howrie antivirals

Question 1

how is HSV spread

Answer 1

person to person via secretions

Question 2

herpes encephalitis

Answer 2

inflammatory process involving brain parenchyma: rapid onset fever, headache, seizure
most commonly HSV1

Question 3

herpes encephalitis treatment

Answer 3

IV ONLY
acyclovir

if resistance documented: cidofovir, foscarnet

Question 4

acyclovir is converted to acyclovir monophosphate by ____

Answer 4

viral kinase

Question 5

acyclovir monophosphate is converted to di and triphosphate by ____

Answer 5

host kinases

Question 6

acyclovir is activated in ____

Answer 6

only selectively in infected cells

Question 7

how does acyclovir inhibit viral DNA synthesis

Answer 7

competes with deoxyGTP for viral DNA polymerase
irreversible binding
chain termination following incorporation into viral DNA

Question 8

what kind of virus is HSV

Answer 8

DNA

Question 9

1st line treatment for herpes encephalitis

Answer 9

acyclovir IV 10 mg/kg/dose q8h
infused over 1 hour

Question 10

how to prevent renal damage with acyclovir

Answer 10

IV fluids
infuse over an hour

Question 11

how can CMV be acquiried

Answer 11

community (saliva, genital secretions, urine)
via blood products (transplant from CMV donor)
congenital CMV at birth through intrauterine transmission

Question 12

populations at risk for CMV

Answer 12

not previously exposed (CMV serology negative)
treatment with lymphocyte depleting agents (chemo)
transplant population (mismatch, lung/small intestine, immunosuppressants)
blood transfusion recipients
pregnant women & their fetuses
AIDS (CD4<50)

Question 13

anti-CMV options

Answer 13

ganciclovir
-valganciclovir
cidofovir
foscarnet

Question 14

ganciclovir mechanism

Answer 14

activated via triphosphorylation– inhibits viral dna polymerase– termination of viral dna elongation

Question 15

ganciclovir adverse

Answer 15

severe penias: monitor WBC frequently
and handling precautions bc teratogenic and carcinogenic

Question 16

when to hold ganciclovir

Answer 16

ANC<500
platelets <25,000
hemoglobin <8

Question 17

valganciclovir dosing

Answer 17

900 mg PO BID= 5 mg/kg q12h of IV ganciclovir

Question 18

when do we use valganciclovir for CMV

Answer 18

for prophylaxis or after initial IV ganciclovir

Question 19

foscarnet mechanism

Answer 19

inhibits DNA polymerase & cleavage of pyrophosphate

Question 20

foscarnet dosing precautions

Answer 20

IV only
adjusted renal
must administer with IV fluids– saline preloadfos

Question 21

foscarnet adverse

Answer 21

renal impairment– both chronic and AKI

Question 22

cidofovir mechanism

Answer 22

cytosine analog, inhibits DNA polymerase

Question 23

cidofovir dosing considerations

Answer 23

dosed with pre meds: probenecid 2 gm PO 3 hours before and 1 gm at hours 2 and 8 post administration

also requires aggressive hydration before and during

Question 24

how does probenecid help with cidofovir

Answer 24

organic anion transporter results in long half life to increase renal toxicity

probenecid inhibits the OAT to reduce injury

Question 25

letermovir is for ___ only

Answer 25

CMV

Question 26

letermovir mechanism

Answer 26

inhibits later stages of viral replication where the newly created viral DNA strands are packaged into shells: inhibits the terminases that do this

Question 26

maribavir drug interactions

Answer 26

increased levels of cyclosporine, tacrolimus, sirolimus

Question 26

when is maribavir used

Answer 26

treatment of post-transplant CMV resistant or refractory to 1st line not for CNS or retinitis

Question 26

when is letermovir used

Answer 26

prophylaxis in hematopoietic stem cell transplant for CMV seropositive recipients

Question 27

maribavir mechanism

Answer 27

competitively inhibits protein kinase of CMV to inhibit protein phosphorylation

Question 28

CMV: life threatening/severe infection initial treatment

Answer 28

ganciclovir 5 mg/kg IV q12h after clinical response can transition to PO valganciclovir

Question 29

CMV: non life threatening/mild to moderate initial treatment

Answer 29

valganciclovir 900 mg PO q12h

Question 30

CMV: 2nd line, intolerant to ganciclovir

Answer 30

foscarnet 60 mg/kg IV q12h x 7-14 days

Question 31

CMV: drug resistance w/ UL54 mutation

Answer 31

cidofovir 5 mg/kg IV and probenecid PO once weekly

Question 32

COVID options: antivirals

Answer 32

ritonavir-boosted nirmatrelvir (paxlovid) remdesivir molnupiravir`

Question 33

COVID adjuncts

Answer 33

dexamethasone tocilizumab

Question 34

when is remdesivir used

Answer 34

treatment of mild-moderate hospitalized or high-risk hospitalized patients 28 days or older

Question 35

remdesivir dosing

Answer 35

200 mg IV loading dose x 1 100 mg daily x 5 days or until hospital discharge

Question 36

remdesivir drug interactions

Answer 36

decreased efficacy due to chloroquine/hydroxychloroquine increased concentrations of warfarin, tacrolimus

Question 37

remdesivir: pregnant, lactating

Answer 37

safe

Question 38

paxlovid boxed warning

Answer 38

drug interactions: CYP3A4

Question 39

when is molnupiravir used

Answer 39

ages 18+ high risk mild-moderate disease unable to take paxlovid

Question 40

molnupiravir: pregnancy/lactation

Answer 40

not recommended

Question 41

COVID: outpatient mild-moderate treatment no O2 above baseline, risk factors for progression to severe disease, onset within 5 days

Answer 41

paxlovid if within 5 days onset molnupiravir if older than 18, unable to take paxlovid, not pregnant

Question 42

COVID: hospitalized, mild to moderate, no O2 above baseline, within 5 days onset, risk for progression older than 12 years

Answer 42

paxlovid remdesivir if unable to take paxlovid

Question 43

COVID: hospitalized, mild to moderate, no O2 above baseline, within 5 days onset, risk for progression younger than 12 years

Answer 43

remdesivir

Question 44

severe COVID: low flow

Answer 44

remdesivir + dexamethasone

Question 45

severe COVID: high flow or noninvasive ventilation

Answer 45

remdesivir dexamethasone tocilizumab anticoagulation prophylaxis

Question 46

severe COVID: ECMO or mechanical ventilation, critical

Answer 46

dexamethasone anticoagulation prophylaxis tocilizumab CRP +