C.5.Agents to treat HSV, VZV, CMV, RSV infection. Anti-influenza agents. Flashcards
mechanism of action of Acyclovir, Valacyclovir, and Famciclovir
thymidine kinase monophosphorylates the agents–> they are bioactivated by host-cell kinases to the triphosphate form
triphosphate form inhibits viral DNA polymerase
how is Acyclovir given?
topical, oral, IV
how can we reduce Cidofovir’s toxic renal effects?
co-administration with probenecid
which agent has the highest bioavailability- acyclovir or Valaciclovir?
valaciclovir–> 70%
acyclovir–> 15%
what is the 1st line agent for CMV?
Ganciclovir
treatment and prophylaxis
list the antiviral agents used for VZV
acyclovir
valaciclovir
famciclovir
ganciclovir
when do we give IV acyclovir
HSV encephalitis and neonatal infection
when do we use acyclovir?
HSV-1, HSV-2, VZV
prophylaxis for immunocompromised
which agent has the longest T1/2- Acyclovir or valaciclovir?
valaciclovir
acyclovir is short
when is valaciclovir &famciclovir used?
VZV (including shingles)
what is the function of antiherpetic agents?
antimetabolites
except Foscarnet!!
what are the indications for giving Ganciclovir
- CNV 1st line
- prophylaxis in solid organ and bone marrow transplantation
- HSV-1, HSV-2, VZV
what type of elimination do we have in Ganciclovir and Foscarnet?
renal
directly proportional to creatinine clearance
what are the side effects of Ganciclovir
bone marrow suppression mucosits, gastroenteritis hepatic dysfunction seizures (in overdose) crystalluria (nephrotoxic)
in which agent is it important to maintain hydration?
Cidofovir
what does Cidofovir do?
it’s activated by host cell kinase and become diphosphate–> which inhibits viral DNA polymerase
what is the resistance mechanism of Cidofovir and Foscarnet?
changes in DNA polymerase gene
what is the mechanism of Foscarnet
inhibits viral RNA and DNA polymerase
what is the 2nd line agent for CMV?
foscarnet
treatment and prophylaxis
when do we give Cidofovir?
HSV
CMV
Adenovirus
HPV
how are Cidofovir and Foscarnet given?
IV
what are the indication for Foscarnet
CMV (2nd line)
HSV
Which agents are active against many acyclovir-resistant strains?
Valaciclovir
Cidofovir
Foscarnet
what is the SE of Cidofovir?
nephrotoxicity
what agents have an additive effect with Cidofovir?
amphotericin B and aminoglycosides
causing NEPHROTOXICTY
what are the SE’s of Foscarnet
- nephrotoxicity
- electrolyte disorders (K+, Mg²+, Ca²+ ↓↓)
- genitourinary ulceration
- CNS effects
which agent when given with Foscarnet against pneumocystis in HIV patients, produces an additive nephrotoxic effect (life-threatening hypocalcemia)
Pentamidine IV
what are Amantadine and Oseltamivir?
anti-influenza agents
is resistance to amantadine common?
yes
is resistant to Oseltamivir common?
no
which anti-influenza agents are used for Influenza A and B virus?
Oseltamivir
Zanamivir
*mainly prophylaxis
for how long does Oseltamivir reduce the duration of flu symptoms, when used prophylaxis?
2-3 days
for how long does Amantadine reduce the duration of flu symptoms, when used prophylaxis?
1-2 days
which anti-influenza agent has potential use in Parkinson’s disease?
Amantadine
how are anti-influenza agents given?
orally
zanamivir–> inhalation
which anti-influenza agents is used only for Influenza A virus?
Amantadine
Rimantadine
what is the mechanism of action of Amantadine?
inhibit M₂ protein–> inhibits viral RNA transcription
what is the mechanism of action of Oseltamivir?
inhibit neuraminidase –> promote virion release
what are the side effects of Amantadine
atropine-like effects
livedo reticularis
GI distress
Dizziness
what are the side effects of Oseltamivir
GI distress
flu-like symptoms
what are the Anti-RSV agents?
Palivizumab
Ribavirin
Pal Riba..
how is Palivizumab given?
parenteral
what is Palivizumab and what does it target?
its a Humanized monoclonal Ab
targets the A- antigen of fusion protein in RSV
when do we give Palivizumab?
prophylaxis in high-risk infants and children:
- prematurity
- congenital heart disease
- bronchopulmonary dysplasia
what are the side effects of Palivizumab?
upper respiratory tract infection, rhinitis
fever
diarrhea
vomiting