin route: IV, Oral, Intraocular for eye
Indications: CMV infections

Question 7

Foscarnet
MOA:
Admin route:
Indications:

Answer 7

MOA: is analogue of pyrophosphate, does not need to be phosphorylated by thymidine kinase enzyme
Admin route: only IV
Indications: HSV/VZV infections resistant to acyclovir, CMV retina/esophog/colitis

Question 8

What are the steps in the viral life cycle?

Answer 8

Attachment, Entry, MRNA production, Protein synthesis, assembly, egress

Question 9

FLU Drugs
What are the viral enzymes inhibited by:
Oseltamivir:
Zanamivir:
Peramivir:
Amantadine:
Rimantadine:

Answer 9

Oseltamivir: Neuraminidase, cant egress
Zanamivir: Neuraminidase
Peramivir: Neuraminidase
Amantadine: M2 Protein
Rimantadine: M2 Protein

Question 10

Oseltamivir
Admin route:
Indications:
 - Past:
 - Present:

Answer 10

Admin route: Oral
Indications:
- Past:
- Present: for Infl A and B, in first 48 hr, kids under 1 yr old +, chemoprophylaxis

Question 11

Zanamivir
Admin route:
Indications:
 - Past:
 - Present:

Answer 11

Admin route: Inhalation
Indications:
- Past:
- Present: kids 7 yrs and older with flu

Question 12

Amantadine
Admin route:
Indications:
 - Past:
 - Present:

Answer 12

Admin route: Oral, lots of resistance
Indications:
- Past:
- Present: No longer used

Question 13

Peramivir
Admin route:
Indications:
 - Past:
 - Present:

Answer 13

Admin route: IV
Indications:
- Past:
- Present: acute flu case where pnt sick less than 48 hrs.

Question 14

Rimantadine
Admin route:
Indications:
 - Past:
 - Present:

Answer 14

Admin route: Oral, lots of resistance
Indications:
- Past:
- Present: No longer used

Question 15

Ribavirin
MOA:
Admin route:
Indication

Used to be only this and Interferon for HCV

Answer 15

MOA: Phosphorylated by adenosine kinase. Interferes with synthesis of guanosine triphosphate.
Admin route: Inhalation, Oral
Indication: RSV infection (inhaled), guanasine analogue, HCV (oral)
CONTRAINDICATED IN PREGNANCY

Question 16

describe use of combination therapy in tx of Chronic Hepatitis C infection.
Describe MOA of each anti-Hep C drugs.

Answer 16

In HCV life - big protein made, PROTEASE cuts it down, RNA Polymerase and NS5B Replicate the Genome, Then NS5A also assembles the protein shell around the new ssRNA.

Notice that they go backward in the alphabet in terms of where they fall in the viral life cycle. First is protease inhib (-Previr), then RNA polymerase inhib (-Buvir), then NS5A assembles (-Asvir)
PBA

Drugs end in -previr (Protease Inhibitor) - inhib HCV NS3/4A
Drugs end in -buvir (RNA Polymerase inhibitor) - inhib HCV NS5B RdRp
Drugs end in -asvir (HCV HS5A inhibitors) - HCV NS5A

Oral admin, 12-24 wk course of tx. Drug combo varies depending on liver status

If Ritonavir is included in the drug combo - know that it inhibits cytochrome P450, which increases life/activity of Paritaprevir and could also have other DRUG INTERACTIONS

Question 17

Be familiar with Tx available for Hepatitis B infections.

Answer 17

The younger you are when you are infected with HBV, the more likely you will develop chronic infection
Drugs for CHRONIC HBV: Pegylated Interferon, Reverse Transcriptase Inhibitors
Chronic will have: surface antigen, anti core antigen, not IgM

Entecavir: Oral, inhibits reverse transcriptase, NOT for HIV

Tenofovir: Target reverse transcriptase, chronic HBV and HIV tx.