5. Agents to treat Herpes simplex (HSV), varicella- zoster (VZV) virus, cytomegalovirus (CMV) and respiratory syncytial virus (RSV) infection. Anti-influenza agents Flashcards
What is the MOA of Acyclovir?
Acyclovir is a guanosine analog converted to acyclo-GTP by viral thymidine kinase (only HSV and VZV) and cellular enzymes → viral DNA polymerase inhibition + chain termination is specific to infected cells, because 1st P-ation requires viral enzyme! only works on replicating viruses; dormant DRG viruses not affected.
List the CMV agents.
- Ganciclovir
- Cidofovir
- Foscarnet
List the RSV medication.
- Ribavirin
- Pavilizumab
List the influenza medications.
- Amantidine
- Rimantidine
- Zanamivir
- Oseltamivir
- Peramivir
List the HHV+VZV agents:
- Acyclovir
- Valacyclovir
- Famicyclovir
- Trifluridine
- Docosonal
What is Famciclovir?
Oral prodrug converted to penciclovir, same MOA as acyclovir same indications as acyclovir, some EBV activity.
What are the indications for Valacyclovir?
- Suppressive Tx - 1x/day orally
- Shingles - for VZV (better activity than acyclovir); best w/in 3 days of sx onset but unclear efficacy in postherpetic neuralgia
- Prophylaxis - same as acyclovir
What is Docosonal?
It is an alcohol derivative that inhibits membrane penetration, 10% cream for herpes labialis.
What are the indications for Trifluridine?
- It is an older, less selective drug.
- Topical/local use as eye drop or solution.
What is the MOA of Ganciclovir?
It is similar to acyclovir, but uses a phosphotransferase in CMV for initial P-ation step.
What are the indications for Cidofovir?
Cidofovir is a dCMP analog, so no initial viral P-ation required → good for resistant HSV/CMV.
What is the MOA of Foscarnet?
Foscarnet causes direct inhibition of viral DNA polymerase, as a PPi analog.
What is the MOA of Amantadine and Rimantadine?
Amantadine and Rimantadine are cyclic amines that target M2 membrane proteins inhibiting uncoating of influenza-A viral mRNA and preventing replication.
What is the MOA of Zanamivir, Oseltamivir and Peramivir?
They are all neuraminidase inhibitors that inhibit neuraminidase needed for viral replication and release.
What is Ribavirin?
Guanosine nucleoside analog used as a Hep C medication.
What is the MOA of Pavilizumab and its indications?
It is a human mAb against F-glycoprotein on RSV surface, that prevents infection in high risk children.
What are the side effects of Acyclovir?
- Renal Impairment - interstitial nephritis and crystalluria via IV use (↓ with slow infusion + hydration)
- CNS effects - delirium, confusion, vertigo, hallucinations (esp. ↑ dose or IV) … similar effects in all these drugs
What is the resistance mechanism behind Acyclovir?
Some HSV strains may not have the necessary thymidine kinase.
What is the route of administration of Acyclovir?
- given as topical creams, orally or IV
- good CNS penetration
What are the indications for Acyclovir?
- Orally 7-10 days for oral/genital HSV daily suppressive tx for recurrent cases IV for HSV encephalitis, neonatal HSV and any serious HSV / VZV cases.
- Prophylaxis - in pregnancy (at wk 36) or immunocompromised / transplant pts (also prevents reactivation)
What are some kinetic parameters to keep in mind with Valacyclovir?
- Valacyclovir is an acyclovir pro-drug
- Dosed 1x/day and better oral bioavailability
What are the side effects of Ganciclovir?
- Myelosuppression - dose-limiting; causes all the -penias; worse in combo with HIV drugs (AZT, etc.)
- mucositis
- fever
- rash
- crystalluria (hydrate!)
- teratogenic
- overdose can cause seizure
What are the indications for Ganciclovir?
- CMV - main use, prophylaxis and tx for retinitis, pneumonia, esophagitis, colitis, combined with anti-CMV hyperimmune serum
- also active against HSV, VZV, EBV, CMV, HHV-6 and 8.
What are the kinetic like for Ganciclovir?
- given IV only but valganciclovir form is oral
- good tissue/CNS penetration
- renal elimination
What are the indications for Cidofovir?
- CMV retinitis - in AIDS patients
- Resistant HSV/VZV infections - strains without thymidine kinase also active against adeno-, polyoma-, pox- and papillomaviruses.
What are the side effects of Cidofovir?
- Nephrotoxic - via tubular secretion of drug; co-admin of probenecid blocks tubular secretion and thus toxicity symptoms (proteinuria, azotemia + metabolic acidosis)
- may cause neutropenia
- teratogenic
What is the mechanism behind Cidofovir resistance?
Viruses with mutated DNA polymerase
What are the kinetics like for Cidofovir?
- Give by IV admin only
- poor CNS penetration (↓ CNS sfx)
- renal elimination
What are the indications for Foscarnet?
Resistant HSV, VZV, CMV strains (Resistance mechanism is the same as cidofovir)
- good for HIV patients that can’t take ganciclovir due to marrow suppression.
What are the indications for Amantadine + Rimantadine?
- Prophylaxis - in high risk groups
- Also work to prevent disease progression in existing infection - ↓ symptoms if taken in first 48 hrs.
What are the indications for Zanamivir, Oseltamivir and Peramivir?
Both influenza A + B, but only within 72 hours of infection.
What is the route of administration for Foscarnet?
given IV and penetrates CNS
What are the side effects of foscarnet?
- Nephrotoxic - causes ATN; ↓ Ca/K/Mg plus pH imbalance
- Seizures - via electrolyte disturbances
- Interaction with pentamidine (for P. jirovecii) → serious hypocalcemia
What are the side effects of Amantadine + Rimantidine?
- GI intolerance and CNS issues (nervousness + ↓ concentration)
- Use reduced dosages in pt > 65 and renal insufficiency
What is the mechanism behind Amantidine and Rimantidine resistance?
Resistance by M2 mutation
What are the side effects of Zanamivir, Oseltamivir and Peramivir?
They are generally well-tolerated.
What is the route of administration for Oseltamivir and Zanamivir?
- Oseltamivir is an oral pro-drug
- Zanamivir is only given nasally are renally cleared
