Antivirals (O'Brien)

Question 1

Anti-herpes/CMV drugs (non-HIV)

Answer 1

acyclovir, ganciclovir, foscarnet

Question 2

Anti-influenza drugs (non-HIV)

Answer 2

amantidine, oseltamivir, zanamivir

Question 3

Acyclovir mechanism

Answer 3

Viral thymidine kinase phos. acyclovir –> monophosphate –> more phos. happens with our thymidine kinase –> blocks DNA synthesis via competitive inhibition of viral DNA synthesis

Question 4

How much phosphorylations does acyclovir undergo

Answer 4

3 (first one is viral thymidine kinase)

Question 5

How is acyclovir administered

Answer 5

topically and IV

Question 6

Is acyclovir a first line agent?

Answer 6

indeed!

Question 7

What toxicity should you worry about for acyclovir?

Answer 7

renal, interactions

Question 8

acyclovir resistance mechanisms

Answer 8

alteration in viral thymidine kinase

Question 9

What drug can you give if pt. is resistant to acyclovir?

Answer 9

foscarnet

Question 10

Anti-CMV agents

Answer 10

ganciclovir, foscarnet

Question 11

ganciclovir mechanism

Answer 11

acyclic guanosine analog; first phos catalyzed by CMV kinase

Question 12

Can ganciclovir be given orally?

Answer 12

no!

Question 13

Ganciclovir active against

Answer 13

CMV (100x>acyclovir)

Question 14

This is used as treatment/prophylaxis for CMV post-transplantation

Answer 14

ganciclovir

Question 15

Ganciclovir toxicity

Answer 15

myelosuppression

Question 16

Foscarnet mechanism of actions

Answer 16

inhibits viral DNA and RNA polymerase, HIV RT

Question 17

Does foscarnet require phos?

Answer 17

No!

Question 18

How is foscarnet administered

Answer 18

IV only

Question 19

Foscarnet used in strains resistant to…

Answer 19

acyclovir

Question 20

Foscarnet toxicities

Answer 20

renal; hyperphosphatemia, hypokalemia/calcemia/magnesemia

Question 21

T:F - Anti-influenza agents must be given quickly after onset of symptoms

Answer 21

true

Question 22

Oseltamivir (tamiflu, oral) and zanamivir (inhaled) are ______ inhibitors

Answer 22

neuraminidase inhibitors (analogs of sialic acid

Question 23

Oseltamivir (tamiflu, oral) and zanamivir (inhaled) have activity against influenza…

Answer 23

A and B

Question 24

Zanamivir is useful against ______-resistance strains

Answer 24

oseltamivir

Question 25

Reverse Transcriptase Inhibitors (RTIs)

Answer 25

RTIs Nucleoside: abacavir, emtricitibine/lamivudine Non-nucleoside: efavirenz Nucleotide: tenofovir HIV protease inhibitors: atazanavir, darunavir, ritonavir Fusion, entry, integration inhibitors: enfuvirtide, maraviroc, dolutegravir

Question 26

What was wrong with AZT?

Answer 26

retroviral replication is error prone and increase mutation frequency and increase resistance

Question 27

What is the standard of care of HIV?

Answer 27

combo therapy

Question 28

How are drugs selected for HIV?

Answer 28

based on pt strain resistance (genotype strain for mutations in RT and protease genes for mutations that can lead to resistance

Question 29

NRTIs=nucleoside reverse transcriptase inhibitors act by...

Answer 29

competitive inhib of RT and incorporation into viral DNA

Question 30

How are NRTIs activated?

Answer 30

cellular phosphorylation to triphosphate

Question 31

How does NRTI resistance occur?

Answer 31

mutations in viral RT

Question 32

NRTI toxicity

Answer 32

lactic acidosis w/ hepatic steatosis (life-threatening) --> due to NRTI-mediated inhib of mitochon fn (causes build-up of triglycerides = hepatic steatosis) --> due to lack of specificity

Question 33

Abacavir is a ____

Answer 33

reverse transcriptase inhib

Question 34

Abacavir toxicity (2)

Answer 34

myocardial infarction (caution exercised in CV disease; potentially increases platelet aggregation) hypersensitivity rxn (can be fatal and with HLAB5701 should never take abacavir)

Question 35

Lamivudine and emtricitabine are ______ analogs and are used in ____ treatment

Answer 35

- cytosine analog | - used in HBV treatment

Question 36

Emtricitabine is a fluorinated analog and is favored because____

Answer 36

longer half life and once daily dosing

Question 37

Truvada is a combo of

Answer 37

emtricitabine and tenofovir

Question 38

What does tenofovir do?

Answer 38

nucleotide analog of adenosine

Question 39

Does tenofovir require phosphorylation?

Answer 39

No! nucleoTIDE

Question 40

Tenofovir mech of action

Answer 40

competitively inhib HIV RT - chain termination after incorporation into DNA

Question 41

Tenofovir is coadministered w....

Answer 41

emtricitabine as a first-line RIT backbone therapy

Question 42

Tenofovir toxicity

Answer 42

renal accumulation: tubular necrosis, renal failure, Fanconi's Syndrome

Question 43

Efavirenz is a ____

Answer 43

non-nucleoside RTI

Question 44

Efavirenz binds___and inhibits____

Answer 44

directly to HIV-1 RT and inhibits RNA and DNA-dependent DNA polym activity

Question 45

What kind of inhibitor is efavirenz?

Answer 45

allosteric (NRTIs are competitive)

Question 46

What limits the use of efavirenz?

Answer 46

extensive metabolism/induction via CYP3A4

Question 47

Efavirenz toxicity

Answer 47

nightmares/psychiatric disturbances (at start then resolve)

Question 48

HIV protease inhibitors are pepitdomimetics which means they...

Answer 48

mimic peptides and inhibit proteolytic cleavage

Question 49

HIV protease inhibitors toxicity

Answer 49

redistribution and accumulation of body fat (lipodystrophy) increased triglycerides/LDL

Question 50

Ritonavir inhibitor of CYP3A4; used with other PIs to increase their serum levels, which means...

Answer 50

less frequent dosing, more tolerability ("boosting")

Question 51

Ritonavir toxicity

Answer 51

increase triglycerides/LDL; elevated serum aminotransferase levels

Question 52

Name the three HIV protease inhibitors

Answer 52

ritonavir; atazanavir; darunavir

Question 53

Maraviroc is a...

Answer 53

entry inhibitor/CCR5 receptor antagonist

Question 54

Maraviroc binds...

Answer 54

selectively to CCR5

Question 55

Maraviroc used in...

Answer 55

HIV-1 strains resistant to other drugs

Question 56

Enfuvirtide is a...

Answer 56

fusion inhibitor

Question 57

Enfuvirtide binds to...

Answer 57

gp41

Question 58

Enfuvirtide is given by...

Answer 58

subq injection (peptide)

Question 59

What is the treatment for experienced HIV pt w/ ongoing HIV replication?

Answer 59

enfuvirtide

Question 60

Dolutegravir is a....

Answer 60

integrase strand transfer inhibitor (INSTIs)

Question 61

Dolutegravir inhibits...

Answer 61

viral DNA strand integration in host genome

Question 62

Dolutegravir appears effective in HIV that is...

Answer 62

resistant to other INSTIs