Antivirals Flashcards
Are antivirals virustatic or virucidal?
•All are virustatic, none are virucidal
Why are there limited viral proteins that are potential targets for antiviral drugs?
As viruses utilise host cell enzymes in order to replicate
What are the targets of antivirals?
Stages of the viral replication
What are most antivirals composed of?
Most antivirals are nucleoside anologues, therefore inhibiting nucleic acid synthesis
What are the stages of antiviral drug therapy?
Receptor binding
Cell entry
Uncoating
Nucleic acid synthesis, integration (retroviruses), transcription, viral protein synthesis
Assembly
Release
When might antiviral treatment begin?
Prophylaxis
Pre-emptive therapy (when evidence of infection, but before symptoms are apparent)
Overt disease
Suppressive therapy - (to keep viral replication below the rate that causes tissue damage in asymptomatic infected patient)
Why might maintenance treatment be needed after successful treatment of an episode of overt infection?
Antivirals do not eradicte virus from latently infected cells (e.g herpes viruses)
What viral infections are antivirals used for?
Herpes viruses: HSV 1 and 2, VZV, CMV (aciclovir, famciclovir)
HIV
Hepatitis: Hep B and Hep C (tenofovir)
Respiratory: Influenza - oseltamivir, zanamivir, respiratory syncytial virus (RSV - ribavarin)
When are antivirals given to someone with herpes simplex?
Mucocutaneous: oral, genital, eye, skin
Encephalitis
Immunocompromised - any site
When are antivirals given to someonewith chickenpox?
In those at icnreased risk of complications…
neonate
Immunocompromised
Pregnant
Immunocompetent adult - only begun within 24 hours of onset of rash
What is the specification before giving antivirals to someone with shingles?
Only decreases post-herpetic neuralgia in the immunocompetent patient if begun within 72 hours of onset of symptoms
What are the antivirals used for HSV and VSV?
aciclovir oral, IV, eye ointment, cream
valaciclovir oral
famciclovir oral
foscarnet IV
How does aciclovir work?
- Aciclovir is converted by viral thymidine kinase to ACVMP,
- ACVMP then converted by host cell kinases to ACV-TP (triphosphate)
- ACV-TP, in turn, competitively inhibits and inactivates HSV-specific DNA polymerase
- preventing further viral DNA synthesis
- without affecting the normal cellular processes
When is CMV treated with antivirals?
Only life threatening - or sight threatening CMV infections
e.g HIV patients (CMV retinitis, colitis), transplant recipients(pneumonitis)
May also be used to treat neonates with symptomatic congenital CMV infection
What are potential drugs for CMV?
Gangciclovir IV, ocular implant
Valganciclovir (oral)
Cidofovir (IV)
Foscarnet (IV)
What is the effect of combined anti-retroviral therapy?
Restores immune function in AIDS
Decreaes opportunistic inections
What are antivirals for chronic hepatitis B?
No drug is consistently able to eradicate hepatitis B infection completely.
The goals of the treatment are HBeAg seroconversion, reduction in HBV DNA and normalisation of LFTs.
Indications for treatment include - High viral load in the presence of active hepatitis (as demonastrated by elevated serum transaminases) and/or evidence of inflammation and fibrosis on histology)
Pegylated interferon alpha (subcut.) - most effective in patients with a viral load and serum transaminases greater than twice the upper limit. Interferon is contraindicated in the presence of cirrhosis.
Nucleoside/tide analogues - these inhibit reverse transcription of pre-genomic viral RNA. Major concern is the selection of antiviral-resistant mutations with lon-term treatment. (This is particularly important with older agents such as lamivudine, which may also promote resistance to newer agents as a result of previous antiviral exposure. Tenofovir and entecavir are potent anti-virals with a high barrier to genetic resistance - most appropriate first-line treatment.
Tenofovir
Entecavir
Adefovir
Lamivudine
Emtricitabine
Telbivudine
How long are antivirals for chronic Hep C given?
Often 12 to 48 weeks
What are the current therapies for chronic hepatitis C?
Main aim of the treatment is to eradicate infection.
Cure of the virus is defined as loss of the virus from serum 6months after completing therapy .
Pegylated interferon alpha (subcut) and ribavarin (oral).
Main side effects of pegylated interferon are flu-like symptoms, irritability and depression.
Main side effects of ribavarin are haemolytic anaemia and teratogenicity.
PLUS protease inhibitors (tripple therapy) such as telaprevir and boceprevir.
TRIPLE THERAPY : Pegylated interferon alpha and ribavarin and protease inhibitor (telaprevir)
New directly acting antivirals, incombination (daclatasvir, sofosbuvir)
How are oseltamivir and zanamivir used?
Used in both treatment and prophylaxis of influenza A and B
Not always indicated but if used, should start within 48 hours of onset of symptoms/contact
What is the treatment for respiratory syncytial virus?
Ribavarin - rarely indicated
How do you test for resistance amongst antivirals?
Phenotypic - can virus grow in the presence of compound (HSV)
Genotypic - sequence genome and identify resistance-associated mutations (HIV)
When would you suspect a resistant form of HSV?
In immunocompromised if there is no response to appropriate antiviral doses within 7 days
What is the second line treatment for HSV and CMV if they are resistance to aciclovir?
Foscarnet - usually effective
When is HIV resistance testing performed?
At baseline diagnosis, failing therapy or new treatment approach for other reasons (side effects)
When are trough and peak levels of acivlovir needed to be measured?
When there is renal impairment
