Antivirals Flashcards
How do antivirals work
Usually by inhibiting any one of the important proteins within the virus. Common targets include:
- Nucleic-acid polymerases
- Proteases
- Integrases
- CCR5
- Terminases
What is the complications of poor adherence?
The production of resistance
Name some antivirals and describe briefly how they work; also give some side effects
Aciclovir
- Guanosine analogue, blocking viral DNA extension
- Activated by viral thymidine kinase
- SE: neuro/nephrotoxicity
Valaciclovir
- Aciclovir precursor
Famciclovir
- Similar to acyclovir
- SE: Neuro/nephrotoxicity
Ganciclovir
- Nucleoside analogue
- SE: BM suppression
Valganciclovir
- Ganciclovir precursor
Foscarnet
- Pyrophosphate analogue
- Inhibits nucleic acid synthesis
- SE: nephrotoxicity
Cidofovir
- Nucleoside phosphonate
- Similar action to foscarnet
- SE: nephrotoxicity
What is the treatment of HSV 1/2?
Act Very Fast:
- Aciclovir
- Valaciclovir
- Famciclovir
Encephalitis:
- IV aciclovir 10mg/kg
- Treat for 21 days if confirmed
Resistant:
- Foscarnet
- Cidofovir
What is the treatment for VZV
Not treated unless:
- Immunocompromised
- Pregnant
- Neonate
- Adults with pneumonitis
- Children with complications
Treat with
- Acicloviro
What is the treatment for CMV?
Treat if:
- Immunocompromised
- HIV
- Pregnancy
- Congenital
Treat with:
- Ganciclovir
- Valganciclovir
If neutropaenic
- Foscarnet
- Cidofovir
If bone marrow transplant patient:
- Pre-emptive therapy (monitor CMV viral load and treat when >1000 copies/ml)
- Acute therapy (ganciclovir -> foscarnet -> cidofovir)
What is the treatment for EBV?
Complicates immunosuppression:
- Post-transplant lymphoproliferative disease
Treat with:
- Rituximab (anti-CD20 antibody; clears B cells)
What is the treatment for RSV?
Usually do not give antivirals, unless severe or high risk:
- Pre-term
- Heart/lung disease
- SCID
Treat with:
- Ribavirin (nucleoside analogue)
- IVIG (palivizumab)
What is the treatment for BK virus?
BK is a polyomavirus which causes:
- Haemorrhagic cystitis (BMT)
- BK nephritis (renal transplant)
Treat with:
- Cidofovir IV
- IVIG if nephritis (cidofovir is nephrotoxic)
What is the treatment for adenovirus?
Only a problem in paediatric transplant patients, causing severe multi-organ failure.
Treat with:
- Cidofovir +/- IVIG
How does antiviral resistance develop? What must happen in this situation?
Suboptimal drug levels give rise to the selection of resistant viruses
In resistance:
- Resort to 2nd line drugs
- May have cross-resistance
How can resistance be prevented?
- Combination therapy
- Adherence
- testing for resistance (genotypic/phenotypic testing)
Describe resistant HSV
Only an issue in the immunocompromised
- Mutated viral TK means aciclovir not effective
- Cross-resistance to ganciclovir
- Use foscarnet or cidofovir
- HOWEVER, 5 percent will be mutated in DNA polymerase, meaning foscarnet or cidofovir will be ineffective
Describe resistant CMV
Only an issue in the immunocompromised
