ANTIVIRUS

Langkah-langkah siklus replikasi virus

-attachment of the virus to the host cell
-entry of the virus through the host cell membrane
-uncoating of viral nucleic acid
-synthesis of early regulatory protein (nucleic acid po
lymerases)
-synthesis of RNA or DNA
-synthesis of late,structural proteins
-assembly (maturation) of viral particles
-release from the cell
Antiviral agents can potentially target any of these
step.
Agents to treat Herpes simplex virus (HSV) &
Varicella-zoster virus (VZV)

ACYCLOVIR
-prodrugmetabolism—acyclovir triphosphate
 inhibit viral DNA synthesis.
-clinical activity against: HSV-1; HSV-2 ; VZV.
-in vitro: against:EBV; CMV; HHV-6.
-admin: oral / i.v.
-widely distributed
–excretion: renal
-ADR: well tolerated ; nausea,vomiting ,diarhea
Valacyclovir
-oral admin.metabolism acyclovir
-serum level : 3-5 x oral acyclovir
-clinical uses:* first or recurrent genital herpes
*a 1 day treatment for orolabial
*effective in preventing CMV di
sease
* decrease duration of zoster-
associated pain
-ADR: well tolerated; nausea, vomiting,rash.
FAMCICLOVIR
-prodrugmetabolizedPenciclovir,
-in vitro,active against:HSV-1;HSV-2; VZV;EBV; HBV
-oral admin.bioavailability 70%
-clinical use: first and recurrent genital herpes,chronic
daily supression of genital herpes,acute zoster.
-ADR: well tolerated;headache, diarhea,nausea.

PENCICLOVIR
-active metabolite of famciclovir
-topical (cream) effecive for recurrent herpes labialis.

DOCOSANOL
-preventing viral entry into cell and subsequent viral
replication;topical use in recurrent oro labial herpes.
TRIFLURIDINE
-Incorporation of trifluridine triphosphate into both
viral and host DNA prevents its systemic use
-Application of 1% solution is effective in treating
keratoconjunctivitis and recurrent epithelial keratitis
due to HSV-1 and HSV-2.
-trifluridine alone or in combination with interferon
alpha succesfull in treating of acyclovir resistant
HSV infection.
AGENTS TO TREAT CYTOMEGALOVI-
RUS (CMV) INFECTIONS.

GANCICLOVIR
--active compound competitively inhibit viral DNA poly-
merase and causes termination of viral DNA elongation
-in vitro activity against:CMV, HSV, VZV, EBV, HHV-6,
and KSHV.
-Activity against CMV 100 x Acyclovir.
-admin:oral , I.v. , intraocular implant ,direct intravitre
al to treat CMV retinitis.
-ADR:myelosuppression,nausea,diarhea,fever,rash,
headache,insomnia,eripheral neuropathy.
VALGANCICLOVIR
-prodrugoral admin.metab. byintestinal & hepatic
esterasesganciclovir.
-Excretion: renal
-clinical uses: CMV retinitis in patients with AIDS and
preventionof CMV infection in high risk kidney,heart
transplant
-ADR: is the same wiyh ganciclovir.
FOSCARNET
-inhibits viral DNA polymerase, RNA polymerase and HIV reverse
transcriptase directly without requiring activation by phosphory
latiob.
-active against:HSV, VZV, CMV, EBV, HHV-6, KSHV and HIV-1.
-preparatin: intravenous formulation only.
-clearance: kigney.
-clinical uses: CMV retinitis
-ADR: renal impairment, hypo or hypercalcemia, hypo or hyper
phosphatemia,hypokalemia,hypomagnesemia.penile ulcera
tion, nasea,vomiting,anemia,elevation of liver enzmes
CIDOFOVIR
-invitro activity:CMV ,HSV-1, HSV-2 , VZV, EBV, HHV-6
,KSHV,adenovirus,poxviruses,polyoma-viruses
human papilloma virus
-inhibit DNA synthesis.
-i.v. administrationeffective for CMV retinitis
-ADR: nephrotoxicity,uveitis,ocular hypotony,neutrope
nia,metabolic acidosis
ANTIRETROVIRAL AGENTS
*Nucleoside/Nucleotide reverse transcriptase inhibitors
(NRTIs)
*Nonnucleoside reverse transcriptase inhibitors
(NNRTIs)
*Protease inhibitors (PIs)
*Fusion inhibitors
The NRTIs act by competitive inhibition of HIV-1 reverse
Transcriptase and also can be incorporated into the grow-
ing viral DNA chain to cause termination.Each requires
Intracytoplasmic activation via phosphorylation by cellular
enzymes to the phosphate form. Most have activity against
HIV-2 as well as HIV-1.
NRTI treatment should be suspended in the setting of rapid
ly rising aminotransferase level,progressive hepatomegaly
or metabolic acidosis of unkown cause.
ABACAFIR
-abs:oral,well absorbed,unaffected by food
-guanosine analog
-K65R mutation is associated with reduce
susceptibility to lamivudine,abacafir,tenofovir,
emtricitabine
-ADR:
hypersensitivity reactionnausea,vomiting, diarhea
pharyngitis, cough,skin rash.
-Didanosine
-Emtricitabin
-Lamifudine
-Stavudine
-Tenofovir
-Zalcitabine
-Zidovudine
The use of antiretroviral agents in
pregnancy
Recommended agents Alternate agents

NRTIs
-Zidovudin, Lamivudine Didanosine,Emtricitabine
Stavudine, Abacafir
NNRTIs
Nevirapine

Protease inhibitor (Pis)

Nelfinavir, Saquinafir-s Indinafir, lopinafir/ritona
vir
 NONNUCLEOSIDE
REVERSTRANSCRIPTASE INHIBITORS
Delavirdine Efavirenz Nevirapine

Protease inhibitors
Amprenavir Atazanavir
Fosamprenavir Indinavir
Lopinavir/Ritonavir Nelfinavir
Ritonavir Saquinavir
Tipranavir