Chapter 37: Anti-Virals

Question 1

–Ciclovirs act by what general mechanism? Name 3 major drugs

Answer 1

They are first phosphorylated by viral kinases and then * Inhibit DNA polymerase *
Acyclovir
Ganciclovir
Cidofovir (first phosphorylated by cellular enzymes)

Question 2

What is the drug of choice for HSV?

Answer 2

Acyclovir

Question 3

What is the drug of choice for VZV?

Answer 3

Acyclovir or Famciclovir

Question 4

What is the prodrug of acyclovir that has a better oral bioavailability?

Answer 4

Valacyclovir

Question 5

How do viruses become resistant to acyclovir?

Answer 5

Mutated viral thymidine kinase

Question 6

What are some major adverse effects of acyclovir?

Answer 6

Renal Failure (IV)
TTP
HUS
Encephalopathy

Question 7

What is the 5’ monophosphate that is used to treat CMV?

Answer 7

Ganciclovir

Question 8

What are the major adverse effects of ganciclovir?

Answer 8

neutropenia, thrombocytopenia, anemia, fever, phlebitis

Question 9

Which is more toxic to host enzymes, acyclovir or ganciclovir?

Answer 9

ganciclovir

Question 10

How can viruses become resistant to ganciclovir?

Answer 10

mutated DNA polymerase; lack of viral kinase

Question 11

What is the prodrug of ganciclovir?

Answer 11

Valganciclovir (has better oral availability)

Question 12

What is the MOA of cidofovir?

Answer 12

Inhibits viral DNA polymerase; does not require phosphorylation by viral kinase like acyclovir and ganciclovir. Instead it uses cellular enzymes.

Question 13

Cidofovir is used for ___?

Answer 13

CMV retinitis in the immunocompromised

Acyclovir resistant HSV

Question 14

Cidofovir has a ____ half life and requires co-administration with ____? Why?

Answer 14

Long

Probenecid

Question 15

What is the major adverse effect of Cidofovir and how do you limit this toxicity?

Answer 15

Nephrotoxicity - probenecid

other adverse effects include neutropenia, metabolic acidosis, decreased intra-ocular pressure

Question 16

What are NRTIs? MOA?

Answer 16

Nucleoside Reverse Transcriptase Inhibitors

First phosphorylated by cell kinases. THEN Inhibit nucleotide binding to the reverse transcriptase

Question 17

Which NRTI does not need to be phosphorylated by cellular enzymes before inhibiting reverse transcriptase?

Answer 17

Tenofovir

Question 18

What is Zidovudine used for?

Answer 18

HIV

General prophylaxis and during pregnancy to reduce risk of fetal transmission.

Question 19

Lamivudine is used to treat ____?

Answer 19

Hep B

Question 20

What are the major adverse effects of NRTIs (zidovudine, lamivudine…)

Answer 20

Neutropenia, anemia

Pancreatitis, lactis acidosis, optic neuritis, peripheral neuropathy

Question 21

Foscarnet MOA?

Answer 21

DIRECTLY inhibits viral DNA polymerase by mimicking pyrophosphate
(does not need activation by viral kinase!)

FOScarnet - pyroPHOSphate analogue

Question 22

Foscarnet dose limiting adverse effect?

Answer 22

Renal impairment

Question 23

Clinical use of foscarnet?

Answer 23

HSV (when acyclovir fails)

CMV (when ganciclovir fails)

Question 24

Name three major NNRTIs?

Answer 24

Efavirenz
Nevirapine
Delavirdine

Question 25

MOA of NNRTIs?

Answer 25

Bind near catalytic site of reverse transcriptase

Question 26

Do NOT mix NNRTIs with _______? But should use in combination with other drugs, why?

Answer 26

Protease inhibitors Resistance develops quickly though

Question 27

Major adverse effects of NNRTIs?

Answer 27

Rash, psychiatric effects like depression, dizziness and insomnia.

Question 28

Raltegravir MOA?

Answer 28

Inhibits HIV integrase

Question 29

What are the major adverse effects of Raltegravir?

Answer 29

Suicide risk, renal failure, rhabdomyolysis Hypercholesterolemia (first aid)

Question 30

"Navirs" MOA

Answer 30

Protease inhibitors - prevent maturation of new viruses "NAVIR tease a protease for being fat" (How? Virion assembly depends on HIV-1 protease, bc it cleaves HIV mRNA into its functional parts. Inhibiting viral protease prevents this.)

Question 31

Oseltamivir and zanamivir MOA? Clinical application?

Answer 31

Inhibit viral neuraminidase , causing newly synthesized virions to remain attached to host cell. Influenza A & B

Question 32

What is the difference between oseltamivir and zanamivir in terms of prophylaxis and treatment?

Answer 32

Osteltamivir - Both prophyl and treatment | Zanamivir - Treatment only

Question 33

What drug can be used to treat serious human disease like H5N1 and H1N1?

Answer 33

Oseltamivir

Question 34

Adverse effects of neuraminidase inhibitors?

Answer 34

Bronchospasm, respiratory depression Zanamivir administered via inhaler

Question 35

Do not use protease inhibitors in what type of patients?

Answer 35

Hepatic Impairment | Concurrent admin of P450 substrates

Question 36

Major adverse effects of protease inhibitors?

Answer 36

Dyslipidemia - increased cholesterol, triglycerides Hyperglycemia "NAVIR tease a protease for being FAT!"

Question 37

Drug of choice for RSV?

Answer 37

Ribavirin in aerosol form

Question 38

The major adverse effects of ribavirin

Answer 38

hemolytic anemia

Question 39

Do not use ribavirin in these patients

Answer 39

**pregnant (severe teratogen)** Pts with hepatic problems Pts with cardiac disease

Question 40

Ribavirin can be used to treat ___?

Answer 40

RSV and Hep C (with IFN alpha)

Question 41

Proposed MOA of ribavirin?

Answer 41

inhibit inosine monophosphate dehydrogenase (IMP dehydrogenase)

Question 42

How do interferons interfere with viruses?

Answer 42

They activate signaling cascades that enhance antiviral proteins, like protein kinase B. Block DNA AND RNA replication

Question 43

IFN - alpha clinical applications? Adverse effects?

Answer 43

HBV, HCV, Kaposi Sarcoma, CML, Hairy Cell Leukemia, Malignant Melanoma, RCC Neutropenia, myopathy, gastric hemorrhage, aplastic anemia

Question 44

Amantadine clinical application and MOA?

Answer 44

Tx influenza A and Parkinson disease | MOA block M2 protein channel to prevent acidification

Question 45

Major adverse effects of amantadine and rimantidine

Answer 45

neuroleptic malignant syndrome, exacerbation of mental disorder

Question 46

Maraviroc MOA and clinical application

Answer 46

Blocks CCR5....CCR5 strains of HIV | HIV tx

Question 47

Enfuvirtide (T-20)

Answer 47

Inhibits gp41 fusion and so blocks HIV attachment Can cause Guillain Barre Give paraenterally with 2x daily injection