Mi - Antivirals Flashcards
why is zoonoses more common
closer contact
travel
global warming
personal - eat plants, sleep, exercise
what is the Tx for most viral infections
NOTHING - just rest
which virus would you always treat
HIV
purpose of Tx of virals
reduce mortality / morbidity
reduce transmission
post exposure prophylaxis
what areas of cell cycle do antivirals target
transcription
translation
host cell lysis
what components of host can antivirals target
upregulate immune sustem
downregulate immune system - eg steroids
limits of antivirals
host immune capacity
adherence
resistance
toxicity
interactions
what type of viruses are herpes
DNA
which type of virus cause acute infection
RNA
which type of virus causes chronic infection
DNA
- eg HSV, EBV
when is HSV Tx used (7)
encephalitis
mucocutaenous (some)
genital lesions (most)
HSV suppression
HSV prophylaxis
VZV - encephalitis / chicken pox / shingles
VZV post exposure prophylaxis
who gets HSV prophylaxis
transplant pt
mortality of HSV encephalitis
50% if untreated
Tx of HSV encephalitis (inc dose)
IV acyclovir 10mg/kg 3x day
Tx for genital herpes
valacyclovir or acyclovir
what is acyclovir
guanosine analogue
(exam Q++)
how does acyclovir work
viral DNA synthesis inhibitors
how can you give acyclovir
oral / IV
when is acyclovir always given IV
encephalitis
what is valacyclovir
prodrug that is metabolised into acyclovir
how is valacyclovir given
only orally
2nd line Tx for HSV/VZV
foscarnet
cidofovir
when is 2nd line tx for HSV/VZV used
acyclovir resistant
what activates acyclovir
viral thymidine kinase
(exam Q ++)
MoA of foscarnet
DNA polymerase inhibitor
MoA of cidofovir
cytidine analogue
how can you become acyclovir resistant
mutation in viral thymidine kinase that means acyclovir not taken up into viral genome
who gets CMV Tx
neonates
transplant pt
when is CMV Tx given
congenital CMV
prophylaxis
CMV disease (ie not just infection)
Sx / signs / organ dysfunction with CMV+ specimens
what complications can CMV cause
colitis
pneumonitis
hepatitis
retinitis
bone marrow suppression
(main 5)
also:
encephalitis / ventriculitis
nephritis
cystitis
myocarditis
what sign is seen on CMV colitis biopsy histology
owl’s eye
what drugs are used to Tx CMV
ganciclovir
valganciclovir
what type of drugs are ganciclovir and valganciclovir
guanosine analogues
SE of ganciclovir
bone marrow toxicity
who is CI to get ganciclovir
BM transplant recipients (causes bone marrow toxicity)
how is ganciclovir given
IV
how is valganciclovir given
oral
2nd line Tx for CMV
foscarnet
3rd line Tx for CMV
cidofovir
4th line Tx for CMV
maribavir
SE of foscarnet / cidofovir
nephrotoxic
what drugs are used in prophylaxis for CMV
valganciclovir
letermovir (MAB)
who is given valganciclovir prophylaxis for CMV
solid organ transplant pt
who is given letermovir prophylaxis for CMV
bone marrow transplant pt
Sx of acute EBV
tonsilar swelling
when would you treat acute EBV and what would you give
if tonsils are so swollen that airway is impinged
- steroids
what is the chronic EBV infection in immunocompromised pts called
post transplant lymphoproliferative disease (PTLD)
who do you need to treat for EBV
PTLD pts
what happens in PTLD
latently EBV infected B cells turnover lots, causing polyclonal expansion which can –> lymphoma
Tx of PTLD
reduce immunosuppression
rituximab (anti CD20)
list some resp viruses
influenza
rhinovirus
RSV
covid
parainfluenza
adenovirus
spectrum of disease in resp viruses
asymptomatic
common cold
pneumonia
resp failure
what proteins coat influenza
haemagluttanin
neuraminidase
reservoir of influenza
water birds
post exposure prophylaxis for influenza
oseltamivir
what does rsv cause
bronchiolitis
prevention of RSV
palivizumab (vaccination - MAB)
tx for bronchiolitis
supportive
? IVIG / ribavirin
what causes disease in covid
overexaggerated inflam response
tx for early infection with covid
nirmatrelvir / ritonavir
remdesivir
molnupiravir
how is nirmatrelvir given
oral
how is remdesivir given
IV
tx for late infection with covid
steroids
baricitinib
IL6 inhibitors
who gets steroids / baricitinib for covid
those on o2 support
how is early vs late tx for covid different
early = targets virus
late = targets host response
how does oseltamivir work
directly inhibits the influenza neuraminidase
tx for monkeypox
tecoviromat
who needs monkeypox tx (3 reasons, 3 examples for each)
severe disease - >100 lesions, encephalitis , sepsis
anatomical concerns - eyes / throat / bladder
high risk - immunocompromised, pregnant, child
what Sx does BK virus cause
none - almost everyone has had it
who gets Sx with BK virus
transplant pts (bone marrow and renal)
what complication does a bone marrow transplant patient get with BK virus
haemorrhagic cystitis
Mx of haemorrhagic cystitis due to BK in BMT pts
bladder washouts
reduce immunosuppression
cidofivir if severe
what complication do renal transplant pts get with BK virus
BK nephritis and ureteric stenosis
mx of BK nephritis and ureteric stenosis due to BK virus in renal transplant pts
reduce immunosuppression
? IVIG
what sx does adenovirus commonly cause
none
GI sx
conjunctival infections
who gets severe adenovirus disease
transplant, esp paediatric transplant
what sx does severe adenovirus give
disseminated / invasive disease
tx for severe adenovirus
none approved
? cidofivir / brincidofivir / IVIG
what is cellular immunotherapy
take immune cells out of donor’s arm, put them with the virus you want to target and let them become activated against that virus, then put them into the immune suppressed recipient
how is drug resistance tested for
phenotypic - cell culture and plaque reduction assay
genotypic - sequencing / resistance mutations
for which viruses do we do phenotypic drug resistance testing
HSV
for which viruses do we do genotypic drug resistance testing
HIV routinely
also can do HBV, HCV, CMV
main mechanism of resistance to acyclovir
thymidine kinase mutation (95%)
who gets drug resistance
immunosuppressed (>99%)
name a mutation for influenza H1N1 that confers resistance to oseltamivir
H257Y - neuraminidase mutation
when are Igs given (3 categories and an example virus for each)
pre exposure prophylaxis - pavilizumab (RSV)
post exposure prophylaxis - HBV Ig, rabies Ig, VZV Ig
therapeutic - IVIG (CMV) or rituximab (EBV)
