howrie antivirals Flashcards
how is HSV spread
person to person via secretions
herpes encephalitis
inflammatory process involving brain parenchyma: rapid onset fever, headache, seizure
most commonly HSV1
herpes encephalitis treatment
IV ONLY
acyclovir
if resistance documented: cidofovir, foscarnet
acyclovir is converted to acyclovir monophosphate by ____
viral kinase
acyclovir monophosphate is converted to di and triphosphate by ____
host kinases
acyclovir is activated in ____
only selectively in infected cells
how does acyclovir inhibit viral DNA synthesis
competes with deoxyGTP for viral DNA polymerase
irreversible binding
chain termination following incorporation into viral DNA
what kind of virus is HSV
DNA
1st line treatment for herpes encephalitis
acyclovir IV 10 mg/kg/dose q8h
infused over 1 hour
how to prevent renal damage with acyclovir
IV fluids
infuse over an hour
how can CMV be acquiried
community (saliva, genital secretions, urine)
via blood products (transplant from CMV donor)
congenital CMV at birth through intrauterine transmission
populations at risk for CMV
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)
anti-CMV options
ganciclovir
-valganciclovir
cidofovir
foscarnet
ganciclovir mechanism
activated via triphosphorylation– inhibits viral dna polymerase– termination of viral dna elongation
ganciclovir adverse
severe penias: monitor WBC frequently
and handling precautions bc teratogenic and carcinogenic
when to hold ganciclovir
ANC<500
platelets <25,000
hemoglobin <8
valganciclovir dosing
900 mg PO BID= 5 mg/kg q12h of IV ganciclovir
when do we use valganciclovir for CMV
for prophylaxis or after initial IV ganciclovir
foscarnet mechanism
inhibits DNA polymerase & cleavage of pyrophosphate
foscarnet dosing precautions
IV only
adjusted renal
must administer with IV fluids– saline preloadfos
foscarnet adverse
renal impairment– both chronic and AKI
cidofovir mechanism
cytosine analog, inhibits DNA polymerase
cidofovir dosing considerations
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
how does probenecid help with cidofovir
organic anion transporter results in long half life to increase renal toxicity
probenecid inhibits the OAT to reduce injury
letermovir is for ___ only
CMV
letermovir mechanism
inhibits later stages of viral replication where the newly created viral DNA strands are packaged into shells: inhibits the terminases that do this
maribavir drug interactions
increased levels of cyclosporine, tacrolimus, sirolimus
when is maribavir used
treatment of post-transplant CMV resistant or refractory to 1st line
not for CNS or retinitis
when is letermovir used
prophylaxis in hematopoietic stem cell transplant for CMV seropositive recipients
maribavir mechanism
competitively inhibits protein kinase of CMV to inhibit protein phosphorylation
CMV: life threatening/severe infection initial treatment
ganciclovir 5 mg/kg IV q12h
after clinical response can transition to PO valganciclovir
CMV: non life threatening/mild to moderate initial treatment
valganciclovir 900 mg PO q12h
CMV: 2nd line, intolerant to ganciclovir
foscarnet 60 mg/kg IV q12h x 7-14 days
CMV: drug resistance w/ UL54 mutation
cidofovir 5 mg/kg IV
and probenecid PO once weekly
COVID options: antivirals
ritonavir-boosted nirmatrelvir (paxlovid)
remdesivir
molnupiravir`
COVID adjuncts
dexamethasone
tocilizumab
when is remdesivir used
treatment of mild-moderate hospitalized or high-risk hospitalized patients
28 days or older
remdesivir dosing
200 mg IV loading dose x 1
100 mg daily x 5 days or until hospital discharge
remdesivir drug interactions
decreased efficacy due to chloroquine/hydroxychloroquine
increased concentrations of warfarin, tacrolimus
remdesivir: pregnant, lactating
safe
paxlovid boxed warning
drug interactions: CYP3A4
when is molnupiravir used
ages 18+ high risk mild-moderate disease unable to take paxlovid
molnupiravir: pregnancy/lactation
not recommended
COVID: outpatient mild-moderate treatment
no O2 above baseline, risk factors for progression to severe disease, onset within 5 days
paxlovid if within 5 days onset
molnupiravir if older than 18, unable to take paxlovid, not pregnant
COVID: hospitalized, mild to moderate, no O2 above baseline, within 5 days onset, risk for progression
older than 12 years
paxlovid
remdesivir if unable to take paxlovid
COVID: hospitalized, mild to moderate, no O2 above baseline, within 5 days onset, risk for progression
younger than 12 years
remdesivir
severe COVID: low flow
remdesivir + dexamethasone
severe COVID: high flow or noninvasive ventilation
remdesivir
dexamethasone
tocilizumab
anticoagulation prophylaxis
severe COVID: ECMO or mechanical ventilation, critical
dexamethasone
anticoagulation prophylaxis
tocilizumab CRP +
