Antivirals Flashcards
Which viral infections require antivirals and why?
covid - rep failure
chickenpox - varicella pneumonitis
herpes - encephalitis
viral hep - chronic hep C
Mpox - eye lesions
Which viruses do you always treat?
HIV
Aims of antiviral treatment
reduce mortality
reduce morbidity (severity/duration)
prevent the occurrence in those at risk
reduce transmission from people infected
Which viral processes can antivirals interfere with?
reverse transcription (retroviruses)
transcription
translation
release (cell lysis)
Herpesviruses - what type of virus are they?
DNA viruses
What is the difference in disease course of RNA and DNA viruses?
RNA - acute infection
(except retroviruses)
DNA viruses - acute asymptomatic acute infection and then chronic infection and you never clear them
Key difference between meningitis and encephalitis
encephalitis is inflammation of the brain parenchyma (the brain tissue itself)
-> fever, reduced GCS, seizures, CN abnormalities,
-> usually viral or autoimmune
-> very deadly, 1/2 people with untreated HSV encephalitis will die
Meningitis -> inflammation in the lining of the neck
-> stiff neck, photophobia,
-> usually bacterial
Key difference between meningitis and encephalitis
encephalitis is inflammation of the brain parenchyma (the brain tissue itself)
-> fever, reduced GCS, seizures, CN abnormalities,
-> usually viral or autoimmune
-> very deadly, 1/2 people with untreated HSV encephalitis will die
Meningitis -> inflammation in the lining of the neck
-> stiff neck, photophobia,
-> usually bacterial
Mx of viral encephalitis
IV aciclovir 10 mg/kg TDS
start on suspicion, then get MRI and LP
What encephalitis causes does aciclovir work for?
HSV
varicella
What drug type is aciclovir?
guanosine analogue
4-5x/d
what drug type is valaciclovir?
pro drug - guanosine analogue
oral only
more expensive
TDS
Differences between aciclovir and valaciclovir
valaciclovir pro drug - guanosine analogue
A: oral and IV, 4-5x/d
V: oral only, TDS
What activates aciclovir/valaciclovir
viral thymidine kinase
CMV - when do we worry about it?
immunosuppressed patients
what can CMV cause
colitis
pneumonitis
hepatitis
retinitis
BM suppression
encephalitis/ventriculitis
nephritis
cystitis
myocarditis
When do we treat CMV infection?
only if there is CMV disease
if someone is immunosuppressed and has CMV infection you may monitor the viral load regularly and treat if it Strats going up
When do we treat CMV infection?
only if there is CMV disease
if someone is immunosuppressed and has CMV infection you may monitor the viral load regularly and treat if it Strats going up
CMV drugs
1st line: guanosine analogue
ganciclovir (IV - SE: BM suppression, CI in BM transplant recipients)
valganciclovir (PO)
2nd foscarnet (IV/intravitreal SE: nephrotoxic)
BMT patients with CMV disease - what drug?
2nd line drugs after aciclovir/valaciclovir
EBV management - when antivirals?
if patient had transplant
in renal transplant patients
PTLD ->
PTLD
post transplant lymphoproliferative disease (polyclonal infection)
seen post EBV infection in immunocompromised
oncogenic - you get B sx and this can also progress to lymphoma
can also give rituximab
Influenza - what antivirals can you use?
oseltamivir (tamiflu) - PO or NG
zanamivir (can be inhaled or given IV)
What type of drug is oseltamivir?
neuraminidase inhibitor
Commonest cause of children under 2 being admitted to hospital?
RSV infection -> bronchiolitis
what drug could you use for RSV bronchiolitis?
Ribavirin (not strong evidence for it)
IVIG
What meds can you give to prevent RSV disease?
Palivizumab
Nirsevimab - not yet licensed, but longer duration of effect
Palivizumab
monoclonal Ab that sticks to fusion protein of RSV
Treatments for covid
early infection (to prevent severe disease)
- nirmatrelvir/ritonavir (Paxlovid) - many drug interactions
- remdesivir (IV)
- molnupiravir (PO but less effective than above)
- sotrovimab
Infection (late) - focus on host and not the virus
- steroids
- baricitinib ()
- IL-6 inhibitor ()
Oseltamivir - MoA
directly inhibits neuraminidase of influenza virus (it is what lets the virus get out of an infected cell)
M-pox antiviral
Tecoviromat
Who is at high risk of tecoviromat?
immunocompormised/pregnant/paediatric
indications to treat m-pox
> 100 lesions
sepsis
encephalitis
sensitive areas of infection
immunocompromised?
what vaccine can you give to prevent mpox?
smallpox?
what vaccine can you give to prevent mpox?
smallpox?
BK virus - what drugs can you give>
cidofivir (+probe
BK virus - what is it?
Adenovirus - who needs Mx?
transplant patients, especially paediatric
can give IVIG
can try cifofovir/xxxfovir
Cellular immunotherapy
adoptive immunotherapy
virus specific cytotoxic T cells
donor lymph
???
Drug resistance with antivirals - causes and issues
diversity, selection pressure
treatment failure
2nd line drugs are usually less effective and more toxic
Drug resistance with antivirals - causes and issues
diversity, selection pressure
treatment failure
2nd line drugs are usually less effective and more toxic
Drug resistance testing
- phenotypic testing (cell culture, different concentrations of antivirals, check for replication) - mainly HSV
- genotypic (sequencing/resistance mutations) - mainly HIV and some Hep
Main mechanism of resistance against aciclovir in HSV
thymidine kinase mutations (95%) -> drug cannot activate itself and work
(DNA polymerase mutations are a second much rarer cause - 5%)
Drug resistance in flu
H257y - neuraminidase mutation that gives resistance to XXX but not XXX
PEP
Hep B
Rabies
Variclella zoster
