5. Agents to treat Herpes simplex (HSV), varicella-zoster (VZV) virus, cytomegalovirus (CMV) and respiratory syncytial virus (RSV) infection. Anti-influenza agents Flashcards
Agents to treat Herpes simplex (HSV), varicella-zoster (VZV) virus, cytomegalovirus (CMV)
Acyclovir (ACV) Cidofovir Foscarnet Ganciclovir Valganciclovir Penciclovir Famciclovir Trifluridine
Acyclovir (ACV)
Guanosine analog
MOA: DNA chain termination.
Monophosphorylated by the viral thymidine kinase → triphosphorylated by host kinase. The ACV-TP is selective for viral DNA polymerase.
No eradication of latent.
Indications: selective but low spectrum: VZV and HSV
IV treatment - herpes encephalitis, neonatal
Oral treatment - ophthalmic zoster, Genital herpes
Topical treatment - labial herpes
Administration: IV, Oral or topical.
Distribution: well, including CNS
Elimination: kidney (glomerular + tubular)
Adverse effect: well tolerated
depend on the site of administration
Cidofovir
MOA: DNA chain termination. (DNA polymerase inhibitor)
Phosphorylation does not depend on viral thymidine kinase.
Indications: CMV and resistance HSV/CMV, others
Administration: IV
Distribution: weak CNS penetration
Elimination: kidney (tubular)
Adverse effect: nephrotoxic (given with probenecid and normal saline to prevent), neutropenia, metabolic acidosis.
Foscarnet
MAO: Does not require phosphorylation
Reversible inhibition of DNA and RNA polymerase enzymes
Administration: IV
Distribution: well CNS penetration, accumulates in bone
Elimination: kidney (glomerular + tubular)
Spectrum: HSV, VZV (acyclovir resistance), CMV
Adverse effect: nephrotoxic (hypocalcemia, hypokalemia, hypomagnesemia, hyper/hypo phosphate ), anemia, nausea, fever, bone alterations.
Ganciclovir and Valganciclovir
ACV analog
MAO: Similar to ACV
Administration: IV (Valganciclovir: oral)
Distribution: well (+ CNS penetration)
Elimination: kidney (glomerular + tubular)
Spectrum: CMV (retinitis)
Adverse effect: neutropenia (dose dependant), teratogenic, carcinogenic.
Penciclovir and Famciclovir
guanosine analog
MAO: Metabolized to penciclovir-TP and inhibits DNA polymerase
Famciclovir is a prodrug of Penciclovir
Administration:
Penciclovir: Local
Famciclovir: Oral
Spectrum: VZV, HSV
Adverse effect: Headache and nausea
Trifluridine
thymidine analog
MAO: Causes defective DNA synthesis => inhibition of viral replication.
Administration: Local (ophthalmic)
Spectrum: HSV
Treatment of respiratory syncytial virus (RSV)
Ribavirin
Palivizumab
Ribavirin
synthetic guanosine analog
Effective against a wide range of RNA and DNA viruses (HSV, VZ, influenza A, B, RSV, HCV
Administration: oral, aerosol (used to be used, RSV)
in case of HSV: combined for 12-48 weeks orally
in case of RSV infection in children: 3-7 days inhaled
Adverse effects: Dose dependant hemolytic anemia and bone marrow suppression | Teratogenic
Palivizumab
monoclonal antibody against RSV
Prophylactic
I.M injection
Anti-influenza agents
Neuraminidase inhibitors
combination of Amantadine* + Rimantadine
Neuraminidase inhibitors
Oseltamivir
Zanamivir
Oseltamivir and Zanamivir
Spectrum: Effective against type A and B
Oseltamivir
Administration: oral
Pharmacokinetics: good distribution, renal elimination
Adverse effects: GI discomfort and nausea (can be alleviated by taking drug with food)
Zanamivir
Administration: inhalation
Pharmacokinetics: deposited in the oropharynx
Adverse effects: irritation of the respiratory tract, bronchospasms (used with caution in patients with asthma or COPD
