[항바이러스제 각론] 항바이러스제 분류와 각각의 기능

Antiviral Agents

 

Antivirals for Herpesviruses

 

- Acyclovir / valacyclovir

- Penciclovir / famciclovir

- Ganciclovir / valganciclovir

- Foscarnet

- Cidofovir

 

Acyclovir and Valacyclovir

 

    Acyclovir (ACV): analogue of 2`-deoxyguanosine

    Valacyclovir (VCV)

    : L-valyl ester of ACV,  rapidly converted to ACV ,

      Higher oral bioavailability than ACV (54% vs. 15-21%)

 

Mechanism of action

  : Inhibit the synthesis of viral DNA by competing with 2`-deoxyguanosine triphosphate as a

    substrate for viral DNA polymerase

   Clinical uses : HSV infection, VZV infection

    S/E : reversible nephropathy, GI disturbance,

           phlebitis on IV site, headache

 

 

Penciclovir and Famciclovir

 

    Penciclovir (PCV) : structurally similar to ganciclovir

                                    poor oral bioavailability (5%)

    Famciclovir (FCV) : diacetyl-6-deoxy analogue of PCV,

                             metabolized to PCV by deacetylation

                             good oral bioavailability (41-75%)

Mechanism of action : similar ACV

Clinical uses : 

  1. PCV - topical cream (1%) for herpes labialis

  2. FCV – HSV or VZV infections              

 

Ganciclovir

 

Mechanism of action : similar to acyclovir

   : GCV triphosphate inhibits viral DNA polymerase

    → inhibition of viral replication

Clinical uses : prophylaxis & therapy for CMV infection in immunocompromised hosts

S/E : BM suppression(neutropenia, thrombocytopenia)

             renal insufficiency,  fever ,  GI disturbance,       

             phlebitis

 

Valganciclovir

 

L-valyl ester prodrug of Ganciclovir (GCV)

Converted to GCV by VGCV hydrolase

   in GI tract or liver

Oral bioavailability: 61% (vs. GCV: 5%)

VGCV 900mg = GCV iv 5mg/kg

Clinical uses : same as GCV

 

 

Forscarnet

 

Trisodium phosphonoformate

 :  organic analogue of inorganic pyrophosphate 

  → formation of complexes with viral DNA polymerase

  → prevent cleavage of pyrophophate from triphosphate nucleoside

  → inhibition of viral DNA replication

Clinical uses : CMV infections (esp, CMV retinits)

                            ACV-resistant HSV or VZV infections

S/E : renal impairment, E` imbalance (↓K, ↓Ca, ↓Mg),

           N/V, headache

 

 

Cidofovir

 

Competitive inhibitor of viral (to a lesser extent, host cell) DNA polymerase

Broad anti-herpesvirus activity

  : active against GCV or foscarnet-resistant CMV

Treatment of CMV retinitis in AIDS patients

Adverse effect

  : neutropenia, metabolic acidosis, ocular hypotony

    Nephrotoxicity

 

 

Interferon Alfa

 

Antiviral action by inhibiting viral RNA transcription and translation

IM or SQ injection

Tx for hepatitis B & C, human herpesvirus 8 (Kaposi’s sarcoma), papillomavirus infection

A/E: influenza-like Sx, GI distrubance, CNS dysfunction, BM suppression

 

 

Clinical Uses of Anti-Herpetic agents

 

Antiviral drug	Clinical efficacy	Form
Acyclovir	HSV, VZV	IV, PO
Valacyclovir	HSV, VZV	PO
Penciclovir	HSV	Topical
Famciclovir	HSV, VZV	PO
Ganciclovir	CMV	IV, PO
Foscarnet	GCV-resistant CMV, CMV retinitis in AIDS; ACV-resistant HSV & VZV,	IV, intravitreal
Cidofovir	GCV or foscarnet-resistant CMV, CMV retinitis in AIDS	IV
Interferon-α	Hepatitis –B & C	IM or SQ

 

 

Antiviral agents for respiratory viral infections

 

Anti-Influenza agents

  - Amantadine & rimantadine

  - Zanamivir & oseltamivir

Ribavirin

 

 

Amantadine and Rimantadine

: Prophylaxis and Tx for influenza A

 

Neuraminidase inhibitors

 

Neuraminidase

permits the virus to penetrate to the surfaces of cells

necessary for the optimal release of virus from infected cells

Neuraminidase inhibitors

Zanamivir (Relenza, Inhalation), oseltamivir (Tamiflu, po)

Permivir IV

 

 

Ribavirin

 

guanosine analogue that has incomplete purine ring

Mechanism of action

  : Ribavirin triphosphate interfere with viral transcription such as the capping and elongation of mRNA and inhibit ribonucleoprotein.

Clinical uses

   : RSV infection (aerosol),

     Hepatitis-C (oral ribavirin in combination with interferon),

     Hantan virus infection, Lassa fever

S/E : anemia, bronchospasm (aerosol), rash

 

 

Antiviral drug	Clinical efficacy
Amantadine, rimantadine	Influenza  A
Zanamivir, oseltamivir,  peramivir	Influenza  A & B
Ribavirin	Lassa fever, hantavirus (HFRS), hepatitis C (in chronic cases in combination with INF-a), RSV