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ANTIVIRALS

Mary Joyce M. Saborrido, MD

MOA

Major Drugs

Block viral Amantadine penetration/ uncoating Rimantadine Inhibit viral DNA Acyclovir, Ganciclovir, polymerase Foscarnet Inhibit viral RNA Foscarnet, Ribavirin polymerase Inhibit viral RT AZT, DDI, DDC, d4T, 3TC Inhibit viral aspartate Indinavir, Ritonavir, protease Saquinavir Inhibit viral Zanamivir, Oseltamivir neuramidase

Viral penetration inhibitors


Amantadine Rimantadine

Amantadine & Rimantadine


MOA: (-) attachment, penetration, & uncoating of Inf A USE: Prophylaxis only Form: PO AE: CNS effects Resistance: altered M2 matrix/ H proteins

Viral nucleic acid synthesis inhibitors


Antiherpetics

Acyclovir
MOA: ACV ACV monoPO4 ACV triPO4 DNA polymerase (DNA chain termination) USE: HSV & VZV Form: Topical, PO, IV AE: IV (Crsytalluria & Neurotoxic) Resistance: due to change in DNA polymerase / dec. activity of TK

TK Host cellsTK

Famciclovir & Valacyclovir


MOA: same as ACV Activity against strains resistant to ACV, but not TK- strains Form: PO (well absorbed)

Ganciclovir

MOA: same as ACV (not DNA chain termination) USE: HSV, VZV, CMV (prop & Tx) Form: PO, IV, retinal implant AE: Dose limiting hematotoxicity, mucositis, fever, rash, crystalluria, Seizures in OD Resistance: same as ACV

Foscarnet

MOA: Not an antimetabolite, but still (-) DNA & RNA polymerases USE: Identical to GCV, but > activity versus resistant strains of HSV Form: IV AE: Dose limiting nephrotoxicity w/ ATN, electrolyte imbalance dec. Ca+2 tremors & seizures

Viral nucleic acid synthesis inhibitors


Anti-myxovirus drugs

Ribavirin

MOA: RBV monoPO4 IMP DH RBV triPO4 viral RNA polymerase & end-capping of viral RNA USE: RSV, Inf A & B, Lassa fever, Hantavirus, adjunts to alpha-intf in Hepa C Form: Aerosol, Topical, PO, IV AE:Hematotoxic, upper airway irritation, Teratogenic

Reverse Transcriptase Inhibitors (RTIs)


Ant-retrovirus drugs

NRTIs
Components of most combination drug regimens used in HIV infection Used 2 NRTIs w/ PI Use in HAART ( dec viral RNA, inc CD4 cells, dec opportunistic infxn)

Nonnucleoside RTIs
Resistance emerges if used individually Additive/ Synergistic against HIV E.g: Nevirapine, Delaviridine

Zidovudine (Azidothymidine, AZT, ZDV)

MOA: ZDV RT (Viral chain termination) USE: HIV infected w/ dec CD4 ct; Pregnant HIV dec transmission to baby Form: PO; IV AE: Dose limiting hematotoxicity, HA, Asthenia, myalgia, myopathy, peripheral neuropathy, LA Resistance: Mutation in the gene that codes RT

Other NRTIs
MOA: Same as AZT USE: Same as AZT Form: PO AE: Different

Didanosine (Dideoxyinosine, DDI) Zalcitabine (Dideoxycytidine, DDC) Stavudine, D4T

Pancreatitis

Peripheral neuropathy

Peripheral neuropathy

Lamivudine (2Least toxic of NRTIs, but deoxy-3thiacytidine, some GI effects & 3TC) neutropenia

Protease Inhibitors (PIs)


Anti-retrovirus drugs

PIs

MOA: Aspartate protease is a viral enzyme that cleaves precursor polypeptides in HIV buds to form the CHONs of the mature virion core. USE: In combination w/ 2 NRTIs AE: Indinavir (GI distress, asthenia, paresthenia) Saquinavir (one of the least toxic, has very low oral bioavailability) Resistance: Mutation of protease

Viral neuramidase inhibitors


Zanamivir Oseltamivir

Zanamivir & Oseltamivir


MOA: (-) neuramidase of Inf A & B, enzymes that prevent clumping of virions USE: Prophylaxis, dec duration of flu by 23 days Form: Inhaled & PO AE: N & V, Nasal & Throat irritation