Viruses are the ultimate expression of parasitism. They not only take nutrition from the host cell but also direct it metabolic machinery to synthesize new virus particles. viral chemotherapy was considered impossible, as it would require interference with cellular metabolism in the host.
Classification
1. Anti-Herpes virus : idoxurudine, trifluridine, Acyclovir, valacyclovir, Famciclovir, Ganciclovir, Valganciclovir, Cidofovir, Foscarnet, Fomivirsen
2. Anti-Influenza virus: Amantadine, rimantadine, Oseltamivir, Zanamivir
3. Anti-Hepatitis virus/nonselective antiviral drugs Primarily for hepatitis B: Lamivudine, Adefovir dipivoxil, Tenofovir Primarily for hepatitis C: Ribavirin, Interferon α
4. Anti retrovirus:
(A) neucleoside rivers transcriptas inhibitor: Zidovudine
Didanosine, Stavudine, lamivudine, Abacavir, Emtricitabine, Tenofovir
(B) nonnucleoside reverse transcriptase inhibitors (NNRTIs): Nevirapine, Efavirenz, Delavirdine
(C) Protease inhibitors: Ritonavir, Atazanavir, Indinavir, Nelfinavir, Saquinavir, Amprenavir
(D) Entry (Fusion) inhibitor: Enfuvirtide
(E) CCR5 receptor inhibitor: Maraviroc
(F) Integrase inhibitor: Raltegravir
Acyclovir
This deoxiguanosine analogue antiviral drug requires a virus specific enzyme for conversion to the active metabolite that inhibits DNA synthesis and viral replication.
Acyclovir is taken by the virus infected cells. Because of selective generation of the active inhibitor in the virus infected cell and its greater inhibitory effect on viral DNA synthesis, acyclovir has low toxicity for host cells: a several hundred-fold chemotherapeutic index has been noted.
Pharmacokinetics
Only about 20% of an oral dose of acyclovir is absorbed. It is little plasma protein bound and is widely distributed attaining CSF concentration that is 50% of plasma concentration. After topical application, it penetrates cornea well. Acyclovir is primarily excreted unchanged in urine, both by glomerular filtration and tubular secretion; plasma t½ is 2–3 hours.
Use
Acyclovir is very usefull in patients with normal as well as deficient immune status.
genital Herpes simplex generally caused by type 2 virus can be treated by topical, oral or parenteral acyclovir depending on stage & severity of disease.
Primary disease: Topical treatment has low efficacy; 5% ointment is applied locally 6 times a day for 10 days. This is useful if started early and in mild cases. Late and more severe cases should receive oral therapy (1 g/day in 5 divided doses or 400 mg TDS for 10 days) in addition to local therapy. Both local and oral therapies afford symptomatic relief and rapid healing of lesions, but do not prevent recurrences
Mucocutaneous H. simplex It is a type-1 virus disease, remains localized to lips and gums; does not usually require specific treatment, but acyclovir skin cream may provide some relief. Spreading lesions may be treated with 10 day oral acyclovir. The disease often gets disseminated in immunocompromised individuals and may be treated with oral or i.v. acyclovir (15 mg/kg/day) for 7 days, but recurrences are not prevented.
H. simplex encephalitis (type-1 virus): Acyclovir 10 to 20 mg/kg/8 hr i.v. for >10 day is the drug of choice. Treatment is effective only if started early: delay precludes salutary effect on mortality and neurological complications.
Side effects
topical: Stinging & burning sensation after each application. oral: The drug is used for headache, nausea, malaise and some CNS effects. Intravenous: Rashes, sweating, emesis and fall in BP occur only in few patients. Dose-dependent decrease in g.f.r. is the most important toxicity; occurs especially in those with kidney disease; normalises on discontinuation of the drug
Amantadine
Chemically, it is a unique tricyclic amine unrelated to any nucleic acid precursor, but inhibits replication of influenza A virus. the activity of amantadine is strain specific, influenza b is not affected. H5N1 and H1N1 strains of Influenza A are resistant in most areas. it appears to act an early step (possibly uncoating) as well as at a late step (viral assembly) in viral replication. protein designated M2 which acts as an Ion channel has been identify as one of is targets of action. Resistance to amantadine develops by mutation causing amino acid substitutions in the M2 protein.
Uses
Prophylaxis of influenza A2 during an epidemic or seasonal influenza, especially in high risk patients. Influenza season and epidemics generally last ~ 2 months, and only this period needs to be covered by prophylaxis.