Chapter 37: Viral Infections

Question 1

Maraviroc MOA

Answer 1

blocks the chemokine receptor CCR5

CCR5 is what some HIV strains use for attachment and host entry

Question 2

What is the approved use of Maraviroc?

Answer 2

Used to tx HIV strains that use CCR5

Used in combo with other HIV drugs

Question 3

Which drug blocks HIV attachment and entry by inhibiting gp41 mediated fusion of HIV envelope w/host plasma membrane?

Answer 3

Enfuvirtide (T-20)

Question 4

Enfuvirtide is a peptide that must be administered ___

Answer 4

parenterally with twice daily injections

Question 5

Which drug blocks the M2 proton channel of influenza virus A and can also be used to treat Parkinson disease? (thus blocks uncoating)

Answer 5

Amantadine

Question 6

Which drug - amantadine or rimantadine - has fewer adverse effects? What are these adverse effects?

Answer 6

Rimantadine has less

Neuroleptic malignant syndrome; exacerbation of mental disorders

Question 7

Which drugs are most commonly used to treat influenza A - inhibitors of viral uncoating or neuraminidase inhibitors?

Answer 7

neuraminidase inhibitors

Question 8

Acyclovir MOA?

Answer 8

monophosphorylated by viral kinases (thmidine kinase), which leads to inhibition of DNA synthesis in virus-infected cells by inhibiting DNA polymerase

Question 9

Drug of choice for HSV or VZV?

Answer 9

Acyclovir

Question 10

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

Answer 10

valacyclovir

Question 11

How do you develop acyclovir resistance?

Answer 11

mutation in viral thymidine kinase

Question 12

Famciclovir use?

Answer 12

HSV infections and shingles (VZV reinfection)

Question 13

Penciclovir use?

Answer 13

Used as an ointment to treat cold sores caused by HSV

Question 14

Which drug is used to treat CMV but can cause neutropenia, thrombocytopenia, anemia, fever, and renal toxicity?

Answer 14

Ganciclovir

Question 15

Which drug is used to treat CMV retinitis and must be co- administered with probenecid?

Answer 15

Cidofovir

Question 16

Cidofovir MOA?

Answer 16

Inhibits CMV DNA polymerase…

Unlike the other “clovirs” cidofovir is phosphorylated by cellular enzymes (NOT VIRAL ENZYMES!)

Question 17

What is the major issue with cidofovir?

Answer 17

nephrotoxicity is a major adverse effect

(unbalanced) tradeoff - only needs to be administered once a week!

Question 18

Vidarabine, idoxuridine, and trifluridine usage?

Answer 18

HSV keratitis

Question 19

Rank ACT, ACV, and ganciclovir from most selective to least selective

Answer 19

Most - AVC –> ganciclovir –> ACT - Least

Question 20

What are the serious negative side effects of AZT (zidovudine)?

Answer 20

bone marrow suppression –> neutropenia and anemia

Question 21

What is the major cause of toxicity in zidovudine?

Answer 21

inhibition of mitochondrial DNA polymerases + phosphorylated AZT accumulates in all dividing cells in the body

Question 22

Zidovudine MOA?

Answer 22

anti HIV nucleoside analogue - phosphorylated by cellular kinases and then inhibit viral reverse transcriptase

Question 23

Which nucleoside/nucleotide analogue has less toxicity and can be used to treat HBV?

Answer 23

lamivudine

Question 24

What drug can you use to treat serious HSV or CMV infections where acyclovir or ganciclovir have failed?

Answer 24

foscarnet

Question 25

foscarnet MOA? dose limiting adverse effect?

Answer 25

mimics the pyroFOSphate product of DNA polymerization renal impairment

Question 26

Name the four NNRTIs. What is the clinical use? Major adverse effect? Why do you need to administer with other drugs?

Answer 26

Efavirenz Nevirapine Delavirdine Etravirine HIV Rash Resistance develops quickly

Question 27

What is the MOA of NNRTIs?

Answer 27

bind near the catalytic site of reverse transcriptase and inhibit the enzyme

Question 28

What is the MOA of raltegravir?

Answer 28

inhibits integrase (viral enzyme that helps HIV get into cellular genome)

Question 29

What is the major risk factor of raltegravir and what is its approved use?

Answer 29

suicide risk HIV but ONLY IN COMBO w other anti-HIV drugs

Question 30

Which drugs inhibit HIV protease?

Answer 30

-navirs you "navir" tease a protease

Question 31

How do the HIV protease inhibitors work?

Answer 31

they prevent maturation of new viruses

Question 32

Do not administer HIV protease inhibitors with...

Answer 32

P450 substrates or to patients with severe hepatic impairment

Question 33

what is the major adverse effect of protease inhibitors?

Answer 33

dylipidemia - increased cholesterol and triglycerides

Question 34

Which protease inhibitor is combined with other protease inhibitors to reduce the # of pills that need to be taken per day?

Answer 34

ritonavir

Question 35

NNRTIs and protease inhibitors should NOT be administered together why?

Answer 35

both classes of drugs undergo hepatic metabolism

Question 36

NNRTI class toxicity?

Answer 36

liver toxicity efavirenz nevirapine delavirdine etravirine

Question 37

What are the common side effects of NRTIs? (zidovudine, stavudine, lamivudine, tenofovir...)....what is the underlying cause?

Answer 37

lactic acidosis neutropenia myelosuppresion myopathy mitochondrial DNA polymerase toxicity

Question 38

Zanamivir and Oseltamivir MOA? Clinical app?

Answer 38

inhibits influenza neuramidase influenza A & B

Question 39

What are the differences between zanamivir and oseltamivir?

Answer 39

O - prophylaxis and tx; used to treat bird and swine flu Z - prophylaxis only; inhaler form

Question 40

Fomivirsen (unknown MOA) clinical app?

Answer 40

CMV retinitis

Question 41

WHat drug with an unknown MOA can be used to tx RSV and in combo with interferon alpha, Hep C?

Answer 41

ribavirin

Question 42

Docosanol clinical app?

Answer 42

HSV

Question 43

Interferon alpha clinical app

Answer 43

``` Hep C, hep B kaposi sarcoma CML hairy cell leuk malignant melanoma renal cell carcinoma ```

Question 44

interferon alpha can cause what besides flu symptoms?

Answer 44

autoimmune disease, neutropenia, thrombocytopenia

Question 45

Imiquimod

Answer 45

tx HPV, basal cell carcinoma, and actinic keratosis can cause skin irritation so wash hands before and after